Postnatal Confinement Care

Breast Cancer n Underarm Products

2012-01-27T20:39:00.000-08:00

From Medscape Medical News > Oncology

Link Between Parabens and Breast Cancer?

Roxanne Nelson

January 26, 2012 — Can the use of antiperspirants and deodorants increase the risk for breast cancer?

Data from a study published online January 12 in the Journal of Applied Toxicology could relieve some of the fears about using underarm products, but could also raise questions and concerns.

The issue centers on exposure to alkyl esters of p-hydroxybenzoic acid (parabens), which are widely used as antimicrobial preservatives in pharmaceuticals, foods, and cosmetics. About 10 years ago, note the researchers, studies began to reveal that parabens had estrogenic properties, and estrogen plays a central role in the development, growth, and progression of breast cancer.

In this new study, researchers in the United Kingdom examined 160 breast-tissue samples obtained from 40 patients who had undergone a mastectomy for primary breast cancer. They found that 99% of samples had traces of at least 1 paraben, and that 60% had traces of 5 different parabens.

Importantly, 7 of the women reported never having used underarm products. This suggests that the parabens originated from another source, note the authors.

The source of the parabens measured in this and in previous studies cannot be identified; it is also not clear if the paraben traces come from long-term accumulation, current exposure, or a combination of both.

Parabens are only one part of a much bigger picture.

"I do think that the parabens are only one part of a much bigger picture," said lead author Philippa D. Darbre, PhD, a reader in oncology at the University of Reading, United Kingdom.

"That is not to say that they do not contribute, but the issue is bigger," she told Medscape Medical News. "Parabens are only one component...of personal care products. What is needed now is...a map of what chemicals there are in a human breast in the modern world and how they distribute across the breast, especially in relation to the site of the tumor."

Adding to the Evidence

In their study, Dr. Darbre and colleagues found a disproportionate incidence of breast cancer in the upper outer quadrant of the breast. In all 40 women, levels of n-propylparaben were higher in the axilla region than in the mid or medial regions (Wilcoxon matched pairs test, P = .004 and P = .021, respectively).

This finding is not unusual; a number of studies over the past several decades have reported that a disproportionately high number of breast tumors in women originate in the upper outer quadrant of the breast, "for which a definitive explanation remains lacking," the authors write. This disproportionality has been increasing in the United Kingdom, and now exceeds 50% of breast cancers.

"The detection of intact esters is more suggestive of a dermal route of exposure," said Philip W. Harvey PhD, a registered toxicologist at Covance Laboratories Ltd, North Yorkshire, United Kingdom, who was not involved in the study. "Oral exposure results in the rapid conversion of the esters to the common metabolite p-hydroxybenzoic acid in both gut and liver. The skin has a much lower esterase capacity, which may explain the fact that 5 different intact paraben esters were found."

Dr. Harvey told Medscape Medical News that the gradient or differential concentrations between zones with the highest levels in the axilla are consistent with a dermal route of exposure. "If the residues derive from dermal sources, the highest concentrations are likely to be at the site of exposure," said Dr. Harvey, who is editor-in-chief of the Journal of Toxicology. "That the axilla shows the highest concentrations is consistent with local application and implicates any products applied there."

He emphasized that Dr. Darbre and colleagues did not investigate causal mechanisms of breast cancer, and did not claim that either parabens or underarm products actually caused the cancer in the patients studied. "However, it does add to the dataset that these weakly estrogenic chemicals are found in significant quantities in estrogen-sensitive tissue," he noted. "Not all women will be sensitive to this, but...there will be a proportion of women who are sensitive."

Causal Relationship Undetermined

Personal care products have been used since the days of Cleopatra, but unprecedented quantities are being used nowadays, and are ultimately being released into the environment, explained Dr. Darbre. Investigations have shown that there is widespread aquatic environmental pollution stemming from use, and therefore little doubt that these chemicals are entering human tissues. The human breast has "become a sink for lipophilic compounds due to its high adipose tissue content," she said.

However, in a previous paper, Dr. Darbre and colleagues pointed out that it remains to be determined whether there is any causal relation between individual or combinations of chemicals and the development of breast cancer (CML Breast Cancer. 2010;22:113-122). The real environmental impact of estrogenic chemicals needs to comprise the entire chemical load in the breast.

An increasing number of environmental chemicals with estrogenic properties have been measured in human breast tissues, the authors of that paper write, which shows that the human breast is exposed to many estrogenic compounds in low doses and over a long period of time. These chemicals could act synergistically to "produce an estrogenic stimulus even at concentrations at which each alone would be ineffective."

There is a gap in our understanding of the combined effect of different chemicals in a single human breast, the authors note, because reports of measurements to date have generally evaluated only single groups of chemicals in any one study group.

"In the meantime, I remain rather ambivalent about hounding just one chemical," said Dr. Darbre. "My advice remains as always — to cut down on, or cut out as much as possible, overall use of personal care products, especially those left on the skin around the breast area."

"When even the water systems are now having to remove personal care product compounds from them, we must be simply using too much in the modern world — too much for our own bodies and too much even for the environment," she added. "The only way forward at the moment is for us all to cut down."

Higher Levels Seen

In this study, Dr. Darbre and her team measured the concentrations of 5 parabens at 4 serial locations in the human breast, from the axilla to the sternum, using tissue samples collected in from 2005 to 2008.

The authors found that at least 1 paraben ester was quantifiable in 158 of 160 specimens (99%), and that all 5 esters were quantifiable in 96 of 160 specimens (60%).

The overall median value for total parabens in the breast tissue was 85.5 ng/g (range, 0.0 to 5134.5 ng/g). This level is 4 times higher than the 20.6 ng/g seen in a smaller previous study, which was also led Dr. Darbre (J Appl Toxicol. 2004;24:5-13).

The highest values were observed for n-propylparaben, at 16.8 ng/g (range, 0.0 to 2052.7), and methylparaben, at 16.6 ng/g (range, 0.0 to 5102.9). They were much lower for n-butylparaben, at 5.8 ng/g (range, 0.0 to 95.4), ethylparaben, at 3.4 ng/g (range, 0.0 to 499.7), and isobutylparaben, at 2.1 ng/g (range, 0.0 to 802.9).

More Research Needed

Dr. Harvey noted that the dataset is sparse and there is a need for further research. "The rising incidence of breast cancer in recent decades points to environmental or lifestyle factors, and chemical exposure — of which the cosmetics scenario is one of the most obvious for direct dermal exposure — is just one implicated factor, together with all the other known factors for breast cancer," he said.

In addition, the regulatory toxicology dataset on parabens as a whole needs to be updated, he added, noting that European regulators are slowly taking steps on information that is coming to light, specifically reducing permitted concentrations of some paraben esters.

"The wisdom of putting estrogenic chemicals in any dermal product must be questioned, particularly compounds with an old regulatory toxicology dataset that probably does not achieve adequate modern standards, and particularly where current-use patterns already indicate that there is insufficient margins of safety in some groups, such as children," Dr. Harvey said.

It is easy to say that there is no evidence of parabens or cosmetics being associated with a health effect if the research has not been done.

"The whole area is poorly researched, but it's now time to coordinate funding and support into a few key areas of environmental endocrine disruption and human health, and the cosmetics scenario is one of the most promising to study in a controlled way," he emphasized. "It is easy to say that there is no evidence of parabens or cosmetics being associated with a health effect if the research has not been done; indeed, the statement is misleading to the public."

Michael J. Thun, MD, vice president emeritus of epidemiology and surveillance research at the American Cancer Society, cautioned that this analysis not be misinterpreted. "The purpose was not to study whether parabens in general or underarm deodorants affect breast cancer risk," he said. "Rather, it examined the levels and anatomic distribution of various paraben compounds in the excised breasts of 40 women with breast cancer."

However, he agrees that more research is needed. "Questions have been raised about their safety because parabens are absorbed through the skin and trace amounts can be detected in tissues, including breast tissue," he explained. "Parabens weakly mimic the effects of estrogen, a hormone known to play a role in breast cancer. No study has yet shown that the concentration of parabens in breast tissue taken from women with breast cancer are higher than that in breast tissue of women without breast cancer. A well-designed study of this issue would be useful."

The Genesis Breast Cancer Prevention Appeal funded the salary of a clinical research fellow and the cost of the liquid chromatography–tandem mass spectrometry analysis. The authors have disclosed no relevant financial relationships.

J Appl Toxicol. Published online January 12, 2012. Abstract

Antirheumatic Drugs and Pregnancy: A Primer

2012-01-02T22:01:00.000-08:00

From Medscape Rheumatology > Ask the ExpertsAntirheumatic Drugs and Pregnancy: A PrimerRobert I. Fox, MD, PhDPosted: 12/13/2011QuestionIn a patient taking methotrexate (MTX) for psoriatic arthritis or rheumatoid arthritis, how long of a washout period should be considered before she can safely attempt to conceive? Is there any published information on the long-term use of MTX being related to birth defects or abnormal deliveries once MTX is stopped?Response from Robert I. Fox, MD, PhD Chief, Rheumatology Clinic, Scripps Memorial Hospital, La Jolla, CaliforniaWomen taking methotrexate for arthritis should discontinue this drug and use contraception for at least 3 months before conception based on the recommendations of the American College of Rheumatology.There have been several published studies in the older literature that suggest that for structural anomalies, the critical time interval off methotrexate is from 8 to 10 weeks after the first day of the last menstrual period and the critical dose associated with fetal defects is ≥ 10 mg/week.MTX is a potent abortifacient, and its use during pregnancy is associated with multiple skeletal abnormalities. Methotrexate-induced developmental toxicity is strongly related to when the drug is given and also the dose. There is no evidence that the duration of treatment or the "net total dose" is a predictor of miscarriage or fetal malformation.What About Other Antirheumatic Therapies?Several other examples of antirheumatic therapy and pregnancy are reviewed below:Hydroxychloroquine crosses the placenta. However, there does not appear to be fetal toxicity with hydroxychloroquine doses used for the treatment of connective tissue disorders.Leflunomide (LEF) was teratogenic in animal models, and effective contraception is essential for women of childbearing potential for whom LEF is prescribed. LEF is considered by the US Food and Drug Administration as a "Category X" drug in terms of the risks associated with its use in pregnancy. LEF-treated patients should "wash out" drug using cholestyramine and then wait at least 90 days before attempting pregnancy.Infliximab: According to the manufacturer's prescribing information, infliximab should be given to a pregnant woman only if clearly needed. This information is available at http://www.remicade.com/remicade/assets/HCP_PPI.pdf. However, no maternal toxicity, embryotoxicity, or teratogenicity to infliximab was observed in a murine toxicity model conducted by the manufacturer. Rates of live births, miscarriages, and therapeutic terminations do not appear to be significantly different in women exposed to infliximab during pregnancy according to a registry maintained to track birth defects in women receiving tumor necrosis factor inhibitors during pregnancy.Adalimumab: Studies in monkeys have not revealed harm to the fetus when adalimumab was given during pregnancy. There are no well-controlled studies in humans.Certolizumab pegol: There are no well-controlled studies of certolizumab pegol in pregnant or lactating women. Studies in rats showed that pegylated Fab fragments did not cross the placenta and did not reveal evidence of harm to the fetus. However, exposure to certolizumab pegol during pregnancy is too limited to draw any conclusions.

Moderate Soy Consumption OK for Breast Cancer Survivors

2011-11-11T18:16:00.001-08:00

From Medscape Medical News > OncologySandra YinNovember 7, 2011 (Washington, DC) — It is all right for breast cancer survivors to consume moderate amounts of soy foods, Bette Caan, PhD, a senior research scientist who specializes in nutritional epidemiology at the Division of Research at Kaiser Permanente Northern California in Oakland told attendees here at the American Institute for Cancer Research (AICR) Annual Research Conference 2011 on Food, Nutrition, Physical Activity and Cancer in a session on cancer treatment and survivorship.Dr. Caan sought to clarify the highly charged topic of whether soy is safe for breast cancer survivors by reviewing the epidemiologic literature.Soy has been touted in the mainstream media as "the miracle bean" and laypeople read about everything from the "joy of soy" to the "dark side of soy." It is not surprising that the public and experts are confused, Dr. Caan acknowledged. Part of the problem is conflicting data.Soy foods can either increase the risk for breast cancer progression or decrease the risk, she observed. Evidence suggests that lifetime endogenous estrogen exposure increases the risk for breast cancer. So people were afraid to tell breast cancer survivors that it was okay to eat soy.Clinicians have several options based on the epidemiologic literature, and some routinely advise against soy in the diet of patients with breast cancer, Dr. Caan noted, "and I don't think the current science supports that at all."No Evidence of HarmAfter reviewing the 7 epidemiologic studies, Dr. Caan said there was no evidence that soy is harmful for women with breast cancer, and pointed out that 6 of the 7 studies demonstrate some type of benefit.On the basis of the lack of harm and the benefits reported in the studies she cited, clinicians might want to recommend that patients with breast cancer begin eating whole soy foods to treat breast cancer, but she cautioned that she doesn't think existing data were strong enough to justify that."What I do think is that they could adopt a stance of permitting use in patients who want to begin eating reasonable amounts of soy foods or for whom soy foods already represent a normal part of their diet," Dr. Caan said.The data support this option, and she said they were consistent with the American Cancer Society (ACS) position.The ACS is in the process of rewording its guidelines. The old ones said that up to 3 servings of traditional soy foods per day are unlikely to be harmful. According to Dr. Caan, those guidelines may be revised to state that women with breast cancer can eat moderate amounts of soy foods.She added 1 caveat: to avoid concentrated sources of soy, such as pills, powders, or supplements containing high amounts of isoflavones, because data are lacking on the risks and benefits. "We still need to proceed with caution," she said.The discussion heated up during the session's Q&A when another presenter, Leena Hilakivi-Clarke, PhD, professor of oncology at Georgetown School of Medicine, Washington, DC, whose talk focused primarily on animal research, shared her advice on soy consumption. If a woman had been consuming soy before diagnosis, it would be perfectly safe to eat the same amount or maybe increase it a little bit, she said. But her recommendation was more cautious for another subgroup. "If she had not eaten any soy beforehand, my opinion is that she shouldn't start before we know whether it's safe or not," she said.A member of the audience took issue with the latter advice. "First, when human data exists, it should surpass animal data," said Mary L. Hardy, MD, medical director at the Simms/Mann University of California at Los Angeles Center for Integrative Oncology. Nor was she convinced that models using a vectorized mouse or rat were an appropriate model for humans. "Third, If we're moving people toward a plant-based diet, and we take out a really good source of plant-based nutrition, how are we taking with one hand and giving with another?"Because her patients have heard from the media or uninformed physicians that soy is bad, Dr. Hardy said they "freak out" because they see soy in everything, as it is used as an emulsifier and a flow agent. "They'll think they can't eat anything, which can be confusing and demoralizing," she said. "I'm very hesitant for that advice to be promulgated, when I think it's going to cause at many levels more harm than good."Later Dr. Hardy told Medscape Medical News that she agreed with Dr. Caan's recommendations. But she had another concern about Dr. Hilakivi-Clarke's advice. In her practice, she actively encourages people to eat a plant-based diet and reduce their dependence on red meats. Taking away meat and then soy would confuse patients who want to identify a good-quality protein source, she said. What's more, the average breast cancer patient whose tumor was caught early and is responsive is probably many times more likely to face risk for heart disease than breast cancer, so it wouldn't make sense to take away a heart-healthy food that lowers cholesterol, she said. "I think inappropriately discouraging soy use is going to cause problems."Dr. Caan told Medscape Medical News that either you eat soy or you don't. If you enjoy soy as part of your diet, you can continue to eat it because more evidence suggests that it's beneficial. Referring to the other speaker's advice that patients with breast cancer who have never eaten soy should not start to eat it to treat their cancer, she said, "Who are those people? You're giving a warning to people who don't exist."Dr. Caan and Dr. Hilakivi-Clarke have disclosed no relevant financial relationships. Dr. Hardy serves on the scientific advisory board of Dean Foods, which makes soy milk.American Institute for Cancer Research (AICR) 2011Annual Research Conference on Food, Nutrition, Physical Activity and Cancer. Presented November 3, 2011.

Prenatal health and your baby

2011-11-09T22:00:00.001-08:00

Did you know that having a healthy pregnancy and baby actually starts before you get pregnant? Taking care of yourself when you’re thinking about becoming pregnant is important. This includes: Eating healthy foods and getting regular exercise. Canada’s Food Guide offers tips and advice for healthy eating at all stages of life. Aiming for at least 30 minutes of moderate exercise, 5 days a week. Making sure your vaccines are up-to-date. Check with your doctor to ensure you are properly protected against illnesses like rubella, chickenpox and influenza. Getting these vaccines will help protect your baby. Talking to your doctor about any prescription drugs you are taking to find out whether they are safe during pregnancy.Vitamins before pregnancy:If you are planning to get pregnant, you should be taking folic acid. Folic acid (also called folate or folacin) is a vitamin that helps a baby’s neural tube develop properly during pregnancy. The neural tube becomes your baby’s brain and spinal cord. Neural tube defects (NTD) result from openings in the spinal cord that do not close properly during early pregnancy, causing spina bifida and anencephaly. Folic acid protects against NTDs and can also lessen the risk of other problems at birth, such as cleft palates or heart, genital and urinary defects. Although certain foods (fortified grains, spinach, lentils, chick peas, asparagus, broccoli, peas, Brussels sprouts, corn, and oranges) have folic acid, it can be hard to get enough from diet alone. Most healthy women should take a daily multivitamin with 0.4-1.0 mg of folic acid, for at least 2 to 3 months before getting pregnant, throughout pregnancy, and then after birth for as long as they breastfeed. Women who have diabetes or epilepsy, and women with a family history of NTDs (a sibling, parent or cousin with the condition), or who have already had a baby with an NTD need a higher dosage, and should supplement their diet with between 0.8 and 4 mg of folic acid daily. Talk to your health care professional if you aren’t sure how much you should take.Vitamins during pregnancy: You should take a multivitamin during pregnancy that includes between 16 and 20 mg of iron. You should also take vitamin D. Your doctor may recommend up to 2000 IU/day. Not getting enough vitamin D during pregnancy will affect how much vitamin D your baby has at birth. A baby born to a mother who is vitamin D deficient is more likely to have vitamin D deficiency rickets. Cow’s milk, margarine and some soy beverages produced in Canada are fortified with vitamin D. If you don't use these products, if you do not have much exposure to sunlight or your skin is covered much of the time outside—especially if you do not take vitamin D supplements—then you are more likely to be vitamin D deficient.How much weight should I gain during my pregnancy?Weight gain is an important part of supporting your growing baby and placenta, which provides your baby with the nutrients he needs. Women who gain the recommended amount of weight during pregnancy have fewer complications that can lead to things like caesarean section, high blood pressure, and low or high birth weight for your baby. How much should I eat during pregnancy?Your baby is counting on you to provide all the nutrients she needs to grow healthy and strong. Making smart choices about food will help you both stay healthy during and after pregnancy. Also, be sure to prepare food carefully so that you avoid illnesses such as listeriosis or salmonella infection.Canada’s Food Guide suggests how much you should eat from each food group:Vegetables and fruit are a source of vitamins, minerals and fibre.7-8 servings/dayChoose at least one dark green and one orange vegetable or fruit every day.Grain products are an important source of energy from carbohydrates.6-7 servings/dayMake at least half of the grain products whole grain.Milk and alternatives are nutritious sources of calories, as well as calcium and vitamin D. Some alternatives (such as fortified soy beverage) have vitamin D added. Check labels for calcium and vitamin D content.2 servings/day Drink skim, 1% or 2% cow’s milk or fortified soy beverage each day.Meat and alternatives are important sources of iron and protein. 2 servings/dayChoose a variety of lean meat, poultry, and de-boned fish, eggs, tofu, dried peas, beans and lentils.At least 2 servings of fish /week are recommended.Oils and fats2-3 tbsp a day Canada’s Food Guide also recommends an extra 2-3 servings from any one of the 4 food groups every day. Be sure to drink plenty of water throughout the day.Is there anything I should avoid consuming while pregnant? Fish with higher levels of mercury (such as shark, swordfish and fresh tuna) should be avoided, because mercury can harm a developing baby. Canned, chunk light tuna generally has a lower amount of mercury than other tuna, but should still be eaten in moderation, with no more than 150 g a month. Avoid raw fish, which may contain bacteria or parasites that can make you sick. Limit caffeine, and consider cutting it out of your diet completely while pregnant. Certain medications can also be dangerous to your baby during pregnancy. If you are on any medications, talk to your doctor about whether you should keep taking them when pregnant.How can I stay active during pregnancy?Staying active during your pregnancy will help ease your aches and pains and may help with your mood. It’s also a good way to ensure you have the energy you need for your pregnancy and delivery. Some suggestions for physical activity include: regular walking, swimming, low-impact aerobics, prenatal exercise classes, and yoga.If you weren’t already active before your pregnancy, start slowly and speak to your health care provider before starting a new exercise routine.Can I drink alcohol while I am pregnant?If you drink alcohol during your pregnancy, the alcohol goes to the baby through your bloodstream. Drinking alcohol during pregnancy can cause fetal alcohol spectrum disorder (FASD, a serious condition that can affect a child for life.If you are thinking about getting pregnant, it’s best to stop drinking alcohol now. Then you’ll know for sure that your baby will be safe from FASD. Women who find it hard to stop drinking, or who already have a child with FASD, should get help before getting pregnant.Can I smoke or take recreational drugs while I am pregnant?Avoid smoking and drug use during pregnancy. These can be dangerous to your growing baby and increase the risk of Sudden Infant Death Syndrome.If you are thinking about getting pregnant, it’s best to stop drinking alcohol, smoking or doing recreational drugs now. Then you’ll know for sure that your baby will be safe. If you are already pregnant, you should stop drinking alcohol, smoking or doing recreational drugs completely.For more information: Fetal alcohol spectrum disorder: What you should know about drinking during pregnancy Depression in pregnant women and mothers: How it affects your child Prenatal nutrition, a resource by Health Canada Healthy pregnancy, a resource by Health Canada Healthy Beginnings, a book on pregnancy from the Society of Obstetricians and Gynaecologists of Canada (SOGC). Healthy eating, exercise and weight gain: Before and during pregnancy, from SOGC. Pregnancy and breastfeeding resources, MotheriskReviewed by the CPS Public Education Advisory CommitteePosted: August 2011This information should not be used as a substitute for the medical care and advice of your physician. There may be variations in treatment that your physician may recommend based on individual facts and circumstances.Canadian Paediatric Society2305 St. Laurent Blvd.,Ottawa, Ont. K1G 4J8Phone: 613-526-9397, fax: 613-526-3332

'Safe Sleep'

2011-10-24T18:25:00.000-07:00

From Medscape Medical NewsUpdated AAP Policy Statement Stresses 'Safe Sleep'Fran LowryOctober 21, 2011 (Boston, Massachusetts) — The American Academy of Pediatrics (AAP) has expanded its recommendations to ensure a safe sleeping environment for infants and to further reduce the risk for sudden infant death syndrome (SIDS) in a new policy statement.The recommendations were announced here at the AAP 2011 National Conference and Exhibition by pediatrician and SIDS researcher Rachel Moon, MD, from the Children's National Medical Center, Washington, DC, who led the task force that updated the policy statement.Since 1992, when the AAP recommended that all babies be placed on their backs to sleep, deaths from SIDS have declined dramatically; however, sleep-related deaths from other causes, including suffocation, entrapment, and asphyxia, have increased, Dr. Moon said.She told Medscape Medical News that the new policy statement has 3 important changes.First and foremost is the recognition that breastfeeding protects against SIDS."In 2005, there was a lot of evidence that breastfeeding was great for preventing infant mortality in general, but not SIDS specifically. But since 2005, there has been a lot of research that has shown that breastfeeding is protective against SIDS, and we wanted to emphasize that and make that change," Dr. Moon said.The second change is an emphasis on immunization."There's been a lot of press out there about how immunizations may cause SIDS. Again, there's been research to show that this is absolutely not the case. In fact, if you are immunized, your risk of SIDS drops by 50%. We wanted to make that clear; we wanted to put that out there," she said.The third big change, Dr. Moon said, is the recommendation against using bumper pads in cribs to reduce accidental smothering."We have expanded the recommendations in the policy statement to focus not only on SIDS, but on other deaths that can occur. That is why we are recommending against the cushions that go along the sides of the crib," she said. "Children can be suffocated by them."Other key recommendations are: Always use a firm sleep surface. Car seats and other sitting devices are not recommended for routine sleep. The baby should sleep in the same room as the parents, but not in the same bed (room sharing without bed sharing). Keep soft objects or loose bedding out of the crib. Wedges and positioners should not be used. Offer a pacifier at nap time and bedtime. Avoid covering the infant's head or overheating. Do not use home monitors or commercial devices marketed to reduce the risk for SIDS. Supervised, awake tummy time is recommended daily to facilitate development and minimize the occurrence of positional plagiocephaly (flat heads).Eve R. Colson, MD, from the Yale University School of Medicine, New Haven, Connecticut, told Medscape Medical News that she is very happy to see this focus on preventing accidental deaths."As a director of our nursery and somebody who is really into medical education of families and of staff, I am glad to see this because we have seen lots of accidental deaths," Dr. Colson, who was not a member of the policy statement task force, said."We, at Yale, have been so upset by the increased number of deaths in beds happening in New Haven and surrounding areas. In my opinion, the adult bed is not a safe place and I'm glad they've come out with this recommendation."Dr. Colson said she understands "totally" that parents like to be close to their babies, and she encourages this. She said she takes a very sensitive approach when explaining to parents why the adult bed is not safe for babies."We get SIDS deaths in our emergency room, but we also get babies who have suffocated because somebody rolled on them or they have ended up underneath a pillow or got trapped between the mattress and the wall. This is what we have seen and we want to prevent that."Dr. Moon and Dr. Colson have disclosed no relevant financial relationships.American Academy of Pediatrics (AAP) 2011 National Conference and Exhibition. Presented October 17, 2011.

Infants Should Sleep on Their Backs, in Parents' Room

2011-10-21T19:02:00.000-07:00

From Reuters Health InformationBOSTON (Reuters) Oct 18 - Putting babies to sleep on their backs on a firm crib mattress in the same room as the parents is among recommendations on a list of safe sleep guidelines for infants released on Tuesday.The American Academy of Pediatrics first said in 1992 that infants should be placed in a non-prone position for sleeping to curb sudden infant deaths.The latest report, published October 17 in Pediatrics, recommends infants sleep wholly on their backs for every sleep, noting that side sleeping is unsafe.Some supervised awake-time spent on the tummy is recommended.A series of 18 recommendations from the academy are intended to help guide parents, health care providers and others who care for infants following an increase in sleep-related deaths over the last few years.The expanded recommendations focus broadly on creating a safe sleep environment that can reduce the risk of sudden infant death syndrome, suffocation, entrapment and asphyxia, the report said.The guidelines also recommend soft objects and loose bedding like quilts, pillows and even bumper pads not be kept in cribs.Infants should not have routine sleep time in sitting devices like car seats and strollers and should not sleep in a bed where they might suffocate, according to the guidelines.The recommendations, geared to infants up to one year old, also emphasize the importance of regular prenatal care for pregnant women and encourage smoke-free environments for pregnant women and children.SOURCE: http://bit.ly/ofygWN Pediatrics 2011.

Keep your baby safe

2011-10-11T19:34:00.001-07:00

Injury is the leading cause of death among children in Canada. Some of the biggest dangers to babies are falls, burns or scalds, drowning, choking, suffocation or strangulation, and car crashes. The good news is that these injuries are almost always entirely preventable. Parents can take steps to protect their new baby by: Recognizing everyday risks early, and taking precautions. Anticipating a baby’s new skills, and being prepared. Paying special attention at extra busy times of day. Actively supervising. The best way to prevent injury is to watch, listen and stay nearby. When you have to move away from your baby, put him in a safe place, like his crib. Remember: Your infant can’t lift her head until she is about 4 months old, when her neck muscles are stronger, and then only for a short time. She can’t avoid conditions or objects that make it hard for her to breathe. Your infant can squirm and move along a surface long before she can turn over by herself. Even a newborn can wriggle enough to fall off the change table, bed or sofa. Your infant can grasp and shake things, reach for dangling objects, wave a fist and push down firmly with his legs—and fast enough to knock hot or sharp things from your hand.Before you bring your baby home Make sure your crib has a permanent label with detailed manufacturing information, instructions and a warning statement about mattress size and proper use. Never use a crib that is missing this label, or one made before 1987. Check that all the crib bars are present and secure. The mattress should be firm, flat and fit tight within the crib frame. Sheets are smooth and tight-fitting as well. Corner posts shouldn’t be higher than 3 mm (1/8 inch) above the end panels. The frame must be solid, with no cut-out designs or openings where a baby could catch her head. Crib sides should lock securely in place when raised. Mattress support hangers must be secured by bolts and closed hooks. Don’t use a crib where these hooks are “Z” or “S”-shaped. Be sure to check for loose fittings regularly, especially whenever the crib is moved. Place the crib away from windows, window coverings and blind cords. Do not use bumper pads, pillows, lambskins, quilts, stuffed toys or comforters in the crib. Hang mobiles out of reach of your infant’s hands and fasten them securely to both sides of the crib. Don’t use a bassinet or cradle. Even an infant’s weight and movement can make them tip or collapse. Make sure that shelving or any heavy furniture is anchored securely to the wall. Install a smoke alarm in your baby’s room and check all the household smoke alarms to be sure they are working. Install a carbon monoxide detector in your home. Once baby is home, your precautions and behaviour will help protect her against the most common types of injury. Falls Never leave your infant unattended, or in a carrier on any raised surface, such as a bed, sofa or change table. Make sure your change table has a guard rail and safety strap, and always use them. If the phone rings while you are changing a diaper, take your baby with you to answer it or just let it ring. Store everything you need to change a baby within easy reach, so you don’t have to turn away. Make sure your baby sling or front carrier is appropriate for your baby’s age and size. It should support her head and shoulders and have small leg openings, so she can’t slip out. If you bend over, hold your baby against you with one hand so she won’t fall.Burns or scalds Smoke alarms should be installed on every level of the home and in every sleeping area. Check alarms once monthly to be sure they are working, and change the batteries twice each year, when you change the clocks in the spring and fall. Do not allow smoking in your home. Many house fires are caused by careless smoking or children playing with smoking materials such as lighters and matches. Also, cigarettes and butts are poisonous to young children. Set your hot water heater temperature to 49°C (120°F), or put an anti-scald device on your faucets. A baby’s skin burns very easily. Before bathing, check the water temperature with your elbow or wrist. It should feel warm, not hot. Bathe your baby away from the faucets, and remove him from the tub before running the hot water again. Never carry a baby and a hot drink at the same time. Use plastic mats instead of a table cloth that your baby might pull on and cause a spill of hot liquid. Don’t heat breast milk or formula in a microwave. Dangerous “hot spots” can burn an infant’s mouth. Warm a bottle in a pot of hot water instead, and test the milk on your wrist before feeding.Drowning An infant can drown—very quickly and quietly—in as little as 5 cm (2 inches) of water. Always watch and have at least one hand on your baby when she’s in the bathtub, wading pool or near any standing water. Have everything you need for bathing at hand, so that you never have to turn away. Don’t use a bath seat or ring. They are not safe. Never leave your baby alone in the bath with a brother or sister, even for a few seconds. Do not use a cell phone during bath time. If you must answer the telephone, take baby with you. Choking, suffocation or strangulation Vacuum often, and never leave small objects within a baby’s reach. He will put anything and everything in his mouth. Remove crib mobiles as soon as your baby is 4 months old or pushing up on hand and knees. Use a one-piece soother small enough for infants, with a shield to prevent him from sucking the nipple too far into his mouth. Discard any soother that shows any sign of wear or is more than 2 months old. Get rid of toys with pull strings longer than 20 cm (8 inches) or small, loose or breakable parts that a baby could swallow or inhale. Any object that is small enough to fit inside a toilet paper roll is a choking hazard. Don’t use bibs with ties, or hang pacifiers, a necklace or anything else around an infant’s neck that might catch and strangle her. Keep all plastic bags or wrapping out of reach and out of sight. Car safety All infants need a rear-facing car seat for their first ride home from the hospital. Your baby will use this seat whenever you travel-- even the shortest distance-- for one year or longer. Infants may use a forward-facing car seat once they are at least one year old and at least 10 kg, however it is best to rear-face as long as possible, so look for a car seat with the highest rear-facing weight and length limits once your child has outgrown their first car seat. Install the car seat in the middle of the rear seat—never in the front or near an airbag. Read the manufacturer’s instructions for the car seat and follow all age, height and weight specifications. Secure the car seat using the Universal Anchorage System (UAS or LATCH), which is now mandatory in all car models. Follow both the car seat and car manual instructions. If the UAS system does not secure the seat adequately, then use the seat belt, as indicated in the car seat instructions. Check that the car seat does not move more than 2.5 cm (1 inch) forward or from side to side once it is installed. Harness straps should be threaded just at or below your baby’s shoulders. The chest clip should be at armpit level and the harness should fit snugly. Tuck a blanket around your baby if needed instead of using a bunting bag. Don’t use a car seat that has been in a car crash, even a minor one. It is not safe. Never leave your baby unattended in a car, even to run a quick errand.For more information: Car seat safety Water safety for young children Transportation of infants and children in motor vehicles, a statement of the Canadian Paediatric Society Transport Canada: Safety in the carReviewed by the CPS Injury Prevention CommitteeUpdated: March 2009 This information should not be used as a substitute for the medical care and advice of your physician. There may be variations in treatment that your physician may recommend based on individual facts and circumstances.Canadian Paediatric Society2305 St. Laurent Blvd.,Ottawa, Ont. K1G 4J8Phone: 613-526-9397, fax: 613-526-3332

Moms May Think Softer Is Safer for Sleeping Babies

2011-08-24T21:23:00.001-07:00

From Reuters Health InformationBy Genevra PittmanNEW YORK (Reuters Health) Aug 23 - Lots of African American moms put soft bedding such as pillows and blankets where babies sleep, despite warnings that the cushioning increases the risk of infant death, according to a new study.That's because many parents are under the impression that a soft sleeping environment means the baby will be more comfortable or will be protected from injuries, said Dr. Rachel Moon."There's this impression that soft is safe," said Dr. Moon, one of the authors of the new study from Children's National Medical Center in Washington, D.C."But when it comes to babies' sleep environment, soft is not safe, it's actually dangerous."Researchers know that black babies are at least twice as likely as white, Latino, and Asian babies to die of accidental suffocation, strangulation or sudden infant death syndrome (SIDS). While some of that higher incidence may be related to genetics, much of it is probably due to parents unknowingly putting infants in a dangerous sleeping place or position, Dr. Moon said.To find out whether black families know about the risks, Dr. Moon and her colleagues conducted one-on-one interviews and small group discussions with 83 black mothers in D.C. and Maryland with a new baby at home.The researchers asked women if they used soft bedding and bumper pads in their baby's crib or other sleeping location -- and why or why not.More than of half of the moms reported using soft bedding for their baby, according to findings published August 22nd in Pediatrics. They told researchers they wanted to make sure the babies were comfortable and warm, or that they used pillows as a barricade on beds and sofas, or to prop babies up."We were surprised that people use (soft bedding) because they think it's going to make their baby safer," Dr. Moon told Reuters Health. "We weren't that surprised that people use it to make the babies comfortable."Some mothers thought doctors' recommendations to use a "firm sleep surface" included a bed where a sheet was tucked tightly over pillows -- but that's still a dangerous sleep situation, the researchers warned.Moms also used bumper pads on cribs if they worried that a baby would hit its head on the railings or get an arm or leg stuck. Some, the researchers found, also thought the bumper pads were cute.But just like with pillows and blankets, bumper pads pose a suffocation risk to babies, Dr. Moon said. "There really isn't any need for bumper pads," especially for very young babies, she added.Dr. Fern Hauck, a SIDS researcher at the University of Virginia in Charlottesville, said she understood the desire to make babies comfortable with soft bedding in hopes that they'll sleep better and longer.But, "babies can pretty much sleep anywhere," she told Reuters Health. "If you get them used to a firm crib mattress, they're going to sleep fine on a firm crib mattress."She said that pediatricians have to talk to new parents about all SIDS and suffocation risks, and "really get a little more of a dialogue going" about the safest way for a baby to sleep. Grandparents, friends, and anyone else who would be taking care of the baby also need to have that conversation, Dr. Hauck added.And it's important to know that although the interviews were only done with black mothers, parents of all races may misinterpret a pediatrician's recommendations or what constitutes a safe sleeping environment, said Dr. Debra Weese-Mayer, a pediatrician at Northwestern University Feinberg School of Medicine in Chicago.The study "is a very humbling lesson that even though we think we're giving a very clear message (about sleep surfaces), if the parent and the caretaker are interpreting it in a way different from what we intended, we're not doing a very good job," Dr. Weese-Mayer said."If it can save some babies because we do a better job of translating our recommendations, that's wonderfully important."SOURCE: http://bit.ly/oqyquwPediatrics 2011.

Women May Not Need to Delay Pregnancy After an Initial Miscarriage

2011-08-10T19:53:00.000-07:00

From Medscape Medical News

Laurie Barclay, MD

August 11, 2010 — Women may not need to delay pregnancy after an initial miscarriage, according to the results of a retrospective, Scottish population–based cohort study reported Online First August 5 in the BMJ.
"How long a couple should wait before trying for another pregnancy after a miscarriage is controversial," write Eleanor R. Love, from the University of Aberdeen in Aberdeen, Scotland, and colleagues.
"Some clinicians believe that there is little justification for delaying the next pregnancy, as an increased interpregnancy interval is unlikely to improve perinatal outcomes, whereas a new viable pregnancy and the birth of a child could enhance the women's chances of recovery....

