Reuters Health Information
By Frederik Joelving
NEW YORK (Reuters Health) May 18 - Maternal measles antibodies wane earlier than previously thought, leaving infants susceptible to the virus for several months under current immunization guidelines, Belgian researchers report in a May 18th online paper in BMJ.
While not recommending an overhaul of general vaccination age -- currently 12 months in both Belgium and the US -- they said infants with special exposure to measles may need to be immunized at six months.
"We could recommend to vaccinate earlier, but because of good coverage here in Belgium we do not want to lose people" by adding an extra trip to the doctor, said lead author Dr. Elke Leuridan of the University of Antwerp in Wilrijk, Belgium.
Dr. Leuridan and colleagues studied 207 healthy mother-child infant pairs. Eighty-seven of the mothers had been vaccinated against measles and 120 had natural immunity.
The researchers collected venous blood during pregnancy (week 36, 10 ml), at birth (cord blood, 10 ml) and in infants at 1, 3 and 12 months (2 ml). In addition, they took samples randomly at either 6 or 9 months.
They used an enzyme-linked immunosorbent assay to measure the amount of measles immunoglobulin G (IgG) in the blood, calibrating the assay against the international reference preparation of measles antigen. The samples were considered positive if the corrected optical density was greater than 0.2, and negative if it was less than 0.1.
Overall, vaccinated women had lower IgG titers than naturally immune women (779 vs. 2687 milli-International Units per milliliter, or mIU/mL; p<0.001). The same pattern was seen for the infants at all ages (p<0.001).
Maternal antibodies persisted for a median of 3.8 months in infants of naturally immune mothers and for 1 month in babies of vaccinated women. In a linear mixed model, 99% of babies of vaccinated mothers had lost their maternal antibodies after six months, compared to 95% of babies of naturally immune women. Breast feeding, parity, gestational age, birth weight, educational level, day care attendance and cesarean section were not significant in the model.
The findings are consistent with earlier studies showing that measles susceptibility is growing every year, Dr. Leuridan said. Yet, she added, "it is quite new that it is such a large gap."
Part of the reason for the expanding gap, she said, could be the increasing age of mothers and the general success of immunization in lowering overall exposure to the virus.
Dr. Archana Chatterjee, of Creighton University School of Medicine in Omaha, Nebraska, said current immunization practice is based on the theoretical assumption that maternal antibodies might interfere with the necessary replication of the vaccine virus.
She called the new study "food for thought," noting that larger studies are needed before considering guideline changes. For instance, small amounts of maternal antibodies that went undetected in the study in principle might interfere with the vaccine, she said.
Still, Dr. Chatterjee said, "it certainly is something that gives us pause."
http://www.bmj.com/cgi/content/abstract/340/may18_2/c1626
BMJ 2010.
Monday, February 28, 2011
Tuesday, February 15, 2011
Periconceptional Fever/Influenza Linked to Specific Congenital Birth Defects
From Reuters Health Information CME
News Author: Megan Brooks
CME Author: Désirée Lie, MD, MSEd
NEW YORK (Reuters Health) February 4, 2011 — New research confirms that women who develop influenza or a fever of 101°F or higher during the periconceptional period are at increased risk of delivering a baby with certain congenital heart defects, most notably right-sided obstructive lesions in all infants and atrioventricular septal defects (AVSD) in infants with Down syndrome.
However, maternal use of antipyretic agents in the setting of fever or influenza may attenuate these associations, the researchers reported in the January 24 online issue of The Journal of Pediatrics.
Dr. Adolfo Correa, Medical Officer in the National Center on Birth Defects and Developmental Disabilities, part of the Centers for Disease Control and Prevention, in Atlanta, Georgia, led the study.
"Although our findings are consistent with a few previous studies, the literature on the associations we found is still somewhat limited for drawing conclusive clinical implications," Dr. Correa noted in an e-mail to Reuters Health.
"Further efforts are needed to corroborate our findings and to elucidate the reasons for the observed associations. From a precautionary perspective, women planning to become pregnant should avoid exposure to influenza or other febrile illnesses and seek preconception care," the researcher added.
Maternal febrile illness and hyperthermia have been linked to a variety of birth defects, especially those involving the central nervous system, Dr. Correa and colleagues note in their report. Associations between maternal fever and hyperthermia with congenital heart defects are "less clear-cut," they say.
Moreover, while associations between congenital heart defects and some viral illnesses, particularly rubella, have been well documented, studies on the role of influenza in risk of congenital heart defects have yielded mixed results.
Dr. Correa and colleagues investigated associations between maternal fever and influenza and congenital heart defects using data from the Baltimore-Washington Infant Study, an epidemiologic study of congenital heart defects conducted between 1981 and 1989 in Maryland, Washington DC, and northern Virginia.
Cases were 2,361 infants with congenital heart defects and controls were 3,435 infants without congenital heart defects.
Participating mothers were asked whether they had a fever of 101°F or higher, had influenza, or used an antipyretic agent (acetaminophen, salicylate, or nonsteroidal anti-inflammatory agent) during the period extending from 3 months prior to pregnancy through the end of the third month of pregnancy.
For congenital heart defects overall, no significant associations were found with fever, influenza, or fever/influenza.
However, for specific defects, significant associations were found for right-sided obstructive defects and maternal fever (OR 2.04), influenza (OR 1.75) and fever/influenza (OR 1.69).
These findings were most notable for tricuspid atresia in the setting of fever (OR 7.54), influenza (OR 6.04), and fever/influenza (OR 5.46) and for pulmonary atresia with intact ventricular septum in the setting of influenza (OR 2.71) and fever/influenza (OR 2.80), the researchers reported.
And in infants with Down syndrome, the authors found significant associations between atrioventricular septal defects and periconceptional fever (OR 1.92), influenza (OR 1.66) and fever/influenza (OR 1.66). No significant associations were evident between other cardiac phenotypes and fever, influenza or both.
Maternal antipyretic use tended to decrease these associations, as mentioned.
Dr. Correa and colleagues say the link between fever and influenza and AVSD only in infants with Down syndrome may be "spurious" or it may represent an "important gene-environment interaction that warrants further investigation."
J Pediatr. Published online January 24, 2011. Abstract
Clinical Context
Congenital heart defects continue to be a leading cause of morbidity and mortality in children, and maternal exposures during pregnancy may contribute to the risk for such defects. Maternal fever has been linked to birth defects, especially those of the central nervous system, and studies have noted an almost 2-fold increase in the risk for aggregate congenital heart defects with maternal fever and influenza.
This is a case-control study of infants in a population-based cohort to examine the association between maternal fever or influenza during the 3 months before and after conception and the risk for congenital heart defects.
News Author: Megan Brooks
CME Author: Désirée Lie, MD, MSEd
NEW YORK (Reuters Health) February 4, 2011 — New research confirms that women who develop influenza or a fever of 101°F or higher during the periconceptional period are at increased risk of delivering a baby with certain congenital heart defects, most notably right-sided obstructive lesions in all infants and atrioventricular septal defects (AVSD) in infants with Down syndrome.
However, maternal use of antipyretic agents in the setting of fever or influenza may attenuate these associations, the researchers reported in the January 24 online issue of The Journal of Pediatrics.
Dr. Adolfo Correa, Medical Officer in the National Center on Birth Defects and Developmental Disabilities, part of the Centers for Disease Control and Prevention, in Atlanta, Georgia, led the study.
"Although our findings are consistent with a few previous studies, the literature on the associations we found is still somewhat limited for drawing conclusive clinical implications," Dr. Correa noted in an e-mail to Reuters Health.
"Further efforts are needed to corroborate our findings and to elucidate the reasons for the observed associations. From a precautionary perspective, women planning to become pregnant should avoid exposure to influenza or other febrile illnesses and seek preconception care," the researcher added.
Maternal febrile illness and hyperthermia have been linked to a variety of birth defects, especially those involving the central nervous system, Dr. Correa and colleagues note in their report. Associations between maternal fever and hyperthermia with congenital heart defects are "less clear-cut," they say.
Moreover, while associations between congenital heart defects and some viral illnesses, particularly rubella, have been well documented, studies on the role of influenza in risk of congenital heart defects have yielded mixed results.
