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.
Sunday, September 12, 2010
Psychological Violence During Pregnancy Linked to Postnatal Depression
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.
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
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.
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.
Tuesday, September 7, 2010
Surgery or Chemo First in Advanced Ovarian Cancer? New Data Fuel Debate
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.
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.
Monday, September 6, 2010
Acyclovir, Valacyclovir in First Trimester Not Linked to Major Birth Defects
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.
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
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.
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.
Wednesday, September 1, 2010
One Third of First-Time Pregnancies Delivered by Cesarean
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.
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.
Tuesday, August 31, 2010
Antimicrobial Prophylaxis Recommended for All Cesarean Deliveries
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.
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
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
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
Saturday, August 28, 2010
Early Age at Menopause Linked to Angina Post MI
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
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
Saturday, August 14, 2010
The Diagnosis of Gestational Diabetes
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 OGTT Only 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 abnormal glucose 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
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 OGTT Only 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 abnormal glucose 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
Wednesday, August 11, 2010
Prenatal Cigarette Exposure Increases Risk for Psychiatric Illness Into Adulthood
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.
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.
Monday, August 9, 2010
Risks for Preterm Births May Be Higher Among Overweight and Obese Mothers
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.
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
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.
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
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.
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.
Thursday, July 22, 2010
No Pap Smears for Women Under 21: Guidelines
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.
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
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.
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
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.
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.
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