Current guidelines from the World Health Organization recommend that women should wait for at least six months before trying again, whereas others suggest a delay of up to 18 months, based on reports that interpregnancy intervals of 18-23 months after a live birth can enhance maternal and perinatal outcomes in the next pregnancy."

The goal of this study was to evaluate the optimal interval to subsequent pregnancy after miscarriage in a first recorded pregnancy. At Scottish hospitals between 1981 and 2000, a total of 30,937 women who had a miscarriage in their first recorded pregnancy and subsequently became pregnant were followed up during the second pregnancy. The main study outcome was miscarriage, live birth, termination, stillbirth, or ectopic pregnancy in the second pregnancy, and secondary endpoints were rates of cesarean and preterm delivery, low birth weight infants, preeclampsia, placenta previa, placental abruption, and induced labor in the second pregnancy.

Compared with an interval of 6 to 12 months between the miscarriage and second conception, an interval less than 6 months was associated with lower risks for repeated miscarriage (adjusted odds ratio [OR], 0.66; 95% confidence interval [CI], 0.57 - 0.77), termination (OR, 0.43; 95% CI, 0.33 - 0.57), and ectopic pregnancy (OR, 0.48; 95% CI, 0.34 - 0.69). The risk for an ectopic second pregnancy was greater with an interpregnancy interval exceeding 24 months (OR, 1.97; 95% CI, 1.42 - 2.72), as was the risk for termination (OR, 2.40; 95% CI, 1.91 - 3.01).

Compared with women who had an interpregnancy interval of 6 to 12 months, those who conceived again within 6 months and had a live birth in the second pregnancy were less likely to have a cesarean delivery (OR, 0.90; 95% CI, 0.83 - 0.98), preterm delivery (OR, 0.89; 95% CI, 0.81 - 0.98), or low-birth-weight infant (OR, 0.84; 95% CI, 0.71 - 0.89). However, they were more likely to have labor induced (OR, 1.08; 95% CI, 1.02 - 1.23).

"Women who conceive within six months of an initial miscarriage have the best reproductive outcomes and lowest complication rates in a subsequent pregnancy," the study authors write.

Limitations of this study include potential lack of uniformity in documenting gestational age and outcomes of interest as well as possible misclassification. This study also evaluated only miscarriages that led to hospital contact, and the findings therefore cannot be generalized to all women with a miscarriage.
"Our research shows that it is unnecessary for women to delay conception after a miscarriage," the study authors conclude. "As such the current WHO [World Health Organization] guidelines may need to be reconsidered. In accordance with our results, women wanting to become pregnant soon after a miscarriage should not be discouraged."

In an accompanying editorial, Julia Shelley, associate professor of health and social development at Deakin University in Melbourne, Australia, discusses some of the methodologic issues regarding this study and earlier studies.
"[A]ll of the studies have selection and measurement biases that cast doubt on the value and generalisability of their findings," Dr. Shelley writes. "Of greatest concern is that women with short interpregnancy intervals are more fertile than those whose subsequent pregnancy occurs later because these women seem to have better pregnancy outcomes and fewer complications. Further research into this question may need to wait for data from more sophisticated linked primary care and hospital datasets or specifically designed research studies that can measure and account for such differences, even if they will not be able to control for them."

BMJ. 2010;341:c3967. Abstract

CDC Issues Revised Guidelines for Postpartum Contraceptive Use

2011-07-25T18:38:00.000-07:00

From Medscape Education Clinical Briefs

News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD

Released: 07/12/2011

Clinical Context

Planning for contraception after delivery is a critical element of family planning, and the US Centers for Disease Control and Prevention (CDC) provides a review of all available contraceptive methods in its current recommendations.
Progestin-only hormonal contraceptives are safe to initiate immediately after delivery, and they can be used among women who are breast-feeding.
Intrauterine devices (IUDs) can be placed immediately after delivery. Although there is a higher risk for expulsion immediately after delivery, continuation rates of IUDs at 6 months postpartum is similar regardless of when the device is placed.
Women should not initiate contraception with a diaphragm or cervical cap until 6 weeks postpartum.
The use of combined hormonal contraception during the postpartum period is a complicated issue, and the current recommendations revise previous guidelines issued by the CDC in 2010.

Study Synopsis and Perspective

The CDC has updated its guidelines for postpartum contraceptive use, according to revised recommendations reported in the July 8 issue of MMWR. Morbidity and Mortality Weekly Report.
The new statement, which updates the CDC's U.S. Medical Eligibility Criteria for Contraceptive Use, 2010, advises postpartum women not to use combined hormonal contraceptives during the first 21 days after delivery because of a high risk for venous thromboembolism (VTE).
"The postpartum period is an important time to initiate contraception because women are accessing the health-care system and might have increased motivation to avoid another pregnancy," write Naomi K. Tepper, MD, from the Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC, and colleagues.
"Ovulation can occur as early as 25 days postpartum among nonbreastfeeding women, underscoring the importance of initiating contraception in the very early postpartum period."
The revised guidelines affirm the importance of starting contraception during the postpartum period to prevent unintended pregnancy and short birth intervals, which are associated with adverse health outcomes for the mother as well as for the infant. These include greater risks for low birth weight and preterm birth.
The 2010 CDC recommendations offered evidence-based guidance for choosing a contraceptive method, considering patient-specific characteristics or medical conditions, such as the postpartum period.

New Guidelines More Stringent
On the basis of subsequent evidence, the World Health Organization (WHO) updated its recommendations regarding the safety of combined hormonal contraceptives among postpartum non–breast-feeding women. Compared with control participants, women in the first 42 days of the postpartum period have a 22-fold to 84-fold increased risk for VTE.
The new WHO guidelines were therefore more restrictive concerning use of combined hormonal contraceptives during the first 42 days after delivery, especially in women who had other risk factors for VTE.
To review the WHO recommendations and underlying evidence base, the CDC therefore convened a group of 13 ad hoc reviewers. On the basis of available evidence concerning the safety of combined hormonal contraceptive use in postpartum women, the CDC has now concluded that the high risk for VTE during the first 21 days after delivery should preclude use of combined hormonal contraceptives in this time frame.

Although the risk for pregnancy is very low during the first 21 days postpartum, it increases thereafter, and ovulation before first menses is common.

From 21 to 42 days after delivery, women with risk factors for VTE generally should not use combined hormonal contraceptives, but these are thought to be safe during this period for women without risk factors for VTE. Risk factors for VTE include age 35 years or older, previous VTE, thrombophilia, known thrombogenic mutations, immobility, transfusion at delivery, body mass index of at least 30 kg/m², postpartum hemorrhage, peripartum cardiomyopathy, post cesarean delivery, preeclampsia, or smoking.
The CDC has issued no restrictions on the use of combined hormonal contraceptives in women who delivered more than 42 days previously.
"Health-care providers assessing a woman's individual risk also should consider any other characteristics or medical conditions that might impact the classification," the guidelines authors write.
"For postpartum women, this might include examining the recommendations for other risk factors for VTE, such as known thrombogenic mutations (category 4) or history of VTE with risk factors for recurrence (category 4), both of which pose an unacceptable health risk for combined hormonal contraceptive use, whether or not women are postpartum."

Recommendations on Other Contraceptive Methods
The CDC recommendations are unchanged regarding progestin-only contraceptives (progestin-only pills, depot medroxyprogesterone acetate injections, and implants), IUDs, and contraceptive methods other than combined hormonal contraceptives.
These methods can be started immediately after delivery and are safe for postpartum women, including those who are breast-feeding.
However, clinicians should consider that combined hormone contraceptives may hinder successful breast-feeding.
Insertion of IUDs, including the levonorgestrel-releasing IUD and copper-bearing IUD, immediately after delivery, is not associated with an increase in complications. Rates of IUD expulsion are somewhat higher when they are inserted within 28 days of delivery, but continuation rates at 6 months are similar regardless of whether IUD insertion takes place immediately postpartum or is delayed.
Condoms can be safely used at any time, but use of the diaphragm and cervical cap should be delayed to 6 weeks postpartum. Another option in women who have completed their childbearing is to consider postpartum sterilization.
The CDC guidelines authors expressed concern regarding access to contraceptive methods.
Unlike progestin implants, IUDs, and other methods requiring a follow-up visit to a provider, combined hormonal contraceptives could be started by the woman herself at the appropriate time if she is issued a prescription or is given a sample in advance, either before hospital discharge or at a postpartum visit.
"Postpartum contraception is important for the health of mother and infant, and education for both health-care providers and women should focus on the range of contraception options and the safety of most of these methods during the postpartum period," the guidelines authors conclude.

MMWR Morb Mortal Wkly Rep. 2011;60:878-883.

Fetal Exposure to Environmental Contaminants May Underlie CHD

2011-05-08T22:43:00.000-07:00

From Medscape Medical News

Environmental Link to Congenital Heart Disease Strengthened

Brian Hoyle

May 2, 2011(Denver, Colorado) — Maternal exposure to compounds present in crude oil, cleaning agents, and stain removers has been linked to an increased risk for congenital heart disease (CHD) in a study presented here at the Pediatric Academic Societies and Asian Society for Pediatric Research 2011 Annual Meeting.

CHD "is a major cause of childhood death and life-long health problems, so identifying risk factors contributing to CHD is important to public health. Environmental causes of CHD have been suspected, and animal studies have linked certain chemicals to CHD as potential teratogens, but the link has remained unproven," Gail McCarver, MD, professor of pediatrics at the Medical College of Wisconsin and Children's Research Institute, Milwaukee, told Medscape Medical News.

To probe whether human exposure to a battery of volatile organic compounds and halogens increased the risk for CHD, Dr. McCarver and her colleagues tested meconium as a means of assessing fetal exposure to the solvents.

"Meconium monitoring is an established and valid means of assessment of fetal exposure," Dr. McCarver noted in an interview with Medscape Medical News.

Meconium from 135 newborns diagnosed with CHD and 432 newborns without CHD, as determined by echocardiography, was examined for 17 compounds using gas chromatography–mass spectrometry for volatile organic compounds and gas chromatography–electron capture detector for halogens.

Both techniques were exquisitely sensitive, with detection limits in the parts-per-trillion range.

Infants of diabetic mothers and infants identified with chromosomal abnormalities linked to CHD were excluded from the study. Demographic data, information concerning family history of CHD, and maternal history of the use of tobacco, alcohol, illicit drugs, and vitamins were collected. Mothers and infants were genotyped for 2 genes implicated in CHD: ADH, which encodes alcohol dehydrogenase, and CYP2E1, which encodes cytochrome P450 2E1.

The infants with CHD were significantly more likely to be smaller at birth, born at an earlier gestational age, white, have a family history of CHD, and born to a woman who smoked tobacco (P < .05 for all).

Of the 567 infants, 82% had detectable levels of 1 or more of the examined solvents. Infants with CHD more often displayed fetal exposure to ethylbenzene (P < .001), meta/ortho/para-xylene (P < .001), benzene (P < .01), tetrachloroethylene (P < .05), and dichloroethylene (P < .05).

When the data were examined on the basis of race, fetal exposure to ethyl benzene (a component of crude oil) and the inhaled vapors of vehicle emissions, gasoline, and cigarette smoke increased the risk for CHD 4-fold in white infants, but not in black infants.
Exposure to trichloroethylene (a common degreasing chemical that is a component of a variety of cleaners and spot removers) increased CHD risk 2-fold in white infants and 8-fold in black infants.

Maternal obesity; tobacco smoking; the use of alcohol, illicit drugs, or vitamins; exposure to other solvents; and presence/absence of ADH and CYP2E1 were not significant CHD risk factors.

The association between ethylbenzene and CHD — described by Dr. McCarver as "novel and important for public health" — might explain previous reports linking smoking during pregnancy and CHD, and might heighten public health concerns about events such as the recent oil spill in the Gulf of Mexico.

"This is the first report that exposure to ethyl benzene, a compound present in crude oil, is associated with CHD. This association is troubling, particularly concerning recent oil spills," Dr. McCarver told Medscape Medical News.

The data also implicate tetrachloroethylene as a teratogen and strengthen the validity of the noninvasive examination of meconium as a means of analyzing fetal exposure to environmental compounds.

"This is valuable work. But it could, perhaps, be a whole bunch more insightful if we had more of a history of maternal exposure and its relation to pregnancy. This would allow a more accurate assessment of exposure as a causal factor," Robert Geller, MD, from Emory University School of Medicine, Atlanta, Georgia, told Medscape Medical News.

Data gathered throughout pregnancy are limited at present, Dr. Geller added.
Dr. McCarver and Dr. Geller have disclosed no relevant financial relationships.

Pediatric Academic Societies (PAS) and Asian Society for Pediatric Research 2011 Annual Meeting: Abstract 1150.1. Presented April 30, 2011.

Babies Lose Maternal Measles Antibodies After a Few Months

2011-02-28T19:00:00.001-08:00

Reuters Health Information

By Frederik Joelving

NEW YORK (Reuters Health) May 18 - Maternal measles antibodies wane earlier than previously thought, leaving infants susceptible to the virus for several months under current immunization guidelines, Belgian researchers report in a May 18th online paper in BMJ.

While not recommending an overhaul of general vaccination age -- currently 12 months in both Belgium and the US -- they said infants with special exposure to measles may need to be immunized at six months.

"We could recommend to vaccinate earlier, but because of good coverage here in Belgium we do not want to lose people" by adding an extra trip to the doctor, said lead author Dr. Elke Leuridan of the University of Antwerp in Wilrijk, Belgium.

Dr. Leuridan and colleagues studied 207 healthy mother-child infant pairs. Eighty-seven of the mothers had been vaccinated against measles and 120 had natural immunity.

The researchers collected venous blood during pregnancy (week 36, 10 ml), at birth (cord blood, 10 ml) and in infants at 1, 3 and 12 months (2 ml). In addition, they took samples randomly at either 6 or 9 months.

They used an enzyme-linked immunosorbent assay to measure the amount of measles immunoglobulin G (IgG) in the blood, calibrating the assay against the international reference preparation of measles antigen. The samples were considered positive if the corrected optical density was greater than 0.2, and negative if it was less than 0.1.

Overall, vaccinated women had lower IgG titers than naturally immune women (779 vs. 2687 milli-International Units per milliliter, or mIU/mL; p<0.001). The same pattern was seen for the infants at all ages (p<0.001).

Maternal antibodies persisted for a median of 3.8 months in infants of naturally immune mothers and for 1 month in babies of vaccinated women. In a linear mixed model, 99% of babies of vaccinated mothers had lost their maternal antibodies after six months, compared to 95% of babies of naturally immune women. Breast feeding, parity, gestational age, birth weight, educational level, day care attendance and cesarean section were not significant in the model.

The findings are consistent with earlier studies showing that measles susceptibility is growing every year, Dr. Leuridan said. Yet, she added, "it is quite new that it is such a large gap."

Part of the reason for the expanding gap, she said, could be the increasing age of mothers and the general success of immunization in lowering overall exposure to the virus.

Dr. Archana Chatterjee, of Creighton University School of Medicine in Omaha, Nebraska, said current immunization practice is based on the theoretical assumption that maternal antibodies might interfere with the necessary replication of the vaccine virus.

She called the new study "food for thought," noting that larger studies are needed before considering guideline changes. For instance, small amounts of maternal antibodies that went undetected in the study in principle might interfere with the vaccine, she said.

Still, Dr. Chatterjee said, "it certainly is something that gives us pause."

http://www.bmj.com/cgi/content/abstract/340/may18_2/c1626
BMJ 2010.

Periconceptional Fever/Influenza Linked to Specific Congenital Birth Defects

2011-02-15T19:00:00.000-08:00

From Reuters Health Information CME

News Author: Megan Brooks
CME Author: Désirée Lie, MD, MSEd

NEW YORK (Reuters Health) February 4, 2011 — New research confirms that women who develop influenza or a fever of 101°F or higher during the periconceptional period are at increased risk of delivering a baby with certain congenital heart defects, most notably right-sided obstructive lesions in all infants and atrioventricular septal defects (AVSD) in infants with Down syndrome.

However, maternal use of antipyretic agents in the setting of fever or influenza may attenuate these associations, the researchers reported in the January 24 online issue of The Journal of Pediatrics.

Dr. Adolfo Correa, Medical Officer in the National Center on Birth Defects and Developmental Disabilities, part of the Centers for Disease Control and Prevention, in Atlanta, Georgia, led the study.

"Although our findings are consistent with a few previous studies, the literature on the associations we found is still somewhat limited for drawing conclusive clinical implications," Dr. Correa noted in an e-mail to Reuters Health.

"Further efforts are needed to corroborate our findings and to elucidate the reasons for the observed associations. From a precautionary perspective, women planning to become pregnant should avoid exposure to influenza or other febrile illnesses and seek preconception care," the researcher added.

Maternal febrile illness and hyperthermia have been linked to a variety of birth defects, especially those involving the central nervous system, Dr. Correa and colleagues note in their report. Associations between maternal fever and hyperthermia with congenital heart defects are "less clear-cut," they say.

Moreover, while associations between congenital heart defects and some viral illnesses, particularly rubella, have been well documented, studies on the role of influenza in risk of congenital heart defects have yielded mixed results.

Dr. Correa and colleagues investigated associations between maternal fever and influenza and congenital heart defects using data from the Baltimore-Washington Infant Study, an epidemiologic study of congenital heart defects conducted between 1981 and 1989 in Maryland, Washington DC, and northern Virginia.

Cases were 2,361 infants with congenital heart defects and controls were 3,435 infants without congenital heart defects.

Participating mothers were asked whether they had a fever of 101°F or higher, had influenza, or used an antipyretic agent (acetaminophen, salicylate, or nonsteroidal anti-inflammatory agent) during the period extending from 3 months prior to pregnancy through the end of the third month of pregnancy.

For congenital heart defects overall, no significant associations were found with fever, influenza, or fever/influenza.

However, for specific defects, significant associations were found for right-sided obstructive defects and maternal fever (OR 2.04), influenza (OR 1.75) and fever/influenza (OR 1.69).

These findings were most notable for tricuspid atresia in the setting of fever (OR 7.54), influenza (OR 6.04), and fever/influenza (OR 5.46) and for pulmonary atresia with intact ventricular septum in the setting of influenza (OR 2.71) and fever/influenza (OR 2.80), the researchers reported.

And in infants with Down syndrome, the authors found significant associations between atrioventricular septal defects and periconceptional fever (OR 1.92), influenza (OR 1.66) and fever/influenza (OR 1.66). No significant associations were evident between other cardiac phenotypes and fever, influenza or both.

Maternal antipyretic use tended to decrease these associations, as mentioned.

Dr. Correa and colleagues say the link between fever and influenza and AVSD only in infants with Down syndrome may be "spurious" or it may represent an "important gene-environment interaction that warrants further investigation."

J Pediatr. Published online January 24, 2011. Abstract
Clinical Context

Congenital heart defects continue to be a leading cause of morbidity and mortality in children, and maternal exposures during pregnancy may contribute to the risk for such defects. Maternal fever has been linked to birth defects, especially those of the central nervous system, and studies have noted an almost 2-fold increase in the risk for aggregate congenital heart defects with maternal fever and influenza.

This is a case-control study of infants in a population-based cohort to examine the association between maternal fever or influenza during the 3 months before and after conception and the risk for congenital heart defects.

FDA Approves First 3-Dimensional Mammography System

2011-02-15T18:37:00.001-08:00

From Medscape Medical News > Alerts, Approvals and Safety Changes > FDA Approvals

Steven Fox

February 14, 2011 — The US Food and Drug Administration (FDA) has approved the first mammography system employing 3-dimensional (3-D) imaging, and preclinical studies show that the new technology is 7% more accurate than traditional 2-D mammography in spotting breast tumors.

The new technology is to be marketed as the Selenia Dimensions System and is being manufactured by Hologic, Inc. The system is an upgrade to Hologic's currently available 2-D system.

The system has already been approved in Latin America, Europe, and in Asia.

In approving the device for use in the United States, the FDA assessed results from 2 studies in which radiologists reviewed 2-D and 3-D images from more than 300 mammography studies.

In both studies, radiologists viewing both 2-D and 3-D images were 7% more likely to accurately distinguish between cancerous and noncancerous lesions compared with viewing 2-D images alone.

"Physicians can now access this unique and innovative 3-D technology that could significantly enhance existing diagnosis and treatment approaches," said Jeffrey Shuren, MD, JD, who directs the FDA's Center for Devices and Radiological Health in a press release.

Previous studies have shown that 2-D imaging techniques do not always provide clear images of breast masses, as overlapping skin and other anatomical features can obscure tumors and sometimes create the appearance of a tumor when there is none.

A caveat is that the combination of 2-D and 3-D images approximately doubled the radiation dose to which women were exposed, but the new technology increases efficacy, which presumably will help cut down on the need for follow-up exams. At this time, about 10% of women who undergo 2-D mammography are called back for follow-up X-rays, only to find out later that masses spotted with the 2-D systems are noncancerous.

Mammography Quality Standards require that healthcare professionals undergo 8 hours of instruction before using the new 3-D technology. The FDA also stipulates that the manufacturer provide each user with a manual that defines tests required to maintain quality control.

Early Introduction of Solid Foods Linked to Risk for Early Childhood Obesity

2011-02-08T17:51:00.000-08:00

From Medscape Medical News
Laurie Barclay, MD

February 7, 2011 — Early introduction of solid foods is linked to a risk for early childhood obesity, according to the results of a prospective prebirth cohort study reported online February 7 in Pediatrics.

"Parental feeding practices during early infancy, such as the timing of solid food introduction, may be 1 key modifiable determinant of childhood obesity," write Susanna Y. Huh, MD, MPH, from the Division of Gastroenterology and Nutrition, Children's Hospital Boston in Boston, Massachusetts, and colleagues.
"Data suggest that the introduction of solid foods earlier than 4 months of age is associated with increased body fat or weight in childhood or with greater weight gain during infancy, which itself predicts later adiposity. Other studies have found no association between the timing of solid food introduction and body fat or an association between delayed introduction of solid foods after 6 months and greater adiposity."

The goal of the study was to evaluate the association between timing of introduction of solid foods during infancy and obesity at age 3 years, defined as a body mass index for age and sex at the 95th percentile or above, using a cohort of 847 children enrolled in Project Viva. Timing of introduction of solid foods was categorized as younger than 4 months, ages 4 to 5 months, and 6 months or older. Logistic regression models were applied separately for infants who were breast-fed for at least 4 months ("breast-fed"; n = 568; 67%) and for infants who were never breast-fed or in whom breast-feeding was stopped before age 4 months ("formula-fed"; n = 279; 32%). These models were adjusted for child and maternal factors, including change in weight-for-age z score from 0 to 4 months as a marker of early infant growth.

Obesity was present in 75 children (9%) at age 3 years.
The timing of solid food introduction was not associated with odds of obesity in breast-fed infants, (odds ratio, 1.1; 95% confidence interval [CI], 0.3 - 4.4). However, introducing formula-fed infants to solid foods before age 4 months was associated with a 6-fold increase in odds of obesity at age 3 years, which was not explained by rapid early growth (odds ratio after adjustment, 6.3; 95% CI, 2.3 - 6.9).

"Among infants who were never breastfed or those who stopped breastfeeding before the age of 4 months, the introduction of solids before the age of 4 months was associated with a sixfold increase in the odds of obesity at the age of 3 years," the study authors write.

Limitations of this study include possible residual confounding; some loss of the cohort to follow-up; limited generalizability to more socioeconomically disadvantaged populations; and small numbers in some cells, leading to possible chance results.

"Among infants breastfed for 4 months or longer, the timing of the introduction of solid foods was not associated with the odds of obesity," the study authors conclude. "Increased adherence to guidelines regarding the timing of solid food introduction may reduce the risk of obesity in childhood."

The National Institutes of Health supported this study. The study authors have disclosed no relevant financial relationships.

Pediatrics. Published online February 7, 2011. Abstract

AAP Issues New Guidelines for Management of Iron Deficiency

2011-01-19T17:32:00.000-08:00

From Medscape Medical News

Jim Kling

October 14, 2010 — Correction: The original text of this article described the daily iron dose for infants 6 to 12 months as 11 mg/kg. This is incorrect.
The dose should be 11 mg/day.

October 5, 2010 (San Francisco, California) — Iron deficiency is one of the most common, yet undetected, problems among children. Here at the American Academy of Pediatrics (AAP) 2010 National Conference and Exhibition, the American Association of Pediatrics released a clinical report, with guidelines for iron intake in infants and children and to improve screening methods.

The clinical report, entitled Diagnosis and Prevention of Iron Deficiency and Iron Deficiency Anemia in Infants and Young Children (0–3 Years of Age), was published online October 5 in Pediatrics. It is a revision of a 1999 policy statement.

Iron deficiency can have long-term irreversible effects on a child's cognitive and behavioral development. By the time a child develops iron-deficiency anemia, it might be too late to prevent future problems. "The body has a preferential tracking of iron. Red blood cells take precedence over the iron requirements of the brain. By the time you get iron-deficiency anemia, you've been iron-deficient for a long time," said Frank Greer, MD, professor of pediatrics at the University of Wisconsin School of Medicine and Public Health in Madison, and a coauthor of the report.

The 1999 guidelines call for children to have their hemoglobin checked sometime between 9 and 12 months of age, and again between 15 and 18 months of age. However, the existing test misses many children with iron deficiency and iron-deficiency anemia. Even those found to be iron deficient frequently receive no follow-up testing or treatment, according to Dr. Greer.

Although supplementing all children with iron would reduce iron deficiency, such a program does not have widespread support in the medical community at this point. That's partly because toddlers, who are the most widely affected group, have a wide range of diets and it is unclear what foods to fortify.

Liquid iron supplements or vitamins could be used, but there is a risk for iron overload in some populations, according to Michael K. Georgieff, MD, professor of pediatrics and child psychology and director of the Center for Neurobehavioral Development at the University of Minnesota in Minneapolis. Dr. Georgieff was on the AAP's committee on nutrition from 1993 to 1999 and played a key role in the 1999 guidelines.

"Iron supplementation and awareness of iron nutrition has probably been one of the most successful public health programs in the United States. In the 1960s, iron deficiency was probably 30% to 40%. Today, it may be under 10%. But in trying to eliminate that last 10%, you have to consider it in terms of exposing kids to [too much] iron," said Dr. Georgieff.

No single screening test is available that will accurately characterize the iron status of a child, he noted. In the report, the AAP recommends 4 protocols for screening for iron deficiency and iron-deficiency anemia, including combinations of several tests and follow-up protocols. "It's burdensome," Dr. Greer admitted.

"Since we're not going to do universal supplementation, we need to identify kids who are at risk for iron deficiency and start targeting them," said Dr. Georgieff, who studies the neurodevelopmental effects of iron deficiency in children.

The AAP report identified several factors associated with iron deficiency and iron-deficiency anemia, including prematurity or low birth-weight, lead exposure, exclusive breastfeeding past 4 months of age without iron supplements, and weaning to foods that don't include iron-fortified cereals or iron-rich foods. Infants with special healthcare needs might also be at risk. Children of low economic status, particularly those of Mexican American descent, are also of concern, according to the report, which recommends selective screening for these individuals.

The guidelines also address means to prevent iron deficiency through a diet of foods naturally rich in iron, such as meat, shellfish, legumes, iron-rich fruits and vegetables, and iron-fortified cereals. Fruits rich in vitamin C help iron absorption. Some children might require liquid iron supplements or chewable vitamins to get sufficient iron.

The AAP recommends varying amounts of iron based on a child's age:

* Term, healthy infants have sufficient iron for the first 4 months of life. Because human breast milk contains very little iron, breastfed infants should be supplemented with 1 mg/kg per day of oral iron from 4 months of age until iron-rich foods (such as iron-fortified cereals) are introduced.
* Formula-fed infants will receive adequate iron from formula and complementary foods. Whole milk should not be used before 12 months.
* Infants 6 to 12 months of age need 11 mg/day of iron a day. When infants are given complementary foods, red meat and vegetables with high iron content should be introduced early. Liquid iron supplements can be used if iron needs are not met by formula and complementary foods.
* Toddlers 1 to 3 years of age need 7 mg per day of iron. It is best if this comes from foods such as red meats, iron-rich vegetables, and fruits with vitamin C, which enhance iron absorption. Liquid supplements and chewable multivitamins can also be used.
* All preterm infants should have at least 2 mg/kg of iron per day until 12 months of age, which is the amount of iron in iron-fortified formulas. Preterm infants fed human milk should receive an iron supplement of 2 mg/kg per day by 1 month of age; this should be continued until the infant is weaned to iron-fortified formula or begins eating foods that supply the required 2 mg/kg of iron.

American Academy of Pediatrics (AAP) 2010 National Conference and Exhibition. Presented October 5, 2010.

Recommendation of 6 Months of Breast-Feeding Scrutinized

2011-01-19T04:27:00.000-08:00

From Medscape Medical News

Emma Hitt, PhD

January 18, 2011 — The evidence in favor of 6 months of exclusive breast-feeding has come under scrutiny in a new study published by the BMJ.

A review article assessing the evidence was published by researcher Mary Fewtrell, MD, from the Child Nutrition Research Center at the University College London Institute of Child Health, United Kingdom, and colleagues was published online January 13 in the BMJ.

Current World Health Organization guidelines recommend that infants be exclusively breast-fed for 6 months; that is, with a diet that excludes solids or any fluids other than breast milk, including infant formulas. These guidelines, announced in 2001, were adopted by the United Kingdom in 2003.
Exclusive breast-feeding may not adequately meet infants' energy needs for a full 6 months.

"The critical question is whether the United Kingdom should alter its advice on the introduction of complementary foods while new evidence is assembled," the authors note.

The current report maintains that this change in policy occurred without formal consideration of the scientific evidence. Since the announcement of the World Health Organization guidelines, findings from a number of studies suggest that breast milk may not be a reliable single source of nutrition for the first 6 months of life. In addition, the European Food Safety Authority recently concluded that it was safe to introduce complementary foods between 4 and 6 months' of age for infants residing in the European Union.

In the current study, Dr. Fewtrell and colleagues reassessed the evidence in favor of 6 months of exclusive breast-feeding and concluded that exclusive breast-feeding may not adequately meet infants' energy needs for a full 6 months. Higher rates of iron deficiency anemia are an additional concern, having been linked to poorer long-term mental, motor, and social development. Furthermore, existing data suggest an increased risk for reaction to certain allergens (eg, gluten, which has been linked to celiac disease) when their introduction is delayed past 6 months.

Even in the case of protection from infection — considered to be a clear benefit of breast-feeding — a study conducted in Spain showed that these benefits largely accrue to infants breast-fed for 3 months, providing little "extra" benefit thereafter. However, a large study based in the United States did find that infants breast-fed exclusively for more than 6 months had a lower risk for otitis media and pneumonia when compared with infants who were breast-fed exclusively for 4 to 6 months.

Dr. Fewtrell and colleagues conclude that, in light of data that have accumulated during the last 10 years (ie, since the World Health Organization guidelines came out in 2001), the time is ripe for an evidence-based reappraisal of the United Kingdom's stance in this important, yet controversial, area.

According to independent commentator Richard Aubry, MD, MPH, a professor of obstetrics and gynecology at Upstate Medical University in New York, this work does not add any new evidence about the pros and cons regarding adding other foods earlier than 6 months' age.

He told Medscape Medical News that clinicians "need to keep the message clear: Exclusive breast-feeding is the preferred method for feeding the baby until approximately 6 months of age, and then mothers should be encouraged to continue breast-feeding as long as they can. These are the specific terms and overall advice by [the American Congress of Obstetricians and Gynecologists]."

This study was not commercially funded. Three of the 4 authors of the study report having performed consultancy work and/or received research funding in the past 3 years from companies that manufacture infant formulas and baby foods.

BMJ. Published online January 13, 2011.

Frozen Hope: Fertility Preservation for Women with Cancer

2011-01-12T21:47:00.000-08:00

From Journal of Midwifery & Women's Health

Gwendolyn P. Quinn, PhD; Susan T. Vadaparampil, PhD, MPH; Paul B. Jacobsen, PhD; Caprice Knapp, PhD; David L. Keefe, MD; Geri E. Bell, BS

Posted: 03/12/2010; J Midwifery Womens Health. 2010;55(2):175-180. © 2010 Elsevier Science, Inc.

Abstract

Young women diagnosed with cancer have the option of preserving their fertility by using assisted reproductive technology (ART) techniques prior to undergoing cancer treatment. This article presents a composite case of a young woman with cancer who had many unanswered emotional and ethical questions about her future as a parent. Fertility preservation techniques, including preimplantation genetic diagnosis (PGD), and related patient education are described.
Current literature regarding reproductive counseling for cancer survivors is reviewed. Resources for providing psychosocial support for decisions about fertility preservation are lagging behind the rapid pace of scientific advancements in cancer treatment and ART.
As more young women are surviving cancer and taking steps to preserve fertility, there is great need for the provision of psychologic support services and the establishment of ethical guidelines to aid them on this path.
Women's health care providers can provide support to cancer survivors facing fertility and parenting issues by becoming knowledgeable about the long-term aspects of decision making and developing educational materials and guidelines for these patients.

Introduction

The number of young women diagnosed with cancer is increasing.[1] Recent data indicate the most common types of cancer occurring among women aged 15 to 29 are cancers of the female genital system, lymphoma, thyroid cancer, melanoma, and breast cancer.[1] Advances in cancer treatment have resulted in an increased number of long-term survivors. Young women who are diagnosed with cancer must make decisions about their reproductive future at a time when they are emotionally fragile. In addition to processing the cancer diagnosis and associated treatment choices, the decisions required concerning preserving future fertility and the time constraints associated with judgments can understandably be emotionally distressing. Women without cancer who are diagnosed with infertility have typically had at least a year in which to process their desire for a child and understand the barriers and benefits for each of the assisted reproductive technologies that may be available to their unique situation. The traditional reproductive counseling and the time frame for decision making offered to a woman or a couple experiencing infertility may not be available to a woman with a cancer diagnosis. This article presents a composite case of a young woman with cancer who faced infertility due to her cancer treatment but hoped to have a biologic child in the future. The case is examined in light of what is known and not yet known about the medical and psychosocial aspects of fertility preservation for women with cancer.
Cancer and Infertility

The best treatment for cancer may lead to impaired fertility or the complete loss of fertility. However, rates of infertility vary depending on a number of factors, including cancer site, type of treatment, and the age of the patient. Infertility in cancer patients can be caused by the cancer or the type of cancer treatment received. Exact infertility rates are not known, because there are no valid measures for women to establish that fertility was present prior to treatment. Women who undergo chemotherapy or radiation for malignancies during reproductive years have a 40% to 80% chance of losing fertility. The treatments that produce the greatest risk for infertility include alkylating agents such as cyclophosphamide, methotrexate, and fluorouracil in chemotherapy; total body radiation; and external beam radiation in a field that includes the ovaries. Both chemotherapy and radiation can cause premature ovarian failure for females, often leading to premature menopause.

Fertility Preservation

Rapidly improving assisted reproductive technologies and therapies offer some opportunities to preserve the fertility of female patients receiving chemotherapy and/or radiation. The emerging field of proteomics is leading the way toward the identification of proteins involved in oocyte maturation, embryo development, and implantation that could improve assisted reproduction techniques. Assisted reproductive technology (ART) consists of clinical treatments and laboratory procedures that include the handling of human oocytes, sperm, or embryos, with the intent of establishing a pregnancy. This includes, but is not limited to, in vitro fertilization (IVF), intracytoplasmic sperm injection, gamete intrafallopian transfer, zygote intrafallopian transfer, embryo biopsy, preimplantation genetic diagnosis (PGD), embryo cryopreservation, oocyte or embryo donation, and gestational surrogacy. Table 1 includes definitions of each type of procedure.

There are currently only two established options for fertility preservation for women with cancer: 1) oophoropexy, moving the ovaries out of the range of radiation, and 2) embryo cryopreservation, the freezing of fertilized eggs via IVF for later use. Additional techniques for fertility preservation, such as oocyte cryopreservation (freezing unfertilized eggs) and ovarian tissue cryopreservation (freezing strips of ovarian tissue, which may be transplanted either orthotopically within the pelvis or heterotopically within subcutaneous tissue), are less established and not widely available. All options must typically be considered and undertaken prior to the initiation of treatment.

There are also ethical, spiritual, and legal issues related to decision making about fertility preservation, such as the disposition of stored embryos. These issues often concern health care professionals as well and may pose barriers to the discussion of or assistance with the use of ART.Some patients and their families choose to consider posthumous parenting, that is, they intend to use the stored embryos whether or not the patient survives. Although this is an ethically charged situation, the American Society for Reproductive Medicine recommends that health care professionals do not deny patients assistance for this form of reproduction and also advises that "precise instructions" be given by the patient in the event of his or her death. The precise instructions for the disposition of DNA are part of the informed consent counseling, and patients are required to outline the procedures for future use of the stored embryos (e.g., willed to a spouse or parent, discarded, donated, etc.) If these procedures are followed, this can reduce the need for legal involvement to determine ownership of the stored embryos in the event of the patient's death or in the case of divorce. The United Kingdom also regulates the disposition of embryos through informed consent. Information about this practice is not readily available from other countries.