Dr. Correa and colleagues investigated associations between maternal fever and influenza and congenital heart defects using data from the Baltimore-Washington Infant Study, an epidemiologic study of congenital heart defects conducted between 1981 and 1989 in Maryland, Washington DC, and northern Virginia.
Cases were 2,361 infants with congenital heart defects and controls were 3,435 infants without congenital heart defects.
Participating mothers were asked whether they had a fever of 101°F or higher, had influenza, or used an antipyretic agent (acetaminophen, salicylate, or nonsteroidal anti-inflammatory agent) during the period extending from 3 months prior to pregnancy through the end of the third month of pregnancy.
For congenital heart defects overall, no significant associations were found with fever, influenza, or fever/influenza.
However, for specific defects, significant associations were found for right-sided obstructive defects and maternal fever (OR 2.04), influenza (OR 1.75) and fever/influenza (OR 1.69).
These findings were most notable for tricuspid atresia in the setting of fever (OR 7.54), influenza (OR 6.04), and fever/influenza (OR 5.46) and for pulmonary atresia with intact ventricular septum in the setting of influenza (OR 2.71) and fever/influenza (OR 2.80), the researchers reported.
And in infants with Down syndrome, the authors found significant associations between atrioventricular septal defects and periconceptional fever (OR 1.92), influenza (OR 1.66) and fever/influenza (OR 1.66). No significant associations were evident between other cardiac phenotypes and fever, influenza or both.
Maternal antipyretic use tended to decrease these associations, as mentioned.
Dr. Correa and colleagues say the link between fever and influenza and AVSD only in infants with Down syndrome may be "spurious" or it may represent an "important gene-environment interaction that warrants further investigation."
J Pediatr. Published online January 24, 2011. Abstract
Clinical Context
Congenital heart defects continue to be a leading cause of morbidity and mortality in children, and maternal exposures during pregnancy may contribute to the risk for such defects. Maternal fever has been linked to birth defects, especially those of the central nervous system, and studies have noted an almost 2-fold increase in the risk for aggregate congenital heart defects with maternal fever and influenza.
This is a case-control study of infants in a population-based cohort to examine the association between maternal fever or influenza during the 3 months before and after conception and the risk for congenital heart defects.
FDA Approves First 3-Dimensional Mammography System
From Medscape Medical News > Alerts, Approvals and Safety Changes > FDA Approvals
Steven Fox
February 14, 2011 — The US Food and Drug Administration (FDA) has approved the first mammography system employing 3-dimensional (3-D) imaging, and preclinical studies show that the new technology is 7% more accurate than traditional 2-D mammography in spotting breast tumors.
The new technology is to be marketed as the Selenia Dimensions System and is being manufactured by Hologic, Inc. The system is an upgrade to Hologic's currently available 2-D system.
The system has already been approved in Latin America, Europe, and in Asia.
In approving the device for use in the United States, the FDA assessed results from 2 studies in which radiologists reviewed 2-D and 3-D images from more than 300 mammography studies.
In both studies, radiologists viewing both 2-D and 3-D images were 7% more likely to accurately distinguish between cancerous and noncancerous lesions compared with viewing 2-D images alone.
"Physicians can now access this unique and innovative 3-D technology that could significantly enhance existing diagnosis and treatment approaches," said Jeffrey Shuren, MD, JD, who directs the FDA's Center for Devices and Radiological Health in a press release.
Previous studies have shown that 2-D imaging techniques do not always provide clear images of breast masses, as overlapping skin and other anatomical features can obscure tumors and sometimes create the appearance of a tumor when there is none.
A caveat is that the combination of 2-D and 3-D images approximately doubled the radiation dose to which women were exposed, but the new technology increases efficacy, which presumably will help cut down on the need for follow-up exams. At this time, about 10% of women who undergo 2-D mammography are called back for follow-up X-rays, only to find out later that masses spotted with the 2-D systems are noncancerous.
Mammography Quality Standards require that healthcare professionals undergo 8 hours of instruction before using the new 3-D technology. The FDA also stipulates that the manufacturer provide each user with a manual that defines tests required to maintain quality control.
Steven Fox
February 14, 2011 — The US Food and Drug Administration (FDA) has approved the first mammography system employing 3-dimensional (3-D) imaging, and preclinical studies show that the new technology is 7% more accurate than traditional 2-D mammography in spotting breast tumors.
The new technology is to be marketed as the Selenia Dimensions System and is being manufactured by Hologic, Inc. The system is an upgrade to Hologic's currently available 2-D system.
The system has already been approved in Latin America, Europe, and in Asia.
In approving the device for use in the United States, the FDA assessed results from 2 studies in which radiologists reviewed 2-D and 3-D images from more than 300 mammography studies.
In both studies, radiologists viewing both 2-D and 3-D images were 7% more likely to accurately distinguish between cancerous and noncancerous lesions compared with viewing 2-D images alone.
"Physicians can now access this unique and innovative 3-D technology that could significantly enhance existing diagnosis and treatment approaches," said Jeffrey Shuren, MD, JD, who directs the FDA's Center for Devices and Radiological Health in a press release.
Previous studies have shown that 2-D imaging techniques do not always provide clear images of breast masses, as overlapping skin and other anatomical features can obscure tumors and sometimes create the appearance of a tumor when there is none.
A caveat is that the combination of 2-D and 3-D images approximately doubled the radiation dose to which women were exposed, but the new technology increases efficacy, which presumably will help cut down on the need for follow-up exams. At this time, about 10% of women who undergo 2-D mammography are called back for follow-up X-rays, only to find out later that masses spotted with the 2-D systems are noncancerous.
Mammography Quality Standards require that healthcare professionals undergo 8 hours of instruction before using the new 3-D technology. The FDA also stipulates that the manufacturer provide each user with a manual that defines tests required to maintain quality control.
Tuesday, February 8, 2011
Early Introduction of Solid Foods Linked to Risk for Early Childhood Obesity
From Medscape Medical News
Laurie Barclay, MD
February 7, 2011 — Early introduction of solid foods is linked to a risk for early childhood obesity, according to the results of a prospective prebirth cohort study reported online February 7 in Pediatrics.
"Parental feeding practices during early infancy, such as the timing of solid food introduction, may be 1 key modifiable determinant of childhood obesity," write Susanna Y. Huh, MD, MPH, from the Division of Gastroenterology and Nutrition, Children's Hospital Boston in Boston, Massachusetts, and colleagues.
"Data suggest that the introduction of solid foods earlier than 4 months of age is associated with increased body fat or weight in childhood or with greater weight gain during infancy, which itself predicts later adiposity. Other studies have found no association between the timing of solid food introduction and body fat or an association between delayed introduction of solid foods after 6 months and greater adiposity."
The goal of the study was to evaluate the association between timing of introduction of solid foods during infancy and obesity at age 3 years, defined as a body mass index for age and sex at the 95th percentile or above, using a cohort of 847 children enrolled in Project Viva. Timing of introduction of solid foods was categorized as younger than 4 months, ages 4 to 5 months, and 6 months or older. Logistic regression models were applied separately for infants who were breast-fed for at least 4 months ("breast-fed"; n = 568; 67%) and for infants who were never breast-fed or in whom breast-feeding was stopped before age 4 months ("formula-fed"; n = 279; 32%). These models were adjusted for child and maternal factors, including change in weight-for-age z score from 0 to 4 months as a marker of early infant growth.
Obesity was present in 75 children (9%) at age 3 years.
The timing of solid food introduction was not associated with odds of obesity in breast-fed infants, (odds ratio, 1.1; 95% confidence interval [CI], 0.3 - 4.4). However, introducing formula-fed infants to solid foods before age 4 months was associated with a 6-fold increase in odds of obesity at age 3 years, which was not explained by rapid early growth (odds ratio after adjustment, 6.3; 95% CI, 2.3 - 6.9).
"Among infants who were never breastfed or those who stopped breastfeeding before the age of 4 months, the introduction of solids before the age of 4 months was associated with a sixfold increase in the odds of obesity at the age of 3 years," the study authors write.
Limitations of this study include possible residual confounding; some loss of the cohort to follow-up; limited generalizability to more socioeconomically disadvantaged populations; and small numbers in some cells, leading to possible chance results.