Preimplantation Genetic Diagnosis for Hereditary Cancers

The concerns of individuals affected with cancer regarding biologic parenthood are often focused on the health risks for future children. Carriers of genetic mutations, such as women with mutations in the BRCA1/2 genes, may have additional concerns about passing on hereditary cancers to future offspring. For those survivors who are concerned about the possibility of transmitting a serious hereditary cancer to their future children, limited biologic parenting options are available. Preimplantation genetic diagnosis is one option for parents who want to avoid this dilemma.

Preimplantation genetic diagnosis is a procedure used in conjunction with IVF to screen for specific genetic or chromosomal abnormalities before transferring the fertilized eggs into the woman. Preimplantation genetic diagnosis involves microsurgical removal of one or two blastomeres (embryos) at the six- to eight-cell stage, usually 3 days after fertilization. At this stage, the cells of the embryo have not differentiated into particular body tissues, and there is not likely to be damage to the resulting embryo. Biopsies of embryos are analyzed to detect genetic abnormalities arising from the maternal or paternal chromosomes. However, since diagnostic tests are performed on a single cell, the possibility of misdiagnosis must be considered. Preimplantation genetic diagnosis results are usually available within 48 hours after biopsy, which corresponds to day 5 after egg retrieval. Depending on their original quality, embryos may or may not reach the blastocyst stage, which is the final stage of in vitro development.[9] Usually on day 5, embryos free of genetic defects are transferred into the patient; however, some women or couples may choose to cryopreserve affected embryos. Currently data are not collected on the health of offspring born through the use of PGD, so it is unknown if there are related long-term health consequences.

Preimplantation genetic diagnosis has been accomplished for both cancer-specific disorders such as adenomatous polyposis coli, BRCA1/2, retinoblastoma, Li-Fraumeni syndrome, and von Hippel-Lindau syndrome, as well as disorders predisposing to neoplasia (Fanconi anemia, Wiskott-Aldrich syndrome).[11–13] The PGD procedure has been performed for a little over a decade and involves the use of IVF so parents can select the embryos that are implanted into the uterus. Embryos are tested for genetic status at the early stages of development. The ability to use PGD testing for all cancer types is not currently possible. The regulations developed for PGD testing and the types of cancers for which embryos can be tested vary by country and availability within each country. For example, the ability to use PGD for BRCA became available in 2006; however, other hereditary cancers, such as familial adenomatous polyposis, have been tested for in the Netherlands since 2004, although BRCA testing of embryos is not allowed there.[13] Thus, although the availability of PGD testing for certain cancer types varies by country and facility, the psychosocial issues women face over certain issues such as embryo selection are quite similar. One option for PGD is to implant only those embryos that are found to be unaffected. Some parents still may choose to implant affected embryos with the knowledge that the potential for hereditary syndromes is high. In the past, options for hereditary cancer mutation carriers included not having children or undergoing amniocentesis or other forms of prenatal diagnosis. Preimplantation genetic diagnosis allows parents to avoid terminating a pregnancy and/or risking the health of the fetus or the mother.

In Europe, guidelines regulate which clinics can perform PGD and for which diseases they can screen. In the United Kingdom, the Human Fertilisation and Embryology Authority (HFEA) governs which procedures are acceptable and provides guidelines as to how these procedures should be performed. It also licenses clinics that wish to use any type of ART. Currently, no such oversight exists in the United States.[14] At present, HFEA has approved PGD to test for 50 disorders, including hereditary breast and ovarian cancers, which can be caused by a mutation in the BRCA1/2 genes. Mutations in BRCA1/2 are passed down in families in an autosomal dominant pattern, and children of individuals with a BRCA1/2 mutation have a 50% chance of inheriting it. Women who carry the BRCA1/2 gene have an 80% lifetime risk of developing breast cancer and approximately a 40% risk of developing ovarian cancer. With such a high risk for developing cancer, the HFEA considers it appropriate to allow PGD for this cancer predisposition gene.

The use of PGD in the United States is predicted to be approximately 20% across all embryos created via IVF; however, it is not known specifically which abnormalities or conditions PGD testing has been used for.[11] Almost 2000 babies have been born after the process of PGD since it was developed in 1989.[15] There are no published reports of increased fetal defects or late effects in babies born using PGD, but it is possible abnormalities may occur later in life as a result of the procedure.[9,10,13] Preimplantation genetic diagnosis cannot detect all genetic irregularities because only a limited number of chromosomes can be tested per procedure, and misdiagnosis may still occur.Prenatal diagnosis (amniocentesis or chorionic villus sampling) may still need to be considered after use of PGD to determine if the fetus carries a genetic abnormality.

Cancer and Parenting

Although cancer presents obstacles to becoming a parent, an experience with a major illness can also make survivors excellent parents, with greater emotional resilience and appreciation for parenthood. However, the decision to become a biologic parent after cancer must be weighed with the obstacles of the time and expense of fertility preservation procedures such as IVF. Adoption remains an option, but cancer survivors may experience difficulty in becoming qualified as adoptive parents. Survivors seeking adoption may encounter discrimination from US adoption agencies because of the survivor's physical health and condition.Some US agencies require an applicant to be at least 5 years post-treatment before he or she can qualify as a potential adoptive parent. Some cancer survivors have had success qualifying for the adoption of foreign-born children through international adoption agencies. Additionally, infertility treatments and adoption procedures may be too costly for some survivors, especially after an expensive battle with cancer.

In addition to concerns about cancer recurrence and parenting, survivors often have psychosocial concerns related to pregnancy and parenting, many of which mirror issues faced by any woman considering the use of ART. These concerns focus primarily on risks of birth defects or cancer in offspring; anxiety about hormonal factors related to pregnancy or infertility treatment increasing a risk of cancer recurrence, leaving the spouse/partner to raise the child if the parent with cancer dies; and conflicts about using ART because of ethical beliefs or religious beliefs, as some religions prohibit the use of donor gametes

Reproductive Counseling for Cancer Survivors

Canada and Schover[22] identified the need for research to promote improved patient education regarding cancer and reproductive health. Although the researchers indicate oncologists would probably be the ideal health care professionals for cancer patients to have in-depth discussions with regarding fertility preservation and future parenting, they further note that time constraints may make this unrealistic. However, their objective is to promote better information about the risks of infertility to the newly diagnosed cancer patient, a communication initiative for which other researchers have made a similar plea. Although this is a crucial first step on the road to improved quality of life in cancer survivors and risk management for infertility, it does not fully address the decision-making issues the patient must consider in rapid time.

There is little research about the psychosocial decision making of newly diagnosed cancer survivors regarding fertility and PGD choices. Unlike infertility in couples without a cancer diagnosis, the impending infertility of a cancer patient and the need for treatment provides a narrow window of time for patient counseling. Although some patients, similar to the woman in this case study, perceive stored embryos and oocytes as "frozen hope," decisions about the future of the stored embryo can be agonizing. Recent studies have begun to examine patient choices for the donation or destruction of stored embryos.

One study conducted in an Australian population among 235 couples with banked embryos found 27% would donate to stem cell research or infertility research, whereas 15% would consider donating to another couple.
However, the disagreement rate among the couples was high, with more than 40% disagreeing over each of the options.Additionally, 90% of the couples indicated they would want to discuss donation with a health care professional rather than make the decision alone. The majority preferred a fertility specialist or scientist as their choice for the discussions. This study highlights the fact that deciding to pursue ART is only the beginning of the decision-making process that may span several years.

Other researchers have begun to examine how patients feel about stored embryos and oocytes in fertility clinics. An emerging trend indicates patients may enter reproductive counseling with one set of ideas about stored embryos and feel differently after a successful pregnancy or failed attempts.[26–28] However, no studies have examined this meaning among women who stored embryos or oocytes due to cancer treatment.

There are currently no guidelines specifically tailored for the reproductive counseling needs of newly diagnosed cancer patients, especially for those who may have concerns about hereditary cancer syndromes. Peshkin et al.suggest strong support for such guidelines and continued collaborations among providers who work in oncology, cancer genetics, and ART.Conclusion

Finishing cancer treatment and transitioning from patient to survivor does not end the psychologic trauma of cancer. There are a plethora of issues that survivors often face after their cancer is in remission that affect quality of life. This case report illustrates the loss of fertility often experienced by a cancer survivor as a result of treatment. Young women with genetic mutations, such as those in the BRCA1/2 genes, may have additional concerns about passing on hereditary cancers to future offspring. Considering PGD to avoid passing the mutation may allow parents to select only healthy embryos, but decisions about the fate of embryos that are mutation carriers remain perplexing.

Decisions about using fertility preservation typically must be made at the same time as other decisions about treatment of a life-threatening diagnosis. Ethical, religious, financial, and other implications of preserving her fertility confront the woman before she begins cancer treatment. This leaves limited time for the patient to consider the implications of her choices and how she may feel about her reproductive options at a later date.

Given that 2.5 million young adults in the United States have survived cancer, more research is needed on the psychosocial aspects of parenthood, particularly to identify the psychosocial needs of survivors regarding cryopreservation and PGD. The resources for providing support for using ART and PGD lag behind the rapid advance of technology. Table 2 provides a list of online sources of information for patients and health care professionals. Communication guidelines should be developed for informing cancer patients of the emotional and psychosocial impact of fertility preservation, with particular regard to future decision making. More research is needed to develop educational resources specific to this population that will aid the women newly diagnosed with cancer in decision making. Although social support is an important aspect of survivorship, the medical community can also provide support by assigning social workers or counselors to survivors and to the newly diagnosed who are facing fertility and parenting issues.

Breast-Feeding for Less Than 1 Month Linked to Increased Risk for Type 2 Diabetes

2010-09-12T03:32:00.000-07:00

From Medscape Medical News

Laurie Barclay, MD

September 10, 2010 — Breast-feeding for less than 1 month is linked to an increased risk for type 2 diabetes, according to the results of a study reported in the September issue of the American Journal of Medicine.

"We have seen dramatic increases in the prevalence of type 2 diabetes over the last century," said lead author Eleanor Bimla Schwarz, MD, MS, from the University of Pittsburgh in Pittsburgh, Pennsylvania, in a news release.
"Diet and exercise are widely known to impact the risk of type 2 diabetes, but few people realize that breastfeeding also reduces mothers' risk of developing the disease later in life by decreasing maternal belly fat."

The goal of the study was to examine the associations between duration, exclusivity, and consistency of lactation with the risk for type 2 diabetes in a well-studied cohort of women, aged 40 to 78 years, representative of the overall population.
This cohort consisted of 2233 female members of Kaiser, a large, integrated healthcare delivery organization in California, who were enrolled in the Reproductive Risk factors for Incontinence Study at Kaiser (RRISK), between 2003 and 2008.
The investigators controlled for age, parity, race, education, hysterectomy, physical activity, tobacco and alcohol use, family history of diabetes, and body mass index using multivariable logistic regression.

Of the study sample, 1828 were mothers; more than half (56%) had breast-fed an infant for at least 1 month. Compared with nulliparous women, those who consistently breast-fed all of their children for at least 1 month had a similar adjusted risk for type 2 diabetes (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.56 - 1.81), whereas mothers who had never breast-fed an infant had greater risk (OR, 1.92; 95% CI, 1.14 - 3.27). Compared with mothers who exclusively breast-fed for 1 to 3 months, those who never exclusively breast-fed were more likely to have gone on to have type 2 diabetes (OR, 1.52; 95% CI, 1.11 - 2.10).

"Risk of type 2 diabetes increases when term pregnancy is followed by <1 month of lactation, independent of physical activity and body mass index in later life," the study authors write. "Mothers should be encouraged to exclusively breast-feed all of their infants for at least 1 month."

Limitations of this study include observational design subject to residual confounding, recall or reporting bias leading to possible misclassification of women's lactation history, and lack of data on women's level of obesity or insulin resistance at the time of pregnancy.

"Our study provides another good reason to encourage women to breastfeed their infants, at least for the infant's first month of life," said Dr. Schwarz. "Clinicians need to consider women's pregnancy and lactation history when advising women about their risk for developing type 2 diabetes."

The National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Child Health and Development supported this study. The study authors have disclosed no relevant financial relationships.

Am J Med. 2010;123:863.e1-863.e6.

Psychological Violence During Pregnancy Linked to Postnatal Depression

2010-09-12T03:18:00.000-07:00

From Medscape Medical News

Fran Lowry

September 9, 2010 — Psychological violence during pregnancy by an intimate partner is strongly linked to postnatal depression, independent of physical or sexual violence.
This finding, published online September 6 in The Lancet, has important implications for prevention policies because most focus only on physical violence, Ana Bernarda Ludermir, MD, from Universidade Federal de Pernambuco, Recife, Brazil, and her colleagues conclude.

"Our results have both clinical and public health implications," Dr. Ludermir told Medscape Medical News. "Interventions for victims of partner violence have included a variety of approaches, such as the use of women's empowerment protocols, referral to shelters, transitional housing, legal advice, and psychological support. However, there is still insufficient evidence on the effectiveness of such interventions in improving psychosocial health."

Most Common Form of Partner Violence

In this prospective cohort study, which was undertaken between July 2005 and December 2006 in Recife, northeastern Brazil, Dr. Ludermir and her team enrolled pregnant women aged 18 to 49 years who were in their third trimester and who were attending primary healthcare clinics.

The women were interviewed during pregnancy and after delivery. The antenatal interview was done most often at the healthcare clinic, although some were done at home at the woman's request. Most of the follow-up interviews were done at home at a median of 8.1 months (interquartile range, 5.2 – 10.2 months) after the antenatal interview.

The investigators used the Edinburgh Postnatal Depression Scale (EPDS) to assess postnatal depressive symptoms. The form of partner violence in pregnancy was assessed with a validated questionnaire.

Of the 1045 women who were included in the final analysis, 270 women (25.8%; 95% confidence interval [CI], 23.2 – 28.6) had postnatal depression.

The most common form of partner violence was psychological (28.1%; 95% CI, 4 – 31.0).

Table 1. Forms of Psychological Violence Reported by Respondents

Type of Violence No. of Women % of Women (95% CI)
Insulted you or made you feel bad about yourself 247 23.6 (21.1 – 26.3)
Belittled you or humiliated you in front of others 127 12.2 (10.2 – 14.3)
Done things to scare or intimidate you on purpose 84 8.0 (6.5 – 9.9)
Threatened to hurt you or someone you care about 81 7.8 (6.2 – 9.5)

CI = confidence interval

The frequency of psychological violence during pregnancy was positively associated with postnatal depression. Although this association was reduced after adjustment, women reporting the highest frequency of psychological violence were more than twice as likely to have postnatal depression, even after adjustment, than those who had not experienced psychological violence, the researchers report.

Psychological violence was more common than physical or sexual violence, and this is in keeping with findings from previous studies, Dr. Ludermir said. "We need to understand more about why psychological violence occurs and develop interventions to prevent it from occurring, as well as treatments to reduce its impact."

She added that prenatal care could provide an opportunity to identify women at risk. "Currently, we place emphasis, and rightly so, on preventing and treating physical violence, but psychological violence is also a serious problem, as this study shows. Interventions that might prevent psychological violence or help treat its consequences could reduce the substantial burden of postnatal depression that affects mothers, children, and the healthcare system as a whole.”

Dr. Ludermir noted that her study had some important limitations, including the use of the EPDS questionnaire to ascertain postnatal depression. "EPDS is a symptom questionnaire, and there is much debate about the appropriate criteria for defining depression and its relationship with the need for treatment," she noted. "Also, partner violence is more common in women with limited schooling and who live in poverty, so the high frequency of partner violence could reflect the characteristics of the community we studied. It is possible that violence was actually underreported because of the associated stigma and shame."

Screening Not Currently Recommended, But Should Be

In an accompanying editorial, Rachel Jewkes, MD, from the Medical Research Council, Pretoria, South Africa, writes that emotional abuse probably has a greater importance in women's mental ill-health than originally thought "and should therefore receive more attention from researchers and health services."

She adds that the high prevalence of postnatal depression reported in the study "shows the great need for improved mental healthcare."

Finally, Dr. Jewkes points out that emotional abuse screening in pregnant women is not currently recommended by official bodies, such as the American Congress of Obstetricians and Gynecologists, but suggests that it should be.

There is mounting evidence, she writes, "that guidelines should include questions about emotional abuse, as well as physical and sexual abuse. Prevention of all forms of intimate partner violence is very important for improving women's health, particularly their mental health."

Lancet. Published online September 6, 2010.

Both Mothers and Fathers at Risk for Depression in First Year After Child's Birth

2010-09-12T03:12:00.000-07:00

From Medscape Medical News

Deborah Brauser

September 9, 2010 — Although both mothers and fathers are at risk of experiencing incidences of depression by their child's 12th birthday, the highest risk is within their first year post partum, according to researchers from the United Kingdom.

"The main takeaway message for clinicians is that both parents are at risk of developing depression soon after the birth of the baby," Irwin Nazareth, PhD, MBBS, director of the Medical Research Council (MRC) General Practice Research Framework and professor of primary care at University College London, United Kingdom, told Medscape Medical News.

He noted that the UK National Institute for Clinical Excellence has recommended regular screenings for mothers for depression through the antenatal and postnatal period. However, "this should be extended to fathers so that the family is considered as a whole unit. Special attention must also be paid to young parents who have had a past history of depression and those who are socioeconomically deprived."

The study was published online September 6 in the Archives of Pediatrics and Adolescent Medicine.

Paucity of Paternal Depression Research

Although past research has shown that parental depression is associated with adverse outcomes for their children in behavior, development, and cognition, most have focused only on maternal depression, write the study authors.

"The effect of a new baby on the father has received little attention," said Dr. Nazareth. "This study was hence done to ascertain the extent of the problem and to identify those groups of fathers who were at particular risk of depression. Moreover, we believe that simultaneously studying the effect of the birth of the baby both on fathers and mothers provides us a much fuller picture of the wider effects of birth on the family unit."

He also noted that his investigative group at the MRC "has always had a special interest in mental health problems in primary care" and that this particular study resulted from 8 years of research work undertaken by lead study author Shreya Dave, PhD, MSc, BSc.

For this study, the investigators evaluated data from between 1993 and 2007 from The Health Improvement Network database, which includes information on almost 5 million primary care patients from the United Kingdom. They then identified a cohort of 86,957 mother-father-child units.

Patient records and read code entries were also assessed for unipolar depression, antidepressant prescriptions, and sociodemographic information, including follow-up data up to the child's 12th birthday.

Both Parents Experience Depression

The investigators found that 19,286 of the mothers and 8012 of the fathers had an episode of depression during the period between their child's birth up to the age of 12 years.

Of these moms, 77% experienced 1 episode of depression, 18% had 2 episodes, and 5% had 3 or more episodes. Of the depressed fathers, 83% had 1 episode, 14% had 2, and 3% had 3 or more.

The overall incidences of depression during this same period for mothers were 7.53 per 100 person-years vs 2.69 per 100 person-years for fathers.

However, the depression rates were highest for both parents during the first year after the child's birth at 13.93 per 100 person-years for mothers and 3.56 for fathers.

"What was striking in this study was the extent of the depression in fathers vs mothers and how the first year of the birth of the baby was in particular a risk period for both parents," said Dr. Nazareth.

The researchers write that in addition to such things as poor parental sleep and change in responsibilities, the high rates of depression found during the first year post partum may be partly due "to a resumption of antidepressant use following a break during pregnancy and breastfeeding."

Finally, both mothers and fathers who were between the age of 15 and 24 years at the birth of their child were significantly more likely to be depressed than parents older than 25 years, as were those who had a history of depression and were in the highest quintile for deprivation.

Dr. Nazareth noted that this link was particularly interesting. "This informs general practitioners on the need to consider closer monitoring of these at risk groups from early pregnancy and soon after."

In addition, the study authors write that future research should examine other factors potentially associated with parental depression, such as the couple's relationship quality and stressful events, as well as the effects of this depression on the child's health and development.

Awareness, Screenings Needed

"This was an interesting study that addresses an important issue that hasn't been clearly resolved in research and, in fact, has been the subject of some debate over the past 10 years," James Paulson, PhD, associate professor and clinical psychologist in the Department of Pediatrics at Eastern Virginia Medical School at Children's Hospital of the King's Daughters in Norfolk, told Medscape Medical News, when contacted for comment.

"That issue is depression in mothers during the first year post partum, which clearly has negative connotations for the family," he added. "This study works strongly in favor of the argument that depression is something that's happening in postpartum — not only in mothers but also in fathers — more than at any other time point during parenthood."

Dr. Paulson, who was not involved with this study, recently conducted a meta-analysis looking specifically at prenatal and postpartum depression in fathers.

"I thought it was great that these investigators included paternal depression in their methodology, which I think we'll find in more and more studies. This article really underscores the point that depression is happening more often in fathers."

He noted that, due to continuing stigma, men often do not admit to having depression and often do not seek help. "I also think they're less likely to recognize depression as depression when they experience it. So I think increasing awareness will really help ring that bell for more people."

Although Dr. Paulson had no concerns with this study, he said that he would have liked to have seen more about what was going on within the family and not just an exclusive focus on the individual parents.

"Turning the focus more toward the family is very important for moving this field forward, and it gives us a lot more traction in terms of what we can do for catching depression, for intervening, and for minimizing its effect on the family and the child," he explained.

"For clinicians, I think the number 1 takeaway is that when working with expecting new parents — and I think we need to start thinking about this during the pregnancy — realize that this a situation where depression is a much higher risk than it is at any other time point," concluded Dr. Paulson. "Take whatever steps are needed to screen for depression in both mothers and fathers because clearly this is a risk that occurs in both parents."

This study was funded in part through a grant from the MRC. The study authors and Dr. Paulson have disclosed no relevant financial relationships.

Arch Pediatr Adolesc Med. Published online September 6, 2010.

Surgery or Chemo First in Advanced Ovarian Cancer? New Data Fuel Debate

2010-09-07T23:27:00.000-07:00

From Medscape Medical News
Janis C. Kelly

September 6, 2010 — Primary debulking surgery before adjuvant chemotherapy is the standard of care for patients with advanced ovarian cancer, but new data from a multinational study suggest that patients with stage IIIC or IV disease might do as well with neoadjuvant chemotherapy followed by surgery.

Lead author Ignace Vergote, MD, PhD, from Leuven University Hospitals in Belgium, told Medscape Medical News that outcomes were essentially the same in terms of overall and progression-free survival, and suggested that the neoadjuvant approach might lower the risk for postoperative death, grade 3 or 4 hemorrhage, infection, and venous complications.

Dr. Vergote emphasized that this applies only to stage IIIC and IV patients. "Primary surgery should remain the treatment of choice in patients with earlier stages of ovarian cancer," he said.

The trial was a collaborative study by researchers from the European Organization for Research and Treatment of Cancer Gynaecological Cancer Group and the National Cancer Institute of Canada Clinical Trials Group, and included researchers in Belgium, Norway, Canada, Scotland, England, the Netherlands, Italy, and Spain.

In the September 2 issue of the New England Journal of Medicine, Dr. Vergote and colleagues report data from 632 patients with stage IIIC or IV epithelial ovarian carcinoma, fallopian-tube carcinoma, or primary peritoneal carcinoma. Patients were randomized to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery (interval debulking surgery).

The hazard ratio for death was 0.98 for neoadjuvant chemotherapy vs primary debulking. The hazard ratio for progressive disease was 1.01.

The strongest predictor of overall survival was the complete resection of all macroscopic disease in both the primary debulking and neoadjuvant chemotherapy groups.

Residual tumor was 10 mm or less (described as optimal debulking) in 41.6% of patients in the primary debulking group and in 80.6% of patients in the neoadjuvant chemotherapy group. However, data provided in the supplementary online appendix to the paper show that complete resection was achieved in fewer than half of the patients who had tumors 10 mm or less after primary debulking, but in two thirds of those who had tumors 10 mm or less after neoadjuvant chemotherapy.

Differences by Country

There were also striking differences in surgical completeness by country. Belgium accounted for the majority of patients in the study; there was no residual disease in 62.9% of Belgian patients treated with primary debulking and in 87.3% of those treated with neoadjuvant chemotherapy.

No other country approached these results with primary debulking. Rates for no residual disease ranged from 3.9% in the Netherlands to 11.1% in Canada.

Similarly, rates for no residual disease with neoadjuvant chemotherapy ranged from 27.7% in the Netherlands to 42.9% in the United Kingdom.

Median survival was 44.98 months in patients who had no residual disease after primary debulking surgery and 27.01 months in those after neoadjuvant chemotherapy. Five-year survival was 31.31% in patients with no residual disease after primary debulking surgery and 17.52% after neoadjuvant chemotherapy.

Interestingly, median and 5-year survival were both better in patients who had some residual tumor (1 to 10 mm) after primary debulking surgery (32.26 months and 23.47%, respectively) than in those who had no residual disease after neoadjuvant chemotherapy (27.01 months and 17.52%, respectively).

Complete resection of all macroscopic disease was the strongest predictor of survival.

Adverse Events Caveat

Dr. Vergote emphasized to Medscape Medical News that this trial consisted only of patients with extensive stage IIIC or IV disease, and the outcomes should not be compared with those in patients with stage IIIB or earlier-stage ovarian carcinoma. He also noted the importance of ruling out other primary tumors (especially of gastrointestinal origin) when selecting patients for neoadjuvant chemotherapy.

The researchers concluded that "neoadjuvant chemotherapy is not inferior to primary cytoreductive surgery for patients with stage IIIC or IV ovarian carcinoma. No significant advantages of neoadjuvant therapy or primary debulking surgery were observed with respect to survival, adverse effects, quality of life, or postoperative morbidity or mortality."

Dr. Vergote later explained that although the study design did not permit a statistically valid comparison of adverse effects, the lower incidence of postoperative death, grade 3 or 4 hemorrhage, infection, and venous complications is clinically important, as is the greatly reduced operative time required after neoadjuvant chemotherapy.

Dr. Vergote said that the data also suggest that patients with very small metastases seem to do better with primary debulking surgery, whereas those with larger tumors seem to do better with neoadjuvant chemotherapy and interval debulking.

"My advice is to estimate how difficult surgery will be. For example, if the patient is 75 years old and [computed tomography] scan plus laparoscopy show extensive tumors that will require a lot of bowel resection, I would consider neoadjuvant chemotherapy rather than primary surgery," Dr. Vergote said. "It is important to be aggressive, regardless of the approach. The goal is no residual tumor, not 'less than 10 mm' residual tumor."

Operative time is another consideration. Dr. Vergote said that primary surgery in very extensive stage III or IV ovarian cancer might require 7 hours, whereas surgery for a similar patient after neoadjuvant therapy might require only 4.5 hours.

American Expert Has Concerns

Dr. Vergote suggested that the lower complete resection rates in this study, compared with data from major American cancer centers, might reflect differences in patient population, in that American series might have included patients with less extensive disease.

Robert E. Bristow, MD, director of gynecologic oncology at the University of California Irvine Medical Center in Orange, who reviewed the study for Medscape Medical News, was not completely convinced.

"The researchers are to be congratulated for completing this big, multi-institution study," Dr. Bristow said. "However, the conclusions challenge the conventional wisdom on treatment of advanced ovarian cancer. Nearly all other studies show that patients who undergo primary debulking surgery do better."

Dr. Bristow expressed concerns about the completeness of surgery in this study. He said that in the United States, generally, optimal debulking rates (less than 10 mm residual disease) are above 70% (compared with 41% in this study), and two thirds of those are complete, with no residual disease (compared with 19.2% in this study) .

"It may be that in some of the institutions in this study, the primary debulking surgery performed was not significantly different from no surgery at all," Dr. Bristow said. "This is an important study, but results are not necessarily transferable to surgical oncology clinical practice. I would like to see it replicated with participating hospitals where the optimal debulking rate is 75% or better and two thirds of those patients have no residual disease."

Dr. Vergote and Dr. Bristow have disclosed no relevant financial relationships.

Acyclovir, Valacyclovir in First Trimester Not Linked to Major Birth Defects

2010-09-06T20:43:00.000-07:00

From MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Hien T. Nghiem, MD

August 25, 2010 — Exposure to acyclovir or valacyclovir in the first trimester of pregnancy is not associated with an increased risk for major birth defects, according to the results of a large, population-based, historical cohort study reported in the August 25 issue of the Journal of the American Medical Association.

"Herpes simplex and herpes zoster infections are common and often treated with antiviral drugs including acyclovir, valacyclovir, and famciclovir," write Björn Pasternak, MD, PhD, and Anders Hviid, MSc, DrMedSci, from Statens Serum Institut in Copenhagen, Denmark. "Safety of these antivirals when used in the first trimester of pregnancy is insufficiently documented."

The goal of the study was to examine associations between use of acyclovir, valacyclovir, and famciclovir during the first trimester of pregnancy and the risk for major birth defects, using a cohort of 837,795 live-born infants in Denmark from January 1, 1996, to September 30, 2008. Infants diagnosed with chromosomal abnormalities, genetic syndromes, birth defect syndromes of known cause, or congenital virus infections were excluded.

Individual-level data regarding dispensed antiviral drugs, birth defect diagnoses categorized with use of a standardized classification scheme, and potential confounders were derived from nationwide registries. The primary study endpoint was prevalence odds ratios (PORs) of any major birth defect diagnosed before age 1 year within the first year of life, by antiviral drug exposure.

A major birth defect was diagnosed in 40 (2.2%) of 1804 infants whose mothers used acyclovir, valacyclovir, or famciclovir in the first trimester and in 19,920 infants (2.4%) whose mothers were not exposed to these drugs (adjusted POR, 0.89; 95% confidence interval [CI], 0.65 - 1.22).

In the specific antiviral drugs, 32 (2.0%) of 1561 infants with first-trimester exposure to acyclovir were diagnosed with a major birth defect (adjusted POR, 0.82; 95% CI, 0.57 - 1.17), as were 7 (3.1%) of 229 infants with first-trimester exposure to valacyclovir (adjusted POR, 1.21; 95% CI, 0.56 - 2.62). Only 26 infants were exposed to famciclovir during the first trimester; of these, 1 infant (3.8%) was diagnosed with a birth defect. Although no associations between antiviral drug exposure and 13 different subgroups of birth defects were apparent in exploratory analyses, there were only a small number of exposed cases in each subgroup.

"In this large nationwide cohort, exposure to acyclovir or valacyclovir in the first trimester of pregnancy was not associated with an increased risk of major birth defects," the study authors write.

Limitations of this study include inability to capture defects diagnosed after age 1 year, exclusion of abortions, incomplete evaluation of maternal comorbidity, and possible unmeasured confounding. A major limitation is that nonadherence to the dispensed drugs would obscure teratogenic effects, if present. Because there were few exposed cases in each subgroup of major defects, teratogenic effects cannot be ruled out with certainty.

"Our study... has immediate clinical implications and may support informed decisions on safety when prescribing antivirals for herpes infections in early pregnancy," the study authors conclude. "Acyclovir is the most extensively documented antiviral and should therefore be the drug of choice in early pregnancy, while data on valacyclovir and famciclovir are still insufficient.
Future research on antiherpetic antivirals and mother-child health should include safety studies with regard to spontaneous abortion and preterm birth, and during breastfeeding."

Editorial: Still Some Remaining Issues

In an accompanying editorial, James L. Mills, MD, MS, and Tonia C. Carter, PhD, from the National Institutes of Health in Bethesda, Maryland, note that because of limitations, this study does not answer the key question of whether acyclovir is a teratogen.

"[This study] is helpful in demonstrating the safety of acyclovir in pregnancy, but additional strategies must be developed to resolve the remaining issues," Drs. Mills and Carter write. "At a time when the health care system in the United States is facing enormous financial challenges, it is important not to ignore any sources of data that could answer critical medical questions."

The Danish Medical Research Council and the Lundbeck Foundation supported this study. The study authors have disclosed no relevant financial relationships. The editorial work was funded by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development.

JAMA. 2010;304:859-866, 905-906.

Clinical Context

Herpes simplex and herpes zoster infections are common. More than 1% of women acquire herpes simplex during the first trimester of pregnancy. Herpes simplex is often treated with antiviral drugs including acyclovir, valacyclovir, and famciclovir. Individuals who experience at least 6 recurrences of genital herpes within 1 year usually require episodic or long-term suppressive treatment. The US Food and Drug Administration has classified acyclovir, valacyclovir, and famciclovir as category B drugs in pregnancy. However, the safety of these antivirals when used in the first trimester of pregnancy has been insufficiently documented.

The aim of this study was to investigate associations between exposure to acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and the risk for major birth defects.

Preemies Not Born in Specialized Level III Hospitals More Likely to Die

2010-09-06T04:34:00.000-07:00

From Medscape Medical News

Fran Lowry

August 31, 2010 — Very low birth weight (VLBW) and very preterm (VPT) infants who are born in centers that are not specially equipped or experienced to manage such births have higher rates of neonatal and predischarge death compared with similar infants who are born in highly specialized level III hospitals.

The finding, from an analysis of data from previously published studies, appears in the September issue of the Journal of the American Medical Association.

"For more than 30 years, guidelines for perinatal regionalization have recommended that [VLBW] infants be born at highly specialized hospitals, most commonly designated as level III hospitals," write Sarah Marie Lasswell, MPH, from the Centers for Disease Control and Prevention, Atlanta, Georgia, and colleagues. "Despite these recommendations, some regions continue to have large percentages of VLBW infants born in lower-level hospitals."

The aim of this study was to evaluate the relationship between hospital level and care at birth and neonatal (the first 4 weeks after birth) and predischarge mortality for VLBW infants weighing 1500 g (53 ounces) or less and for VPT infants of 32 weeks' or less gestation.

In analyzing data from 37 VLBW studies comprising 104,944 infants, the investigators found that there was a 62% increase in odds of neonatal and predischarge death for infants born in non–level III hospitals compared with those born in level III hospitals (38% vs 23%; adjusted odds ratio [OR], 1.62; 95% confidence interval [CI], 1.44 - 1.83).

When the investigators restricted their analysis to 9 studies with higher-quality evidence comprising 46,318 infants, they noted similar results. There was a 60% increase in the odds of neonatal or predischarge mortality for VLBW infants born at non–level III hospitals compared with infants born in level III hospitals (36% vs 21%; adjusted OR, 1.60; 95% CI, 1.33 - 1.92).

Results were even worse for extremely low birth weight infants — weighing 1300 g (35 ounces) or less — born in non–level III hospitals. Those infants had an estimated 80% increase in odds of neonatal or predischarge mortality compared with infants born at level III hospitals (59% vs 32%; adjusted OR, 1.80; 95% CI, 1.31 - 2.46.)

Data from an analysis of 4 studies comprising 9300 infants showed that VPT infants born in lower-level hospitals had a 55% increase in odds of neonatal or predischarge mortality compared with infants born in level III hospitals (15% vs 17%). When only the 3 studies that were ranked as adequate and high quality were analyzed, the estimate of death was reduced to a 42% increased odds of death (7% vs 12%; adjusted OR, 1.42; 95% CI, 1.06 - 1.88).

The researchers add that meta-regression by year of publication did not reveal a change over time (slope, 0.00; P = .87).

Among the study limitations, the authors note that they excluded non-English studies and unpublished data from their meta-analysis and suggest this might be a potential source of bias in their study selection. Other potential causes of bias include inadequate definitions of hospital levels, inadequate descriptions of hospital capabilities, and variability of confounding factors among the studies.

"The results of this review confirm a primary premise on which perinatal regionalization systems are based: high risk infants have higher mortality rates when born outside hospitals with the most specialized levels of care," the authors conclude. "Although they represent less than 2% of U.S. births, 55% of infant deaths occur among VLBW infants. Strengthening perinatal regionalization systems in states with high percentages of VLBW and VPT infants born outside of level III centers could potentially save thousands of infant lives every year."

JAMA. 2010;304:992-1000.

One Third of First-Time Pregnancies Delivered by Cesarean

2010-09-01T00:22:00.000-07:00

From Medscape Medical News
Fran Lowry

August 30, 2010 — The rate of cesarean deliveries in the United States is continuing its upward trajectory, according to a new study released today. Now accounting for 30% of all deliveries, the rate of cesarean delivery has increased 50% from 1996 to 2007 and shows no signs of diminishing.

Results of a large, retrospective, observational study conducted by the National Institute of Child Health and Human Development and National Institutes of Health, in collaboration with 12 institutions across the United States, show that:

•1 in 3 women pregnant for the first time are now being delivered by cesarean.
•Repeat cesarean after a previous caesarean delivery now accounts for one third of all cesarean deliveries.
•The rate of trial of labor after a previous cesarean is low, at 29%, and the success rate for a trial of labor has declined to 57%.
•44% of women attempting vaginal delivery had their labor induced, and their rate of cesarean delivery is twice as high as women who have spontaneous labor.
•Half of cesarean deliveries were conducted before 6 cm of cervical dilation — which is considered an early phase of labor, especially in first-time mothers — induced labor, or women who are attempting vaginal birth after cesarean delivery (VBAC).

The results were announced by lead researcher Jun Zhang, PhD, MD, from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The findings are published in the September issue of the American Journal of Obstetrics and Gynecology.

Speaking at a teleconference today, Dr. Zhang told reporters he was particularly surprised by the finding that 1 of every 3 first-time mothers are delivering via cesarean.

"This has important consequences for future pregnancies, since vaginal delivery after C-section is still thought to be somewhat risky, despite recommendations by the American College of Obstetrics and Gynecology (ACOG) to the contrary," he said.

Another surprising finding was that many cesarean deliveries are being done very early in labor, before 6 cm of dilation, Dr. Zhang added.