"Among infants breastfed for 4 months or longer, the timing of the introduction of solid foods was not associated with the odds of obesity," the study authors conclude. "Increased adherence to guidelines regarding the timing of solid food introduction may reduce the risk of obesity in childhood."
The National Institutes of Health supported this study. The study authors have disclosed no relevant financial relationships.
Pediatrics. Published online February 7, 2011. Abstract
Laurie Barclay, MD
February 7, 2011 — Early introduction of solid foods is linked to a risk for early childhood obesity, according to the results of a prospective prebirth cohort study reported online February 7 in Pediatrics.
"Parental feeding practices during early infancy, such as the timing of solid food introduction, may be 1 key modifiable determinant of childhood obesity," write Susanna Y. Huh, MD, MPH, from the Division of Gastroenterology and Nutrition, Children's Hospital Boston in Boston, Massachusetts, and colleagues.
"Data suggest that the introduction of solid foods earlier than 4 months of age is associated with increased body fat or weight in childhood or with greater weight gain during infancy, which itself predicts later adiposity. Other studies have found no association between the timing of solid food introduction and body fat or an association between delayed introduction of solid foods after 6 months and greater adiposity."
The goal of the study was to evaluate the association between timing of introduction of solid foods during infancy and obesity at age 3 years, defined as a body mass index for age and sex at the 95th percentile or above, using a cohort of 847 children enrolled in Project Viva. Timing of introduction of solid foods was categorized as younger than 4 months, ages 4 to 5 months, and 6 months or older. Logistic regression models were applied separately for infants who were breast-fed for at least 4 months ("breast-fed"; n = 568; 67%) and for infants who were never breast-fed or in whom breast-feeding was stopped before age 4 months ("formula-fed"; n = 279; 32%). These models were adjusted for child and maternal factors, including change in weight-for-age z score from 0 to 4 months as a marker of early infant growth.
Obesity was present in 75 children (9%) at age 3 years.
The timing of solid food introduction was not associated with odds of obesity in breast-fed infants, (odds ratio, 1.1; 95% confidence interval [CI], 0.3 - 4.4). However, introducing formula-fed infants to solid foods before age 4 months was associated with a 6-fold increase in odds of obesity at age 3 years, which was not explained by rapid early growth (odds ratio after adjustment, 6.3; 95% CI, 2.3 - 6.9).
"Among infants who were never breastfed or those who stopped breastfeeding before the age of 4 months, the introduction of solids before the age of 4 months was associated with a sixfold increase in the odds of obesity at the age of 3 years," the study authors write.
Limitations of this study include possible residual confounding; some loss of the cohort to follow-up; limited generalizability to more socioeconomically disadvantaged populations; and small numbers in some cells, leading to possible chance results.
"Among infants breastfed for 4 months or longer, the timing of the introduction of solid foods was not associated with the odds of obesity," the study authors conclude. "Increased adherence to guidelines regarding the timing of solid food introduction may reduce the risk of obesity in childhood."
The National Institutes of Health supported this study. The study authors have disclosed no relevant financial relationships.
Pediatrics. Published online February 7, 2011. Abstract
Wednesday, January 19, 2011
AAP Issues New Guidelines for Management of Iron Deficiency
From Medscape Medical News
Jim Kling
October 14, 2010 — Correction: The original text of this article described the daily iron dose for infants 6 to 12 months as 11 mg/kg. This is incorrect.
The dose should be 11 mg/day.
October 5, 2010 (San Francisco, California) — Iron deficiency is one of the most common, yet undetected, problems among children. Here at the American Academy of Pediatrics (AAP) 2010 National Conference and Exhibition, the American Association of Pediatrics released a clinical report, with guidelines for iron intake in infants and children and to improve screening methods.
The clinical report, entitled Diagnosis and Prevention of Iron Deficiency and Iron Deficiency Anemia in Infants and Young Children (0–3 Years of Age), was published online October 5 in Pediatrics. It is a revision of a 1999 policy statement.
Iron deficiency can have long-term irreversible effects on a child's cognitive and behavioral development. By the time a child develops iron-deficiency anemia, it might be too late to prevent future problems. "The body has a preferential tracking of iron. Red blood cells take precedence over the iron requirements of the brain. By the time you get iron-deficiency anemia, you've been iron-deficient for a long time," said Frank Greer, MD, professor of pediatrics at the University of Wisconsin School of Medicine and Public Health in Madison, and a coauthor of the report.
The 1999 guidelines call for children to have their hemoglobin checked sometime between 9 and 12 months of age, and again between 15 and 18 months of age. However, the existing test misses many children with iron deficiency and iron-deficiency anemia. Even those found to be iron deficient frequently receive no follow-up testing or treatment, according to Dr. Greer.
Although supplementing all children with iron would reduce iron deficiency, such a program does not have widespread support in the medical community at this point. That's partly because toddlers, who are the most widely affected group, have a wide range of diets and it is unclear what foods to fortify.
Liquid iron supplements or vitamins could be used, but there is a risk for iron overload in some populations, according to Michael K. Georgieff, MD, professor of pediatrics and child psychology and director of the Center for Neurobehavioral Development at the University of Minnesota in Minneapolis. Dr. Georgieff was on the AAP's committee on nutrition from 1993 to 1999 and played a key role in the 1999 guidelines.
"Iron supplementation and awareness of iron nutrition has probably been one of the most successful public health programs in the United States. In the 1960s, iron deficiency was probably 30% to 40%. Today, it may be under 10%. But in trying to eliminate that last 10%, you have to consider it in terms of exposing kids to [too much] iron," said Dr. Georgieff.
No single screening test is available that will accurately characterize the iron status of a child, he noted. In the report, the AAP recommends 4 protocols for screening for iron deficiency and iron-deficiency anemia, including combinations of several tests and follow-up protocols. "It's burdensome," Dr. Greer admitted.
"Since we're not going to do universal supplementation, we need to identify kids who are at risk for iron deficiency and start targeting them," said Dr. Georgieff, who studies the neurodevelopmental effects of iron deficiency in children.
The AAP report identified several factors associated with iron deficiency and iron-deficiency anemia, including prematurity or low birth-weight, lead exposure, exclusive breastfeeding past 4 months of age without iron supplements, and weaning to foods that don't include iron-fortified cereals or iron-rich foods. Infants with special healthcare needs might also be at risk. Children of low economic status, particularly those of Mexican American descent, are also of concern, according to the report, which recommends selective screening for these individuals.
The guidelines also address means to prevent iron deficiency through a diet of foods naturally rich in iron, such as meat, shellfish, legumes, iron-rich fruits and vegetables, and iron-fortified cereals. Fruits rich in vitamin C help iron absorption. Some children might require liquid iron supplements or chewable vitamins to get sufficient iron.
The AAP recommends varying amounts of iron based on a child's age:
* Term, healthy infants have sufficient iron for the first 4 months of life. Because human breast milk contains very little iron, breastfed infants should be supplemented with 1 mg/kg per day of oral iron from 4 months of age until iron-rich foods (such as iron-fortified cereals) are introduced.
* Formula-fed infants will receive adequate iron from formula and complementary foods. Whole milk should not be used before 12 months.
* Infants 6 to 12 months of age need 11 mg/day of iron a day. When infants are given complementary foods, red meat and vegetables with high iron content should be introduced early. Liquid iron supplements can be used if iron needs are not met by formula and complementary foods.
* Toddlers 1 to 3 years of age need 7 mg per day of iron. It is best if this comes from foods such as red meats, iron-rich vegetables, and fruits with vitamin C, which enhance iron absorption. Liquid supplements and chewable multivitamins can also be used.
* All preterm infants should have at least 2 mg/kg of iron per day until 12 months of age, which is the amount of iron in iron-fortified formulas. Preterm infants fed human milk should receive an iron supplement of 2 mg/kg per day by 1 month of age; this should be continued until the infant is weaned to iron-fortified formula or begins eating foods that supply the required 2 mg/kg of iron.
American Academy of Pediatrics (AAP) 2010 National Conference and Exhibition. Presented October 5, 2010.
Jim Kling
October 14, 2010 — Correction: The original text of this article described the daily iron dose for infants 6 to 12 months as 11 mg/kg. This is incorrect.
The dose should be 11 mg/day.
October 5, 2010 (San Francisco, California) — Iron deficiency is one of the most common, yet undetected, problems among children. Here at the American Academy of Pediatrics (AAP) 2010 National Conference and Exhibition, the American Association of Pediatrics released a clinical report, with guidelines for iron intake in infants and children and to improve screening methods.
The clinical report, entitled Diagnosis and Prevention of Iron Deficiency and Iron Deficiency Anemia in Infants and Young Children (0–3 Years of Age), was published online October 5 in Pediatrics. It is a revision of a 1999 policy statement.
Iron deficiency can have long-term irreversible effects on a child's cognitive and behavioral development. By the time a child develops iron-deficiency anemia, it might be too late to prevent future problems. "The body has a preferential tracking of iron. Red blood cells take precedence over the iron requirements of the brain. By the time you get iron-deficiency anemia, you've been iron-deficient for a long time," said Frank Greer, MD, professor of pediatrics at the University of Wisconsin School of Medicine and Public Health in Madison, and a coauthor of the report.
The 1999 guidelines call for children to have their hemoglobin checked sometime between 9 and 12 months of age, and again between 15 and 18 months of age. However, the existing test misses many children with iron deficiency and iron-deficiency anemia. Even those found to be iron deficient frequently receive no follow-up testing or treatment, according to Dr. Greer.
Although supplementing all children with iron would reduce iron deficiency, such a program does not have widespread support in the medical community at this point. That's partly because toddlers, who are the most widely affected group, have a wide range of diets and it is unclear what foods to fortify.
Liquid iron supplements or vitamins could be used, but there is a risk for iron overload in some populations, according to Michael K. Georgieff, MD, professor of pediatrics and child psychology and director of the Center for Neurobehavioral Development at the University of Minnesota in Minneapolis. Dr. Georgieff was on the AAP's committee on nutrition from 1993 to 1999 and played a key role in the 1999 guidelines.
"Iron supplementation and awareness of iron nutrition has probably been one of the most successful public health programs in the United States. In the 1960s, iron deficiency was probably 30% to 40%. Today, it may be under 10%. But in trying to eliminate that last 10%, you have to consider it in terms of exposing kids to [too much] iron," said Dr. Georgieff.
No single screening test is available that will accurately characterize the iron status of a child, he noted. In the report, the AAP recommends 4 protocols for screening for iron deficiency and iron-deficiency anemia, including combinations of several tests and follow-up protocols. "It's burdensome," Dr. Greer admitted.
"Since we're not going to do universal supplementation, we need to identify kids who are at risk for iron deficiency and start targeting them," said Dr. Georgieff, who studies the neurodevelopmental effects of iron deficiency in children.
The AAP report identified several factors associated with iron deficiency and iron-deficiency anemia, including prematurity or low birth-weight, lead exposure, exclusive breastfeeding past 4 months of age without iron supplements, and weaning to foods that don't include iron-fortified cereals or iron-rich foods. Infants with special healthcare needs might also be at risk. Children of low economic status, particularly those of Mexican American descent, are also of concern, according to the report, which recommends selective screening for these individuals.
The guidelines also address means to prevent iron deficiency through a diet of foods naturally rich in iron, such as meat, shellfish, legumes, iron-rich fruits and vegetables, and iron-fortified cereals. Fruits rich in vitamin C help iron absorption. Some children might require liquid iron supplements or chewable vitamins to get sufficient iron.
The AAP recommends varying amounts of iron based on a child's age:
* Term, healthy infants have sufficient iron for the first 4 months of life. Because human breast milk contains very little iron, breastfed infants should be supplemented with 1 mg/kg per day of oral iron from 4 months of age until iron-rich foods (such as iron-fortified cereals) are introduced.
* Formula-fed infants will receive adequate iron from formula and complementary foods. Whole milk should not be used before 12 months.
* Infants 6 to 12 months of age need 11 mg/day of iron a day. When infants are given complementary foods, red meat and vegetables with high iron content should be introduced early. Liquid iron supplements can be used if iron needs are not met by formula and complementary foods.
* Toddlers 1 to 3 years of age need 7 mg per day of iron. It is best if this comes from foods such as red meats, iron-rich vegetables, and fruits with vitamin C, which enhance iron absorption. Liquid supplements and chewable multivitamins can also be used.
* All preterm infants should have at least 2 mg/kg of iron per day until 12 months of age, which is the amount of iron in iron-fortified formulas. Preterm infants fed human milk should receive an iron supplement of 2 mg/kg per day by 1 month of age; this should be continued until the infant is weaned to iron-fortified formula or begins eating foods that supply the required 2 mg/kg of iron.
American Academy of Pediatrics (AAP) 2010 National Conference and Exhibition. Presented October 5, 2010.
Recommendation of 6 Months of Breast-Feeding Scrutinized
From Medscape Medical News
Emma Hitt, PhD
January 18, 2011 — The evidence in favor of 6 months of exclusive breast-feeding has come under scrutiny in a new study published by the BMJ.
A review article assessing the evidence was published by researcher Mary Fewtrell, MD, from the Child Nutrition Research Center at the University College London Institute of Child Health, United Kingdom, and colleagues was published online January 13 in the BMJ.
Current World Health Organization guidelines recommend that infants be exclusively breast-fed for 6 months; that is, with a diet that excludes solids or any fluids other than breast milk, including infant formulas. These guidelines, announced in 2001, were adopted by the United Kingdom in 2003.
Exclusive breast-feeding may not adequately meet infants' energy needs for a full 6 months.
"The critical question is whether the United Kingdom should alter its advice on the introduction of complementary foods while new evidence is assembled," the authors note.
The current report maintains that this change in policy occurred without formal consideration of the scientific evidence. Since the announcement of the World Health Organization guidelines, findings from a number of studies suggest that breast milk may not be a reliable single source of nutrition for the first 6 months of life. In addition, the European Food Safety Authority recently concluded that it was safe to introduce complementary foods between 4 and 6 months' of age for infants residing in the European Union.
In the current study, Dr. Fewtrell and colleagues reassessed the evidence in favor of 6 months of exclusive breast-feeding and concluded that exclusive breast-feeding may not adequately meet infants' energy needs for a full 6 months. Higher rates of iron deficiency anemia are an additional concern, having been linked to poorer long-term mental, motor, and social development. Furthermore, existing data suggest an increased risk for reaction to certain allergens (eg, gluten, which has been linked to celiac disease) when their introduction is delayed past 6 months.
Even in the case of protection from infection — considered to be a clear benefit of breast-feeding — a study conducted in Spain showed that these benefits largely accrue to infants breast-fed for 3 months, providing little "extra" benefit thereafter. However, a large study based in the United States did find that infants breast-fed exclusively for more than 6 months had a lower risk for otitis media and pneumonia when compared with infants who were breast-fed exclusively for 4 to 6 months.
Dr. Fewtrell and colleagues conclude that, in light of data that have accumulated during the last 10 years (ie, since the World Health Organization guidelines came out in 2001), the time is ripe for an evidence-based reappraisal of the United Kingdom's stance in this important, yet controversial, area.
According to independent commentator Richard Aubry, MD, MPH, a professor of obstetrics and gynecology at Upstate Medical University in New York, this work does not add any new evidence about the pros and cons regarding adding other foods earlier than 6 months' age.
He told Medscape Medical News that clinicians "need to keep the message clear: Exclusive breast-feeding is the preferred method for feeding the baby until approximately 6 months of age, and then mothers should be encouraged to continue breast-feeding as long as they can. These are the specific terms and overall advice by [the American Congress of Obstetricians and Gynecologists]."
This study was not commercially funded. Three of the 4 authors of the study report having performed consultancy work and/or received research funding in the past 3 years from companies that manufacture infant formulas and baby foods.
BMJ. Published online January 13, 2011.
Emma Hitt, PhD
January 18, 2011 — The evidence in favor of 6 months of exclusive breast-feeding has come under scrutiny in a new study published by the BMJ.
A review article assessing the evidence was published by researcher Mary Fewtrell, MD, from the Child Nutrition Research Center at the University College London Institute of Child Health, United Kingdom, and colleagues was published online January 13 in the BMJ.