The study, called the Consortium on Safe Labor, was conducted to collect comprehensive information on current labor and delivery practice across the United States. It included 12 clinical centers, made up of a total of 19 hospitals, located across 9 ACOG districts. Most were university or community teaching hospitals, and only 2 were nonteaching community hospitals. They were chosen because electronic medical records were available at each institution and because they were geographically representative of all ACOG districts in the United States.

Dr. Zhang told Medscape Medical News that several factors may be driving the increase in cesarean deliveries.

"Delayed child bearing, increased maternal body mass, more twin pregnancies, and low use of vaginal birth after previous C-section, which is increasing because of 2 forces — the increasing C-section rate in first-time mothers and the decrease in VBACs. Put all these together, and it looks as if the upward trajectory may continue for a little while."

He admitted that the study has limitations. The participants are not a random sample of what is going on in the United States, and academic institutions are overrepresented in the study sample, he told Medscape Medical News.

"Although this is quite a comprehensive database, it is not totally representative of the United States population. That is one drawback."

The second is that the study is retrospective.

"We think that the quality of information we have is very good, but we still have to rely on what is recorded in the medical records. We extracted the information from the hospital database, so our data are only as good as the medical record. That is another deficiency."

Dr. Zhang said that reducing this high rate of cesarean delivery will need to focus on preventing unnecessary primary cesarean deliveries "from several aspects."

"First, we need to decrease the rate of cesarean delivery associated with a high rate of induction of labor. Cesarean section for dystocia should be avoided before active phase of labor is established, particularly in nulliparous women, induced labor, and VBAC attempts."

He added that there should be a clinically accepted indication for performing cesarean delivery. Also, physicians and patients should be educated about trial of labor in women with a previous uterine scar.

"We agree with ACOG. They have just issued guidelines that call for increased use of VBAC, and we are in accordance with this," he noted.

S. Katherine Laughon, MD, MS, a fellow and maternal–fetal medicine specialist working with Dr. Zhang, said that barriers to VBAC exist but the study was not set up to address the specific reasons why.

"Recently, there was a National Institutes of Health consensus conference on what are the barriers to women getting access to providers and to healthcare facilities that will provide the opportunity for a trial of labor after a prior cesarean section, and also what are the barriers for physicians," Dr. Laughon said. "This particular study does not address that exact question, but it is something that both clinicians and policy makers at the national level need to investigate and find answers for."

Dr. Zhang and Dr. Laughon have disclosed no relevant financial relationships.

Presented August 30, 2010, in a teleconference at the National Institutes of Health.

Am J Obstet Gynecol. Published online August 13, 2010.

Antimicrobial Prophylaxis Recommended for All Cesarean Deliveries

2010-08-31T04:46:00.000-07:00

From Medscape Medical News
Laurie Barclay, MD

August 25, 2010 — The Committee on Obstetric Practice of the American College of Obstetricians and Gynecologists recommends antimicrobial prophylaxis for all cesarean deliveries unless the patient is already receiving appropriate antibiotics (eg, for chorioamnionitis), according to a Committee Opinion report in the September issue of Obstetrics and Gynecology. This antibiotic prophylaxis should be given within 60 minutes of starting the cesarean delivery.

"Antimicrobial prophylaxis for cesarean delivery has been a general practice for cesarean deliveries because it significantly reduces postoperative maternal infectious morbidity," the committee writes. "These antibiotics have been administered intraoperatively after umbilical cord clamping for two theoretic concerns related to the fetus:
1) antibiotics in neonatal serum may mask newborn positive bacterial culture results; and
2) fetal antibiotic exposure could lead to an increase in newborn colonization or infection with antibiotic-resistant organisms.
Recently, several randomized clinical trials investigated the timing of antimicrobial prophylaxis for cesarean delivery."

Based on surgical research data, antimicrobial prophylaxis to prevent surgical site infection should ideally begin within 30 minutes, and definitely within 2 hours, of skin incision.

For longer surgery, the same dose of antibiotic may need to be given again at intervals of 1 or 2 times the half-life of the drug. The review authors write that "preoperative [antibiotic] administration significantly reduces endometritis and total maternal infectious morbidity compared with administration of antibiotics after umbilical cord clamping."

Antimicrobial prophylaxis for cesarean delivery typically employs narrow-spectrum antibiotics, such as a first-generation cephalosporin, effective against gram-positive bacteria, gram-negative bacteria, and some anaerobic bacteria. A single 1-g intravenous dose of cefazolin usually results in a therapeutic level for 3 to 4 hours, but obese women may need larger doses.

Clindamycin with gentamicin is a reasonable option for women with a significant allergy to β-lactam antibiotics, such as cephalosporins and penicillins.

Studies to date suggest that preoperative antimicrobial prophylaxis does not appear tohave any harmful effects on the mother or infant, nor is it associated with an increase in neonatal infectious morbidity or selection of antimicrobial-resistant bacteria causing neonatal sepsis. However, additional prospective evaluation is needed because these studies lacked sufficient power to assess those outcomes.

"The Committee on Obstetric Practice recommends antimicrobial prophylaxis for all cesarean deliveries unless the patient is already receiving appropriate antibiotics (eg, for chorioamnionitis) and that prophylaxis should be administered within 60 minutes of the start of the cesarean delivery," the committee concludes. "When this is not possible (eg, need for emergent delivery), prophylaxis should be administered as soon as possible."

Obstet Gynecol. 2010;116:791-792.

Vitamin C and E Supplementation May Not Prevent Spontaneous Preterm Birth

2010-08-31T04:26:00.000-07:00

From Medscape Medical News
Laurie Barclay, MD

August 27, 2010 — Vitamins C and E supplementation beginning at 9 to 16 weeks of gestation in nulliparous women at low risk may not reduce spontaneous preterm births, according to the results of a randomized, double-masked, placebo-controlled trial reported in the September issue of Obstetrics & Gynecology.

"Preterm [premature rupture of membranes (PROM)] has been associated with many factors, including ascorbic acid deficiency (vitamin C)," write John C. Hauth, MD, from the University of Alabama at Birmingham, and colleagues from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.
"These observations are of great importance because if vitamin C supplementation reduces the occurrence of preterm PROM, then a deficiency of vitamin C is a modifiable risk factor and supplementation would be a corrective interventional behavior.
Our intent was to assess further the hypothesis that daily maternal antioxidant supplementation with vitamins C and E from early pregnancy would reduce the incidence of spontaneous preterm birth attributable to either spontaneous labor or preterm PROM."

In the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network trial, nulliparous women at low risk were randomly assigned to daily vitamin C and E supplementation or matching placebo to determine the effect on adverse outcomes from pregnancy-associated hypertension.
Participants (n = 10,154) received 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily from 9 to 16 weeks of gestation until delivery.
In this secondary analysis, the studied endpoints included preterm birth attributable to PROM and total spontaneous preterm births (attributable either to PROM or spontaneous labor).

Of 9968 participants with available outcome data, 4992 were in the vitamin group and 4976 in the placebo group. Of 1038 women (10.4%) who delivered preterm, 698 (7.0%) had spontaneous preterm birth, including 356 (7.1%) randomly assigned to daily vitamin C and E supplementation and 342 (6.9%) assigned to placebo. Delivery after preterm PROM occurred in 253 women (2.5%), and delivery after spontaneous preterm labor occurred in 445 (4.5%).

Compared with the placebo group, the supplementation group had similar births attributed to preterm PROM at less than 37 and 35 weeks of gestation, but fewer births before 32 weeks of gestation (0.3% vs 0.6%; adjusted odds ratio, 0.3 - 0.9). Preterm PROM occurring before 32 weeks of gestation was also less frequent in women in the vitamin group (0.36% vs 0.64%; P = .046).

Total spontaneous preterm births across gestation were similar in the placebo group and in the supplementation group.

"Maternal supplementation with vitamins C and E beginning at 9 to 16 weeks of gestation in nulliparous women at low risk did not reduce spontaneous preterm births," the study authors write.

Limitations of this study include possible type 1 (alpha) error, as well as the clinical imprecision of determining the spontaneous preterm birth subcategories of preterm PROM or spontaneous preterm labor.

"Our results, taken in context with similar trials regarding vitamin C and E supplementation, do not support either the clinical use for prevention of spontaneous preterm birth or its neonatal sequelae or further trials of this treatment in similar populations at low risk," the study authors conclude.

Obstet Gynecol. 2010;116:653-658. Abstract

Early Age at Menopause Linked to Angina Post MI

2010-08-28T07:52:00.000-07:00

From Medscape Medical News

Emma Hitt, PhD

August 24, 2010 — Women who have an early menopause, at 40 years or younger, are at higher risk for angina after a myocardial infarction (MI) vs women who experience menopause at 50 years or older, new research suggests.

Susmita Parashar, MD, with Emory University, in Atlanta, Georgia, and colleagues reported their findings in the July 21 online issue of Menopause: The Journal of The North American Menopause Society.

According to the researchers, women who experience early menopause may be at risk for cardiovascular disease morbidity and mortality because of a deprivation of estrogen after menopause; however, "no descriptions of its prognostic importance among women with known coronary heart disease have been reported," which may help in the risk stratification and management of this patient group.

In addition, the study authors note that angina symptom-driven care for women accounts for most costs associated with care in women with coronary heart disease.

In the current study, 493 women were interviewed by telephone 1 year after discharge from the hospital for MI on aspects of behavioral, treatment, and health status measures. Mean age at menopause (AAM) was 45.2 ± 7.8 years.

Participants were classified by AAM: 40 years or younger, 41 to 49 years, and 50 years or older. The researchers then determined whether age predicted 1-year post-MI angina and severity of angina while taking into account pre-MI angina, demographics, comorbidities, MI severity, and quality of care.

Of the women, 132 (26.8%) experienced early menopause at 40 years or younger. These women were more often smokers but otherwise had similar comorbidities and characteristics as women experiencing later menopause both before and after MI.

However, the rate of 1-year angina in women with an AAM of 40 years or younger (32.4%) was double that of women with an AAM of 50 years or older (12.2%) in a multivariable analysis (relative risk, 2.09; 95% confidence interval [CI], 1.38 - 3.17), as was the severity of angina (odds ratio, 2.65; 95% CI, 1.34 - 5.22 for a higher severity level).

"Early menopause is a significant predictor of angina at 1 year after MI, independent of comorbidities, MI severity, and quality of care," Dr. Parashar and colleagues conclude.

According to the researchers, deprivation of endogenous estrogen may increase the extent of vascular inflammation, endothelial and microvascular dysfunction, and coagulation abnormalities; and decrease arterial compliance, all of which could cause angina in the setting of coronary artery disease.

"A simple, inexpensive, and easily administered question regarding age at menopause may help identify high-risk women and guide efforts toward improving treatments and quality of life of post-MI women," they suggest.

Menopause. Published online July 21, 2010. Abstract

The Diagnosis of Gestational Diabetes

2010-08-14T04:08:00.000-07:00

From Medscape Diabetes & Endocrinology
Change Is in the Air
Laura A. Stokowski, RN, MS

08/04/10

A Parallel Epidemic

The word "epidemic" is so overused that it has lost its undercurrent of urgency. We are experiencing epidemics of obesity, high cholesterol, cardiovascular disease, and diabetes. An epidemic has become the norm. Even the word "pandemic," thanks to swine flu, no longer conveys a sense of gravity. New words are needed to describe the overarching implications of a society in which type 2 diabetes afflicts at least 1 in 10 people and, quite possibly, many more.

The prevalence of gestational diabetes mellitus (GDM) will likely grow, as it has in the past, in direct proportion to that of type 2 diabetes.[1] Indications are that GDM already parallels the rapid increase in type 2 diabetes. In a US medical center where the screening method and diagnostic criteria for GDM have remained constant, the prevalence of this complication of pregnancy doubled in 8 years -- a 12% increase per year that cannot be explained by changes in age, ethnic distribution, or previous history of GDM among screened pregnancies.[2]

Arguably more disturbing than the number of people diagnosed with type 2 diabetes or GDM is the number of people who have prediabetes (ie, impaired fasting glucose and/or impaired glucose tolerance).
Currently, an estimated 19% of people over the age of 20 have prediabetes,[3] and this is the pool from which childbearing women are drawn.

Gestational Diabetes Mellitus
Gestational diabetes is glucose intolerance with onset or first recognition during pregnancy.
Pregnancy is already a diabetogenic state, with progressive deterioration of insulin resistance and glucose tolerance that become more significant in the third trimester.

Neonatal problems of offspring of frankly diabetic mothers (eg, congenital defects, spontaneous abortion, fetal macrosomia, birth injury, hypoglycemia, polycythemia, and hyperbilirubinemia) are well described. Exposure to diabetes during gestation also increases the risk for childhood and adult obesity, diabetes, and cardiovascular disease. However, risk for adverse outcomes associated with degrees of maternal hyperglycemia that are short of overt diabetes remains controversial.

In the United States, GDM is commonly diagnosed using either the World Health Organization's criteria (the same as those used to diagnose diabetes in nonpregnant women), or on the basis of a woman's risk of developing diabetes in the future. Neither of these methods links the key metabolic aberration of GDM (ie, maternal hyperglycemia) with the risk for adverse outcomes in the fetus and newborn. Most experts agree that new, more clinically relevant, risk-based criteria for the diagnosis of GDM are needed, especially considering the similarities between GDM and prediabetes. However, levels of maternal glucose intolerance that correlate with poor neonatal outcomes had not been sufficiently ascertained until the results of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study were reported.

The HAPO Study
The HAPO epidemiologic study was the first to conclusively establish a relationship between elevated maternal glucose concentrations and undesirable perinatal outcomes in women not previously diagnosed with diabetes.

The HAPO study clarified the association between multiple adverse outcomes of pregnancy and degrees of hyperglycemia less severe than those diagnostic of diabetes. Data for establishing internationally agreed-upon diagnostic criteria for GDM were also provided. This well-controlled study involved 25,000 women in 9 countries -- a multicultural, ethnically diverse cohort. All women underwent a 2-hour oral glucose tolerance test (OGTT) with a 75-g glucose load at 24-32 weeks' gestation, and random plasma glucose testing at 34-37 weeks. Results were blinded unless a woman's fasting, 2-hour, or random glucose values were elevated to a level that mandated immediate treatment.

Primary outcomes were macrosomia (ie, birth weight > 90th percentile), primary cesarean delivery, and clinical neonatal hypoglycemia and hyperinsulinemia (ie, cord serum C-peptide > 90th percentile). The analysis aimed to determine whether threshold levels of maternal glucose -- for any of the 1-hour, 2-hour, or fasting plasma glucose (FPG) levels -- could be identified for any of the negative outcomes. They found that each of the primary outcomes was associated not only with extremely high maternal glucose concentrations, but in a continuous and graded manner across the full range of observed glucose levels,[9] which precluded easy identification of threshold levels where risk for adverse outcomes rose. The relationship between maternal glucose levels and fetal growth and neonatal outcome seemed to be a basic biologic phenomenon, and not a clearly demarcated disease state, as had previously been thought.

Several secondary outcomes were also evaluated in the HAPO study, including preeclampsia, preterm delivery (ie, delivery at < 37 weeks' gestation), shoulder dystocia and/or birth injury, hyperbilirubinemia, and admission to neonatal intensive care. Shoulder dystocia or birth injury, preterm delivery, and preeclampsia were significantly associated with ≥ 1 elevated glucose values.[9] The blinding of maternal glucose (except when overt diabetes was suggested) is a strength of the HAPO study, because maternal glucose was not a factor in obstetric management. It is also promising that the study's findings did not vary by medical center or country. The results are therefore applicable globally and can be used to develop criteria for classifying gestational diabetes world-wide. Next Step: New Diagnostic Criteria The HAPO investigators did not attempt to translate their findings into new criteria for the diagnosis of gestational diabetes.[8] This task fell to a committee of experts, the International Association of Diabetes and Pregnancy Study Groups (IADPSG), who met to review the data, form a consensus, and make recommendations. A pivotal decision involved the threshold for diagnosing GDM using data from fasting glucose and 2-hour OGTT. This threshold would be somewhat arbitrary, because no inflection points were apparent in the linear relationships between maternal glucose concentrations and outcomes.[8] The IADPSG examined the strong linear associations between risk for neonatal outcomes and the 3 measures of maternal glucose (FPG, 1-hour OGTT, and 2-hour OGTT). The threshold was set at an odds ratio of 1.75, which identified 16.1% of the pregnant population as having GDM (Table 1). Table 1. Proposed and Current Thresholds for the Diagnosis of GDM Maternal glucose test Proposed diagnostic thresholda Above threshold (cumulative %) Current thresholda Fasting plasma glucose 92 mg/dl (5.1 mmol/L) 8.3 95 mg/dl (5.3 mmol/L) 1 hour plasma glucose 180 mg/dl (10 mmol/L) 14.0 180 mg/dl (10 mmol/L) 2 hour plasma glucose 153 mg/dl (8.5 mmol/L) 16.1 155 mg/dl (8.6 mmol/L) aWith 75 g OGTTOnly 1 of these cut-offs (FPG, 1-hour OGTT, or 2-hour OGTT) must be met or exceeded to diagnose GDM, unlike current American Diabetes Association (ADA) criteria, which require 2 elevated glucose levels to diagnose GDM. The proposed thresholds are those for which the odds of having a baby with birth weight, cord C-peptide, or neonatal body fat in the > 90th percentiles are 1.75 times the estimated odds of these outcomes at mean glucose values. Setting the threshold higher would decrease the number of women diagnosed with GDM, but would also fail to identify many women whose glucose concentrations place them at the same risk for adverse pregnancy outcomes, and who might benefit from treatment. In this study, 1.7% of patients were unblinded because of elevated FPG or OGTT results. When these patients are included, the total incidence of gestational diabetes in pregnant women rises to 17.8%.

Glucose Testing Considerations
The finding that slight differences in maternal glucose levels are associated with marked differences in outcomes throws intoclear relief the importance of precision in glucose testing. Odds ratios and frequencies for outcomes increase substantially over relatively small changes in glucose. While the handling of blood samples in research is tightly controlled, the real world typically introduces extensive variability. Even a small error in test results caused by poor handling or analytic technique could result in the misclassification of a patient.

For reliable diagnosis and classification of hyperglycemia in pregnancy, venous plasma or serum glucose must be analyzed with a highly accurate enzymatic method. The collection, handling, and transport of blood samples to minimize pre-analytic glycolysis are extremely important. The IADPSG recommends that only venous samples be used for glucose determination, emphasizing that capillary and venous samples are not interchangeable. If the plasma is not separated promptly, the blood sample should be kept cold, because glycolysis will continue in the presence of red and white blood cells, falsely reducing the patient's blood glucose level by 5-15%. It is often mistakenly believed that as soon as the blood is placed in sodium fluoride (a glycolysis inhibitor), glycolysis will stop, but in fact, sodium fluoride has little effect on glycolysis in the first 1-2 hours after sample collection.Point-of-care glucose testing with handheld glucose meters is not appropriate for the diagnosis of GDM.

Significance of Proposed Guidelines
Lowering the diagnostic threshold will undoubtedly raise the frequency of hyperglycemic disorders seen in clinical practice. This would matter less if it could be shown that a benefit can be derived from improving even mild aberrations in glucose metabolism during pregnancy. The longstanding debate about the value of screening pregnant women for hyperglycemia has centered on uncertainties about the treatment benefit.

Benefit of treating GDM. In May 2008, the US Preventive Services Task Force concluded that there was inadequate evidence to recommend treatment of GDM, largely because of inadequate prospective studies.[14] A subsequent review concluded that treatment of GDM after 24 weeks of pregnancy improves some maternal and neonatal outcomes; however, evidence for screening before 24 weeks' gestation is more sparse.[15] The gestational time at which hyperglycemia screening should be initiated, and the level of hyperglycemia that warrants aggressive intervention remain controversial.[16]

In 2005, the results of ACHOIS (Australian Carbohydrate Intolerance Study in Pregnant Women), a 10-year multicenter randomized trial, were published.[17] ACHOIS assessed whether treating mild GDM would reduce perinatal morbidity and mortality. Treatment with dietary counseling, self glucose monitoring, and insulin when indicated, significantly reduced adverse primary outcomes (ie, perinatal death, shoulder dystocia, and birth trauma), neonatal adipoinsular macrosomia, maternal preeclampsia, and labor induction. Landon and colleagues conducted a randomized controlled trial sponsored by the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (NICHD-MFMU) Network, compared untreated women with mild GDM with those receiving treatment (nutritional counseling, diet therapy, insulin if needed, etc.).[18] Significant reductions in macrosomia, neonatal fat mass, shoulder dystocia, preeclampsia, and cesarean section were seen in the treated cohort.

Both treatment trials revealed a positive effect of treatment in preventing large for gestational age (LGA) births, macrosomia, and shoulder dystocia.
Together, these 2 studies argue convincingly for a treatment benefit for mild GDM.While neither study found significant effects of treatment on neonatal morbidities such as hypoglycemia or hyperbilirubinemia, their findings of reduced neonatal fat mass, LGA, and macrosomia have important implications for long-term child and adult health. Excess neonatal fat and adipoinsular macrosomia are linked to childhood obesity and later development of diabetes. If these findings are real, then the successful treatment of maternal GDM, even mild GDM, could positively influence the health of the next generation.

Health system burden.
Although the new criteria are expected to double the number of women diagnosed with GDM, the rate will be consistent with the high prevalence of obesity and glucose intolerance in the general population. Donald R. Coustan, MD, Professor of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Division of Maternal-Fetal Medicine, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, explained the implications of classifying such a large slice of the pregnant population as having GDM and the potential burden on high-risk maternity care:

"Currently (as of 2007), the Centers for Disease Control and Prevention tells us that 10.7% of adult Americans have diabetes; furthermore, the American Diabetes Association states that 19% of adult Americans have prediabetes. So 17% is not such an extreme prevalence for GDM, which is quite similar to prediabetes in its severity. In the 2 randomized trials of identification and treatment of mild GDM (ACHOIS in Australia and NICHD-MFMU in the US), only 20% and 8%, respectively, of treated patients required insulin; the rest were managed successfully with diet. The burden will be in having adequate numbers of dietitians, and there will likely be creative approaches to educating newly diagnosed women, such as group counseling sessions. Self glucose monitoring could also increase the burden, but these milder forms may not require testing every day."

Others have raised concerns that the higher-risk GDM diagnostic label, irrespective of a woman's degree of glucose control, could stimulate an increase in perinatal interventions, earlier deliveries, caesarean section rates, babies admitted to special care nurseries, healthcare costs,[19] and psychological distress and anxiety related to the diagnosis of GDM.[15]

Implications for Clinical Practice
The IADPSG Consensus Panel recommendations are currently being considered for adoption by leading consumer and professional organizations such as the ADA and the American Congress of Obstetricians and Gynecologists. In a recent update of their position statement on diagnosis and classification of diabetes, the ADA said the following about the consensus panel's recommendations:

"At the time of publication of this update, ADA is planning to work with US obstetrical organizations to consider adoption of the IADPSG diagnostic criteria and to discuss the implications of this change. While this change will significantly increase the prevalence of GDM, there is mounting evidence that treating even mild GDM reduces morbidity for both mother and baby."[11]

If adopted, the new guidelines are expected to have immediate, widespread clinical implications.

Changes in screening for GDM. The detection strategy recommended by the IADPSG has 2 phases:

1.Testing for overt diabetes at the initial prenatal visit. Universal early testing in populations with a high prevalence of type 2 diabetes is recommended; others may choose to test only high-risk groups (Table 2)
2.A 75-g OGTT after an overnight fast at 24-28 weeks' gestation in all women not previously diagnosed with overt diabetes or GDM.

Table 2. Low and High Risk Factors for GDM[4,10]

Low risk for GDM
•Age < 25 years•Normal body weight•No family history (1st degree)of DM•No history of abnormalglucose metabolism•Not of ethnic/racial group with high prevalence of DM (African-Americans, Asian-Americans, Hispanic- Americans, Native Americans, Pacific Islanders)High risk for GDM •Maternal age > 35 years
•Marked obesity
•Personal history of GDM
•Previous infant > 4 kg
•Pre-diabetes
•Glycosuria
•Strong family history of DM
•Hypertension before pregnancy
or in early pregnancy
•Ethnic/racial group with high prevalence of DM (African-Americans, Asian-Americans, Hispanic-Americans, Native Americans, Pacific Islanders)

The proposed screening strategy and cut-offs for the diagnosis of GDM are summarized in Table 3.

Table 3. Proposed Screening for GDM

When Diagnosis Test Cut-off for diagnosis
1st prenatal visit Overt diabetes FPG 126 mg/dL (7.0 mmol/L)
HbA1C ≥ 6.5%
Randoma 200 mg/dL (11.1 mmol/L)
24-28 weeks Gestational diabetes FPG 92 mg/dL (5.1 mmol/L)
75g OGTT-1 hr 180 mg/dL (10.0 mmol/L)
75g OGTT-2 hr 153 mg/dL (8.5 mmol/L)

aConfirmation required.

Women who exceed the threshold for GDM on FPG (92 mg/dl or 5.1 mmol/L) at the first prenatal visit are diagnosed as having gestational diabetes. Women whose FPG at first prenatal visit is below 92 mg/dL (5.1 mmol/L) are tested with a 2-hour OGTT at 24-28 weeks to rule out GDM.

Dr. Coustan addressed the issue of how these guideline changes might affect primary maternity care: "In some ways, life will be easier for clinicians if the new recommendations are adopted:

1.We will go from a 2-step screening procedure (50-g challenge, then 100-g 3-hour OGTT if challenge test is positive) to a 1-step procedure;
2.The glucose load used for the OGTT decreases from 100 g to 75 g, which may improve patient acceptance;
3.The 75-g, 2-hour test is the same as that used in nonpregnant adults, although diagnostic thresholds will be different, so less likelihood of error with the lab doing the wrong test;
4.A single elevated value (out of the 3 blood samples -- FPG, 1-hour, and 2-hour) will be sufficient to diagnose GDM, rather than the current requirement for 2 elevated values (out of 4) . . . this will eliminate the 'borderline' state of one abnormal value and the quandary as to how to treat these patients.
5.With the recommendation from IADPSG about how to diagnose pre-existing diabetes when patients present early in pregnancy with high glucose values, clinicians will be able to remove the ambiguity about how to manage such patients."
Prompt treatment of newly diagnosed women with GDM is important. Most fetal weight accretion occurs in the third trimester, so treatment should begin as soon as the diagnosis is made. Treatment strategies for GDM include dietary modifications, regulated exercise, and pharmacologic agents. Most women can be managed with diet and exercise, and will not require insulin.[20]

Preconception care. As many as half of pregnancies in the US are unplanned.[21] Thus, women with chronic medical conditions such as diabetes might not have the opportunity to take steps to optimize management of their diabetes before becoming pregnant. Adverse outcomes are more likely to occur in women with GDM who do not receive preconception counseling.[22]

When providers are able to do preconception assessment and counseling, women who have prediabetes should be taught how to improve their metabolic control prior to conception, in order to reduce the likelihood of birth defects if they progress to diabetes. Lifestyle interventions have been shown to prevent the progression of prediabetes to diabetes in a randomized trial.[23] With help, women may be able to avoid the risks of a diabetic pregnancy. Every healthcare provider who takes care of a woman of reproductive age has something to contribute to preconception care, by diagnosing prediabetes and helping that individual avoid progression to diabetes and its attendant risks during pregnancy.

Conclusion
If the IADPSG's proposed criteria for GDM diagnosis are adopted, we will be able to identify gravidas who have increased risks for adverse outcomes, such as large, fat, or hyperinsulinemic babies and cesarean section delivery.[8] Along with new evidence for a treatment benefit for GDM, the time may be right for a new approach to the screening of pregnant women for potentially correctable alterations of glucose metabolism. Clinicians should stay tuned for further developments, such as official adoption of the IADPSG recommendations, and be prepared for the changes to clinical practice that will inevitably follow.

References

Prenatal Cigarette Exposure Increases Risk for Psychiatric Illness Into Adulthood

2010-08-11T06:38:00.000-07:00

Megan Brooks

August 3, 2010 — The risk for psychiatric illness is significantly higher in young adults exposed to cigarette smoke in the womb relative to those without prenatal cigarette smoke exposure, even after adjusting for maternal psychiatric illness and other confounding factors, according to a Finnish study reported in the August issue of the Archives of General Psychiatry.

"This association seemed to be robust because it could be found in a large group of diagnoses and the dose relationship was also strong," first study author Mikael Ekblad, BM, of University of Turku, Finland, and colleagues note in the article.

Prenatal smoking exposure impairs fetal growth and modulates brain development, which may alter mental development of the offspring, they point out.

The researchers used population-based, longitudinal registry data to evaluate the effects of prenatal smoking exposure on psychiatric morbidity among 175,869 Finnish young adults born from January 1, 1987, through December 31, 1989, with follow-up lasting 18 to 20 years. They had information on mothers' smoking habits (self-reported) during pregnancy and other relevant background factors, as well as psychiatric history of mothers and offspring.

Smoking during pregnancy was reported by 26,075 mothers (15.3%). Of these, 8866 (34.0%) smoked more than 10 cigarettes a day. In 5487 children (3.2%), maternal smoking history was unknown.

The prevalence of any psychiatric diagnosis was 15.0% after excluding the children with unknown maternal smoking history. The prevalence was 13.7% in unexposed children (the reference group), 21.0% in those exposed to fewer than 10 cigarettes a day (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.47 – 1.60), and 24.7% in those exposed to more than 10 cigarettes a day (aOR, 1.85; 95% CI, 1.74 – 1.96).

Prenatal smoke exposure significantly increased the risk for most of the psychiatric diagnoses, with the exception of schizophrenia and anorexia diagnoses, the study authors report. The strongest effects were seen for psychiatric disorders due to psychoactive substance use and behavioral and emotional disorders. The lack of a statistically significant finding for schizophrenia may be due to a fairly low number of cases in the study.

There were 870 total deaths in the study population (5.7 per 1000), of which 64 (7.4%) were suicides (excluding children with unknown maternal smoking data). After adjusting for confounding factors, young adults exposed to >10 cigarettes a day during gestation had a significantly increased risk for early death (OR, 1.69; 95% CI, 1.31 – 2.19) compared with unexposed young adults. The mortality rate per 1000 children was 4.7 for unexposed children vs 6.3 and 9.1 for exposure to <10 and >10 cigarettes per day, respectively.

Results Generally Mirror Prior Studies

Commenting on the study for Medscape Medical News, David M. Fergusson, PhD, of the Department of Psychological Medicine, Christchurch School of Medicine & Health Sciences in New Zealand, who was not involved in the study, said, "The results are generally consistent with previous research that has suggested that maternal smoking may be associated with increased risks of at least some mental disorders."

In their report, Dr. Ekblad's team points to several study strengths, including a large national study population; the ability to control the child's outcome for maternal mental illness, which has not been done previously in similar large epidemiologic studies; and adjustment for a wide range of background factors, such as 5-minute Apgar scores, the child's birth weight, maternal age, and the mother's psychiatric morbidity before the child's birth.

Limitations of the study include lack of information on alcohol and illicit drug use during pregnancy; self-reported maternal smoking history; potential concern about accuracy of diagnoses; and lack of socioeconomic data, such as parents' educational level and exposure to passive smoke in the home, which can affect risk for psychiatric problems.

"The study," Dr. Fergusson noted, "adds to previous research by being based on a large population (but) is limited by the use of official record data."

The control of confounding factors is "limited," he added, "raising the possibility that the findings may reflect the presence of other factors, which are associated with pregnancy smoking. A further limitation is that the mechanisms by which pregnancy smoking may lead to increased risks of a wide range of mental disorders are by no means clear."

Nonetheless, Dr. Fergusson said this new study further reinforces public health messages regarding the adverse effects of smoking during pregnancy. "It is well known that pregnancy smoking increases the risk of miscarriage, stillbirth, and low-birth-weight infants. The present findings raise the possibility that exposure to pregnancy smoking may have adverse effects on longer-term mental health of offspring," he noted.

Arch Gen Psychiatry. 2010;67:841-849.

Risks for Preterm Births May Be Higher Among Overweight and Obese Mothers

2010-08-09T20:26:00.000-07:00

From MedscapeCME Clinical Briefs

News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD

July 28, 2010 — Risks for preterm births may be higher among overweight and obese mothers, according to the results of a systematic review and meta-analyses reported in the July 20 issue of the BMJ.

The goal of the study was to examine the association of maternal overweight and obesity with preterm birth and low birth weight in singleton pregnancies in developed as well as in developing countries. Sarah D. McDonald, from McMaster University in Hamilton, Ontario, Canada, and colleagues searched MEDLINE and EMBASE from their beginnings, as well as bibliographies of retrieved articles. Inclusion criteria were studies of the effect of overweight and obesity vs a reference group of women with normal body mass index (BMI), on 2 main study endpoints of preterm birth (< 37 weeks) and low birth weight (< 2500 g).

Using a piloted data collection form, 2 investigators independently reviewed titles, abstracts, and full articles; extracted information; and evaluated the quality of the retrieved studies. The 84 studies included in the meta-analyses enrolled a total of 1,095,834 women. Of these studies, 64 were cohort studies and 20 were case-control studies.

Compared with women of normal weight, overweight and obese women had a similar risk for preterm birth overall but an increased risk for induced preterm birth (relative risk [RR], 1.30; 95% confidence interval [CI], 1.23 - 1.37) and a lower risk of having an infant of low birth weight (RR, 0.84; 95% CI, 0.75 - 0.95). The reduction in the risk of having an infant of low birth weight was greater in developing countries vs developed countries (RR, 0.58; 95% CI, 0.47 - 0.71 vs RR, 0.90; 95% CI, 0.79 - 1.01).

Analyses to account for publication bias showed that when imputed "missing" studies were added, the apparent protective effect of overweight and obesity on low birth weight disappeared, whereas the risk for preterm birth appeared significantly higher in overweight and obese women (RR, 1.24; 95% CI, 1.13 - 1.37).

Compared with normal-weight women, very obese women were at 70% greater risk for induced preterm birth before 37 weeks and at 82% greater risk for early preterm birth (before 32 or 33 weeks).

"Overweight and obese women have increased risks of preterm birth and induced preterm birth and, after accounting for publication bias, appeared to have increased risks of preterm birth overall," the study authors write. "The beneficial effects of maternal overweight and obesity on low birth weight were greater in developing countries and disappeared after accounting for publication bias."

Limitations of this review include potential residual confounding and inability to determine causal relationships or underlying mechanisms.

"Future research is needed to try to determine why overweight and obese women are at risk of preterm birth, and to determine effective methods of weight loss in women of childbearing age before pregnancy," the study authors conclude. " ...Clinicians need to be aware that overweight or obesity in women is not protective against having infants of low birth weight and should consider surveillance when indicated. Ideally, overweight or obese women should have prepregnancy counselling so that they are informed of their perinatal risks and can try to optimise their weight before pregnancy."

The Canadian Institute of Health Research supported this study and 2 of its authors. A third study author was supported by the China Scholarship Council.

BMJ. 2010;341:c3428.
Clinical Context

It has become clear that the goals for gestational weight gain should be individualized. In a study by Nohr and colleagues of more than 60,000 term pregnancies, which was published in the December 2008 issue of the American Journal of Clinical Nutrition, researchers found that gestational weight gain of 16 kg or more interacted with a higher prepartum BMI to create a higher risk for delivery via cesarean and a low Apgar score after delivery, as well as a higher risk for postpartum weight retention. However, higher levels of gestational weight gain also reduced the risks for intrauterine growth restriction and a low birth weight at delivery, particularly among women who were underweight before pregnancy.

Other studies suggest that obesity does not protect against deliveries of infants with low birth weight. The current systematic review and meta-analysis addresses the issue of the effect of overweight and obesity on the risks for low birth weight and preterm delivery.

Large Study Assesses Recent Data on Respiratory Morbidity in Late Preterm Neonates

2010-08-09T20:24:00.000-07:00

From MedscapeCME Clinical Briefs

News Author: Emma Hitt, PhD
CME Author: Laurie Barclay, MD

July 28, 2010 — Respiratory morbidity rate in infants born during the late preterm period is substantially increased vs infants born at term, according to the largest investigation to date on the issue.

Judith U. Hibbard, MD, with the Department of Obstetrics and Gynecology at the University of Illinois at Chicago, and colleagues from the Consortium on Safe Labor reported the findings in the July 28, 2010, issue of the Journal of the American Medical Association.

According to the researchers, late preterm births (spanning from 34 weeks and 0 days to nearly 37 weeks of gestation) account for 9.1% of all deliveries and approximately 75% of all preterm births in the United States. Preterm deliveries are known to be associated with increased respiratory morbidity rates, but recent data from a large, US-based study are lacking.

"Given advances in obstetric and neonatal care over the last 20 years, we hypothesized that many published rates of morbidity may overestimate the clinical burden attributable to late preterm birth," the study authors note.

The researchers assessed short-term respiratory morbidity in 19,334 late preterm births and compared it with that of 165,993 term births in a contemporary cohort of deliveries in the United States.

Of the late preterm infants, 36.5% were admitted to a neonatal intensive care unit (NICU), and approximately one third of those had respiratory tract symptoms. By contrast, only 7.2% of the term infants were admitted to a NICU, and less than 10% of those had respiratory tract symptoms.

The incidence of respiratory distress syndrome was 10.5% for infants born late preterm (34 weeks of gestation) vs 0.3% for those born at term (38 weeks). Likewise, in late preterm births vs term births, transient tachypnea of the newborn was present in 6.4% vs 0.4%, pneumonia in 1.5% vs 0.1%, and respiratory failure in 1.6% vs 0.2%. Standard and oscillatory ventilatory support was also more common in late preterm births vs term births.

The risk for respiratory distress syndrome was much higher at 34 weeks of gestation (adjusted odds ratio [OR], 40.1; 95% confidence interval [CI], 32.0 - 50.3) vs 38 weeks of gestation (adjusted OR, 1.1; 95% CI, 0.9 - 1.4). At 37 weeks, the adjusted OR for respiratory distress syndrome was higher at 3.1 (95% CI, 2.5 - 3.7) vs 39 and 40 weeks. For infants born at 38 weeks, the risk for any respiratory morbidity was approximately the same at it was for infants born at 39 or 40 weeks.

Risk for other respiratory disorders, including transient tachypnea of the newborn, pneumonia, and respiratory failure also followed a similar pattern of decreasing with gestational age.

"The results of our study support the recommendation that every effort should be made to delay delivery of infants until at least 38 weeks' gestational age to decrease respiratory morbidity," Dr. Hibbard and colleagues conclude.

This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The study authors have disclosed no relevant financial relationships.

JAMA. 2010;304:419-425.
Clinical Context

Late preterm birth is defined as 34 0/7 to 36 6/7 weeks of gestation. In the United States, 9.1% of all deliveries and three quarters of all preterm births are late preterm births.

Short-term morbidity rate is increased in neonates with late preterm births, especially respiratory morbidity, resulting in specialized care and prolonged neonatal hospital and NICU admissions. However, most previous studies evaluating these outcomes were in study samples more than a decade old or were recruited from small populations.

Prenatal Anxiety Linked to Infant Illnesses and Early Life Antibiotic Use

2010-08-09T20:03:00.000-07:00

From MedscapeCME Clinical Briefs

News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd

August 2, 2010 — Maternal prenatal anxiety and stress are associated with infant illnesses and antibiotic use early in life, according to the results of a study reported online July 19 in Pediatrics.

"Evidence from both animals and humans suggests that maternal prenatal anxiety and stress can have adverse consequences on the offspring's development," write Roseriet Beijers, MSc, from the Behavioural Science Institute in Nijmegen, the Netherlands, and colleagues. "Animal models also show that prenatal stress has programming effects on the physical health of the offspring, such as immune functioning. In human studies, however, physical health outcomes are often restricted to birth complications; studies on the effects of acquiring illnesses are scarce."

The goal of the study was to determine whether maternal prenatal anxiety and stress are related to more infant illnesses and antibiotic use during the first year of life. The study sample consisted of 174 mothers with normal pregnancies and term deliveries who completed third-trimester questionnaires on general and pregnancy-specific anxiety and stress and who were tested for circadian cortisol levels in saliva.

Of the offspring, 71 were firstborns and 91 were boys. Monthly interviews of the mother during the infant's first year of life allowed collection of data concerning infant illnesses and antibiotic use.

Even after adjustment for many relevant confounders, prenatal anxiety and stress predicted considerable variance in infant illnesses and antibiotic use (9.3% for respiratory tract disease, 10.7% for general disease, 8.9% for skin diseases, and 7.6% for antibiotic use), based on hierarchic multiple regressions. In contrast, prenatal anxiety and stress were not associated with digestive tract illnesses.

Limitations of this study include poor generalizability because nearly all mothers were highly educated, lived together with their partner, had healthy pregnancies, and reported relatively mild or moderate prenatal stress. In addition, this study examined prenatal anxiety and stress only during late gestation, and infant health data were based on maternal report.

"This study is 1 of the first to link maternal prenatal anxiety and stress to infant illnesses and antibiotic use early in life," the study authors write. "As such, it provides a starting point for future research in larger and clinical samples. Follow-up studies are necessary to determine whether the effects of prenatal anxiety and stress on infant susceptibility to illnesses are transient, persistent, or even progressive."

The Netherlands Organization for Scientific Research supported this study. The study authors have disclosed no relevant financial relationships.

Pediatrics. Published online July 19, 2010. Abstract
Clinical Context

Different animal models have reported that prenatal stress has programming effects on the physical health of the offspring such as growth and immune functioning. In the same way, maternal stress and anxiety during pregnancy can affect the development of the offspring. Maternal stress can be reflected in diurnal cortisol levels such as higher evening cortisol levels and flattened diurnal rhythms.

This is a prospective study of healthy pregnant women to determine the association between maternal stress and anxiety as measured by questionnaires and by salivary cortisol and infant health in the first year.

No Pap Smears for Women Under 21: Guidelines

2010-07-22T19:45:00.000-07:00

From Reuters Health Information

By Frederik Joelving

NEW YORK (Reuters Health) Jul 21 - Pap smears in women under 21 do more harm than good, new guidelines from the American College of Obstetricians and Gynecologists (ACOG) say.

In most cases such tests reveal only human papillomavirus (HPV) infections, which rarely lead to cervical cancer in women under 21, said Dr. Mark Einstein of the Albert Einstein College of Medicine (no relation) in the Bronx, New York.

"They have a better chance of winning the lottery than getting cancer at that age," said Dr. Einstein, who is an ACOG fellow but did not work on the guidelines.

"Over-screening adolescents is really detrimental to young women," he told Reuters Health. "We increase their anxiety, we increase their time away from school and work."

The new guidelines, published online today in Obstetrics & Gynecology, reinforce earlier recommendations issued this past November. But they add that adolescents with compromised immunity should not wait until 21 to be screened.

Although this group makes up less than one percent of adolescents, said Dr. Einstein, they are much more vulnerable to cancer from HPV.

Prior recommendations called for annual cervical cancer screening to start three years after a woman first becomes sexually active, or by age 21.

In the past 30 years, cervical cancer rates in the United States have fallen by more than half, due in large part to widespread use of cervical cancer screening.

In its November 2009 guidelines, ACOG recommended that women between 21 and 30 years undergo cervical cancer screening once every two years instead of annually. Those 30 and older can be screened once every three years. The new recommendations do not refer to women between 21 and 30.

SOURCE: http://link.reuters.com/juv78m

Obstet Gynecol 2010.

ACOG Issues Less Restrictive Guidelines for Vaginal Birth After Cesarean Delivery

2010-07-22T18:45:00.000-07:00

From Medscape Medical News

Laurie Barclay, MD

July 22, 2010 — Trial of labor after previous cesarean delivery (TOLAC) is safe and appropriate for most women with previous cesarean delivery, including some women with 2 previous cesarean deliveries, according to less restrictive guidelines issued by the American College of Obstetricians and Gynecologists (ACOG). The revised recommendations for planned vaginal birth after cesarean (VBAC) are reported in a practice bulletin published in the August issue of Obstetrics & Gynecology.

"The current cesarean rate is undeniably high and absolutely concerns us as ob-gyns," said ACOG president Richard N. Waldman, MD, in a news release. "These VBAC guidelines emphasize the need for thorough counseling of benefits and risks, shared patient-doctor decision making, and the importance of patient autonomy. Moving forward, we need to work collaboratively with our patients and our colleagues, hospitals, and insurers to swing the pendulum back to fewer cesareans and a more reasonable VBAC rate."

ACOG defines the term trial of labor as a trial of labor in women who have had a previous cesarean delivery, regardless of outcome. Also, the term vaginal birth after cesarean delivery is used to denote a vaginal delivery after a trial of labor.

Benefits of VBAC

ACOG's guidelines indicate the potential advantages of VBAC for the individual patient. These benefits include maternal preference and reduced maternal morbidity and a lower risk for complications in future pregnancies. At the population level, VBAC is also associated with a lower overall rate of cesarean deliveries.

"Approximately 60–80% of appropriate candidates who attempt VBAC will be successful," said statement coauthor Jeffrey L. Ecker, MD, from Massachusetts General Hospital in Boston. "A VBAC avoids major abdominal surgery, lowers a woman's risk of hemorrhage and infection, and shortens postpartum recovery. It may also help women avoid the possible future risks of having multiple cesareans such as hysterectomy, bowel and bladder injury, transfusion, infection, and abnormal placenta conditions (placenta previa and placenta accreta)."

Because failed TOLAC is associated with increased maternal and perinatal morbidity vs elective repeat cesarean delivery, it is important to evaluate individual risks and the likelihood of VBAC when deciding whether TOLAC is a feasible option. A successful VBAC has fewer complications than an elective repeat cesarean delivery, and the new guidelines attempt to point out the risks and benefits of TOLAC in different clinical settings and to offer practical recommendations for treatment and counseling of women who will undergo VBAC.

"The College guidelines now clearly say that women with two previous low-transverse cesarean incisions, women carrying twins, and women with an unknown type of uterine scar are considered appropriate candidates for a TOLAC," Dr. Ecker said. "In making plans for delivery, physicians and patients should consider a woman's chance of a successful VBAC as well as the risk of complications from a trial of labor, all viewed in the context of her future reproductive plans."

ACOG's Revised VBAC Guidelines

The practice bulletin makes the following specific recommendations based on good, consistent scientific evidence (level A):

* TOLAC may be appropriate for most women with 1 previous cesarean delivery via a low transverse incision. These women should be counseled about VBAC and offered TOLAC as a delivery option.
* As part of TOLAC, epidural analgesia may be used for labor.
* For women who have undergone previous cesarean delivery or major uterine surgery, misoprostol should not be used for third-trimester cervical ripening or labor induction.

Also included in the statement are the following recommendations based on limited or inconsistent scientific evidence (level B):

* TOLAC may be considered in women with 2 previous low transverse cesarean deliveries.
* TOLAC may be considered in women with 1 previous cesarean delivery via a low transverse incision who are otherwise appropriate candidates for twin vaginal delivery.
* In women with previous cesarean delivery via low transverse uterine incision who are at low risk for adverse maternal or neonatal outcomes from external cephalic version and TOLAC, external cephalic version for breech presentation is not contraindicated.
* Planned TOLAC is generally not recommended in women at high risk for complications, such as those with classic or T-incision, prior uterine rupture, or extensive transfundal uterine surgery. Also, planned TOLAC is not recommended in women in whom vaginal delivery is contraindicated, such as those with placenta previa.
* In women undergoing TOLAC, it is permissible to induce labor, when appropriate, based on maternal or fetal indications.
* For women with previous cesarean delivery with an unknown uterine scar type, TOLAC is not contraindicated unless there is a high clinical suspicion for a previous classic uterine incision.

Finally, the statement also provides the following recommendations that are based mainly on consensus and expert opinion (level C):

* Women undergoing TOLAC should do so at facilities able to perform emergency deliveries and with staff immediately available to provide emergency care because of unpredictable risks associated with TOLAC.
* When these resources are not available, women should be clearly advised regarding greater risks for TOLAC and management alternatives, and counseling and the management plan should be documented in the medical record.

"It is absolutely critical that a woman and her physician discuss VBAC early in the prenatal care period so that logistical plans can be made well in advance," said coauthor William A. Grobman, MD, from Northwestern University in Chicago, Illinois.

A performance measure proposed by the statement is the percentage of women who are candidates for TOLAC with whom discussion of the risk and benefits of TOLAC vs elective repeat cesarean delivery has been recorded in the medical chart.

"Given the onerous medical liability climate for ob-gyns, interpretation of The College's earlier guidelines led many hospitals to refuse allowing VBACs altogether," Dr. Grobman concluded. "Our primary goal is to promote the safest environment for labor and delivery, not to restrict women's access to VBAC."

Lamaze International's Statement on ACOG Guidelines

In response to the ACOG revised VBAC guidelines, Lamaze International has issued a statement commending the guidelines as a "step in the right direction" in reducing the number of cesarean deliveries. However, Lamaze International is "troubled by elements of the guidelines which continue to support practices that may increase risks and cause undue harm to mother and baby."

The organization questions ACOG's emphasis on uterine rupture, which is rare in VBAC. Lamaze International also points out that ACOG's use of certain language related to "immediately available" emergency resources may cause women to continue to have unfair access to VBAC.

Although Lamaze International takes issue with some of the elements of the revised guidelines, the organization is pleased with ACOG's emphasis on the benefits of a planned VBAC.

Practice Bulletin No. 115, "Vaginal Birth after Previous Cesarean Delivery," is published in the August 2010 issue of Obstetrics & Gynecology.

Obstet Gynecol. 2010;116:450-463.

WHO Guidelines Call for Prompt HIV Testing and Treatment of Newborns

2010-07-22T18:32:00.000-07:00

From Medscape Medical News

Norra MacReady

July 22, 2010 (Vienna, Austria) — Infants born to mothers who are HIV-positive should have their HIV status determined at birth or soon after, with a diagnosis of HIV infection confirmed within 4 to 6 weeks of age, so that treatment can be initiated as early as possible, according to new guidelines issued by the World Health Organization (WHO). The guidelines are available at on the WHO Web site.

As many as one third of HIV-infected infants die before their first birthday, WHO officials said here at AIDS 2010: XVIII International AIDS Conference, in announcing the new treatment guidelines. By age 2 years, mortality is roughly 50%. Prompt diagnosis and treatment improve survival dramatically. "Compelling data show unequivocally that early initiation of treatment reduces mortality 5-fold," Shaffiq Essajee, MD, medical officer, pediatrics and family care, in the HIV Department of WHO, told Medscape Medical News.

WHO is trying to eliminate mother-to-child transmission of HIV completely, perhaps as early as 2015.

"We are expanding significantly the recommendation to identify potentially infected children," Dr. Essajee said. "Previously, we advocated for testing sick children in hospital care settings and children known to be exposed through mother-to-child transmission. Now we're going one step further, saying that every child should have their exposure status ascertained as soon as possible. That's the only way we can then link that child to the appropriate care, testing, and treatment services that they need to prevent the morbidity and mortality that occurs in [HIV-positive] children."

Officials in regions with a high burden of HIV disease, defined as prevalence of more than 1% in the general population, are urged to adopt a strategy of ascertaining a neonate's HIV exposure status and beginning treatment as soon as possible. The very high mortality rates among infected children during their first 2 years of life "makes infants and children the most vulnerable of all people living with HIV," Dr. Essajee said.

WHO has done a good job of closing the treatment gap between children and adults, Dr. Essajee said. By the end of 2008, 276,000 children were receiving treatment; by the following year, that number was up to 355,000. However, until now, most of those efforts have been directed at older children, with distressing consequences. "By the time a child reaches 5 years of age, only 1 in 5 has survived," Dr. Essajee added.

"In the recommendations launched today, we're saying any child under the age of 2 should be treated, because mortality in this age group is so high," said Chewe Luo, MD, PhD, senior advisor for HIV-AIDS in the program division of the United Nations Children's Fund.

Many children are still going undiagnosed, Dr. Luo told Medscape Medical News. "What's critical about these guidelines is that they call for screening these babies as early as 6 weeks, and once you've made the diagnosis, you refer them for treatment."

Infants in impoverished, high-risk regions can have their blood samples dried on filter paper and sent to laboratories for analysis. "This works very well in field conditions," Dr. Luo said. Treatment can begin as soon as the diagnosis is confirmed.

Treatment for HIV-infected children basically is the same as it is for adults — lifelong triple therapy using several different classes of drugs — Dr. Essajee said. Management becomes more complicated if the mother has been on the antiretroviral drug nevirapine during pregnancy, as children exposed to nevirapine in utero may develop resistance to it, so pediatric regimens ideally should include protease inhibitors, as well as triple therapy.

However, Dr. Essajee acknowledges that protease inhibitors can be pricey. "So we tell clinicians that if you don't have access to these expensive and hard-to-get protease inhibitors, treat anyway with the nevirapine you have available, because it's not inevitable that every child will develop a resistance mutation, and even if they do, it's not inevitable that the clinical impact of that resistance mutation will be treatment failure for the child."

"So even if you don't have access to protease inhibitors, don't fall short of initiating aggressive treatment simply because you can't abide by the letter of the law as the WHO has defined it," Dr. Luo urged.

Neither Dr. Essajee nor Dr. Luo has disclosed any relevant financial relationships.

AIDS 2010: XVIII International AIDS Conference. Presented July 20, 2010.

Parenting a VLBW Child May Have Both Positive and Negative Outcomes

2010-07-12T23:45:00.000-07:00

From MedscapeCME Clinical Briefs

News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd

June 29, 2010 — Parenting a very low-birth-weight (VLBW) child has both positive and negative outcomes, according to the results of a prospective cohort follow-up study reported in the June issue of Archives of Pediatric & Adolescent Medicine.

"Long-term outcome studies indicate persistent functional disabilities in a significant proportion of...VLBW children, leading to research interest in parental stress and adaptation to preterm birth and their effects on the family," write Lynn T. Singer, PhD, from Case Western Reserve University in Cleveland, Ohio, and colleagues. "Understanding the experiences of parents of VLBW children is important for medical decision making and the design of intervention programs to improve child outcomes. Children's behavioral and cognitive outcomes are known to be related to maternal psychological status, family stress, financial burden, and maternal coping strategies, all of which have been shown to be affected by VLBW birth."

The goal of the study was to evaluate longitudinal outcomes and factors affecting parental stress and coping in mothers of 113 high-risk VLBW children with bronchopulmonary dysplasia, 80 low-risk VLBW children without bronchopulmonary dysplasia, and 122 term children. These 3 groups had similar demographic characteristics and were followed up from birth to age 14 years.

From November 8, 1989, to February 22, 1992, participants were recruited from level III neonatal intensive care and term nurseries in a large Midwestern region, and they were subsequently followed up at an academic medical center. The main study endpoints were child IQ and self-reported measures of parenting stress, family impact, maternal coping, education, and social support.

Compared with term mothers, mothers of VLBW children had fewer additional years of education (P = .04). Compared with term mothers, mothers of high-risk VLBW children also reported more personal stress (P = .006) and family stress (P = .009) under conditions of low social support, as well as greater child-related stress. Despite greater perceived stress, however, mothers of high-risk VLBW children also reported the highest levels of parenting satisfaction at 14 years. With time, they became less likely to use coping mechanisms of denial (P = .02) and mental disengagement (P = .03).

Except for educational level, mothers of low-risk VLBW infants did not differ from mothers of term children. At 14 years, mothers of low-risk VLBW infants reported the lowest stress of all 3 groups.

"Parenting a VLBW child had both positive and negative outcomes, dependent on child medical risk, child IQ, social support, and maternal coping mechanisms, suggesting that mothers experience posttraumatic growth and resilience after significant distress post partum," the study authors write.

Limitations of this study include reliance on mothers' self-report of stress and coping and long intervals between follow-up visits.

"Although mothers of VLBW children demonstrate significant resilience through their children's early adolescence on the whole, mothers with low social support, with avoidant coping styles, and whose children have significant disabilities should continue to be monitored by health care and education professionals," the study authors conclude. "It will be important to educate health care providers about the role of coping mechanisms and social support in modifying stress. More research is needed into the best ways to support parents of VLBW children and to help them develop adaptive coping mechanisms."

The Maternal and Child Health Program, Health Resources and Services Administration, Department of Health and Human Services, Rockville, Maryland, supported this study. The study authors have disclosed no relevant financial relationships.

Arch Pediatr Adolesc Med. 2010;164:518-524. Abstract

Management of Osteoporosis in Postmenopausal Women: 2010 Position Statement

2010-07-11T23:23:00.000-07:00

Recommendations

Management strategies for osteoporosis in postmenopausal women require assessment of risk factors for BMD-defined osteoporosis and osteoporotic fracture, followed by institution of measures that focus on reducing risk factors through lifestyle changes and, if indicated, pharmacologic therapy.

* All postmenopausal women should be encouraged to employ lifestyle practices that reduce the risk of bone loss and osteoporotic fractures: maintaining a healthy weight, eating a balanced diet, obtaining adequate calcium and vitamin D, participating in appropriate exercise, avoiding excessive alcohol consumption, not smoking, and utilizing measures to prevent falls. Periodic reviews of calcium and vitamin D intake and lifestyle behaviors are useful.
After menopause, a woman's risk of falls should be assessed annually and at any time her physical or mental status changes.
* The physical examination should include an annual measurement of height and weight, along with an assessment for chronic back pain, kyphosis, and clinical risk factors.
* BMD testing is indicated for:
o All postmenopausal women with medical causes of bone loss
o All women age 65 and over
* BMD testing should be considered for postmenopausal women age 50 and older who have one or more of the following risk factors:
o Previous fracture (other than skull, facial bone, ankle, finger, and toe) after menopause
o Thinness (body weight < 127 lbs [57.7 kg] or BMI < 21 kg/m2)
o History of hip fracture in a parent
o Current smoking
o Rheumatoid arthritis
o Excessive alcohol intake
* When BMD testing is indicated, DXA is the preferred technique. The total hip, femoral neck, and posterior-anterior lumbar spine should be measured, using the lowest of the three BMD scores.
* The routine use of biochemical markers of bone turnover in clinical practice is not generally recommended.
* Vertebral fracture must be confirmed by lateral spine radiographs or VFA visualization of fracture at the time of BMD testing. Vertebral fracture is confirmed by height loss >20% of the anterior, mid, or posterior dimension of a vertebra on imaging.
* An adequate intake of both calcium and vitamin D is important for bone health and is recognized as an important component of any osteoporosis prescription-drug regimen. NAMS follows the NOF recommendations of calcium intake of 1,200 mg/day for adults age 50 and older, and vitamin D3 of 800 to 1,000 IU/day.

* NAMS recommends osteoporosis drug therapy in the following populations:
o All postmenopausal women who have had an osteoporotic vertebral or hip fracture
o All postmenopausal women who have BMD values consistent with osteoporosis (ie, T-scores ≤−2.5) at the lumbar spine, femoral neck, or total hip region
o All postmenopausal women who have T-scores from −1.0 to −2.5 and a 10-year risk, based on the FRAX calculator, of major osteoporotic fracture (spine, hip, shoulder, and wrist) of at least 20% or of hip fracture of at least 3%
* It is important to encourage adherence to the treatment plan and to identify barriers to nonadherence. Providing clear information to women regarding their risk for fracture and the purpose of osteoporosis therapy may be the optimal way to improve adherence.
* During therapy, it is appropriate to reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and a follow-up BMD testing. Measurement of BMD has limited use in predicting the effectiveness of antiresorptive therapies for reducing fracture risk. Also, fracture risk reductions from therapy occur much more rapidly than BMD changes. An appropriate interval for repeat BMD testing is after 1 to 2 years of treatment. There appears to be little value in repeat testing if a woman is stable (within the precision error of the original instrument).
* For untreated postmenopausal women, repeat DXA testing is not useful until 2 to 5 years have passed.

* Bisphosphonates are the first-line drugs for treating postmenopausal women with osteoporosis. They have reduced the risk of vertebral fractures by 40% to 70% and reduced the incidence of nonvertebral fracture, including hip fracture, by about half this amount.
* The SERM raloxifene is most often considered for postmenopausal women with low bone mass or younger postmenopausal women with osteoporosis. It prevents bone loss and reduces the risk of vertebral fractures, but its effectiveness in reducing other fractures is uncertain. Extraskeletal risks and benefits are important when considering raloxifene therapy.
* Teriparatide (PTH 1–34) is best offered to postmenopausal women with osteoporosis who are at high risk for fracture. Daily subcutaneous injections have been shown to stimulate bone formation and improve bone density. Therapy is indicated for no more than 24 months.

* The primary indication for systemic ET/EPT is to treat moderate to severe menopause symptoms (eg, vasomotor symptoms). When symptoms are controlled or cease, continued hormone therapy can still be considered for bone effects, weighing its benefits and risks against those of alternative therapies.
* ET/EPT may be a treatment option for a few years of early postmenopause.
* Calcitonin is not a first-line drug for postmenopausal osteoporosis treatment, as its fracture efficacy is not strong and its BMD effects are less than those of other agents. However, it is an option for women with osteoporosis who are more than 5 years beyond menopause. Calcitonin therapy may reduce vertebral fracture risk in women with osteoporosis, although the evidence documenting fracture protection is not strong. It is not recommended for treating bone pain, except bone pain from acute vertebral compression fractures.
* Data are inadequate to make definitive recommendations regarding combination or serial anabolic and antiresorptive drug therapies.
* The treatment of osteoporosis needs to be long term in most women.
* If drug-related adverse effects occur, appropriate management strategies should be instituted. If adverse effects persist, switching to another agent may be required.
* Decisions to discontinue or suspend therapy are based on the woman's risk of fracture and her response to treatment. Given the uncertainties of long-term drug safety, careful monitoring is required. Fracture risk after discontinuing therapy has not been adequately evaluated.

Use of Estrogen and Progestin in Breast Cancer Patients

2010-07-11T20:59:00.000-07:00

Guidelines for Managing Menopausal Symptoms After Breast Cancer: Use of Estrogen and Progestin in Breast Cancer Patients

http://www.medscape.com/viewarticle/581311_2

Use of Estrogen and Progestin in Breast Cancer Patients

Estrogen-containing hormone therapy (HT) is the most effective and well-studied treatment for menopausal vasomotor symptoms and atrophic vaginitis in healthy women,[11] but the efficacy and safety of HT following breast cancer is not established. HT was not effective in controlling hot flashes in tamoxifen users in one retrospective study.[12] Long-term use of combined HT is associated with an increased risk of new breast cancers.[13] The fall in breast cancer incidence seen after 2003 in the United States has been attributed by some to the dramatic drop in HT use following revelation from the Women's Health Initiative study that the risks of HT were not necessarily outweighed by the benefits for healthy women.[13-15] In breast cancer survivors, one randomized controlled trial (RCT) reports a three-fold increased risk of new primary or recurrent breast cancers in HT users.[16] For the two-thirds of women with hormone receptor-positive cancer, a mainstay of treatment is to block the effects of estrogen or reduce its production, and HT may compromise this effect. In addition, combined HT increases breast density, which may compromise the ability of mammography to detect early cancers.[17] Consequently, many women wish to avoid HT following breast cancer.[18] While progestins are effective for menopausal hot flashes following breast cancer,[19-21] their safety is not established. Of concern is that the addition of progestin to estrogen for HT appears to increase the risk of a primary breast cancer.[22]
Tibolone

Tibolone (Livial™, Organon NL) is a synthetic compound with weak estrogenic, progestogenic and androgenic actions. Tibolone (2.5 mg daily) effectively reduces hot flashes[23] and improves vaginal dryness in healthy postmenopausal women. Tibolone may improve sexual function more effectively than standard HT.[24] In the breast, tibolone inhibits the enzyme sulfatase, which regulates the formation of estrogens and hence decreases estrogen stimulation.[25] Tibolone inhibits proliferation of human breast cells and stimulates apoptosis in breast cancer cell lines.[26] The incidence of breast tenderness is low[27] and mammographic density does not increase with tibolone, in contrast to combined HT.[28] The relationship between tibolone use and breast cancer risk is not established. A large observational study suggested an association between tibolone and breast cancer which was less than that seen with combined HT.[29] A large prospective, randomized, placebo-controlled trial of tibolone after breast cancer has recently been halted following reports that the safety of tibolone was not equivalent to placebo (LIBERATE trial, Organon). Tibolone is available in Europe and Australia, but is not in the United States.

Given the evidence for risk or inadequate evidence for safety of available hormonal agents, these are generally avoided following breast cancer. Thus, other options are needed. This presents a clinical conundrum, as nonhormonal therapies have been reported to show only moderate efficacy in treating menopausal hot flashes,[30] and there is little research to date to inform the management of other common menopausal symptoms.

When to Consider Using Estrogen for Menopausal Symptoms Following Breast Cancer

For all women, the use of hormonal treatments for menopausal symptoms is an issue of balancing QoL against risk. For women with no history of breast cancer, the risks of HT appear minimal, particularly for low-risk women taking HT for <5 years.[13] Following breast cancer, current guidelines are to avoid estrogen and tibolone since these may increase the risk of breast cancer recurrence.[124] However, for some women, the benefits of estrogen in terms of symptom reduction and QoL may outweigh these risks.
Ultimately, the decision to take estrogen for severe menopausal symptoms should rest with the patient who is fully informed regarding the potential adverse effects on disease prognosis. A benefit of multidisciplinary care is the ability to calculate individual patient recurrence risks and to use this information in decision making about treatment choices. In addition, if endocrine therapies are producing severe menopausal symptoms with relatively small benefits in terms of recurrence or survival, the multidisciplinary (MD) team may advise that these can reasonably be stopped or adjusted. For women with advanced breast cancer, the issues of QoL are paramount and HT may be considered following discussion with her carers.

Psychotropic Medications Linked to Serious Adverse Drug Reactions in Children

2010-07-02T22:13:00.000-07:00

From Medscape Medical News
Deborah Brauser

July 2, 2010 — Psychotropic medications are associated with adverse drug reactions (ADRs), many of which are serious, in children younger than 17 years, according to a new database study from Danish researchers.

Results also showed that all but one of the psychotropic-related ADRs for children between the ages of birth and 2 years were serious, including birth defects such as neonatal withdrawal syndrome, ventricular septal defects, and premature labor.

These findings were "probably due to the mothers' intake of psychotropic medicine, primarily antidepressants and antipsychotics, during pregnancy," write the study authors.

For the overall patient population, the largest share of reported ADRs came from psychostimulants (42%), followed by antidepressants (31%) and antipsychotics (24.5%).

"The high number of serious ADRs reported for psychotropic medicines in the pediatric population should be a concern for health care professionals and physicians," the study authors write.

In addition, "clinicians must be aware of the risks for the unborn child if they treat pregnant women with [these drugs]," coinvestigator Ebba Hansen, MSc, professor of social pharmacy and director for the FKL-Research Center for Quality in Medicine Use at the University of Copenhagen, Denmark, told Medscape Medical News.

She noted that many of the general practitioners interviewed for this study "thought that SSRI [selective serotonin reuptake inhibitor] antidepressants are harmless. Therefore, we recommend that treatment of pregnant women with psychotropic drugs should be an issue for specialists only."

The study is published online in BMC Research Notes.

ADR Evidence Lacking

Although regulatory authorities have issued warnings about risks associated with the use of psychotropics in pediatric patients, "little evidence has been reported about the ADRs of these medicines in practice," write the study authors.

"Overall, we have very little information about [ADRs] in children, and especially in infants, as vulnerable groups are excluded from the clinical trials that document a medication's efficacy and safety before licensing and marketing," said Professor Hansen.

For this study, her team evaluated 4500 ADRs in children listed in the national Danish ADR database between 1998 and 2007.

"Spontaneous ADR reporting [is] an important contributor to knowledge about safety of medicines," the study authors write. They note that spontaneous reports are "the main source for information about new and previous unknown ADRs."

Serious ADRs Found

Results showed that 429 of the ADRs reported during the study period were for psychotropic medications. Of these, 241 (56%) were deemed serious.

A total of 50% of the psychotropic ADRs reported were for adolescents between the ages of 11 and 17 years (n = 214), of which 45% were serious. Almost 19% were for children between the ages of birth and 2 years (n = 80).

In addition, 39% of the overall psychotropic-related ADRs were from the "nervous and psychiatric disorders" categories. When looking at sex, 59% of the total ADRs reported were for boys.

A total of 79 of the 80 ADRs associated with psychotropics in the children younger than 2 years were serious, and 2 of these were fatal (one was associated with citalopram due to chorioamnionitis and the other with fluoxetine due to persistent fetal circulation).

Finally, 40% of all psychotropic ADRs were associated with the psychostimulants methylphenidate and atomoxetine, whereas 59% of the ADRs reported for antipsychotics were associated with ziprasidone, olanzapine, and risperidone. A total of 61% of the total ADRs reported for antidepressants were with sertraline and citalopram.

When asked about her team's upcoming plans for further research, Professor Hansen reported that 2 studies on ADRs in children associated with vaccines and use of antibiotics have recently been completed — and that both articles are currently pending review. In addition, a new study on ADRs in children treated with psychostimulants is "in the pipeline.

"An interesting idea for study would also be to follow up on the children who were attacked by ADRs [in this study] and see if there are any long-term effects, such as cognitive disturbances," she added.

The study authors have disclosed no relevant financial relationships.

BMC Res Notes. Posted online June 23, 2010.

Surgeon General Urges Exercise for Optimal Health

2010-06-25T21:52:00.000-07:00

From Medscape Internal Medicine
Surgeon General Urges Exercise for Optimal Health
Regina M. Benjamin, MD, MBA

Editor's Note:
The following commentary from US Surgeon General Regina Benjamin, MD, MBA, is a collaboration between the US Department of Health and Human Services (HHS), the American College of Sports Medicine (ACSM), and Medscape.

As Surgeon General, my priorities focus on wellness and prevention. Earlier this year, I released my paper, The Surgeon General's Vision for a Healthy and Fit Nation [2010].

There is, perhaps, no more serious challenges to the nation's health and well-being than those posed by obesity and overweight. Since 1980, obesity rates have doubled in adults and more than tripled in children, and the problem is even worse among black, Hispanic, and Native American children. We see the sobering impact of these numbers in the high rates of chronic diseases, such as diabetes, heart disease, and other chronic illnesses, that are starting to affect our children more and more.

A few months ago, a study from The University of North Carolina [at Chapel Hill] School of Medicine reported that obese children as young as age 3 show signs of an inflammatory response that has been linked to heart disease later in life. I was pleased to join the First Lady for the launch of her Let's Move! campaign to solve the problem of childhood obesity within 1 generation.

Both my Vision for a Healthy and Fit Nation and the First Lady's Let's Move! campaign take a comprehensive approach that engages families and communities, as well as the public and private sectors. My Vision for a Healthy and Fit Nation is an attempt to change the national conversation from a negative one about obesity and illness to a positive conversation about being healthy and being fit. I want to encourage Americans to eat more nutritiously, exercise regularly, and maintain healthier lifestyles.

That is why I am asking healthcare organizations across this country to join the Exercise is Medicine initiative. Exercise is Medicine is a multinational, multiorganizational initiative. It brings physical activity to the forefront of disease prevention and treatment, by making exercise a part of every patient's interaction with a health clinician. Exercise is Medicine strives to provide the essential connection between clinicians, fitness professionals, and the public, so that everyone can receive the guidance they need to stay healthy and active. All the partners in this initiative are dedicated to the idea that exercise is the new medicine. Partners are asked to continue to build, support, and advocate for physical activity as an essential element of global health and well-being by committing to action:

Policy makers are asked to change policies to support physical activity as a major component of health.
Clinicians and fitness professionals are asked to integrate exercise into every patient and client interaction.
Communities, workplaces, and schools are asked to promote physical activity as an essential part of health and well-being.
Members of the public are asked to educate and empower themselves to seek appropriate counseling on physical activity.
As health professionals, we should remember that patients are more likely to change their behavior if they have a meaningful reward -- something more than reaching a certain weight or dress size. The reward has to be something that each person can feel, enjoy, and celebrate. The reward is optimal health that allows people to embrace each day and live their lives to the fullest -- without disease, disability, or lost productivity. I hope you will join the Exercise is Medicine initiative. Together, America can become a Healthy and Fit Nation.

Breast-Feeding Until 4 Months May Protect Infants From Respiratory, GI Infections

2010-06-25T21:25:00.000-07:00

From Medscape Medical News
Laurie Barclay, MD

June 21, 2010 — Breast-feeding until age 4 months is linked to lower rates of respiratory and gastrointestinal (GI) infection morbidity, according to the results of a population-based, prospective, cohort study reported online June 21 in Pediatrics.

"Exclusive breastfeeding seems to decrease the risk of infectious diseases in infancy," Liesbeth Duijts, MD, PhD, from Erasmus Medical Center in Rotterdam, the Netherlands. "However, the World Health Organization has called for more research regarding the benefits for 6 months instead of 4 months of exclusive breastfeeding."

The goal of this study, which was embedded in the Generation R Study, a study from fetal life onward in the Netherlands, was to evaluate the associations of duration of exclusive breast-feeding with upper respiratory tract infections (URTI), lower respiratory tract infections (LRTI), and GI tract infections in infancy.

There were 4164 subjects who completed questionnaires on rates of breast-feeding during the first 6 months (never; partial for < 4 months, not thereafter; partial for 4 - 6 months; exclusive for 4 months, not thereafter; exclusive for 4 months, partial thereafter; and exclusive for 6 months) and doctor-attended URTI, LRTI, and GI infections until age 12 months.

Risks for URTI, LRTI, and GI tract infection until age 6 months were lower in infants who were breast-fed exclusively until age 4 months and partially thereafter vs infants who were never breast-fed.
Adjusted odds ratios (ORs) were 0.65 (95% confidence interval [CI], 0.51 - 0.83) for URTI, 0.50 (95% CI, 0.32 - 0.79) for LRTI, and 0.41 (95% CI, 0.26 -0.64) for GI tract infection. The adjusted OR for LRTIs in infants between the ages of 7 and 12 months was 0.46 (95% CI, 0.31 - 0.69).

For infants who were exclusively breast-fed for at least 6 months, trends were similar. However, partial breast-feeding, even for 6 months, was not associated with significantly lower risks for these infections.

"Exclusive breastfeeding until the age of 4 months and partially thereafter was associated with a significant reduction of respiratory and gastrointestinal morbidity in infants," the study authors write.
"Our findings support health policy strategies to promote exclusive breastfeeding for at least 4 months, but preferably 6 months, in industrialized countries."

Limitations of this study include questionnaires with breast-feeding data available for only 65% of eligible participants of the Generation R Study and possible misclassification related to questionnaire use.

"Biological, cultural, and social constraints related to breastfeeding habits need to be studied more extensively," the study authors write. "The effects of prolonged and exclusive breastfeeding on infectious diseases at older ages in industrialized countries remain to be studied."