Current World Health Organization guidelines recommend that infants be exclusively breast-fed for 6 months; that is, with a diet that excludes solids or any fluids other than breast milk, including infant formulas. These guidelines, announced in 2001, were adopted by the United Kingdom in 2003.
Exclusive breast-feeding may not adequately meet infants' energy needs for a full 6 months.
"The critical question is whether the United Kingdom should alter its advice on the introduction of complementary foods while new evidence is assembled," the authors note.
The current report maintains that this change in policy occurred without formal consideration of the scientific evidence. Since the announcement of the World Health Organization guidelines, findings from a number of studies suggest that breast milk may not be a reliable single source of nutrition for the first 6 months of life. In addition, the European Food Safety Authority recently concluded that it was safe to introduce complementary foods between 4 and 6 months' of age for infants residing in the European Union.
In the current study, Dr. Fewtrell and colleagues reassessed the evidence in favor of 6 months of exclusive breast-feeding and concluded that exclusive breast-feeding may not adequately meet infants' energy needs for a full 6 months. Higher rates of iron deficiency anemia are an additional concern, having been linked to poorer long-term mental, motor, and social development. Furthermore, existing data suggest an increased risk for reaction to certain allergens (eg, gluten, which has been linked to celiac disease) when their introduction is delayed past 6 months.
Even in the case of protection from infection — considered to be a clear benefit of breast-feeding — a study conducted in Spain showed that these benefits largely accrue to infants breast-fed for 3 months, providing little "extra" benefit thereafter. However, a large study based in the United States did find that infants breast-fed exclusively for more than 6 months had a lower risk for otitis media and pneumonia when compared with infants who were breast-fed exclusively for 4 to 6 months.
Dr. Fewtrell and colleagues conclude that, in light of data that have accumulated during the last 10 years (ie, since the World Health Organization guidelines came out in 2001), the time is ripe for an evidence-based reappraisal of the United Kingdom's stance in this important, yet controversial, area.
According to independent commentator Richard Aubry, MD, MPH, a professor of obstetrics and gynecology at Upstate Medical University in New York, this work does not add any new evidence about the pros and cons regarding adding other foods earlier than 6 months' age.
He told Medscape Medical News that clinicians "need to keep the message clear: Exclusive breast-feeding is the preferred method for feeding the baby until approximately 6 months of age, and then mothers should be encouraged to continue breast-feeding as long as they can. These are the specific terms and overall advice by [the American Congress of Obstetricians and Gynecologists]."
This study was not commercially funded. Three of the 4 authors of the study report having performed consultancy work and/or received research funding in the past 3 years from companies that manufacture infant formulas and baby foods.
BMJ. Published online January 13, 2011.
Wednesday, January 12, 2011
Frozen Hope: Fertility Preservation for Women with Cancer
From Journal of Midwifery & Women's Health
Gwendolyn P. Quinn, PhD; Susan T. Vadaparampil, PhD, MPH; Paul B. Jacobsen, PhD; Caprice Knapp, PhD; David L. Keefe, MD; Geri E. Bell, BS
Posted: 03/12/2010; J Midwifery Womens Health. 2010;55(2):175-180. © 2010 Elsevier Science, Inc.
Abstract
Young women diagnosed with cancer have the option of preserving their fertility by using assisted reproductive technology (ART) techniques prior to undergoing cancer treatment. This article presents a composite case of a young woman with cancer who had many unanswered emotional and ethical questions about her future as a parent. Fertility preservation techniques, including preimplantation genetic diagnosis (PGD), and related patient education are described.
Current literature regarding reproductive counseling for cancer survivors is reviewed. Resources for providing psychosocial support for decisions about fertility preservation are lagging behind the rapid pace of scientific advancements in cancer treatment and ART.
As more young women are surviving cancer and taking steps to preserve fertility, there is great need for the provision of psychologic support services and the establishment of ethical guidelines to aid them on this path.
Women's health care providers can provide support to cancer survivors facing fertility and parenting issues by becoming knowledgeable about the long-term aspects of decision making and developing educational materials and guidelines for these patients.
Introduction
The number of young women diagnosed with cancer is increasing.[1] Recent data indicate the most common types of cancer occurring among women aged 15 to 29 are cancers of the female genital system, lymphoma, thyroid cancer, melanoma, and breast cancer.[1] Advances in cancer treatment have resulted in an increased number of long-term survivors. Young women who are diagnosed with cancer must make decisions about their reproductive future at a time when they are emotionally fragile. In addition to processing the cancer diagnosis and associated treatment choices, the decisions required concerning preserving future fertility and the time constraints associated with judgments can understandably be emotionally distressing. Women without cancer who are diagnosed with infertility have typically had at least a year in which to process their desire for a child and understand the barriers and benefits for each of the assisted reproductive technologies that may be available to their unique situation. The traditional reproductive counseling and the time frame for decision making offered to a woman or a couple experiencing infertility may not be available to a woman with a cancer diagnosis. This article presents a composite case of a young woman with cancer who faced infertility due to her cancer treatment but hoped to have a biologic child in the future. The case is examined in light of what is known and not yet known about the medical and psychosocial aspects of fertility preservation for women with cancer.
Cancer and Infertility
The best treatment for cancer may lead to impaired fertility or the complete loss of fertility. However, rates of infertility vary depending on a number of factors, including cancer site, type of treatment, and the age of the patient. Infertility in cancer patients can be caused by the cancer or the type of cancer treatment received. Exact infertility rates are not known, because there are no valid measures for women to establish that fertility was present prior to treatment. Women who undergo chemotherapy or radiation for malignancies during reproductive years have a 40% to 80% chance of losing fertility. The treatments that produce the greatest risk for infertility include alkylating agents such as cyclophosphamide, methotrexate, and fluorouracil in chemotherapy; total body radiation; and external beam radiation in a field that includes the ovaries. Both chemotherapy and radiation can cause premature ovarian failure for females, often leading to premature menopause.
Fertility Preservation
Rapidly improving assisted reproductive technologies and therapies offer some opportunities to preserve the fertility of female patients receiving chemotherapy and/or radiation. The emerging field of proteomics is leading the way toward the identification of proteins involved in oocyte maturation, embryo development, and implantation that could improve assisted reproduction techniques. Assisted reproductive technology (ART) consists of clinical treatments and laboratory procedures that include the handling of human oocytes, sperm, or embryos, with the intent of establishing a pregnancy. This includes, but is not limited to, in vitro fertilization (IVF), intracytoplasmic sperm injection, gamete intrafallopian transfer, zygote intrafallopian transfer, embryo biopsy, preimplantation genetic diagnosis (PGD), embryo cryopreservation, oocyte or embryo donation, and gestational surrogacy. Table 1 includes definitions of each type of procedure.
There are currently only two established options for fertility preservation for women with cancer: 1) oophoropexy, moving the ovaries out of the range of radiation, and 2) embryo cryopreservation, the freezing of fertilized eggs via IVF for later use. Additional techniques for fertility preservation, such as oocyte cryopreservation (freezing unfertilized eggs) and ovarian tissue cryopreservation (freezing strips of ovarian tissue, which may be transplanted either orthotopically within the pelvis or heterotopically within subcutaneous tissue), are less established and not widely available. All options must typically be considered and undertaken prior to the initiation of treatment.
There are also ethical, spiritual, and legal issues related to decision making about fertility preservation, such as the disposition of stored embryos. These issues often concern health care professionals as well and may pose barriers to the discussion of or assistance with the use of ART.Some patients and their families choose to consider posthumous parenting, that is, they intend to use the stored embryos whether or not the patient survives. Although this is an ethically charged situation, the American Society for Reproductive Medicine recommends that health care professionals do not deny patients assistance for this form of reproduction and also advises that "precise instructions" be given by the patient in the event of his or her death. The precise instructions for the disposition of DNA are part of the informed consent counseling, and patients are required to outline the procedures for future use of the stored embryos (e.g., willed to a spouse or parent, discarded, donated, etc.) If these procedures are followed, this can reduce the need for legal involvement to determine ownership of the stored embryos in the event of the patient's death or in the case of divorce. The United Kingdom also regulates the disposition of embryos through informed consent. Information about this practice is not readily available from other countries.
Preimplantation Genetic Diagnosis for Hereditary Cancers
The concerns of individuals affected with cancer regarding biologic parenthood are often focused on the health risks for future children. Carriers of genetic mutations, such as women with mutations in the BRCA1/2 genes, may have additional concerns about passing on hereditary cancers to future offspring. For those survivors who are concerned about the possibility of transmitting a serious hereditary cancer to their future children, limited biologic parenting options are available. Preimplantation genetic diagnosis is one option for parents who want to avoid this dilemma.
Preimplantation genetic diagnosis is a procedure used in conjunction with IVF to screen for specific genetic or chromosomal abnormalities before transferring the fertilized eggs into the woman. Preimplantation genetic diagnosis involves microsurgical removal of one or two blastomeres (embryos) at the six- to eight-cell stage, usually 3 days after fertilization. At this stage, the cells of the embryo have not differentiated into particular body tissues, and there is not likely to be damage to the resulting embryo. Biopsies of embryos are analyzed to detect genetic abnormalities arising from the maternal or paternal chromosomes. However, since diagnostic tests are performed on a single cell, the possibility of misdiagnosis must be considered. Preimplantation genetic diagnosis results are usually available within 48 hours after biopsy, which corresponds to day 5 after egg retrieval. Depending on their original quality, embryos may or may not reach the blastocyst stage, which is the final stage of in vitro development.[9] Usually on day 5, embryos free of genetic defects are transferred into the patient; however, some women or couples may choose to cryopreserve affected embryos. Currently data are not collected on the health of offspring born through the use of PGD, so it is unknown if there are related long-term health consequences.
Preimplantation genetic diagnosis has been accomplished for both cancer-specific disorders such as adenomatous polyposis coli, BRCA1/2, retinoblastoma, Li-Fraumeni syndrome, and von Hippel-Lindau syndrome, as well as disorders predisposing to neoplasia (Fanconi anemia, Wiskott-Aldrich syndrome).[11–13] The PGD procedure has been performed for a little over a decade and involves the use of IVF so parents can select the embryos that are implanted into the uterus. Embryos are tested for genetic status at the early stages of development. The ability to use PGD testing for all cancer types is not currently possible. The regulations developed for PGD testing and the types of cancers for which embryos can be tested vary by country and availability within each country. For example, the ability to use PGD for BRCA became available in 2006; however, other hereditary cancers, such as familial adenomatous polyposis, have been tested for in the Netherlands since 2004, although BRCA testing of embryos is not allowed there.[13] Thus, although the availability of PGD testing for certain cancer types varies by country and facility, the psychosocial issues women face over certain issues such as embryo selection are quite similar. One option for PGD is to implant only those embryos that are found to be unaffected. Some parents still may choose to implant affected embryos with the knowledge that the potential for hereditary syndromes is high. In the past, options for hereditary cancer mutation carriers included not having children or undergoing amniocentesis or other forms of prenatal diagnosis. Preimplantation genetic diagnosis allows parents to avoid terminating a pregnancy and/or risking the health of the fetus or the mother.
In Europe, guidelines regulate which clinics can perform PGD and for which diseases they can screen. In the United Kingdom, the Human Fertilisation and Embryology Authority (HFEA) governs which procedures are acceptable and provides guidelines as to how these procedures should be performed. It also licenses clinics that wish to use any type of ART. Currently, no such oversight exists in the United States.[14] At present, HFEA has approved PGD to test for 50 disorders, including hereditary breast and ovarian cancers, which can be caused by a mutation in the BRCA1/2 genes. Mutations in BRCA1/2 are passed down in families in an autosomal dominant pattern, and children of individuals with a BRCA1/2 mutation have a 50% chance of inheriting it. Women who carry the BRCA1/2 gene have an 80% lifetime risk of developing breast cancer and approximately a 40% risk of developing ovarian cancer. With such a high risk for developing cancer, the HFEA considers it appropriate to allow PGD for this cancer predisposition gene.
The use of PGD in the United States is predicted to be approximately 20% across all embryos created via IVF; however, it is not known specifically which abnormalities or conditions PGD testing has been used for.[11] Almost 2000 babies have been born after the process of PGD since it was developed in 1989.[15] There are no published reports of increased fetal defects or late effects in babies born using PGD, but it is possible abnormalities may occur later in life as a result of the procedure.[9,10,13] Preimplantation genetic diagnosis cannot detect all genetic irregularities because only a limited number of chromosomes can be tested per procedure, and misdiagnosis may still occur.Prenatal diagnosis (amniocentesis or chorionic villus sampling) may still need to be considered after use of PGD to determine if the fetus carries a genetic abnormality.
Cancer and Parenting
Although cancer presents obstacles to becoming a parent, an experience with a major illness can also make survivors excellent parents, with greater emotional resilience and appreciation for parenthood. However, the decision to become a biologic parent after cancer must be weighed with the obstacles of the time and expense of fertility preservation procedures such as IVF. Adoption remains an option, but cancer survivors may experience difficulty in becoming qualified as adoptive parents. Survivors seeking adoption may encounter discrimination from US adoption agencies because of the survivor's physical health and condition.Some US agencies require an applicant to be at least 5 years post-treatment before he or she can qualify as a potential adoptive parent. Some cancer survivors have had success qualifying for the adoption of foreign-born children through international adoption agencies. Additionally, infertility treatments and adoption procedures may be too costly for some survivors, especially after an expensive battle with cancer.
In addition to concerns about cancer recurrence and parenting, survivors often have psychosocial concerns related to pregnancy and parenting, many of which mirror issues faced by any woman considering the use of ART. These concerns focus primarily on risks of birth defects or cancer in offspring; anxiety about hormonal factors related to pregnancy or infertility treatment increasing a risk of cancer recurrence, leaving the spouse/partner to raise the child if the parent with cancer dies; and conflicts about using ART because of ethical beliefs or religious beliefs, as some religions prohibit the use of donor gametes
Reproductive Counseling for Cancer Survivors
Canada and Schover[22] identified the need for research to promote improved patient education regarding cancer and reproductive health. Although the researchers indicate oncologists would probably be the ideal health care professionals for cancer patients to have in-depth discussions with regarding fertility preservation and future parenting, they further note that time constraints may make this unrealistic. However, their objective is to promote better information about the risks of infertility to the newly diagnosed cancer patient, a communication initiative for which other researchers have made a similar plea. Although this is a crucial first step on the road to improved quality of life in cancer survivors and risk management for infertility, it does not fully address the decision-making issues the patient must consider in rapid time.
There is little research about the psychosocial decision making of newly diagnosed cancer survivors regarding fertility and PGD choices. Unlike infertility in couples without a cancer diagnosis, the impending infertility of a cancer patient and the need for treatment provides a narrow window of time for patient counseling. Although some patients, similar to the woman in this case study, perceive stored embryos and oocytes as "frozen hope," decisions about the future of the stored embryo can be agonizing. Recent studies have begun to examine patient choices for the donation or destruction of stored embryos.
One study conducted in an Australian population among 235 couples with banked embryos found 27% would donate to stem cell research or infertility research, whereas 15% would consider donating to another couple.
However, the disagreement rate among the couples was high, with more than 40% disagreeing over each of the options.Additionally, 90% of the couples indicated they would want to discuss donation with a health care professional rather than make the decision alone. The majority preferred a fertility specialist or scientist as their choice for the discussions. This study highlights the fact that deciding to pursue ART is only the beginning of the decision-making process that may span several years.
Other researchers have begun to examine how patients feel about stored embryos and oocytes in fertility clinics. An emerging trend indicates patients may enter reproductive counseling with one set of ideas about stored embryos and feel differently after a successful pregnancy or failed attempts.[26–28] However, no studies have examined this meaning among women who stored embryos or oocytes due to cancer treatment.
There are currently no guidelines specifically tailored for the reproductive counseling needs of newly diagnosed cancer patients, especially for those who may have concerns about hereditary cancer syndromes. Peshkin et al.suggest strong support for such guidelines and continued collaborations among providers who work in oncology, cancer genetics, and ART.Conclusion
Finishing cancer treatment and transitioning from patient to survivor does not end the psychologic trauma of cancer. There are a plethora of issues that survivors often face after their cancer is in remission that affect quality of life. This case report illustrates the loss of fertility often experienced by a cancer survivor as a result of treatment. Young women with genetic mutations, such as those in the BRCA1/2 genes, may have additional concerns about passing on hereditary cancers to future offspring. Considering PGD to avoid passing the mutation may allow parents to select only healthy embryos, but decisions about the fate of embryos that are mutation carriers remain perplexing.