Exclusive breast-feeding until age 4 months and partially thereafter was associated with a significant reduction of respiratory and GI morbidity rates in infants.

The first phase of the Generation R Study was funded by Erasmus Medical Center, Erasmus University Rotterdam, and Netherlands Organization for Health Research and Development (Zon Mw). The present study was supported by an additional grant from Stichting W. H. Kröger (00–048) and AGS Kinderstichting. The study authors have disclosed no relevant financial relationships.

Pediatrics. Published online June 21, 2010.

CDC Commentary: New Safety Data on the HPV Vaccine -- Reassure Your Patients

2010-06-24T01:00:00.000-07:00

From Centers for Disease Control and Prevention (CDC): Expert Commentary

Claudia Vellozzi, MD, MPH

Hello. I'm Dr. Claudia Vellozzi. I'm a family practitioner and the deputy director of CDC's Immunization Safety Office. Our office, along with the Food and Drug Administration monitors the safety of vaccines after they are licensed.

Today, I'm pleased to share with you important safety data on the human papillomavirus, or HPV vaccine as part of the CDC Expert Commentary Series on Medscape.

As healthcare providers, we know that clear communication goes hand in hand with good quality patient care. Talking with your patients about the safety of HPV vaccines can help to address common concerns about vaccination and may lead your patients, or their parents, to make more informed decisions about their health.

Although there are 2 licensed HPV vaccines in use in the United States (Gardasil and Cervarix), we currently have more available data on Gardasil. As of January 1, 2010, 28 million doses of Gardasil have been distributed in the US.

CDC and FDA manage the Vaccine Adverse Event Reporting System (or VAERS), a system which accepts reports for any adverse event after vaccination from healthcare providers, patients, or family members, or manufacturers. VAERS is one of the systems that helps us to monitor the safety of vaccines in this country. It is a front-line system to detect possible safety concerns. VAERS has several limitations. It is always important to keep these in mind when you are reviewing VAERS data.

The main limitations are:

VAERS usually cannot assess causality;
VAERS has variable quality of data;
VAERS lacks denominator data (the total number of vaccinated persons is not known); and,
VAERS is subject to variable reporting (both underreporting and stimulated reporting can occur).
As of January 31, 2010, VAERS had received nearly 16,000 reports of adverse events following Gardasil vaccination. An overwhelming majority of these (over 90%) were non-serious, such as syncope (or fainting), local injection site reactions, dizziness, nausea, and headache. These findings are similar to the safety reviews of other vaccines recommended for a similar age group (such as meningitis and Tdap vaccines).

Based on the review of available vaccine safety monitoring data by FDA and CDC, HPV vaccination continues to be recommended and its benefits continue to outweigh its risks.

Now, let's talk about some of the serious adverse event reports. All serious reports were analyzed by medical experts and additional medical records were requested to better understand the adverse events. Some of the serious reports were reports of venous thrombotic events or VTE. In VAERS, most individuals who reported VTEs post-vaccination were also found to have other high risk conditions documented in their medical records, such as use of oral contraceptives, smoking, obesity, or other contributing factors.

All of the death reports in VAERS were fully investigated, and there was no unusual pattern or clustering that would suggest that they were caused by the HPV vaccine. The reported causes of death could be explained by factors including diabetes, viral illness, illicit drug use, and heart failure.

Like any medication, vaccines can have some side effects. After HPV vaccination, your patients may experience mild events such as local injection site reaction (including soreness, redness, or swelling where the shot was given), and some patients may be prone to syncope. Syncope after vaccination is not uncommon among adolescents and young adults. Be sure your patient is vaccinated while sitting or lying down and is observed for at least 15 minutes after vaccination to avoid potential injury from a fall in the event of syncope. If syncope does occur, observe your patient and evaluate them after they regain consciousness to determine if there is a need for further treatment. Fainting after vaccination itself is usually not a serious event, and patients generally recover within a few minutes.

Remember, one limitation of VAERS is that it cannot determine causality. A report to VAERS is only an association in time, meaning that the adverse event occurred some time after vaccination. CDC and FDA thoroughly investigate all serious reports to better assess whether more studies are needed to help determine if an adverse event could be associated with a vaccine. Although the media has paid particular attention to these adverse event reports, it is important to know and share with your patients that we have not found any information to conclude that these events were associated with the vaccine.

I would like to summarize with the following points:

First, based on the review of available information by FDA and CDC, the HPV vaccine continues to be recommended for girls and women, ages 9 to 26 years, as an important strategy to prevent cervical cancer. Gardasil can protect males against most genital warts and may be given to boys and men, ages 9 through 26 years.

Second, you should consider watching your patients carefully for 15 minutes after any vaccination, including administration of the HPV vaccine, to avoid potential injury from a fall in the event of syncope.

Third, discuss with your patients what to expect and to contact you if they experience additional symptoms after HPV vaccination.

And finally, if your patient experiences any adverse events after HPV vaccination, you or your patient should report them to VAERS. For more information on the safety data of the HPV vaccine, please see the resources on this page. Thank you.

Web Resources
Summary of HPV Adverse Events:
http://www.cdc.gov/vaccinesafety/Vaccines/HPV/gardasil.html.

Questions and Answers about HPV Vaccines (Patient Information)
http://www.cdc.gov/vaccines/vpd-vac/hpv/vac-faqs.htm

Dr. Claudia Vellozzi completed her medical degree at Loyola Stritch School of Medicine in Chicago and her MPH at Johns Hopkins in Baltimore. She is board certified in both Family Medicine and Preventive Medicine.

Dr Vellozzi has extensive clinical and public health experience, both domestically and internationally. Her clinical experience includes starting a clinic for underserved Hispanics in Orange County, California, serving as faculty at a Family Medicine Residency Program in Greeley, Colorado, primary clinical care at a rural hospital in Nigeria and she continues to care for patients one-half day weekly at a Grady Neighborhood clinic, in Atlanta. Her areas of work in public health include HIV/AIDS, vaccines and immunization safety, health services research and maternal infant health. She has worked with the Centers for Disease Control and Prevention, World Health Organization and the Commonwealth Fund.

Dr Vellozzi recently returned to the Immunization Safety Office as Deputy Director and has led the H1N1 vaccine safety surveillance activities at the Centers for Disease Control and Prevention.

Dr Vellozzi has published numerous manuscripts in peer reviewed literature.

More Rapid Weight Gain by Age 1 Year May Improve Neurodevelopment of Preterm Infants

2010-06-06T11:33:00.000-07:00

Laurie Barclay, MD & Désirée Lie, MD, MSEd
From MedscapeCME Clinical Briefs

May 25, 2010 — In preterm infants, more rapid weight gain in the first year of life is associated with modest neurodevelopmental advantages and only small blood pressure (BP)–related effects at school age, according to the results of a study reported online May 17 in Pediatrics.

"More rapid infant weight gain may have benefits, such as to neurodevelopment, as well as risks, such as higher BP," write Mandy B. Belfort, MD, MPH, from Children's Hospital Boston in Boston, Massachusetts, and colleagues. "The balance of risks and benefits of rapid infant weight gain for preterm infants is poorly understood."

The goal of the study was to evaluate the association of infant weight gain with systolic BP (SBP) and IQ at school age in former preterm, low-birth-weight infants. In the Infant Health and Development Program, an 8-center longitudinal study, 911 children born at 37 weeks' gestation or less and weighing 2500 g or less were weighed at term and at 4 and 12 months' corrected ages.

Blood pressure was measured 3 times at 6.5 years, and the Wechsler Intelligence Scale for Children, Third Edition (WISC-III) was administered at 8 years to test IQ. The exposure "infant weight gain" was modeled in linear regression as the 12-month weight z score adjusted for the term weight z score.

At 12 months, median weight z score was –0.7 (interquartile range, –1.5 to –0.0). At 6.5 years, mean SBP was 104.2 ± 8.4 mm Hg, and at 8 years, mean WISC-III total score was 91 ± 18. For each z score additional weight gain from term to 12 months, SBP was 0.7 mm Hg higher, and WISC-III total score was 1.9 points higher, after adjustment for child age, sex, and race and maternal education, income, age, IQ, and smoking.

"In preterm infants, there seem to be modest neurodevelopmental advantages of more rapid weight gain in the first year of life and only small BP-related effects," the study authors write.

Limitations of this study include birth of the cohort in the 1980s, when neonatal intensive care unit practices differed from current practices; and lower socioeconomic status of mothers of the infants in this cohort, possibly limiting generalizability.

"Increased nutritional support for preterm infants after NICU [neonatal intensive care unit] discharge might benefit long-term neurodevelopmental outcomes, with only a small effect on BP-related health," the study authors conclude. "Although small IQ differences are not clinically significant for individuals, shifting the IQ curve of a population upward by a few points can have an important impact."

The National Institutes of Health, the Robert Wood Johnson Foundation, Maternal and Child Health Bureau, and Pew Charitable Trust supported this study. The study authors have disclosed no relevant financial relationships.

Pediatrics. Published online May 17, 2010. Abstract

Clinical Context

Approximately 12.7% of all births in the United States in 2005 were preterm, and there is an increasing burden of neurodevelopmental problems among preterm infants. Although infant weight gain has been associated with a reduced risk for low IQ among preterm infants, it is unclear if greater weight gain in infancy is associated with adverse metabolic factors such as BP.

This is a longitudinal cohort study of preterm infants at 8 US centers to examine the association between weight gain between birth and 12 months and SBP at age 6.5 years and IQ at age 8 years.
•Greater weight gain in the first year for preterm low-birth-weight infants is associated with a small increase in SBP (0.7 mm Hg) at age 6.5 years.
•Greater weight gain in the first year for preterm low-birth-weight infants is associated with a significant increase in IQ at age 8 years

High Caffeine Intake During Pregnancy Linked to Reduced Fetal Length

2010-06-06T11:25:00.000-07:00

News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd

May 26, 2010 — Caffeine intake of 6 or more units per day during pregnancy is associated with impaired fetal length growth, according to the results of a cohort study reported online April 28 in the American Journal of Clinical Nutrition.

"Caffeine is a widely used and accepted pharmacologically active substance," write Rachel Bakker, from Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues from the Generation R Study. "The effect of caffeine intake during pregnancy on fetal growth and development is still unclear."

The goal of the study was to evaluate the associations of maternal caffeine intake from coffee and tea with fetal growth measured during each trimester of pregnancy and with the risks for adverse birth outcomes. From 2001 to 2005, a total of 7346 pregnant women in the Netherlands participated in a population-based prospective cohort study from early pregnancy onward.

Questionnaires were used to determine coffee and tea consumption in the first, second, and third trimesters. Serial ultrasound studies allowed determination of fetal growth characteristics, and hospital record review allowed determination of birth outcomes.

A regular serving of 125 mL of coffee in the Netherlands contains approximately 90 mg of caffeine (caffeinated), decaffeinated coffee contains 3 mg, and tea contains 45 mg per 125-mL serving. This was used as the standard for calculation of daily caffeine consumption.

Each unit of caffeine exposure was based on 1 cup of coffee (90 mg of caffeine), and total caffeine intake was categorized as less than 2 units, 2 to 3.9 units, 4 to 5.9 units, and 6 or more units per day.

Caffeine consumption was not consistently associated with fetal head circumference or with estimated fetal weight in any trimester. In contrast, higher caffeine consumption was associated with smaller first-trimester crown-rump length, second- and third-trimester femur length, and birth length (P for trend < .05). The risk of having a small-for-gestational-age infant at birth was increased in mothers who consumed at least 6 caffeine units per day.

"Our results suggest that caffeine intake of ≥6 units/d during pregnancy is associated with impaired fetal length growth," the study authors write. "Caffeine exposure might preferentially adversely affect fetal skeletal growth. Further studies are needed to assess these associations in non-European populations and to assess the postnatal consequences."

Limitations of this study include observational design with possible residual confounding; and missing data on coffee and tea consumption, which may have led to loss of power.

"Length- or skeletal-related fetal growth characteristics seemed to be most consistently affected from the first trimester onward," the study authors conclude. "Further structural and functional studies are needed to assess organ-specific effects. Our results suggest that pregnant women should be advised to not consume ≥6 caffeine units (.540 mg) per day during pregnancy."

The Erasmus Medical Center Rotterdam, the Erasmus University Rotterdam, and the Netherlands Organization for Health Research and Development (ZonMw) financially supported the first phase of the Generation R Study. One of the study authors was supported by the Netherlands Organization for Health Research.

Am J Clin Nutr. Published online April 28, 2010.

Clinical Context

Caffeine is widely used and freely passes the placenta, thus exposing the fetus to its influence during pregnancy. Caffeine intake during pregnancy has also been associated with higher rates of miscarriage and fetal death as well as lower birth weight, but the associations have been inconsistent.

This is a population-based cohort study embedded in the Generation R Study from fetal life to adulthood conducted in a city in the Netherlands with enrollment between 2001 and 2005 to examine the association between maternal caffeine intake from coffee and tea and fetal and birth growth measures.

Labor Induction Increases Risk of Rare Amniotic Fluid Emboli

2010-05-11T06:02:00.000-07:00

From Reuters Health Information
David Douglas

May 7, 2010 — Labor induction, a multiple pregnancy, and cesarean delivery each increases the risk of rare but deadly amniotic fluid emboli, UK researchers report.

Older ethnic-minority women are also at higher risk, according to the article in the May Obstetrics & Gynecology.

"Induction of labor was associated with a population-attributable risk of 35% in our study, suggesting that, assuming causality, if induction of labor were no longer performed, 35% of cases of amniotic fluid embolism could be prevented," said lead author Dr. Marian Knight of the University of Oxford and colleagues.

Of course, they add, labor induction "clearly will continue, and amniotic fluid embolism remains a very rare complication" — but one to keep in mind when considering the risks and benefits of induction.

Using national UK Obstetric Surveillance System data from 2005 to 2009, the researchers found 60 confirmed cases among an estimate of more than 3 million maternities (for estimated incidence of 2.0 cases per 100,000 births).

They note that this rate, based on prospectively collected data, is lower than reported in retrospective studies from Canada and the U.S. (6.1 and 7.7 cases per 100,000 births, respectively).

After adjustment, amniotic-fluid embolism was significantly associated with induction of labor (odds ratio, 3.86) and multiple pregnancy (odds ratio 10.9). This risk was also higher in older, ethnic-minority women (odds ratio 9.85).

Regarding what she called "a possible increased risk of dying from amniotic fluid embolism amongst ethnic minority women," Dr. Knight speculated in email to Reuters Health that "reasons for this...may be related to underlying additional medical problems or access to care."

Cesarean delivery was associated with postnatal amniotic-fluid embolism (odds ratio 8.84).

The emboli occurred at a median gestation of 39 weeks, within a 6-hour range around delivery. All of the women had at least one cardinal sign of an embolism (shortness of breath, hypotension, hemorrhage, coagulopathy, and premonitory symptoms), and more than a quarter of them had at least four signs.

Fetal membranes ruptured at or before presentation in 92% of cases.

Twelve women died, giving a case fatality rate of 20%. These women were significantly more likely to be from ethnic-minority groups (odds ratio, 11.8).

Seven women received exchange transfusion or plasma exchange. All seven of these women survived, although there were too few of them to be able to infer that this treatment is more effective than other approaches. "These therapies should be regarded as an extension of supportive care and not as a substitute," the investigators said.

Outcomes were known for 37 neonates born to mothers with amniotic fluid embolism before or during delivery. Five of these babies died. The perinatal mortality rate was 135 per 1,000 total births.

"Occurrence of amniotic fluid embolism does appear to be associated with induction of labor and caesarean delivery and it is important therefore that both risks and benefits of labor induction and cesarean delivery are considered by clinicians on an individual basis for all women," Dr. Knight said.

"We have no indication from this study that the occurrence has become more frequent in the UK," she said.

Obstet Gynecol. 2010;115:910-917. Abstract

Reuters Health Information 2010. © 2010 Reuters Ltd.

Malignancy Risk High With Indeterminate Breast Lesions

2010-05-07T19:37:00.001-07:00

From Medscape Medical News
Norra MacReady

May 7, 2010 (San Diego, California) — Indeterminate breast lesions in high-risk women have a relatively high probability of being malignant and should be treated aggressively, investigators reported here at the American Roentgen Ray Society 2010 Annual Meeting.

Of 59 indeterminate lesions identified on magnetic resonance (MR) mammography in 55 women, 13 (22%) proved to be malignant on follow-up MR, mammography, or ultrasound performed 6 months after the initial MR study, said lead author Martin Korzeniowski, MD, from McMaster University in Hamilton, Ontario.

Biopsy or surgical intervention was performed whenever appropriate. The patients all had breast cancer or were deemed to be high risk, either because of personal or family medical history or genetic predisposition.

These findings suggest that "malignant lesions in women with a high risk of breast cancer may present atypically, with an indeterminate morphology or kinetic pattern, and may require more aggressive workup," said Dr. Korzeniowski.

The patients were drawn retrospectively from a database of 727 consecutive magnetic resonance imaging (MRI) scans performed at McMaster University between January 2007 and December 2008. Lesions were classified according to the Breast Imaging Reporting and Data System (BIRADS), developed by the American College of Radiology. Each lesion received a score ranging from 0 (incomplete examination) to 6 (known, biopsy-proven malignancy).

In this study, lesions were considered indeterminate if they could not be definitively classified as suspicious for malignancy but had suspicious abnormalities with a reasonable probability of being malignant (BIRADS 4), or if there was more than a 95% chance that they were malignant (BIRADS 5).

The 59 lesions that met those criteria were followed up within 6 months of the original MRI examination. Of the 13 malignancies, 9 were infiltrating ductal carcinomas, 2 were ductal carcinomas in situ, and 2 were metastatic lymph nodes. The remaining 46 lesions were benign.

The "substantial" cancer yield in this study suggests that follow-up examinations for indeterminate lesions should be performed sooner than is current practice, Dr. Korzeniowski told meeting attendees.

"The rate of cancer these authors found is much higher than other studies have suggested," Constance Lehman, MD, professor of radiology at the University of Washington and director of imaging at the Seattle Cancer Care Alliance, said in an interview with Medscape Radiology. At the University of Washington and other centers, less than 2% of patients with indeterminate lesions turn out to have malignant disease, she said.

"My guess is that their methods of determining if a lesion is indeterminate are different" than those used at other institutions, said Dr. Lehman, who was not involved in this research. Usually, indeterminate lesions must meet specific criteria involving morphology, margins, and enhancement pattern, and are assigned a BIRADS score of 3. Those lesions are considered "probably benign" because they have more than a 98% chance of being benign, she told Medscape Radiology.

Still, Dr. Lehman said, "this is a very interesting study. It is really important for us to continue to evaluate breast MRIs in high-risk women. This research will stimulate more debate."

Dr. Korzeniowski and Dr. Lehman have disclosed no relevant financial relationships.

American Roentgen Ray Society (ARRS) 2010 Annual Meeting: Abstract 018. Presented May 3, 2010.

Late Pregnancy Multivitamins Linked to Prematurity

2010-04-16T21:36:00.000-07:00

From Reuters Health Information

NEW YORK (Reuters Health) Apr 14 - For a woman eating a healthy diet, multivitamin supplements during late pregnancy could do more harm than good, a new study suggests.

British researchers found that a woman's risk of delivering prematurely tripled if she continued taking the prenatal pills into her third trimester.

"These supplements are available over-the-counter in the United Kingdom and frequently promoted as being beneficial for mums-to-be," Dr. Nigel Simpson of the University of Leeds in the U.K., and one of the authors of the study, told Reuters Health by email.

However, some weaknesses in the study may stand in the way of translating the finding into practice, Dr. James Mills, of the U.S. National Institute of Child Health and Human Development told Reuters Health.

While some studies in developing countries have found prenatal supplements to be beneficial, whether or not they are also useful in developed countries has not been thoroughly studied.

Dr. Simpson and his colleagues assessed supplement use by nearly 1,300 pregnant women recruited at Leeds Teaching Hospitals between 2003 and 2006. They reported their findings March 29th in the British Journal of Obstetrics and Gynecology

Overall, slightly more than 4% of newborns weighed less than 2500 grams and were categorized as low birthweight. About the same number of babies were born prematurely.

The team saw no differences in the risks of having a low birthweight baby for the more than 80% of women who took supplements at any point during pregnancy compared with those who took none.

However, the approximately 30% of women taking supplements during their third trimester were three times as likely to have a premature delivery, after adjustment for smoking, alcohol consumption and other relevant factors.

Why this would be true is unclear. One possibility, according to the authors, is that interactions between different vitamins and minerals led to a reduction in the nutrients available for the growing fetus.

And women in the study were already getting enough of most vitamins and minerals contained in prenatal supplements from their diets, with the exceptions of vitamin D, iron, folate, selenium and iodine, note the authors.

The U.S. National Institute of Child Health and Human Development's Dr. Mills said that a few weaknesses of the study make its significance less clear. Since the U.K. stops short of officially recommending prenatal multivitamins, British women who chose to take the supplements may have been those who were already at a greater risk for pregnancy problems.

Dr. Mills also said the relationship with premature delivery could have simply appeared by chance, given the large number of comparisons the researchers made between various birth outcomes and supplement use.

The study team acknowledges that larger, more rigorous studies are necessary to confirm their results. For now, Dr. Simpson says pregnant women probably don't need multivitamins past their first three months, after which time they might actually do harm.

Br J Obstet Gynecol 2010.

Couples' Risk of Break-Up Higher After Pregnancy Loss

2010-04-12T23:16:00.001-07:00

From Reuters Health Information

NEW YORK (Reuters Health) Apr 08 - Studies have shown that married couples' risk of divorce can go up after the death of a child, and now new findings suggest that relationships may also become more fragile after a miscarriage or stillbirth.

In a study of more than 3,700 U.S. married or cohabiting couples who'd had at least one pregnancy, researchers found that those who'd suffered a miscarriage or stillbirth were more likely to break up in subsequent years than couples who had a baby.

Specifically, couples who had a miscarriage were 22% more likely than those who had a live birth to separate during the 15-year study period. With stillbirth, the risk was 40% greater.

And while the increased risk associated with miscarriage was seen within three years of the loss, the risk linked to stillbirth persisted for nearly a decade.

The researchers say their study, published online April 5th in Pediatrics, is the first national study to show that couples who suffer a pregnancy loss are at increased risk of a breakup.

The findings are, however, in line with those from past studies of married couples who've lost a child. Those studies have generally found that while bereavement brings some couples closer together, the general risk of divorce appears to climb after losing a child.

Given that research, the current findings are not unexpected, according to lead researcher Dr. Katherine Gold, of the University of Michigan in Ann Arbor.

However, she told Reuters Health by email, she was "honestly surprised" at the strength of the associations between pregnancy loss and relationship breakups -- as well as how lasting the effects, particularly of stillbirth, appeared to be.

"For miscarriage, we saw the strongest risk in the first 1.5 to 3 years after a loss, but for stillbirth the risk lasted nearly a decade after a loss," Dr. Gold said. "That's a much longer period than I think any of us who work in this area would have guessed."

However, Dr. Gold also stressed that "couples should not look at this study and think that on top of a loss their relationship is doomed." Many couples, she said, cope well and can actually become closer after a pregnancy loss.

Still, the current findings point to a need to understand why these couples are at increased risk of breaking up, she said.

The study included 3,707 married or cohabiting women who had a total of 7,770 pregnancies, including 16% that ended in miscarriage and 2% in a stillbirth.

Among couples who had a live birth, more than 40% broke up within 10 years. But among couples who had a stillbirth, that figure was nearly 60%; meanwhile, close to half of couples who had a miscarriage broke up within a decade.

The findings do not prove that pregnancy loss is the reason for the higher rates of breakups, the authors point out. However, even when the researchers accounted for several other factors related to relationship dissolution -- like younger age, lower incomes and cohabitation rather than marriage -- miscarriage and stillbirth themselves were still associated with higher risks of breakups.

It's also plausible that pregnancy loss would lead to separation for some couples, according to Dr. Gold.

"Loss of a baby can be a devastating effect for a couple," she said, "and this study suggests there can be a ripple effect which probably comes from the stress of how two different people cope with the same event."

She noted that men and women tend to react to grief differently, and that may lead to stress, misunderstandings and conflicts for some couples.

She said it is important for partners to anticipate that they may react differently to their loss, and then talk to each other about how they are coping. They should also know that help is available, the researcher added.

"If a couple is struggling," Dr. Gold said, "it's very important that they know it's OK to get help from a counselor, a therapist, their doctor, or someone from their church."

Pediatrics 2010.

Vitamins C, E Supplementation May Not Reduce Risk for Certain Pregnancy Complications

2010-04-07T06:29:00.000-07:00

From Medscape Medical News
Laurie Barclay, MD

April 6, 2010 — Prenatal vitamin C and E supplementation does not reduce the rate of preeclampsia or gestational hypertension (GH) but is associated with greater risk for fetal loss or perinatal death and preterm prelabor rupture of membranes (PPROM), according to the results of a multicenter, randomized controlled trial reported in the March issue of the American Journal of Obstetrics & Gynecology.

"Several lines of evidence support the hypothesis that oxidative stress, an imbalance between prooxidant and antioxidant forces, plays an essential role in the development of hypertensive disorders of pregnancy," write Hairong Xu, MD, MSc, from Hôpital Ste-Justine and Université de Montréal in Quebec City, Canada, and colleagues from the International Trial of Antioxidants in the Prevention of Preeclampsia (INTAPP) study group. "We sought to investigate whether prenatal vitamin C and E supplementation reduces the incidence of ...GH and its adverse conditions among high- and low-risk women."

Participants were stratified by risk status and were randomly assigned to receive daily supplementation with 1 g of vitamin C and 400 IU of vitamin E, or placebo. The main study endpoint was GH and its associated complications.

Among 2647 women randomly selected, data were analyzed for 2363 women because the trial was stopped prematurely when adverse outcomes from supplementation were recognized. The groups did not differ in the risk for GH and its complications (relative risk [RR], 0.99; 95% confidence interval, 0.78 - 1.26). However, vitamin C and E supplementation was associated with nonprespecified outcomes of an increased risk for fetal loss or perinatal death, as well as with PPROM.

Limitations of this study include reduced power because the trial was stopped prematurely.

"Vitamin C and E supplementation did not reduce the rate of preeclampsia or GH, but increased the risk of fetal loss or perinatal death and ...PPROM," the study authors write. "Despite the fact that the underlying mechanisms remain largely unclear, there is increasing concern that supplementation of vitamins C and E at the doses studied [ie, 1000 mg vitamin C and 400 IU vitamin E (RRR alpha-tocopherol)] may increase the risk of other adverse pregnancy outcomes such as low birthweight and PPROM. Therefore, based on our present knowledge, vitamin C and E supplementation at the above doses cannot be recommended for pregnant women to prevent adverse pregnancy outcomes including [preeclampsia]."

The Canadian Institutes of Health Research supported this study. The study authors have disclosed no relevant financial relationships.

Am J Obstet Gynecol. 2010;202:239.e1-239.e10.

Teenage Boys and Young Men Who Lack Mumps Vaccinations Are at Risk for Reduced Fertility

2010-04-02T22:13:00.000-07:00

From Medscape Medical News
Nancy Fowler Larson

March 31, 2010 — A reduction in mumps vaccinations in the 1990s has produced a spike in infections, raising concerns about fertility issues in men aged 15 to 24 years, according to an article published in the April issue of the British Journal of Urology International.

The introduction of the measles, mumps, and rubella, or MMR, vaccine in 1968 led to a sharp decline — 99% in the United States — in cases of mumps, a contagious viral disease. In the mid-1990s, the inoculation rate plunged in the United States, the United Kingdom, and other locations for 2 reasons: a global shortage of the vaccine, and publicity about its alleged, unproven connections to autism, inflammatory bowel disease, and Crohn's disease. In some parts of the United Kingdom, vaccination rates fell from 91% to 58%.

This failure to vaccinate had clear consequences. In 2001, confirmed cases of mumps hovered close to zero in England and Wales. By 2004, more than 56,000 cases were reported, according to the authors' examination of data spanning a 5-year period. As many as 40% of men who are infected with mumps experience 1 or more complications, including mumps orchitis, which can result in impaired fertility.

"This is of considerable concern as epidemics of mumps orchitis are now being reported more frequently in many countries worldwide," said Niall Davis, research registrar, Department of Urology, Mater Misericordiae Hospital, Dublin, Ireland, in a press release.

One case of mumps can result in 12 secondary infections in a vulnerable population. Today, many of the unvaccinated 15- to 20-year-olds are gathered in close quarters in secondary schools, colleges and universities.

"This clustered environment provides a perfect breeding ground for the virus," write Mr. Davis and colleagues.

Mumps orchitis typically appears 10 days after the disease's hallmark facial swelling, but it can occur up to 6 weeks later. Thirty percent to 50% of men with mumps orchitis, 1 or both testicles will atrophy, resulting in reduced size. Among other findings is the fact that complications can affect fertility even if swelling does not occur. For example, 13% of patients experience subfertility, whether or not they have had testicular atrophy, and up to 50% of patients produce abnormal sperm as long as 3 months after recovery — 24% of adults and 38% of teenagers can have abnormal sperm up to 3 years later.

The term "abnormal sperm" is used to reference sperm count, motility, and/or morphology. A significant relationship was found between the extent of testicular swelling and the degree of sperm abnormalities. The researchers found only a slight (incidence of 0.5%) association between mumps orchitis and testicular cancer.

The investigators call on physicians to become familiar with mumps and its complications and to recommend vaccinations for teenage boys and adult men who are not already inoculated.

"Clinicians should be aware of this epidemiological shift and of the resurgence of mumps orchitis," the authors write. "Unvaccinated male patients in this age group should be offered the MMR vaccine and educated about mumps orchitis and its potential complications."

The study authors have disclosed no relevant financial relationships.

BJU Int. 2010;105:1060-1065.

Acupuncture Reduces Depressive Symptoms During Pregnancy With Few Adverse Effects

2010-03-28T20:24:00.000-07:00

From MedscapeCME Clinical Briefs

News Author: Pam Harrison
CME Author: Laurie Barclay, MD

March 3, 2010 — Targeted acupuncture may offer women with major depression a safe and effective alternative to antidepressant medication, new research suggests.

Investigators at Stanford University School of Medicine in California found that women with major depressive disorder treated with depression-specific acupuncture had a 63% response rate after 12 sessions compared with a 44.3% response rate in 2 combined control groups who were treated with either acupuncture not known to help alleviate depressive symptoms or Swedish massage.

"Pregnancy just by its nature can bring out some underlying psychiatric and emotional issues ... but treatment of depression during pregnancy is critically important so that a woman can maintain her sense of well being and take good care of herself, her fetus and, someday, her child," study coauthor Deirdre Lyell, MD, Stanford University School of Medicine, said in a statement.

Led by Rachel Manber, PhD, the study was published in the March issue of Obstetrics & Gynecology.

Response Rates Significantly Higher

For the study, investigators randomized 150 women whose pregnancies were between 12 and 30 weeks of gestation and who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depressive disorder and who scored at least 14 on the 17-item Hamilton Rating Scale for Depression.

Of the 141 women who eventually entered the study, 52 received depression-specific acupuncture, 49 received control acupuncture, and 49 others received Swedish massage.

Treatments were provided twice a week for the first 4 weeks and then weekly thereafter for 4 additional weeks, with each session lasting about 25 minutes.

The investigators found that response rates were significantly higher in women who received depression-specific acupuncture than for either control group. Response rates in women randomized to the 2 control interventions did not differ significantly from each other at 37.5% for the control acupuncture group vs 50% for the massage group.

On the other hand, remission rates did not differ significantly between women who received depression-specific acupuncture at 34.8% and the combined control groups at 29.5%. They also did not differ between those assigned to the control acupuncture group at 27.5% or the massage group at 31.2%.

Thirty-three of the study participants discontinued treatment before the study endpoint, 30% of them for reasons related to the pregnancy. Some women in both acupuncture groups reported transient discomfort at the point of needle insertion, and 1 woman experienced bleeding at the needle site.

Significantly fewer women who received massage reported any adverse effects compared with the 2 acupuncture groups.

Clinically Meaningful

The study authors point out that the benefits observed with depression-specific acupuncture can be considered "clinically meaningful" when assessed in a broader context of depression studies.

Although there are no randomized controlled trials of antidepressants being used during pregnancy, 1 randomized controlled trial found that interpersonal psychotherapy produced a 52% reduction in Hamilton Rating Scale for Depression scores and a 19% remission rate after 16 weeks of therapy, to which the currently study compares very favorably.

According to the study, antidepressant use during pregnancy doubled between 1999 and 2003, but many women are reluctant to take these medications because of safety concerns. In fact, in this particular study, 94% of the women involved expressed reluctance to take an antidepressant because of their pregnancy.

"Because there’s this concern about medication among pregnant women and their physicians, it’s important to find an alternative," said Dr. Manber.

Results from this study therefore suggest that this standardized acupuncture protocol could be considered a "viable treatment option" for depression during pregnancy, the investigators conclude.

Michael Thase, MD, University of Pennsylvania School of Medicine, cautions that findings from this study are preliminary, although they suggest that depression-specific acupuncture may have value in major depressive disorder in this patient population.

On the other hand, another study assessing depression-specific acupuncture in a broader population of men and women with major depressive disorder failed to find a significant effect from the modality, so evidence supporting acupuncture for the treatment of major depressive disorder is not consistent.

"Still there is reason to be cautious when prescribing antidepressants in pregnancy, and one has to weigh the pros and cons of using an antidepressant on an individual basis,” he told Medscape Psychiatry.

"If these promising findings are confirmed, it would be good to have another option to complement the focused forms of psychotherapy which are currently used for antenatal depression," he added.

The study was funded by the Agency for Healthcare Research and Quality. The study authors and Dr. Thase have disclosed no relevant financial relationships.

Obstet Gynecol. 2010;115:511-520.

Clinical Context

Major depressive disorder may occur in up to 14% of pregnant women, possibly in response to hormonal fluctuations or anticipated lifestyle changes. Depression during pregnancy has been associated with poor birth outcomes and postpartum depression. Untreated depression during pregnancy may harm the mother as well as the baby, particularly if the mother neglects prenatal care or engages in self-destructive behavior.

Although the use of antidepressants during pregnancy doubled between 1999 and 2003, many depressed women are unwilling to take these medications while pregnant because of safety issues. It is therefore important to find a nonpharmacologic, safe yet effective treatment option for depression during pregnancy. Previous studies have shown that acupuncture is an effective treatment of depression in the general population.

Study Highlights

The goal of this randomized controlled trial was to estimate the efficacy of acupuncture for depression during pregnancy.
The study sample consisted of 150 pregnant women between 12 and 30 weeks of gestation who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depressive disorder.
Participants were randomly assigned to receive either depression-specific acupuncture (n = 52) or 1 of 2 active controls: control acupuncture (n = 49) or Swedish massage (n = 49).
All treatments were standardized and lasted 8 weeks (12 sessions).
Junior acupuncturists blinded to treatment assignment needled participants at points prescribed by senior acupuncturists.
The main study endpoint was the Hamilton Rating Scale for Depression, performed by blinded raters at baseline and after 4 and 8 weeks of treatment.
Response rate was defined as having at least a 50% reduction in symptoms.
Analysis of continuous data was by intent-to-treat, with use of mixed-effects models.
Rate of decrease in symptom severity was greater in women who received depression-specific acupuncture vs the combined controls (d = 0.39; 95% confidence interval [CI], −1.31 to 1.65; P < .05) or control acupuncture group alone (P < .05; Cohen's-d = 0.46; 95% CI, −1.24 to 2.31).
In women who received depression-specific acupuncture, response rate (63.0%) was also significantly greater vs the combined controls (44.3%; P < .05; number needed to treat, 5.3; 95% CI, 2.8 - 75.0) and control acupuncture group (37.5%; P < .05; number needed to treat, 3.9; 95% CI, 2.2 - 19.8).
The control groups were not significantly different in symptom reduction and response rates (control acupuncture, 37.5% vs massage, 50.0%).
Rates of adverse events were not significantly different for the 3 treatment groups
Acupuncture-related adverse effects included transient discomfort at the point of needle insertion (7 participants in the control acupuncture group and 14 in the depression-specific acupuncture group) and bleeding at the needling site (1 in the depression-specific acupuncture group).
Massage-related adverse effects included transient discomfort in 5 participants.
None of these adverse effects resulted in study discontinuation.
The investigators concluded that the short acupuncture protocol tested in this study yielded symptom reduction and a response rate similar to those seen with standard depression treatments of similar length.
Study limitations include limited generalizability of the results because of the high education and socioeconomic status, predominance of Caucasians (67%), and exclusion of comorbid mental and medical disorders.
In addition, the massage therapy provided in this study was shorter vs standard practice.

Clinical Implications

Depression during pregnancy is responsive to treatment with a short acupuncture protocol, which could be a viable treatment option for depressed pregnant women. Rate of decrease in symptom severity was greater in women who received depression-specific acupuncture vs the combined controls or control acupuncture group alone.
Response rate (≥ 50% reduction in symptoms) was 63.0% in women who received depression-specific acupuncture, which was significantly greater vs the combined controls (44.3%) and control acupuncture alone (37.5%). Response rate with depression-specific acupuncture was similar to those seen with standard depression treatments of similar length.