Decisions about using fertility preservation typically must be made at the same time as other decisions about treatment of a life-threatening diagnosis. Ethical, religious, financial, and other implications of preserving her fertility confront the woman before she begins cancer treatment. This leaves limited time for the patient to consider the implications of her choices and how she may feel about her reproductive options at a later date.
Given that 2.5 million young adults in the United States have survived cancer, more research is needed on the psychosocial aspects of parenthood, particularly to identify the psychosocial needs of survivors regarding cryopreservation and PGD. The resources for providing support for using ART and PGD lag behind the rapid advance of technology. Table 2 provides a list of online sources of information for patients and health care professionals. Communication guidelines should be developed for informing cancer patients of the emotional and psychosocial impact of fertility preservation, with particular regard to future decision making. More research is needed to develop educational resources specific to this population that will aid the women newly diagnosed with cancer in decision making. Although social support is an important aspect of survivorship, the medical community can also provide support by assigning social workers or counselors to survivors and to the newly diagnosed who are facing fertility and parenting issues.
Gwendolyn P. Quinn, PhD; Susan T. Vadaparampil, PhD, MPH; Paul B. Jacobsen, PhD; Caprice Knapp, PhD; David L. Keefe, MD; Geri E. Bell, BS
Posted: 03/12/2010; J Midwifery Womens Health. 2010;55(2):175-180. © 2010 Elsevier Science, Inc.
Abstract
Young women diagnosed with cancer have the option of preserving their fertility by using assisted reproductive technology (ART) techniques prior to undergoing cancer treatment. This article presents a composite case of a young woman with cancer who had many unanswered emotional and ethical questions about her future as a parent. Fertility preservation techniques, including preimplantation genetic diagnosis (PGD), and related patient education are described.
Current literature regarding reproductive counseling for cancer survivors is reviewed. Resources for providing psychosocial support for decisions about fertility preservation are lagging behind the rapid pace of scientific advancements in cancer treatment and ART.
As more young women are surviving cancer and taking steps to preserve fertility, there is great need for the provision of psychologic support services and the establishment of ethical guidelines to aid them on this path.
Women's health care providers can provide support to cancer survivors facing fertility and parenting issues by becoming knowledgeable about the long-term aspects of decision making and developing educational materials and guidelines for these patients.
Introduction
The number of young women diagnosed with cancer is increasing.[1] Recent data indicate the most common types of cancer occurring among women aged 15 to 29 are cancers of the female genital system, lymphoma, thyroid cancer, melanoma, and breast cancer.[1] Advances in cancer treatment have resulted in an increased number of long-term survivors. Young women who are diagnosed with cancer must make decisions about their reproductive future at a time when they are emotionally fragile. In addition to processing the cancer diagnosis and associated treatment choices, the decisions required concerning preserving future fertility and the time constraints associated with judgments can understandably be emotionally distressing. Women without cancer who are diagnosed with infertility have typically had at least a year in which to process their desire for a child and understand the barriers and benefits for each of the assisted reproductive technologies that may be available to their unique situation. The traditional reproductive counseling and the time frame for decision making offered to a woman or a couple experiencing infertility may not be available to a woman with a cancer diagnosis. This article presents a composite case of a young woman with cancer who faced infertility due to her cancer treatment but hoped to have a biologic child in the future. The case is examined in light of what is known and not yet known about the medical and psychosocial aspects of fertility preservation for women with cancer.
Cancer and Infertility
The best treatment for cancer may lead to impaired fertility or the complete loss of fertility. However, rates of infertility vary depending on a number of factors, including cancer site, type of treatment, and the age of the patient. Infertility in cancer patients can be caused by the cancer or the type of cancer treatment received. Exact infertility rates are not known, because there are no valid measures for women to establish that fertility was present prior to treatment. Women who undergo chemotherapy or radiation for malignancies during reproductive years have a 40% to 80% chance of losing fertility. The treatments that produce the greatest risk for infertility include alkylating agents such as cyclophosphamide, methotrexate, and fluorouracil in chemotherapy; total body radiation; and external beam radiation in a field that includes the ovaries. Both chemotherapy and radiation can cause premature ovarian failure for females, often leading to premature menopause.
Fertility Preservation
Rapidly improving assisted reproductive technologies and therapies offer some opportunities to preserve the fertility of female patients receiving chemotherapy and/or radiation. The emerging field of proteomics is leading the way toward the identification of proteins involved in oocyte maturation, embryo development, and implantation that could improve assisted reproduction techniques. Assisted reproductive technology (ART) consists of clinical treatments and laboratory procedures that include the handling of human oocytes, sperm, or embryos, with the intent of establishing a pregnancy. This includes, but is not limited to, in vitro fertilization (IVF), intracytoplasmic sperm injection, gamete intrafallopian transfer, zygote intrafallopian transfer, embryo biopsy, preimplantation genetic diagnosis (PGD), embryo cryopreservation, oocyte or embryo donation, and gestational surrogacy. Table 1 includes definitions of each type of procedure.
There are currently only two established options for fertility preservation for women with cancer: 1) oophoropexy, moving the ovaries out of the range of radiation, and 2) embryo cryopreservation, the freezing of fertilized eggs via IVF for later use. Additional techniques for fertility preservation, such as oocyte cryopreservation (freezing unfertilized eggs) and ovarian tissue cryopreservation (freezing strips of ovarian tissue, which may be transplanted either orthotopically within the pelvis or heterotopically within subcutaneous tissue), are less established and not widely available. All options must typically be considered and undertaken prior to the initiation of treatment.
There are also ethical, spiritual, and legal issues related to decision making about fertility preservation, such as the disposition of stored embryos. These issues often concern health care professionals as well and may pose barriers to the discussion of or assistance with the use of ART.Some patients and their families choose to consider posthumous parenting, that is, they intend to use the stored embryos whether or not the patient survives. Although this is an ethically charged situation, the American Society for Reproductive Medicine recommends that health care professionals do not deny patients assistance for this form of reproduction and also advises that "precise instructions" be given by the patient in the event of his or her death. The precise instructions for the disposition of DNA are part of the informed consent counseling, and patients are required to outline the procedures for future use of the stored embryos (e.g., willed to a spouse or parent, discarded, donated, etc.) If these procedures are followed, this can reduce the need for legal involvement to determine ownership of the stored embryos in the event of the patient's death or in the case of divorce. The United Kingdom also regulates the disposition of embryos through informed consent. Information about this practice is not readily available from other countries.
Preimplantation Genetic Diagnosis for Hereditary Cancers
The concerns of individuals affected with cancer regarding biologic parenthood are often focused on the health risks for future children. Carriers of genetic mutations, such as women with mutations in the BRCA1/2 genes, may have additional concerns about passing on hereditary cancers to future offspring. For those survivors who are concerned about the possibility of transmitting a serious hereditary cancer to their future children, limited biologic parenting options are available. Preimplantation genetic diagnosis is one option for parents who want to avoid this dilemma.
Preimplantation genetic diagnosis is a procedure used in conjunction with IVF to screen for specific genetic or chromosomal abnormalities before transferring the fertilized eggs into the woman. Preimplantation genetic diagnosis involves microsurgical removal of one or two blastomeres (embryos) at the six- to eight-cell stage, usually 3 days after fertilization. At this stage, the cells of the embryo have not differentiated into particular body tissues, and there is not likely to be damage to the resulting embryo. Biopsies of embryos are analyzed to detect genetic abnormalities arising from the maternal or paternal chromosomes. However, since diagnostic tests are performed on a single cell, the possibility of misdiagnosis must be considered. Preimplantation genetic diagnosis results are usually available within 48 hours after biopsy, which corresponds to day 5 after egg retrieval. Depending on their original quality, embryos may or may not reach the blastocyst stage, which is the final stage of in vitro development.[9] Usually on day 5, embryos free of genetic defects are transferred into the patient; however, some women or couples may choose to cryopreserve affected embryos. Currently data are not collected on the health of offspring born through the use of PGD, so it is unknown if there are related long-term health consequences.
Preimplantation genetic diagnosis has been accomplished for both cancer-specific disorders such as adenomatous polyposis coli, BRCA1/2, retinoblastoma, Li-Fraumeni syndrome, and von Hippel-Lindau syndrome, as well as disorders predisposing to neoplasia (Fanconi anemia, Wiskott-Aldrich syndrome).[11–13] The PGD procedure has been performed for a little over a decade and involves the use of IVF so parents can select the embryos that are implanted into the uterus. Embryos are tested for genetic status at the early stages of development. The ability to use PGD testing for all cancer types is not currently possible. The regulations developed for PGD testing and the types of cancers for which embryos can be tested vary by country and availability within each country. For example, the ability to use PGD for BRCA became available in 2006; however, other hereditary cancers, such as familial adenomatous polyposis, have been tested for in the Netherlands since 2004, although BRCA testing of embryos is not allowed there.[13] Thus, although the availability of PGD testing for certain cancer types varies by country and facility, the psychosocial issues women face over certain issues such as embryo selection are quite similar. One option for PGD is to implant only those embryos that are found to be unaffected. Some parents still may choose to implant affected embryos with the knowledge that the potential for hereditary syndromes is high. In the past, options for hereditary cancer mutation carriers included not having children or undergoing amniocentesis or other forms of prenatal diagnosis. Preimplantation genetic diagnosis allows parents to avoid terminating a pregnancy and/or risking the health of the fetus or the mother.
In Europe, guidelines regulate which clinics can perform PGD and for which diseases they can screen. In the United Kingdom, the Human Fertilisation and Embryology Authority (HFEA) governs which procedures are acceptable and provides guidelines as to how these procedures should be performed. It also licenses clinics that wish to use any type of ART. Currently, no such oversight exists in the United States.[14] At present, HFEA has approved PGD to test for 50 disorders, including hereditary breast and ovarian cancers, which can be caused by a mutation in the BRCA1/2 genes. Mutations in BRCA1/2 are passed down in families in an autosomal dominant pattern, and children of individuals with a BRCA1/2 mutation have a 50% chance of inheriting it. Women who carry the BRCA1/2 gene have an 80% lifetime risk of developing breast cancer and approximately a 40% risk of developing ovarian cancer. With such a high risk for developing cancer, the HFEA considers it appropriate to allow PGD for this cancer predisposition gene.
The use of PGD in the United States is predicted to be approximately 20% across all embryos created via IVF; however, it is not known specifically which abnormalities or conditions PGD testing has been used for.[11] Almost 2000 babies have been born after the process of PGD since it was developed in 1989.[15] There are no published reports of increased fetal defects or late effects in babies born using PGD, but it is possible abnormalities may occur later in life as a result of the procedure.[9,10,13] Preimplantation genetic diagnosis cannot detect all genetic irregularities because only a limited number of chromosomes can be tested per procedure, and misdiagnosis may still occur.Prenatal diagnosis (amniocentesis or chorionic villus sampling) may still need to be considered after use of PGD to determine if the fetus carries a genetic abnormality.
Cancer and Parenting
Although cancer presents obstacles to becoming a parent, an experience with a major illness can also make survivors excellent parents, with greater emotional resilience and appreciation for parenthood. However, the decision to become a biologic parent after cancer must be weighed with the obstacles of the time and expense of fertility preservation procedures such as IVF. Adoption remains an option, but cancer survivors may experience difficulty in becoming qualified as adoptive parents. Survivors seeking adoption may encounter discrimination from US adoption agencies because of the survivor's physical health and condition.Some US agencies require an applicant to be at least 5 years post-treatment before he or she can qualify as a potential adoptive parent. Some cancer survivors have had success qualifying for the adoption of foreign-born children through international adoption agencies. Additionally, infertility treatments and adoption procedures may be too costly for some survivors, especially after an expensive battle with cancer.
In addition to concerns about cancer recurrence and parenting, survivors often have psychosocial concerns related to pregnancy and parenting, many of which mirror issues faced by any woman considering the use of ART. These concerns focus primarily on risks of birth defects or cancer in offspring; anxiety about hormonal factors related to pregnancy or infertility treatment increasing a risk of cancer recurrence, leaving the spouse/partner to raise the child if the parent with cancer dies; and conflicts about using ART because of ethical beliefs or religious beliefs, as some religions prohibit the use of donor gametes
Reproductive Counseling for Cancer Survivors
Canada and Schover[22] identified the need for research to promote improved patient education regarding cancer and reproductive health. Although the researchers indicate oncologists would probably be the ideal health care professionals for cancer patients to have in-depth discussions with regarding fertility preservation and future parenting, they further note that time constraints may make this unrealistic. However, their objective is to promote better information about the risks of infertility to the newly diagnosed cancer patient, a communication initiative for which other researchers have made a similar plea. Although this is a crucial first step on the road to improved quality of life in cancer survivors and risk management for infertility, it does not fully address the decision-making issues the patient must consider in rapid time.
There is little research about the psychosocial decision making of newly diagnosed cancer survivors regarding fertility and PGD choices. Unlike infertility in couples without a cancer diagnosis, the impending infertility of a cancer patient and the need for treatment provides a narrow window of time for patient counseling. Although some patients, similar to the woman in this case study, perceive stored embryos and oocytes as "frozen hope," decisions about the future of the stored embryo can be agonizing. Recent studies have begun to examine patient choices for the donation or destruction of stored embryos.
One study conducted in an Australian population among 235 couples with banked embryos found 27% would donate to stem cell research or infertility research, whereas 15% would consider donating to another couple.
However, the disagreement rate among the couples was high, with more than 40% disagreeing over each of the options.Additionally, 90% of the couples indicated they would want to discuss donation with a health care professional rather than make the decision alone. The majority preferred a fertility specialist or scientist as their choice for the discussions. This study highlights the fact that deciding to pursue ART is only the beginning of the decision-making process that may span several years.
Other researchers have begun to examine how patients feel about stored embryos and oocytes in fertility clinics. An emerging trend indicates patients may enter reproductive counseling with one set of ideas about stored embryos and feel differently after a successful pregnancy or failed attempts.[26–28] However, no studies have examined this meaning among women who stored embryos or oocytes due to cancer treatment.
There are currently no guidelines specifically tailored for the reproductive counseling needs of newly diagnosed cancer patients, especially for those who may have concerns about hereditary cancer syndromes. Peshkin et al.suggest strong support for such guidelines and continued collaborations among providers who work in oncology, cancer genetics, and ART.Conclusion
Finishing cancer treatment and transitioning from patient to survivor does not end the psychologic trauma of cancer. There are a plethora of issues that survivors often face after their cancer is in remission that affect quality of life. This case report illustrates the loss of fertility often experienced by a cancer survivor as a result of treatment. Young women with genetic mutations, such as those in the BRCA1/2 genes, may have additional concerns about passing on hereditary cancers to future offspring. Considering PGD to avoid passing the mutation may allow parents to select only healthy embryos, but decisions about the fate of embryos that are mutation carriers remain perplexing.
Decisions about using fertility preservation typically must be made at the same time as other decisions about treatment of a life-threatening diagnosis. Ethical, religious, financial, and other implications of preserving her fertility confront the woman before she begins cancer treatment. This leaves limited time for the patient to consider the implications of her choices and how she may feel about her reproductive options at a later date.
Given that 2.5 million young adults in the United States have survived cancer, more research is needed on the psychosocial aspects of parenthood, particularly to identify the psychosocial needs of survivors regarding cryopreservation and PGD. The resources for providing support for using ART and PGD lag behind the rapid advance of technology. Table 2 provides a list of online sources of information for patients and health care professionals. Communication guidelines should be developed for informing cancer patients of the emotional and psychosocial impact of fertility preservation, with particular regard to future decision making. More research is needed to develop educational resources specific to this population that will aid the women newly diagnosed with cancer in decision making. Although social support is an important aspect of survivorship, the medical community can also provide support by assigning social workers or counselors to survivors and to the newly diagnosed who are facing fertility and parenting issues.
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