Palpable Breast Cancers More Common in Women Not Having Annual Mammography

2010-03-26T20:01:00.000-07:00

From Medscape Medical News
Laurie Barclay, MD

March 26, 2010 — Palpable breast cancers are more common in women not having annual mammography, according to the results of a study reported in the March issue of the Journal of the American College of Surgeons.
Despite the frequent use of screening mammography, 43% of breast cancers presented symptomatically or as a palpable mass.

"This study confirms the importance of participation in screening mammography, since a palpable presentation was least common in women undergoing mammographic screening at the recommended interval of 1 year," senior author Amy C. Degnim, MD, FACS, associate professor of surgery at the Mayo Clinic in Rochester, Minnesota, told Medscape Ob/Gyn & Women's Health.
"In addition, this study sheds light on the possible impact of reduced breast cancer screening with mammography for women between [the ages of] 40 and 49 [years], as recently recommended by the US Preventive Services Task Force [USPSTF].
Lastly, this study shows that some cancers are still detected by breast self examination [BSE] and by clinical breast examination [CBE] by a healthcare provider, so there is still a role to be defined for these techniques in detecting breast cancer."

A study by the Commission on Cancer in the 1990s showed that the percentage of breast cancer patients presenting with palpable masses decreased from over 70% in 1983 to 44% in 1990, which may be attributable to the increasing use of screening mammography. Before the present study, however, few data have been published since 1990.

Breast Cancer Screening Recommendations

The new findings fuel the controversy over breast cancer screening recommendations. On November 17, 2009, the USPSTF issued new breast cancer screening guidelines recommending against routine mammography screening for women younger than age 50 years and for stopping screening at age 74 years. On the basis of current evidence, the USPSTF also could not determine the additional benefits and harms of CBE beyond screening mammography in women 40 years or older and recommended against teaching BSE.

"[Our] study demonstrates that the recent USPSTF recommendations should be taken with caution," Dr. Degnim said.

After widespread objections to the USPSTF guidelines by the American Cancer Society (ACS), the American College of Radiology (ACR), and others, the ACR and the Society of Breast Imaging jointly issued new recommendations in January 2010.

These guidelines on the use of imaging modalities for breast cancer screening suggest that women at average risk of developing breast cancer should begin annual mammography screening at age 40 years.

"Compared with detection by mammography, palpable breast cancer is larger, more likely to have metastasized, and have worse prognosis and worse survival," Robert A. Smith, PhD, ACS director of cancer screening, told Medscape Ob/Gyn & Women's Health.
"Mammography is the single best tool we have for the detection of breast cancer when it is small, has not spread, and when treatment options are greatest."

"Women with palpable tumors have larger tumor sizes and more advanced stage at presentation," Dr. Degnim agreed. "They also have worse breast cancer–specific survival than those with mammographically detected cancers, even when adjustments are made to compare women with similar tumor size and nodal stage."

Study Findings

The goal of the present study was to determine the method of cancer detection and frequency of screening mammography in women undergoing breast cancer surgery in 2000, using an institutional surgical breast cancer database from the Mayo Clinic. The investigators reviewed medical records to evaluate presentation at time of diagnosis and to characterize it either as "palpable" if the woman presented with a breast complaint or if a new mass was identified on examination or as "screening" if breast cancer was detected on screening mammography.

Dates of prior mammography screening were also recorded, and patients whose cancer was detected by mammogram were compared with those whose tumors were detected by BSE or CBE. Of 592 breast cancers detected, 335 (57%) were identified on screening, 255 (43%) were characterized as palpable, and in 2 patients (<1%), the method of cancer detection was unknown.

In women with a palpable mass, the size of the tumor was significantly larger than in women in whom cancer was detected by mammography (2.6 vs 1.5 cm; P < .0001). Patients with palpable presentation were younger than those with screen-detected cancer (mean age, 57 vs 62 years; P < .0001).

"The study findings are consistent with what is known about the advantage of mammography in detecting breast cancer before it has reached a size when it is palpable; that is, the screen-detected cancers were smaller than the palpable cancers," Dr. Smith said. "The cancers detected on mammography also were less likely to be advanced; that is, not having spread to the axillary lymph nodes. The findings also show that some women will, inevitably, be diagnosed with a palpable tumor before they are due for their next mammogram."

At least 1 prior screening mammogram was documented in 481 women (81%), although most screenings were performed less frequently than once annually. Compared with women who had previous mammography, those who had no previous screening mammography were more likely to have cancer present as palpable (67% vs 39%; P = .0002).

"We know that mammography does not pick up every breast cancer, however we were surprised at how often breast cancer was detected by a palpable mass," coauthor Judy Boughey, MD, FACS, an assistant professor of surgery at Mayo Clinic, said in a news release. "Presentation as a palpable mass was more frequent in those women who had not had a mammogram in the prior 12 months. This finding is even more concerning when you consider the recent recommendations for decreasing the use of mammography because it would result in an even greater proportion of breast cancers being detected by palpation and therefore at more advanced stages."

On the basis of their findings, the study authors concluded that despite the frequent use of screening mammography, 43% of breast cancers presented as a palpable mass or otherwise symptomatic presentation, whereas 57% were detected by mammography. Women who had not had mammography were more likely to present with palpable tumors.

Carol H. Lee, MD, radiologist from the Memorial Sloan-Kettering Cancer Center in New York City, and chair of the ACR Breast Imaging Commission, told Medscape Ob/Gyn & Women's Health that these findings were "not particularly surprising."

"The cancers found by screening were smaller, and it is known that smaller, lower-stage cancers are associated with a better prognosis," Dr. Lee said. "In addition, for cancers of similar size, those that are not palpable cancers have been shown to have a better outcome. In my opinion, this study emphasizes the importance of both screening mammography and BSE and underscores the potential damage that might occur if the USPSTF guidelines are widely followed in terms of delay in breast cancer diagnosis."

Study Strengths and Limitations

"A strength of this study is that it evaluates the frequency of palpable presentation of breast cancer in the modern era, during a time in which screening mammography was widely used, so this is likely very reflective of the current pattern of how breast cancers are discovered," Dr. Degnim said. "Another strength of this study is that the method of presentation could be determined for the vast majority of patients from the medical records, whereas this detailed information is usually not available in large national databases."

"[This study] is informative about the recent screening experience of women with a palpable mass vs those whose breast cancer was detected on mammography, and the tumor characteristics of each group," Dr. Smith said. "It also is informative about the mode of detection among women who had a palpable breast cancer, although there may be a lack of precision between categories of [BSE], incidental breast cancer detection, and 'found by patient, but method unspecified.' "

However, Dr. Smith also noted that the findings are not generalizable to the larger population of women beyond those presenting to the Mayo Clinic in Rochester for breast cancer surgery in 2000, and that the study depended on retrospective chart review for evidence of frequency and data of prior screening.

The study authors agree that these factors limitgeneralizability and also note that the study was set at a tertiary referral center, where patients might be more likely to present with palpable or more advanced tumors, and that the study population was almost exclusively white. These data were from 2000, when only film mammography was used, whereas the current practice is to use digital mammography.

"This study is a case series; it does not appear to be designed to study associations or causalities, and therefore the authors' conclusions are not appropriate because the results are calculated based on events (ie, mammogram vs SBE) that occurred in their cases," Miriam Alexander, MD, MPH, director, General Preventive Medicine Residency, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, told Medscape Ob/Gyn & Women's Health when asked for independent comment. "They were not able to use any measures of association such as odds ratios or relative risks, as this was not a case-control or cohort study or a clinical trial. I do not believe there are epidemiological or statistically valid conclusions that can be drawn from their results; they can only fairly report their results as observations of occurrence."

"I do not believe that studies like this would be considered by the USPSTF in evaluating whether the evidence is supportive, not supportive, or insufficient for screening tests such as mammography or SBE," Dr. Alexander said. "Unfortunately, there are no conclusions that can be drawn from this study as to the use of mammography or SBE for screening. Therefore, I cannot see that there are any clinical implications for changing screening recommendations based on this study."

Research Recommendations

In terms of additional research, Dr. Lee recommended continuing to develop more sensitive imaging methods to detect early breast cancer.

"The study implications remain valid for clinical practice today, since there have not been dramatic changes in participation in screening mammography over the last 10 years," Dr. Degnim said. "Further research is needed to evaluate whether this finding remains true in 2010 and in community-based healthcare settings."

Dr. Smith pointed out that we need to learn more about the duration of time between the first detection of a palpable mass and when women report symptoms to their physician. Although he believes this time is shorter today than in 2000, he suggests that factors contributing to the detection of palpable breast cancer and either quick reporting or delay need to be better understood.

"I do not believe that the results of this study should contribute to clinicians' decision making," Dr. Alexander said. "It is totally appropriate and necessary to continue our quest to minimize the human burden of suffering from breast cancer, but I would not recommend that further research be undertaken along these lines if our goal is to correctly identify and treat significant disease on a population basis.

"If we want to appropriately identify breast cancer from other breast anomalies, and if we want to correctly identify breast cancers that need treating to prevent morbidity and mortality, we should do research to develop tests or methodologies that meet all the criteria for excellent screening tests," Dr. Alexander continued. "There are multiple study designs that could then be employed to demonstrate the strength of the association between the screening test in question and the reduction in disease or its severity or progression, depending on the goals of the researchers."

Detection by BSE

Among the 255 patients with palpable or otherwise symptomatic presentations, 86% of the cancers were found by the patient either incidentally or during BSE, and the remaining 14% were detected during CBE by a physician or other healthcare provider.

"Because we don't know what proportion of women in the sample actually performed routine BSE, we can't conclude anything about the performance of BSE in detecting palpable tumors, nor did the authors report the relative sizes of the palpable tumors that fell into each group," Dr. Smith said. "The finding that CBE accounted for a very small proportion of the detected palpable breast cancers is consistent with recent literature [and]...is consistent with the observation that most women don't practice regular BSE. The ACS does not recommend for or against routine BSE but does emphasize the importance of maintaining a heightened sense of awareness about the presence or absence of breast symptoms."

Clinical Implications

The study authors note that their findings reaffirm the importance of participating in regular screening mammography, because this was associated with a decreased frequency of palpable presentation that was lowest among those women screened at the recommended annual interval. They also suggest that their findings confirm that both BSE and CBE still play a role in detecting breast cancer.

Dr. Smith noted that 71% to 75% of breast cancers diagnosed in the period between 11 and 24 months were detected by mammography screening, which highlights the greater advantage of annual screening vs biennial screening.

"Breast cancers are missed due to human error or because of the limitations of the exam in women with significant breast density," he said. "However, [the study findings] are consistent with the observation that there is a greater likelihood of detecting a palpable tumor the longer the duration from the previous mammogram, but also that mammography is not perfect and that some breast cancers will arise in the period between normal screening exams."

When asked how findings from this study affect ACS' position concerning the recent USPSTF recommendations regarding screening mammography, BSE, and CBE, Dr. Smith responded, "There is clear evidence that mammography saves lives in women 40 years of age and older. As these data show, women at all ages who were detected with a palpable mass were more likely to have a more advanced breast cancer compared with women with breast cancer detected by screening."

Although a higher proportion of women between ages 40 to 49 years were diagnosed with a palpable mass (58% vs 42%), a majority of women older than 40 years who had never had a previous mammogram were between the ages of 40 and 49 years. Dr. Smith noted that among women with prior screening, the risk of being diagnosed with a palpable tumor may have been more similar in younger and older women.

The study showed that a sizeable percentage of breast cancers occurred in women in their 40s (namely, 19%), leading the study authors to state that "Without screening mammography in this age group, at least 48 of these 115 cancers would have been missed, and many more would likely have been missed if both CBE and [BSE] were also omitted."

"In this instance, 'missed' means that these women would have been diagnosed with palpable breast cancer, had worse prognosis, fewer treatment options, and most likely poorer survival," Dr. Smith concluded. "Although ACS recommends routine CBE, we recognize its diminishing contribution to the detection of palpable breast cancer as routine mammography and a heightened sense of awareness account for most breast cancer detection."

Dr. Degnim and the other study authors and experts have disclosed no relevant financial relationships.

J Am Coll Surg. 2010;210:314-318. Abstract

Incontinence After Childbirth May Last Years

2010-03-25T20:29:00.000-07:00

From WebMD Health News
Jennifer Warner

March 25, 2010 — Problems with anal incontinence following childbirth may linger long after childbirth and hurt women’s quality of life and ability to care for their child, a new study finds.

In a previous study, about 38% of women reported new onset of at least one anal incontinence symptom -- such as gas or involuntary passing of stool -- in the 3-6 month period after delivery.

The new study shows that some women may experience bouts of anal incontinence two years after childbirth. More than half of these women are frustrated by their condition, and more than a quarter say it negatively affects their emotional health.

In addition, researchers say nearly one in five mothers with anal incontinence say the condition hinders her ability to care for her child.

“The postpartum period is an important time for parent-child bonding,” researcher Jaime Lo, MD, of the University of Utah, Salt Lake City, and colleagues write in Obstetrics & Gynecology.
“The development of anal incontinence postpartum may have important ramifications for both maternal and child health because it may affect a mother’s ability to care for her child emotionally and physically.”

Postpartum Incontinence Affects Quality of LIfe

In the study, researchers surveyed 1,247 women in Utah who experienced anal incontinence at least once in the two years following childbirth.

The results showed that 68% reported anal incontinence symptoms six months after childbirth, and 45% had symptoms 12 months following childbirth. By two years after childbirth, 28% of women still reported bouts of anal incontinence.

More than half of women with anal incontinence also reported symptoms of urinary incontinence.

Researchers found anal incontinence after childbirth had a significant impact on women’s quality of life in several ways. For example:

22% of women with anal incontinence felt their condition negatively affected their physical recreation.
12% said anal incontinence negatively affected their entertainment activities.
13% said their anal incontinence got in the way of any travel longer than half an hour.
Women with severe anal incontinence symptoms were four to seven times more likely to report negative quality of life than women with mild symptoms.
Researchers say despite persistent symptoms and negative quality of life, few women report their anal incontinence symptoms to their health care provider.

The results suggest that about 80,000 women (2% of births) each year in the United States may have persistent long-term anal incontinence related to childbirth. But only 8,000 will report these symptoms to their health care providers.

Treatment for anal incontinence frequently involves a combination of medication, biofeedback, and exercise. Surgery is also an option.

SOURCES:

Lo, J. Obstetrics & Gynecology, April 2010; vol 115: pp 809-814.

Aspiration of Breast Lumps Reviewed

2010-03-23T19:41:00.000-07:00

From MedscapeCME Clinical Briefs

News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd

03/09/2010;

March 9, 2010 — A review in the March 1 issue of the Canadian Medical Association Journal (CMAJ) describes an "in-office" approach for immediate evaluation of women who present to their family physician with a breast lump.

"As a family physician and a GP [general practice] oncologist who specializes in breast disease, I know how important it is to quickly evaluate breast lumps and reassure women who have benign cysts," lead author Ruth E. Heisey, MD, from University of Toronto, the Princess Margaret Hospital and the Women's College Hospital in Toronto, Ontario, Canada, said in a news release.

"Because 10% of malignant lesions in young women have features consistent with a fibroadenoma, new palpable masses in women of any age should be thoroughly evaluated," Dr. Heisey and coauthor David R. McCready, MD, MSc, also from the University of Toronto, write. "Cysts account for about 25% of all breast lumps and are common in premenopausal women over 35 years of age and uncommon in postmenopausal women unless they have received hormone therapy. In this article, we review an approach to the initial management of palpable breast lumps and describe several techniques for breast lump aspiration in the outpatient setting."

Women who have a breast lump and features suggesting cancer should be referred to a breast surgeon and immediately undergo mammography, ultrasonography, and core biopsy. These features include hard, irregular mass fixed to the skin; palpable ipsilateral lymph nodes; or a puckered "peau d'orange" appearance of the skin.

The family physician can begin in-office workup and management of a palpable breast lump not clinically suspicious for malignant disease. The lump should be aspirated with a fine needle because differentiating cystic from solid lesions using palpation alone can be difficult, and imaging may involve wait time, causing unnecessary anxiety for the patient. However, ultrasound is an alternative initial option to distinguish cystic from solid lumps.

Women with breast implants and those receiving anticoagulant therapy should not undergo aspiration in the family physician's office. When aspiration is performed, a local anesthetic is not needed.

A simple cyst is diagnosed when aspiration yields nonbloody fluid, and the lump completely disappears. Using clock position and distance from the nipple, the physician should precisely document the cyst's location in the breast, and the fluid may be discarded.

However, women should be referred to a surgeon if aspiration yields bloody fluid, if the lump does not disappear completely, or if the lump recurs. In these cases, the aspirate should be sent for pathologic examination by a skilled cytopathologist.

When fine-needle insertion indicates that the breast lump is solid, the needle may be removed without further aspiration, or an aspiration biopsy may be performed and the specimen sent for cytopathologic analysis.

Complications of aspiration may include local discomfort; bruising caused by blood vessel puncture; transient vasovagal reaction; or, uncommonly, a pneumothorax, which can be avoided by moving a lesion close to the chest wall over a rib before aspiration. However, immediate inspiratory and expiratory chest radiographs are indicated if air is drawn into the syringe.

Aspiration is not associated with higher rate of false-positive mammography results if the radiologist is informed about the aspiration site, nor is there any evidence that needle biopsy will cause malignant lesions to spread. Most cancers are diagnosed before surgery by needle or core biopsy.

Women who have a simple cyst should be seen in 6 to 8 weeks to be evaluated for recurrence, which, if present, mandates ultrasonography, mammography, or both, as well as surgical referral. No additional workup is needed for cysts that do not recur.

Women with solid lesions require imaging and surgical referral. Ultrasonography only is recommended for women younger than 30 years, whereas women at least 30 years old should have both mammography and ultrasonography studies.

To ensure concordance between clinical findings and the results of imaging and cytopathologic evaluation of solid breast lumps, triple assessment is recommended (examination, imaging, and aspiration).

Some clinicians opt to defer cytopathologic testing of palpable lumps presumed to be fibroadenomas, but this strategy may result in some breast cancers being missed in young women. Most delays in diagnosing breast cancer in this group occur as a result of falsely reassuring clinical or imaging findings.

"Aspiration of a palpable breast lump allows immediate reassurance for women with breast cysts and timely investigation and referral for women with solid masses," the review authors conclude. "If the lump is a cyst, the aspirated fluid may be discarded provided the fluid is not bloody and the lump disappears. If the lump is solid, triple assessment (clinical examination, breast imaging and fine-needle aspiration cytologic assessment) is warranted."

The review authors have disclosed no financial relationships.

CMAJ. Published online March 1, 2010.

Eating During Labor

2010-03-19T21:38:00.000-07:00

From Medscape Ob/Gyn & Women's Health
Maria I. Rodriguez, MD

Posted: 03/10/2010

Oral intake during labor was identified in the 1940s as a risk factor for gastric aspiration with general anesthesia.

Since that time, restrictions have been placed on the diets of women in labor. At one time, all women in labor were restricted to ice chips in order to reduce the risk for pulmonary aspiration in the small proportion of patients who may require general anesthesia.

With improvements in obstetric anesthesia over subsequent decades, this approach has come under criticism.
Although the physiology of pregnancy does increase a woman's risk for aspiration as a result of delayed gastric emptying, pulmonary aspiration is rare.
Restriction of food and liquid for low-risk women in labor is felt to be potentially harmful by advocates. They cite concern that hunger may exacerbate fatigue and cause psychological stress.

Wide differences exist in the management of caloric intake during labor, varying dramatically by institution and country.Approaches range from "ice chips only" to a liberal diet for women at low risk of needing anesthesia.
New evidence exists to help guide management, although the outcome of pulmonary aspiration is so rare that it is not possible to include it as a study endpoint.

A Cochrane review of 5 randomized, controlled trials involving 3130 women in active labor was published recently. The investigators sought to determine the potential for harm or benefit of fluid or food intake during labor. Singata and colleagues identified 5 studies of sufficient quality to include in their meta- analysis.

All studies included women in active labor who were deemed to be at low risk of needing a general anesthetic. One study looked at complete restriction vs giving women the freedom to eat and drink at will. Two studies looked at allowing water only compared with giving women specific fluids and foods.An additional 2 studies looked at giving water only vs giving women carbohydrate drinks.

Primary outcomes included cesarean delivery, operative vaginal birth, and a 5-minute Apgar score of < 7. Secondary outcomes were duration of labor and maternal nausea or emesis.No statistically significant differences were identified in any primary or secondary outcome.Patient preferences were not considered in this meta-analysis. This level-1 evidence suggests that there is no justification for restriction of access to fluids during labor in low-risk women.

Critical to interpretation of these studies and application of the findings to practice is consideration of what it means to be "low risk."
Exclusion criteria for these studies varied but commonly included preterm labor, multiple gestation, breech position, intent to use analgesia during labor, and "any medical or obstetrical condition increasing risk for instrumental delivery or cesarean."These results may be less generalizable to hospitals with a high rate of cesarean delivery or epidural anesthesia.

In 2007, the American Society of Anesthesiologists updated their obstetric anesthesia guidelines with respect to oral intake during labor.

Their panel of experts agreed that permitting intake of clear liquids during labor for uncomplicated parturients does not increase risk for maternal harm.
The committee, however, highlighted the need for case-by-case consideration for individuals who had additional risk factors for aspiration, such as obesity, diabetes, or a difficult airway.
Obstetric considerations that increase the likelihood of intervention must also be taken into account. The American Congress of Obstetricians and Gynecologists concurs with permitting a modest intake of clear liquids during labor for low-risk patients.

In addition, they advise against ingestion of solid food during labor because no evidence supports a safe time period for such consumption.

This evidence provides an opportunity for reevaluation of our practices toward oral intake in women during labor, and suggests that patient preference should guide oral intake of fluids in low-risk women.
Care should be taken to consider the incidence of cesarean delivery and anesthesia use at a specific hospital when applying these results to one's own practice.
This issue also reminds us of the necessity of close communication between obstetricians and anesthesiologists in individualizing patient care.

Stress During Pregnancy Linked to Higher Risk for Asthma in Offspring

2010-03-19T20:58:00.000-07:00

From Medscape Medical News
Laurie Barclay, MD

March 18, 2010 — Maternal stress during pregnancy is linked to a higher risk for asthma in the offspring, according to the results of a prospective study reported online March 18 in the American Journal of Respiratory and Critical Care Medicine.

"This is the first study in humans to show that increased stress experienced during pregnancy in these urban, largely minority women, is associated with different patterns of cord blood cytokine production to various environmental stimuli, relative to babies born to lower-stressed mothers," lead author Rosalind Wright, MD, MPH, associate physician at Brigham and Women's Hospital in Boston, Massachusetts, said in a news release.

In the Urban Environment and Childhood Asthma Study, the investigators evaluated associations among prenatal maternal stress and cord blood mononuclear cell (CBMC) cytokine responses among 557 families in Boston; Baltimore, Maryland; New York City; St. Louis, Missouri, and other cities. Each child had a parent with history of asthma or allergy.

Prenatal maternal stress was defined as financial hardship, Difficult Life Circumstances (a 26-item survey to assess particular life stressors occurring within the previous 6 months; eg, domestic violence), community violence, and/or stressful neighborhood/block and housing conditions. A composite cumulative stress indicator was created using factor analysis to produce latent variables representing 3 contexts (individual stressors, housing and neighborhood problems).

CBMCs were incubated with innate stimuli (lipopolysaccharide, Poly I:C, CpG, peptidoglycan [PG]), adaptive stimuli (tetanus, dust mite, cockroach), respiratory syncytial virus, phytohemagglutinin, or medium alone. Multiplex enzyme-linked immunosorbent assays were used to measure cytokines. After adjustment for sociodemographic factors, parity, season of birth, maternal asthma and steroid use, prenatal smoking, and birth weight for gestational age, associations among increasing cumulative stress and cytokine responses were evaluated with linear regression.

Among the study cohort, 71% of mothers were black and 19% were Latino, and 69% had an income less than $15,000. Mothers with the highest cumulative stress tended to be older and were more likely to have asthma and to deliver lower–birth weight infants. Higher levels of prenatal stress were associated with increased interleukin 8 production after microbial stimuli (CpG, PIC, PG) and increased tumor necrosis factor-alpha production to microbial stimuli (CpG, PIC). In the adaptive panel, higher stress was related to higher interleukin 13 levels after dust mite stimulation and lower levels of phytohemagglutinin-induced gamma-interferon.

"The cytokine patterns seen in the higher stress groups, which are an indication of how the child's immune system is functioning at birth, may be a marker of increased risk for developing asthma and allergy as they get older," Dr. Wright said. "For example, while the debate continues as to whether primary sensitization to allergens begins before birth, these findings suggest the possibility that prenatal stress may enhance the neonates' response to inhalant antigens, specifically those antigens that the fetus is likely to encounter more directly in utero, like dust mite."

On the basis of these findings, the study authors concluded that prenatal stress was associated with altered innate and adaptive immune responses in CBMCs, and that stress-induced perinatal immunomodulation may affect the expression of allergic disease in these children.

"The current findings suggest that psychological stress is involved in programming of the infant immune response and that this influence begins during pregnancy," said Dr. Wright. "As these infants mature, we will learn how these factors manifest later in terms of the development of asthma and allergy."

Limitations of this study include the possibility that some relationships were observed by chance because of multiple comparisons, in addition to variability and noise in the cytokine assays.

Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and from the National Center for Research Resources, National Institutes of Health, supported this study and Dr. Wright.

Am J Respir Crit Care Med. Published online March 18, 2010.

Is Postmastectomy Radiation Necessary for All Breast Cancer Patients?

2010-03-12T19:44:00.000-08:00

From Medscape Medical News
Roxanne Nelson

March 11, 2010 — Some women with early-stage breast cancer that has spread to only 1 lymph node might not derive a benefit from postmastectomy radiation, according to new data presented during the plenary session at the Society of Surgical Oncology (SSO) Annual Cancer Symposium in St. Louis, Missouri.

Researchers from the University of Texas M.D. Anderson Cancer Center in Houston found that after surgery, adjuvant chemotherapy, and/or hormonal therapy, the risk for local regional recurrence rates were extremely low for patients with T1 and T2 breast cancer with 0 to 3 positive lymph nodes.

At a median follow-up of 94 months (95% confidence interval [CI], 88 to 94), local regional recurrence occurred in only 2.13% (n = 22) of the total number of patients in the study. There was also no statistical difference in the recurrence rates between patients with 1 lymph node metastasis and those with no nodal involvement (3.3% vs 2.1%).

Radiation is indicated for women after a lumpectomy because it reduces the recurrence rate, but the data are less clear after mastectomy, explained senior author Henry Kuerer, MD, PhD. professor and training program director in M.D. Anderson's Department of Surgical Oncology.

Data Could Be Outdated

"We have long-term data, but they are old data," he told Medscape Oncology in an interview. "They are from randomized studies that were conducted in the 1960s to 1980s, and the rates of local regional recurrence were high in these women. A benefit was seen with radiation."

Dr. Kuerer pointed out that in 2005, a meta-analysis of trials conducted in the 1960s to 1980s showed that there was a 66% reduction in locoregional recurrence in women who received postmastectomy radiation, compared with no radiation. The analysis also showed a small survival benefit associated with radiation therapy.

These findings led to a shift in clinical practice, and the National Comprehensive Cancer Network altered their guidelines in 2007 to suggest that stage I and II breast cancer patients with 1 to 3 lymph node metastases "strongly consider" radiation after mastectomy.

The overall 5- and 10-year recurrence rates in those studies ranged from 20% to 25%, which are much higher than what is currently observed, said Dr. Kuerer. "We have not seen that in our own clinical practice."

We have better screening, better detection, better surgical techniques.
In the decades since those studies were conducted, Dr. Kuerer explained, much has changed in the treatment and diagnosis of breast cancer. "We have better screening, better detection, better surgical techniques, and we now have therapies that didn't exist when these early studies were done," he said. "Pathology has also improved, and more extensive examination of lymph nodes is now conducted."

Radiotherapy after mastectomy is effective at decreasing the chances of local regional recurrence in patients with lymph node spread in more than 4 nodes, and where the risk for recurrence is greater than 15%. "The benefit of radiation therapy in this case clearly outweighs the risk, and can offer a survival advantage," he said.

But the use of radiation in patients with early-stage breast cancer with only 1 to 3 positive nodes has been a "hot topic of debate" within the cancer community, Dr. Kuerer explained.

Low Recurrence Rates

The goal of this study was to determine the present-day rates of local regional recurrence to better gauge the potential benefit of postmastectomy radiation in this particular subpopulation of breast cancer patients. Dr. Kuerer and his colleagues conducted a retrospective study in which they evaluated the clinical and pathological factors of 1022 stage I or II breast cancer patients who received a mastectomy at M.D. Anderson between 1997 and 2002.

The median patient age was 55 years and, within this group, 79% had T1 and 21% had T2 tumors. The majority of patients (74%) had no lymph node metastasis, but 26% had 1 to 3 positive nodes. None of the patients in the study received postmastectomy radiation therapy or neoadjuvant therapy, and 77% received adjuvant chemotherapy and/or hormonal therapy.

Node Status and Rates of Local Regional Recurrence (LRR) Number of
Positive Nodes n (%) 5-Year LRR 10-Year LRR
0 753 (74) 1.2% 2.4%
1 180 (18) 2.4% 3.2%
2 69 (7) 3.1% 6.7%
3 21 (2) N/A N/A

There were too few patients in the study with 3 positive nodes to determine rates. Patients who were younger than 40 years, who had T2 tumors with nodal metastasis, and who had estrogen-receptor negative tumors had significantly higher chances of local regional recurrence (P < .01).

"I think that our study should have an impact on how women with early-stage disease and 1 positive lymph node are treated," said Dr. Kuerer, although he cautioned that treatment decisions must always be based on the individual patient.

Monica Morrow, MD, chief of the breast service in the Department of Surgery at Memorial Sloan-Kettering Cancer Center in New York City, doesn't believe that current practice should change just yet.

"The question asked in this study — what is the rate of local recurrence after mastectomy in patients receiving modern systemic therapy and high-quality surgery — is an important one," said Dr. Morrow, who moderated the plenary session at the SSO symposium. However, "this study cannot be used as evidence that radiation therapy can be eliminated, because this was a very selected group of patients."

This study should stimulate other more inclusive studies, but should not be regarded as practice-changing.
She told Medscape Oncology that there were many more patients who received treatment during the same time period, and who received radiation therapy and neoadjuvant chemotherapy, or both. "We don't have any information on how the group who didn't get radiation therapy compares or what percentage of patients they were," she explained. "So this study should stimulate other more inclusive studies, but should not be regarded as practice-changing."

Dr. Kuerer agreed that more studies are needed, and pointed to the international randomized SUPREMO trial, which is currently enrolling patients. The trial is designed to evaluate the role of chest-wall radiation therapy after mastectomy in women who are at intermediate risk for locoregional recurrence, with 1 to 3 involved lymph nodes.

"However," he said, "it may be a decade before we have that information."

Society of Surgical Oncology's Annual Cancer Symposium: Abstract 47. Presented March 6, 2010.

Vaginal Birth After Cesarean Delivery

2010-03-11T18:47:00.000-08:00

From Medscape Medical News
Draft NIH Consensus Statement Released
Laurie Barclay, MD

March 10, 2010 — An independent expert panel released today a draft consensus statement on vaginal birth after cesarean delivery (VBAC) at the close of a 3-day conference.

The National Institutes of Health (NIH) Consensus Development Conference on Vaginal Birth After Cesarean (VBAC): New Insights, was held from March 8-10 in Bethesda, Maryland. When choosing VBAC or repeat cesarean delivery, parents' preferences and risk factors should be carefully considered, the panel said.

VBAC was not generally accepted as a viable option until the 1980s. VBAC rates in the United States have increased steadily until they reached 28% in 1996, but they have consistently decreased since 1996, despite a steady increase in the rates of repeat cesarean delivery.

The current overall cesarean delivery rate is 31%, whereas the VBAC rate is less than 10%.

"The exact causes of these shifts are not known and are likely multifactorial," Catherine Y. Spong, MD, chief, and Caroline Signore, MD, medical officer, Pregnancy and Perinatology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, told Medscape Ob/Gyn & Women's Health.

"On one hand, the VBAC rate peaked in the mid-1990s, and then there was the publication of some studies that suggested increased risk with VBAC vs a repeat cesarean; at the same time, there was the malpractice crisis, especially in obstetrics, and the [American Congress of Obstetricians and Gynecologists] guidelines were modified to require that a physician capable of performing an emergency cesarean is immediately available through active labor. These events may have started the decline in VBAC utilization," Dr. Spong explained.

The panel noted that pregnant women, even those at low risk for complications, currently have limited access to clinicians and facilities capable of and willing to offer a trial of labor after previous cesarean delivery.

"Many women bemoan the fact that they have not had access to a trial of labor after prior cesarean section," Consensus Development Panel Chair F. Gary Cunningham, MD, Beatrice and Miguel Elias Distinguished Chair in Obstetrics and Gynecology at the University of Texas Southwestern Medical Center at Dallas, said during a telebriefing held after the conference.

The consensus conference aimed to explore the reasons underlying the changing practice patterns resulting in lower rates of VBAC, to clarify the clinical risks and benefits of both types of delivery procedures, and to describe the interaction of these risks with legal, ethical, and economic forces affecting clinician and patient choices regarding VBAC.

"A frequently cited concern [about VBAC] is the concern of safety — specifically the risk of uterine rupture, along with other risks," Dr. Spong and Dr. Signore said.
"In addition, there are nonclinical factors, including hospital practices and physician practices, professional society guidelines, medicolegal concerns, personal preferences of patients and clinicians, insurance policies, and economic considerations."

VBAC a Reasonable Option for Many

Despite the lack of widespread availability, a trial of labor is a reasonable option for many women with a previous cesarean delivery, and it is successful in nearly 75% of cases, the panel concluded.

Women in whom VBAC may be considered are those with 1 prior cesarean section, a single low transverse incision, singleton gestation, and no medical or obstetrical complicating conditions.
Data to support the safety of VBAC in women not meeting these criteria are lacking. Age itself does not preclude VBAC, but the rates of large babies, hypertension, diabetes, and dysfunctional labor are higher in older women.

Maternal mortality is lower for women who have a trial of labor, regardless of whether the baby is ultimately delivered vaginally or by cesarean section.
However, women who have an unsuccessful trial of labor and undergo repeat cesarean delivery have higher morbidity rates than those who have a successful VBAC.

Further complicating decision-making regarding VBAC is that benefits for the mother may come at the price of increased risks for the baby, and vice versa.
Although hysterectomy rates are similar for both forms of delivery, risk for uterine rupture is higher in women who have a trial of labor. VBAC has been linked to reduced abnormalities of placental growth and position in subsequent pregnancies. However, high-quality evidence about medical and nonmedical risk factors is limited or lacking.

"In general, there are short- and long-term risks and benefits for both the mother and the baby that need to be considered," Dr. Spong and Dr. Signore said. "Basically, they include — for the mother — risks of uterine rupture, transfusion and hemorrhage, operative risks including injury to the bowel and bladder, hysterectomy, death, infection, problems with placentation in subsequent pregnancies, [and] possible risk of stillbirth and ectopic pregnancies. For the baby, the risks include transition problems for the newborn, respiratory distress, neonatal encephalopathy and hypoxic ischemic encephalopathy, death, and brachial plexus injury."

Current VBAC Guidelines Should be Reassessed

The panel recommended that current VBAC guidelines from professional societies be reassessed, particularly the recommendation for "immediate availability" of surgical and anesthesia personnel before a trial of labor can be offered.

According to 2 recent surveys of hospital administrators, 30% of hospitals no longer offer a trial of labor or VBAC services because they could not meet the immediate availability standard suggested by the American College of Obstetricians and Gynecologists and the American Society of Anesthesiologists guidelines. However, the panel found no evidence that outcomes were improved by the immediate availability of surgical and anesthesia personnel.

" 'Nonmedical' factors affecting VBAC utilization [were also] considered at the conference, based on talks by expert presenters," Dr. Spong and Dr. Signore said. "The panel [considered], for example, the influence of hospital administrative policies, healthcare expenditures, resource utilization, the threat of malpractice litigation and the associated financial ramifications (insurance premiums, settlements and awards), the impact of professional society recommendations and standards, the role of maternal and provider preferences, understanding how risk is communicated and understood, the medical ethics of choice and access to childbirth options, and availability of surgical and anesthesiology staff."

Other Recommendations

Other recommendations of the panel are that malpractice concerns be addressed and that additional research be performed to better understand the medical and nonmedical factors that affect decision making for women with previous cesarean deliveries. Also needed are clear, evidence-based risk assessment tools to facilitate the decision-making process from early pregnancy through delivery, considering individual risk factors as well as maternal values and preferences.

"All women who have had a prior cesarean section should talk to their provider about VBAC and reassess the safety of a trial of labor," panel member Emily Spencer Lukacz, MD, MAS, associate professor of clinical reproductive medicine at the University of California–San Diego, said during the telebriefing.

Some women prefer to attempt a trial of labor because they would like their partner to be involved in the delivery, they perceive labor and vaginal delivery as deeply empowering, and/or they believe it will enhance maternal–infant bonding, breast-feeding, and recovery. In contrast, preferences favoring planned cesarean delivery include scheduling convenience, avoidance of labor pain or possible emergency cesarean section, and/or desire for surgical sterilization at the time of delivery.

The panels hopes the conference findings will have important implications for health services planning as well as for informed clinical decisions. The panel strongly urged policymakers and healthcare providers to collaborate in developing and implementing appropriate strategies to address and alleviate malpractice concerns.

"Pregnancy is something of a risky endeavor," concluded Carol J. Rowland Hogue, PhD, MPH, Jules & Uldeen Terry Professor of Maternal and Child Health at Emory University in Atlanta, Georgia. "Problems occur irrespective of the mode of delivery.... It's a tradeoff between making the pregnancy as safe as possible for the mother and making the pregnancy as safe as possible for the baby."

The statement issued by the impartial, independent Consensus Development Conference panel synthesized their evaluation of the available evidence from a systematic literature review prepared through the Agency for Healthcare Research and Quality Evidence-Based Practice Centers program by the Oregon Evidence-Based Practice Center. The panel included 15 experts in obstetrics and gynecology, urogynecology, maternal and fetal medicine, pediatrics, midwifery, clinical pharmacology, medical ethics, internal medicine, family medicine, perinatal and reproductive psychiatry, anesthesiology, nursing, biostatistics, epidemiology, healthcare regulation, and risk management, and a public representative.

The panel also considered evidence from expert presentations and audience input at the conference to provide a basis for informed patient and clinician decisions concerning VBAC. The statement also includes specific recommendations for future research.

The draft consensus statement is available on the NIH Consensus Development Program Web site.

NIH Consensus Development Conference on (VBAC): New Insights. March 8-10, 2010.

Feeding Challenges in the Late Preterm Infant

2010-03-10T23:30:00.000-08:00

From Neonatal Network
Karen Cleaveland, MSN, APRN, NNP-BC

Abstract
A late preterm infant is defined as one born between 34 and 36 6/7 weeks of completed gestation. The rate of late preterm births has risen 18 percent since the late 1990s. Data are beginning to emerge concerning morbidity rates and the risks these newborns face with regard to feeding difficulties, temperature instability, hypoglycemia, and hyperbilirubinemia.
Feeding challenges place these vulnerable infants at risk for prolonged hospital stays and readmission after discharge. To better address the unique needs of late preterm infants, providers should establish individual feeding orders. This article offers research-based suggestions for caring for these infants in the newborn nursery and the postpartum unit as well as parent teaching guidelines.

Introduction
Late preterm infants represent the most rapidly growing segment of preterm births in the U.S., accounting for 72 percent of the 12.7 percent preterm birth rate in 2005. This population of preterm infants is often cared for within the general newborn setting using the feeding guidelines for healthy term infants.

The staff of the newborn nursery often regards these infants as being term because they are usually of normal size and have a more mature appearance than preterm infants born after shorter gestations.

Compared with term infants, however, late preterm infants are at higher risk for excessive weight loss, feeding intolerance, hyperbilirubinemia, hypoglycemia, hypothermia, respiratory distress, apnea of prematurity, and a weak suck.

And, because of the increased risks these infants face, they also have higher morbidity and mortality than term infants. It is therefore necessary to recognize and treat this late preterm infant population with its own feeding and care guidelines instead of using guidelines for term infants. It is also vital to formulate a specific set of discharge planning teaching guidelines for them.

Feeding Challenges

Feeding challenges in the late preterm infant have been shown to be related to immature sucking and swallowing reflexes, which lead to improper latch-on for the breastfeeding infant as well as inadequate intake in the bottle-feeding infant.
As noted earlier, sucking, swallowing, and breathing must synchronize smoothly and effectively, with highly accurate timing and coordination, for safe and efficient oral feeding.[11]
Late preterm infants often have fewer awake-alert periods and less postural stability than their full-term counterparts, which often results in inadequate caloric intake. Decreased feeding combined with low energy stores and high energy demands place these infants at risk for inadequate hydration.

Health care providers and mothers may assume that the infant has ingested an adequate volume of milk when he falls asleep at the breast, when in reality the infant has exceeded his energy stores and has shut down without adequate caloric intake. Parents need to be educated regarding their infant's feeding cues, sleep-wake cycles, and how to promote postural stability.

Behaviors such as rooting, mouthing, and finger sucking indicate feeding readiness. Ensuring that the hips are flexed and the head and neck are aligned with the trunk provides appropriate postural stability, improving feeding success in the late preterm infant.

Immature brain development in late preterm infants is often overlooked because they are considered stable compared with extremely low birth weight premature infants. During the final few weeks of gestation, movements become smoother, oral motor skills more coordinated, and states of alertness more predictable.

This relates directly to why late preterm infants fail at feeding when they are discharged without the proper instructions being given to their caregivers. It is necessary that the nursing staff and parents, as well as the pediatric providers, receive education in achieving safe and effective oral feedings in late preterm infants.

The medical issues described earlier also make late preterm infants more susceptible to having a decreased state of arousal as well as poor endurance, resulting in early fatigue during feeding.

Asthma Severity Remains Stable in Pregnant Women Continuing Their Medication

2010-03-05T20:48:00.000-08:00

From Medscape Medical News
Laurie Barclay, MD

March 5, 2010 — Asthma severity during pregnancy is similar to severity in the previous year if women continue to take their prescribed medication but is more severe if they discontinue it, according to the results of a study reported in the March issue of Obstetrics & Gynecology.

"Early investigators suggested a rule of thirds: in one third of women, asthma improves during pregnancy; in one third, asthma becomes worse; and in one third it remains the same," write Kathleen Belanger, PhD, from Yale University School of Public Health in New Haven, Connecticut, and colleagues. "However, assessment of improvement has often been subjective, and exacerbations have been measured by hospitalizations and emergency department visits. No studies have used the more common clinical endpoints of symptoms and medication use to assess exacerbation during pregnancy."

The goal of this study was to assess the effect of patient-related or treatment-related factors on asthma severity during pregnancy among women recruited before 24 weeks of gestation through private obstetricians and hospital clinics.
In-person and telephone interviews allowed gathering of symptom and medication data. Of 872 women with physician-diagnosed asthma, 686 had active asthma; of these, 641 women with complete data were analyzed. Changes in asthma severity, measured by the Global Initiative for Asthma, were evaluated during each month of pregnancy with use of cumulative logistic regression models for repeated measures.

Prepregnancy asthma severity and use of medication according to Global Initiative for Asthma guidelines significantly and profoundly affected the course of asthma.
No other factors analyzed were significant risk factors for clinically meaningful changes in asthma severity, defined as a 1-step change in the Global Initiative for Asthma category. These included race, age, atopic status, body mass index (BMI), parity, fetal sex, and smoking.

The most benefit from appropriate treatment was observed in women with milder asthma, with a 62% decreased risk for worsening asthma among those with intermittent asthma (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.23 - 0.64) and a 52% decreased risk among those with mild persistent asthma (OR, 0.48; 95% CI, 0.28 - 0.84). The gestational month or trimester was not consistently associated with changes in asthma severity.

"Asthma severity during pregnancy is similar to severity in the year before pregnancy, provided patients continue to use their prescribed medication," the study authors write.
"If women discontinue medication, even mild asthma is likely to become significantly more severe."

Limitations of this study include failure to directly measure lung function; and collection of symptom and medication data by interview, which could result in recall errors.

"Recent research indicates that the fetus may experience significant risk from exacerbations of asthma in the mother," the study authors conclude.
"The American College of Obstetricians and Gynecologists (the College) recommends continuation of medication for the health of both mother and fetus. The current paper provides empirical support for the College guidelines: exacerbations during pregnancy are best prevented when the mother uses asthma medication appropriate to her level of symptoms."

The National Institutes of Health supported this study. The study authors have disclosed no relevant financial relationships.

Obstet Gynecol. 2010;115:559-567. Abstract

High Plasma Folate Levels in Pregnancy May Increase Asthma Risk for Offspring

2010-03-04T19:36:00.000-08:00

From Medscape Medical News

Deborah Brauser

March 4, 2010 (New Orleans, Louisiana) — Children of mothers with high plasma folate levels during pregnancy appear to have an increased risk of developing asthma by the age of 3 years, according to a sampling from the Norwegian Mother and Child Cohort (NMCC) study presented in a poster session here at the American Academy of Allergy, Asthma and Immunology 2010 Annual Meeting.

"Norway provides a unique opportunity to address the question of possible deleterious consequences of high folate intake during pregnancy because the food supply there is not fortified with folates,"

"It's one of the few places where you can look at whether the supplementation, which is clearly good from the point of view of decreasing birth defects, could potentially also have some adverse effects,"

Recent Studies Question Folic Effects

Previous research has consistently shown that the periconceptional intake of folic acid reduces the risk for neural tube defects in infants, leading to the increased use of these supplements and to the fortification of foods with folic acid in the United States and other countries.

However, a recent study showed that high dietary supplementation with folic acid and other methyl donors in pregnant mice led to allergic asthma phenotypes, through epigenetic changes, in offspring.

In another study recently conducted by Dr. London's research team, an association was found between folate supplements used during early pregnancy and an increased risk for respiratory disease in children up to the age of 18 months.

For this study, they examined data on 507 mothers from the population-based NMCC who had plasma folate levels measured during their second trimester of pregnancy, and who had children with asthma at the age of 3 years. The folate levels of 1455 mothers of healthy controls were also measured.

"The age of 3 isn't a perfect phenotype because that's early to diagnose asthma, but that was the age that the kids were at the time of the study," explained Dr. London.

A Linear Increase Found

Results showed that mothers in the top quintile of plasma folate had children with an increased risk for asthma at age 3 (adjusted odds ratio [OR], 1.66; 95% confidence interval [CI], 1.16 - 2.37), relative to mothers in the bottom quintile.

In addition, the investigators found "a trend of linear increase across quintiles" (P = 0.007). Children of mothers with folate levels between the 70th and 95th percentiles had an OR of 1.34 (95% CI, 1.03 - 1.73), whereas children of mothers with levels above the 95th percentile had an OR of 1.44 (95% CI, 1.08-1.93).

"In other words, as the mother's folate level increased, so did the risk of asthma in their child," said Dr. London.

"Overall, this study showed small effects, but it definitely doesn't mean that people shouldn't use folates," she noted. "It just raises the possibility that, as a population, maybe we're reaching folate repletion. It's also possible that there could be a double-edged sword to folate supplementation; certainly it's looking like that may be the case in some cancer studies. However, at this stage, I wouldn't want to be quoted as saying that we should rethink how much folate people are getting."

The investigators next plan to follow-up with these children to "an age when asthma can be more reliably diagnosed," and through to age 7. They've received funding to assess the epigenetic effects of folate supplementation. "In these women, we're going to be looking at cord blood DNA, and looking at whether the patterns of methylation are different according to folate levels and asthma status in the child," explained Dr. London.

Caution Urged

"The findings were consistent with literature from animal models where folic acid could possibly lead to a higher risk for asthma," said Juan Celedón, MD, DrPH, associate professor of medicine at Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts.

"However, I think that there are some cautions with this study," added Dr. Celedón, who was not involved in the research. "First, you can't diagnose asthma until the age of 6, so further follow-up of those kids is needed. Second, they did not measure any objective markers of allergy. And third, they didn't show a mechanism. All that said, the findings are very intriguing,"

"We just need to be very cautious in this area," he told Medscape Allergy & Clinical Immunology. "A woman takes folic acid to protect against neural tube defects and it's been very, very effective for that. I think we need to be extraordinarily careful and need to assess this thoroughly before we can begin to make any recommendations [for] current practice in regard to changing or even reducing folic acid during pregnancy."

This study was funded by the Norwegian Research Council. The NMCC study was funded by the Norwegian Ministry of Health and a grant from the National Institute of Environmental Health Sciences/National Institutes of Health. Dr. London and Dr. Celedón have disclosed no relevant financial relationships.

American Academy of Allergy, Asthma and Immunology (AAAAI) 2010 Annual Meeting: Abstract 505. Presented February 28, 2010.

Children of Psychiatrically Ill Parents at Risk for Mental Disorders

2010-03-04T19:04:00.000-08:00

From Medscape Medical News
Allison Gandey

March 4, 2010 — Children of 2 parents with schizophrenia or bipolar disorder are more likely to develop these or other mental disorders, a new national study shows.

Young people with both parents diagnosed as having schizophrenia were 27% more likely to develop the illness.
The risk of bipolar disorder was similar at almost 25%.

In contrast, people with only 1 parent with a psychiatric illness were much less likely to develop mental disorders. Just 7% of those with a parent with schizophrenia developed the disease.
Only 4% of people with 1 parent with bipolar disorder had the disorder.

The population-based study of 2.7 million people in Denmark is published in the March issue of Archives of General Psychiatry.

Irving Gottesman has been a leader in psychiatric genetic epidemiology for many decades.
"I think we set a world record in terms of the number of parent couples we looked at," lead investigator Irving Gottesman, PhD, from the University of Minnesota Medical School in Minneapolis, said during an interview. "Our cohort included 196 couples with 270 offspring — this is very large," he said.

"Irving Gottesman has been a leader in psychiatric genetic epidemiology for many decades," James Potash, MD, from Johns Hopkins University in Baltimore, Maryland, told Medscape Psychiatry.

"This gigantic study gives us hard numbers to help assess risk," he said.

Large Study

The research team linked data from the Danish civil registration system to the Danish psychiatric central register. Investigators wanted to determine the risk of schizophrenia, bipolar disorder, unipolar depressive disorder, or any diagnosis.

The risk for any psychiatric disorder in offspring with both parents with schizophrenia was close to 68%. For 2 parents with bipolar disorder, the risk was 44%.

During an interview, Dr. Gottesman acknowledged the increased risk, but he also pointed to the high numbers that suggest no diagnosis at all.

"This is something that was cut from the paper because there wasn't enough space to elaborate, but if you do the math and follow the numbers through, you will see high rates with no later diagnosis," he said.

For children with both parents with schizophrenia, the chance of no diagnosis was 73%. For children with both parents with bipolar disorder, the rate was 75%.

"This is good news for many people," Dr. Gottesman said.

Weighing the Risk

Dr. Potash said he agrees that most offspring will not be diagnosed as having mental disorders. "The risk is certainly higher, but many won't become ill." He also points out that this study is consistent with previous work.

"For the practicing clinician," Dr. Gottesman said, "I think this paper speaks to the importance of taking a careful family history."

He notes the many challenges of the intake interview — particularly when it comes to discussing psychiatric health. "People are often embarrassed about mental disorders and keep them secret. Not everyone in a family will necessarily know."

Dr. Gottesman points out that it can be helpful to ask related questions about alcohol and drug use, including more subtle questions about weekly consumption.

Arch Gen Psychiatry. 2010;67:252-257.

Maternal Physical Characteristics, Lifestyle Habits Predict Early Fetal Growth

2010-03-01T06:37:00.000-08:00

From MedscapeCME Clinical Briefs

News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd

CME Released: 02/18/2010; Valid for credit through 02/18/2011

February 18, 2010 — Maternal physical characteristics and lifestyle habits are independently associated with early fetal growth, according to the results of a study reported in the February 10 issue of the Journal of the American Medical Association.

"Adverse environmental exposures lead to developmental adaptations in fetal life," write Dennis O. Mook-Kanamori, MD, MSc, from Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues. "The influences of maternal physical characteristics and lifestyle habits on first trimester fetal adaptations and the postnatal consequences are not known."

The goal of this study was to determine the risk factors and outcomes associated with first-trimester growth restriction. In Rotterdam, the Netherlands, between 2001 and 2005, a total of 1631 mothers with a known and reliable first day of their last menstrual period and a regular menstrual cycle were enrolled. The investigators evaluated associations of maternal physical characteristics and lifestyle habits with first-trimester fetal growth, and then subsequently looked at the associations of first-trimester fetal growth restriction with the risks for adverse birth outcomes and postnatal growth acceleration until age 2 years.

Between gestational ages of 10 weeks 0 days and 13 weeks 6 days, an ultrasound study was performed to measure first-trimester fetal growth based on crown-to-rump length. Primary study endpoints included preterm birth, defined as gestational age of less than 37 weeks; low birth weight (< 2500 g); and small size for gestational age (lowest fifth birth centile); as well as postnatal growth measured until age 2 years.

Maternal age was positively associated with first-trimester fetal crown-to-rump length, based on multivariate analysis (difference per maternal year of age, 0.79 mm; 95% confidence interval [CI], 0.41 -1.18 per SD score increase). Factors associated with a shorter crown-to-rump length were higher diastolic blood pressure and higher hematocrit level (differences, −0.40 mm; 95% CI, −0.74 to −0.06 and −0.52 mm; 95% CI, −0.90 to −0.14 per SD increase, respectively).

Shorter fetal crown-to-rump lengths were reported for mothers who both smoked and did not use folic acid supplements vs mothers who were nonsmokers and optimal users of folic acid supplements (difference, −3.84 mm; 95% CI, −5.71 to −1.98).

Compared with normal first-trimester fetal growth, adverse outcomes associated with first-trimester growth restriction included preterm birth (4.0% vs 7.2%; adjusted odds ratio [OR], 2.12; 95% CI, 1.24 - 3.61), low birth weight (3.5% vs 7.5%; adjusted OR, 2.42; 95% CI, 1.41 - 4.16), and small size for gestational age at birth (4.0% vs 10.6%; adjusted OR, 2.64; 95% CI, 1.64 - 4.25).

For each SD decrease in first-trimester fetal crown-to-rump length, there was a postnatal growth acceleration until age 2 years (SD score increase, 0.139 per 2 years; 95% CI, 0.097 - 0.181).

"Maternal physical characteristics and lifestyle habits were independently associated with early fetal growth," the study authors write. "First-trimester fetal growth restriction was associated with an increased risk of adverse birth outcomes and growth acceleration in early childhood....Further studies are needed to assess the associations of first-trimester growth variation on the risks of disease in later childhood and adulthood."

Limitations of this study include possible misclassification of gestational age because of inability to measure the timing of ovulation and implantation, and possible recall bias confounding dating of the last menstrual period.

In an accompanying editorial, Gordon C.S. Smith, MD, PhD, from the University of Cambridge in Cambridge, United Kingdom, notes that this study adds to the body of evidence suggesting that growth and placental function in the first trimester of pregnancy significantly affect fetal and infant growth.

"Hence, complications of late pregnancy may, at least for some women, already be determined in the first 3 months postconception, even before a woman has sought prenatal care," Dr. Smith writes. "The multiple associations described suggest that combined ultrasonic and biochemical screening in early pregnancy may be able to identify women at high risk of complications in late pregnancy. The challenges for future research are to produce robust screening tests with acceptable levels of detection and prediction, and to identify interventions that are effective in improving outcome when a pregnancy has been identified as high risk."

The first phase of the Generation R Study was supported financially by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, and the Netherlands Organization for Health Research. One of the study authors (Dr. Jaddoe) has received funding from the Netherlands Organization for Health Research. The other study authors have disclosed no relevant financial relationships.

Dr. Smith reports that he has been a member of preterm labor advisory boards for GlaxoSmithKline. Funding for his editorial was provided by Cambridge National Institute for Health (NHS) Research Biomedical Research Centre, Cambridge University Hospitals, NHS Foundation Trust.

JAMA. 2010;303:527-534, 561-562. Abstract

Clinical Context

Human growth and development rates are highest in the first trimester of pregnancy, and first-trimester crown-to-rump length is used as a dating method in obstetrics and as an assessment of fetal growth. However, the relationship between fetal growth restriction in the first trimester and pregnancy and postnatal outcomes is still unknown.

This is a population-based, prospective cohort study to examine the association between maternal characteristics and lifestyle habits and first-trimester crown-to-rump length, and the association between growth restriction and neonatal and postnatal outcomes to 2 years.

Older Maternal Age Linked to Increased Risk for Autism in Children

2010-03-01T06:28:00.000-08:00

From MedscapeCME Clinical Briefs

News Author: Caroline Cassels
CME Author: Hien T. Nghiem, MD

February 16, 2010 — Advanced maternal age significantly increases the risk of having a child with autism irrespective of paternal age, a large population-based study suggests.

The research, conducted by investigators at UC Davis Health System, Sacramento, California, shows that the incremental risk of having a child with autism increased by 18% for every 5-year increase in maternal age.

"These data show that the risk of having a child with full-syndrome autism increases with maternal age, but increased risk from advancing paternal age primarily occurs among younger mothers (<30)," the researchers, led by senior investigator Irva-Hertz-Picciotto, PhD, MPH, write.

According to lead study author Janie Shelton, a doctoral student, the study challenges the hypothesis that the father's age is a key factor in increasing autism risk.

"It shows that while maternal age consistently increases the risk of autism, the father's age only contributes an increased risk when the father is older and the mother is under 30 years old.
Among mothers over 30, increases in the father's age do not appear to further increase the risk of autism," Ms. Shelton said in a statement.

The study was published online February 8 in Autism Research.

According to the study, previous research on autism and paternal age have yielded conflicting results on whether mothers, fathers, or both contribute to an increased risk for autism in children.

To determine the independent or dependent effect from each parent, the researchers gathered electronic records for all births in California between January 1, 1990, and December 31, 1999. The records incorporated detailed demographic information, including the age of both parents.

To identify which children would subsequently develop autism, the investigators obtained electronic records identifying children born during the study period who later received an autism diagnosis from California's Department of Developmental Services. For the study, autism was defined as a diagnosis of full-syndrome autism at a California regional center.

The final study sample included 4.9 million births and 12,159 cases of autism. The researchers report that for older mothers there was a stepwise progression in the risk of having a child who would later be diagnosed as having autism, irrespective of the father's age.

"We demonstrate that advancing maternal age increases the risk of autism independent of father's age, while advancing father's age increases the risk of autism primarily for mothers under 30. Among mothers over 30, we observed a small increased risk only among fathers 40+; even at the highest age group, the increase was smaller and less precise than that for fathers 30-34 among younger mothers," the researchers write.

At this point, the reason parental age influences autism risk is not clear. "We still need to figure out what it is about older parents that puts their children at greater risk for autism and other adverse outcomes, so we can begin to design interventions," Dr. Hertz-Picciotto said in a statement.

The study authors have disclosed no relevant financial relationships.

Autism Res. Published online February 8, 2010.

Clinical Context

In recent decades, the diagnosis of autism has increased. Autism is a pervasive developmental disorder of which deficits in social skills and communication, as well as repetitive and restricted behaviors, occur before age 3 years. Between 1990 and 2001, there has been a 7-fold increase in cumulative incidence observed among 5-year-olds in California. Known factors can explain this finding such as changes in the diagnostic criteria and a shift towards younger age at diagnosis. Studies have linked advancing parental age as a risk factor for autism. However, reports on autism and parental age have yielded conflicting results on whether mothers, fathers, or both, contribute to increased risk.

The aim of this study was to analyze restricted strata of parental age in a 10-year California birth cohort to determine the independent or dependent effect from each parent.

Study Highlights

To establish the cohort of this study, the investigators linked autism cases from California Department of Developmental Services records to state birth files (1990-1999). Subsequently, only singleton births with complete data on parental age and education were included (n = 4,947,935; cases = 12,159).

The net effects of maternal and paternal age on the risk for autism after adjustment for potential confounders were modeled by logistic regression, with the parental age terms specified either as continuous or categoric.
aORs for the effects of advancing paternal (maternal) age were also estimated with use of stratified multivariate logistic regression in strata defined by narrow (5-year) maternal (paternal) age groups.
The covariates adjusted in all models were parental education, year of child's birth, race or ethnicity of mother and father, mother's parity, and insurance payment.

Results demonstrated that children with autism were more likely than control subjects to be men, to have older parents, and to be either non-Hispanic white or Asian vs children without autism.
In multivariate logistic regression models, advancing maternal age increased the risk for autism monotonically regardless of the paternal age.
Compared with mothers aged 25 to 29 years, the aOR for mothers older than 40 years was 1.51 (95% CI, 1.35 - 1.70) vs mothers younger than 25 years (aOR, 1.77; 95% CI, 1.56 - 2.00).
In contrast, autism risk was associated with advancing paternal age (> 40 years), primarily among mothers younger than 30 years (aOR, 1.59; 95% CI, 1.37 - 1.85) vs the reference group of fathers aged 25 to 29 years (aOR, 0.76; 95% CI, 0.70 - 0.82).
Among mothers 30 years and older, the aOR was 1.13 (95% CI, 1.01 - 1.27) for fathers 40 years and older vs fathers aged 25 to 29 years, almost identical to the aOR for fathers younger than 25 years.
Based on the first examination of heterogeneity in parental age effects, it appears that a women's risk of delivering a child who develops autism increases throughout her reproductive years, whereas the father's age (> 40 years) confers an increased risk for autism when the mother is younger than 30 years but has limited effect when the mother is older than 30 years.
Additionally, the recent trend towards delayed childbearing contributed approximately a 4.6% increase in autism diagnoses in California between 1990 and 1999.

Clinical Implications

According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, autism is a pervasive developmental disorder of which deficits in social skills and communication, as well as repetitive and restricted behaviors, occur before age 3 years.
The risk of having a child with autism increases with older maternal age, but the increased risk from advancing paternal age occurs when the mother is younger (age < 30 years).

Prenatal and Postnatal Tobacco Exposure and Behavioral Problems in 10-year-old

2010-02-28T06:38:00.000-08:00

From Environmental Health Perspectives
Children: Results from the GINI-plus Prospective Birth
Simon Rückinger; Peter Rzehak; Chih-Mei Chen; Stefanie Sausenthaler; Sibylle Koletzko; Carl-Peter Bauer; Ute Hoffmann; Ursula Kramer; Dietrich Berdel; Andrea von Berg; Otmar Bayer; H.-Erich Wichmann; Rüdiger von Kries; Joachim Heinrich

Posted: 02/18/2010; Environmental Health Perspectives. 2010;118(1):150-154. © 2010 National Institute of Environmental Health Sciences

Abstract
Background: Prenatal and postnatal tobacco exposure have been reported to be associated with behavioral problems. However, the magnitude of the association with tobacco exposure at specific periods of exposure is unclear.

Objective: We assessed the relative risk of behavioral problems in children who had been exposed to tobacco smoke in utero and postnatally.

Methods: We analyzed data from a prospective birth cohort study in two cities in Germany: the German Infant Nutrition Intervention. Our sample included 5,991 children born between 1995 and 1998 as well as their parents. We measured behavioral problems using the Strength and Difficulties Questionnaire (SDQ) at follow-up 10 years after birth. According to prespecified SDQ cutoff values, children were classified as "normal," "borderline," or "abnormal" according to the subscales "emotional symptoms," "conduct problems," "hyperactivity/inattention," "peer-relationship problems," and a total difficulties score. Smoke exposure and further covariates were assessed using parent

Results: Compared with children not exposed to tobacco smoke, children exposed both pre- and postnatally to tobacco smoke had twice the estimated risk [95% confidence interval (CI), 1.4-3.1] of being classified as abnormal according to the total difficulties score of the SDQ at 10 years of age.

Children who were only prenatally exposed had a 90% higher relative risk (95% CI, 0.9-4.0), whereas children who were only postnatally exposed had a 30% higher relative risk (95% CI, 0.9-1.9).
These results could not be explained by confounding by parental education, father's employment, child's time spent in front of computer or television screen, being a single father or mother, or mother's age.

Conclusions: Prenatal exposure to tobacco smoke is associated with behavioral problems in school-age children.
Although our findings do not preclude the influence of postnatal exposure, prenatal exposure seems to be more important.

Introduction
Exposure of children to tobacco smoke, whether postnatal or in utero, is a well-known risk factor for various adverse health outcomes (DiFranza et al. 2004).

An increased risk for intrauterine growth retardation, sudden infant death syndrome, and asthma are well-known adverse effects of in utero tobacco exposure (Higgins 2002).
In addition, effects of in utero tobacco exposure on behavioral problems have been reported in various experimental and epidemiologic studies (Ernst et al. 2001; Eskenazi and Castorina 1999; Wakschlag et al. 2002; Weitzman et al. 2002) including some longitudinal studies (Markussen Linnet et al. 2006; Wakschlag et al. 1997). Prospective studies that systematically assess a broad range of behavioral problems outcomes are sparse.

Many studies have found an association between smoking in pregnancy and behavioral problems among children (Batstra et al. 2003; Roza et al. 2009; Saxton 1978).

An independent effect of postnatal tobacco exposure on behavioral development has also been suggested (Braun et al. 2006, 2008; Fergusson et al. 1993; Weitzman et al. 1992; Williams et al. 1998). However, specifically delineating the impact of prenatal versus postnatal tobacco exposure is a challenging task: Children whose mothers have smoked during pregnancy are likely to be exposed to tobacco smoke after birth. Furthermore, many studies use cross-sectional designs where recall bias may play an important role. The specific roles of pre- and postnatal exposure are not yet clarified.

In this study, we analyzed data from the German Infant Nutritional Intervention (GINI), a large prospective birth cohort that also contains comprehensive follow-up. GINI's prospective design and the comprehensive questions on tobacco smoke exposure at various time points provide the opportunity to disentangle the impacts of prenatal and postnatal tobacco exposure on behavioral problems. In a subset of this study, Gehring et al. (2006) tested the validity of the questionnaire-derived data on environmental tobacco smoke by measuring air nicotine and urine cotinine; the misclassification rate was below 7%, which is in line with that of other similar studies. We measured behavioral problems using the Strength and Difficulties Questionnaire (SDQ) (Goodman 1997), which allows assessment of a broad range of behavioral problems.

http://www.medscape.com/viewarticle/716414?src=mp&spon=9&uac=71630FV

Mom's Diet During Pregnancy May Alter Infant's Allergies

2010-02-23T05:37:00.000-08:00

From Reuters Health Information

NEW YORK (Reuters Health) Feb 19 - Eating lots of vegetables and fruits during pregnancy may lower the chance of having a baby with certain allergies, hint study findings from Japan.

Greater intake of green and yellow vegetables, citrus fruit, and veggies and fruits high in beta carotene may lessen the risk of having a baby with eczema, Dr. Yoshihiro Miyake at Fukuoka University and colleagues found.

Foods high in vitamin E similarly may lessen the risk of having a wheezy infant, they reported online January 22nd in Allergy.

Beta carotene and vitamin E are two of many antioxidants thought to benefit health. But prior investigations of maternal antioxidant intake and childhood allergies offered conflicting findings. This area of research "is still developing," Dr. Miyake noted in an email to Reuters Health.

In the current study, Dr. Miyake's team evaluated vegetable and fruit intake during pregnancy in 763 women, as well as eczema or allergic wheeze in their infants.

The women were 30 years old on average and about 17 weeks pregnant at enrollment.. When their babies were between 16 and 24 months old, the women provided birth and breastfeeding history, number of older siblings, and exposure to smoke.

The team found that 21% of the youngsters wheezed or had a "whistling in the chest in the last 12 months," and fewer than 19% had eczema.

According to the investigators, mothers who ate greater amounts of green and yellow vegetables, citrus fruits, or beta carotene while pregnant were less apt to have an infant with eczema.

For example, after allowing for other eczema risk factors, eczema was more common among infants whose mothers ate the least versus the most green and yellow vegetables - 54 and 32 infants, respectively.

Likewise, higher intake of vitamin E during pregnancy was associated a reduced likelihood of having a wheezy infant -- a finding that supports previous investigations from the U.S. and U.K.

Boosting intake of green and yellow vegetables, citrus fruits, and antioxidants such as beta-carotene and vitamin E among pregnant women "deserves further investigation as measures that would possibly be effective in the prevention of allergic disorders in the offspring," the researchers conclude.

Allergy 2010.

Study Does Not Support HPV Vaccine in Older Women

2010-02-19T00:10:00.000-08:00

From Medscape Medical News
Janis C. Kelly

February 17, 2010 — Findings from a natural-history study of human papillomavirus (HPV) have led the investigators to conclude that the "potential benefit" of HPV vaccination in older women (≥42 years) is "low."

The research team, led by Ana Cecilia Rodríguez, MD, from the Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, in San José, Costa Rica, found that the rate of new HPV infections declines with age and that new infections usually do not progress to grade 2 or 3 cervical intraepithelial neoplasia (CIN) in older women.

The investigators found that infections at baseline were more likely to persist in older than in younger women (P < .01 for a comparison of 8 groups). Furthermore, most of the grade 2 or worse CIN disease that was detected during follow-up (66 of 85 cases) was associated with infections already present at baseline.

The 7-year study of Costa Rican women — the largest ever to examine age, HPV persistence, and cervical cancer precursors — was published online February 15 in the Journal of the National Cancer Institute.

This is a great paper.
"This is a great paper, the longest follow-up study to date available on women in a broad age range," said Silvia Franceschi, MD, who was approached by Medscape Oncology for independent comment.

Dr. Franceschi, who is coordinator of the epidemiology and biology cluster at the International Agency for Research on Cancer in Lyon, France, noted that there seems to be very little to gain by vaccinating women older than 25 years or so.

"The 'dangerous' or persistent infections may be already there and will not be eliminated by the current HPV vaccines," she added. "The pharmaceutical industry's claim that vaccine should be given to older women because HPV infections are more dangerous after a certain age has been proven not to be true."

More Than 9000 Women, 7-Year Follow-Up in HPV Study

The researchers screened more than 9000 women, 18 to 97 years, in Costa Rica. Those with CIN 2 disease or worse at enrollment were treated and not followed any further. Among the remaining participants, those at low risk for CIN 2 or worse were rescreened at 5 to 7 years (passively followed), whereas higher-risk participants and subsets of low-risk women and initially sexually nonactive women were rescreened annually or semiannually (actively followed) for up to 7 years.

As noted above, most women diagnosed with CIN 2 or worse during the study period were already infected with a carcinogenic HPV strain (prevalent infection) at the time of initial testing.

Regardless of the woman's age, most newly detected HPV resolved and did not lead to CIN 2 or worse during the study period. Total cumulative CIN 2+ associated with newly appearing infections ranged from 2.1% to 6.2% over the first 3 years of follow-up.

Age-related changes in immunity have also been a concern, and the data showed that women older than 34 years were not at greater risk than younger women for progression to CIN3+ after 3 years. Newly detected infections led to a CIN3+ diagnosis in 0 of 17 women 34 years or older and in 5 of 41 (12.2%) women younger than 34 years.

Furthermore, rates of newly detected HPV infections declined sharply with age, from 35.9% in women 18 to 25 years to 13.5% in women 42 years and older in the actively followed group.

Among infections present at first examination, persistent infections were more common among women 42 years or older than among younger women.

The researchers conclude that cervical cancer risk is determined by the previous overt duration of carcinogenic HPV infections, not by genital warts caused by HPV 6 or HPV 11, and not by age. New infections, which are the only type that can be prevented by currently available HPV vaccination, carry little near-term cancer risk at any age, and most of them resolve within 2 to 3 years, say the investigators.

Vaccinating girls before they become sexually active reduces the chance that a new carcinogenic HPV infection will persist for the 25 to 30 years required to cause invasive cervical cancer, write the researchers. However, they remind clinicians that most HPV infections are benign. "[A] focus on HPV persistence, and avoidance of overreaction to HPV infections that are likely to resolve spontaneously, is essential for a rational introduction of HPV testing into cervical cancer screening programs."

By Age 30, Most Women Already Have HPV

"The HPV vaccines that are available now are prophylactic," Dr. Rodríguez told Medscape Oncology. "They can only prevent getting infected; they do not treat infections that are already present. In a given population with an average age at first sexual intercourse of around 15 to 17 years, to vaccinate women after the age of 30 is not cost-efficient."

"By age 30, most women would have been infected with the HPV types covered by the vaccines, and women are not getting that many new infections; therefore, the residual benefit provided by the vaccine is very small," she added.

We were surprised by the distinct persistence pattern observed for the group of prevalent infections among women 42+ years of age.
"We were surprised by the distinct persistence pattern observed for the group of prevalent infections among women 42+ years of age. For all other prevalent infections and for all incident infections, regardless of the woman's age, the chance of persistence was very similar," Dr. Rodríguez said. Persistence for 6 or more years of carcinogenic HPV infections detected by polymerase chain reaction (PCR) at baseline was 5.1% in women 18 to 25 years of age, 14.4% in women 26 to 33 years of age, 12.2% in women 34 to 41 years of age, and 18.2% in women 42 years or older. This was the key element that supported the authors' conclusion that previous infection duration, not a woman's age, determines subsequent risk.

This raises the question of whether there might be possible residual benefit of vaccination at older ages to prevent reacquisition of HPV types that were apparently cleared when the woman was younger. "Thus far, there is some evidence that reappearance of previously cleared infections is a very rare event and that those that reappear do not carry high risk for CIN 2+, but this requires confirmation," Dr. Rodríguez said.

HPV Screening Interval Should Probably Be 2.5 Years or Longer

This study offers some guidance on HPV screening. Dr. Rodríguez told Medscape Oncology that HPV screening data must be interpreted according to the frequency of screening, rather than the woman's age.

A single HPV-positive finding in a screening program must be not cause for alarm at any age.
"A single HPV-positive finding in a screening program must be not cause for alarm at any age," Dr. Franceschi said. "An HPV-positive test should just be repeated after approximately 12 months, and only persistent infections should be investigated in depth. If histologically proven, they are treated. PCR assays should not be used in screening programs, because they detect too many harmless infections."

The ideal HPV screening interval has yet to be determined, but Dr. Rodríguez said that previous analyses from the study suggested that HPV screens should at least 2.5 years apart, and could be longer.

The most important study limitation, note the authors, is that the conclusion that newly detected HPV infections typically do not progress to CIN 2 or worse at any age might not hold beyond the 7 years of follow-up. Dr. Rodríguez said that the researchers plan to revisit the cohort approximately 20 years after the initial screening visit.

Dr. Rodríguez and Dr. Franceschi have disclosed no relevant financial relationships.

J Natl Cancer Inst. 2010;102:305-324.