Obstetrics

VANCOUVER – Women with epilepsy have fertility rates comparable with healthy women in the general population, according to results from the first prospective observational cohort study to make the comparison.

During the year-long Women With Epilepsy: Pregnancy Outcomes and Deliveries (WEPOD) study, 70% of women with epilepsy and 67% of healthy control women became pregnant, and there was no significant difference in the mean time to pregnancy between those with and without epilepsy (6 months vs. 9 months, respectively), Dr. Page Pennell reported at the annual meeting of the American Academy of Neurology.

Live births occurred in 82% of pregnancies of women with epilepsy and 80% of controls, while miscarriages occurred in 13% and 20%, respectively. Both of those rates are very similar to the general population. Another 5% of pregnancies in women with epilepsy were ectopic, terminated due to chromosomal abnormality, or lost to follow-up.

“These findings should reassure women with epilepsy and clinicians when counseling women with epilepsy who are planning pregnancy,” said Dr. Pennell, director of research for the division of epilepsy in the department of neurology at Brigham and Women’s Hospital in Boston. She is a primary investigator of the study along with Dr. Jacqueline French, professor of neurology at NYU Langone Medical Center and Dr. Cynthia Harden, system director of epilepsy services at Mount Sinai Beth Israel, both in New York.

“I think overall the findings are more in the light of myth busting. ... We don’t necessarily see a lot of problems with fertility, yet the literature suggests that the birth rates are much lower,” Dr. Harden said in an interview.

“It’s really the first solid evidence, and it’s nice because in a sea of bad news for women when it comes to family planning and achieving pregnancy and pregnancy outcomes, I think this was very positive to say that their ability to achieve pregnancy was no different than what was reported by a control population without epilepsy,” Dr. Katherine Noe, an epilepsy specialist at the Mayo Clinic in Scottsdale, Ariz., said when asked to comment on the study.

“There was certainly reason to be concerned,” said Dr. Noe, who was not involved in the study. “We have a lot of data saying that babies exposed to antiepileptic drugs are more likely to have malformations, and so you could have a baby that already early in pregnancy has severe malformations that would be more likely to end in spontaneous abortion.”

Dr. Noe said that pregnancy registry data indicate that women with epilepsy may be more likely to have a pregnancy that ends in a miscarriage. Investigators for several studies published in 2015 reported that women with epilepsy face greater risk for morbidity and adverse outcomes at the time of delivery and during pregnancy than women without epilepsy (JAMA Neurol. 2015;72[9]:981-8 and Lancet. 2016;386[10006]:1845–52). Women with epilepsy also have been thought to be more prone to infertility for various reasons, including menstrual irregularities, polycystic ovarian syndrome related to antiepileptic medications, and early menopause, she said.

Three previous studies had reported that women with epilepsy had birth rates as low as only one-quarter to one-third that of women without epilepsy. There have been many reasons reported for why that might be the case, including lower marriage rates, sexual dysfunction, lower libido (in both men and women with epilepsy), and increased number of anovulatory cycles, or greater choice to not become pregnant, Dr. Pennell said.

The WEPOD study enrolled 89 women with epilepsy and 109 healthy controls who were seeking to become pregnant and had stopped using contraception within 6 months of enrollment or were about to stop using it. The investigators excluded women with infertility, polycystic ovarian syndrome, endometriosis, endocrine disorder, and heavy smoking, or who were not in an exclusive heterosexual relationship with a significant other or spouse.

Participants received iPod touch devices with an app with which they tracked menses and intercourse, as well as antiepileptic drug use and seizures in women with epilepsy. “This was a particularly novel part of the study,” Dr. Harden said. It allowed the investigators to track adherence very well. Participants logged about 87% of their days in the app, and the investigators could see when the entries were made.

Women in both groups had a mean age of about 31 years and mean body mass index of about 25 kg/m². Overall, 52%-58% had undergone a prior pregnancy. Women with epilepsy, compared with controls, were less often Asian (17% vs. 6%) or African American (16% vs. 1%). The education level of participants was “fairly similar” between the groups, and slightly more women with epilepsy were unemployed (21% vs. 10%). Women with epilepsy also were more often married than were controls (89% vs. 75%).

During the study, 36% of women with epilepsy were still having seizures. At enrollment, most of the women’s seizure types were generalized (30%) or focal only (63%). Dr. Pennell noted that the antiseizure medications that the women were taking were typical for women of reproductive age: lamotrigine monotherapy (44%), levetiracetam monotherapy (28%), monotherapy with a strong enzyme-inducing drug (12%), other polytherapy (10%), polytherapy with a strong enzyme-inducing drug (6%), other monotherapy (3%), or no antiseizure medication (2%). A few women either added or stopped drugs during the study. A total of 18 women with epilepsy and 15 healthy controls dropped out.

As expected, age affected the likelihood of becoming pregnant, as well as number of prior pregnancies. Body mass index did not affect the likelihood of becoming pregnant, while white race and being married increased the likelihood.

In future analyses, the investigators are planning on checking whether ovulatory rates, frequency of intercourse, and time of intercourse had any impact on pregnancy, and in women with epilepsy, they will check the effect of the type of antiseizure medication and seizure-related factors.

“I think our findings will stand with future analyses.” Dr. Harden said. “The most interesting future findings may come from within the epilepsy group,” she said, noting that older antiepileptic medications have been previously associated with difficulty conceiving.

The WEPOD study was funded by the Milken Family Foundation, the Epilepsy Therapy Project, and the Epilepsy Foundation.

[email protected]

VANCOUVER – Women with epilepsy have fertility rates comparable with healthy women in the general population, according to results from the first prospective observational cohort study to make the comparison.

During the year-long Women With Epilepsy: Pregnancy Outcomes and Deliveries (WEPOD) study, 70% of women with epilepsy and 67% of healthy control women became pregnant, and there was no significant difference in the mean time to pregnancy between those with and without epilepsy (6 months vs. 9 months, respectively), Dr. Page Pennell reported at the annual meeting of the American Academy of Neurology.

Live births occurred in 82% of pregnancies of women with epilepsy and 80% of controls, while miscarriages occurred in 13% and 20%, respectively. Both of those rates are very similar to the general population. Another 5% of pregnancies in women with epilepsy were ectopic, terminated due to chromosomal abnormality, or lost to follow-up.

“These findings should reassure women with epilepsy and clinicians when counseling women with epilepsy who are planning pregnancy,” said Dr. Pennell, director of research for the division of epilepsy in the department of neurology at Brigham and Women’s Hospital in Boston. She is a primary investigator of the study along with Dr. Jacqueline French, professor of neurology at NYU Langone Medical Center and Dr. Cynthia Harden, system director of epilepsy services at Mount Sinai Beth Israel, both in New York.

“I think overall the findings are more in the light of myth busting. ... We don’t necessarily see a lot of problems with fertility, yet the literature suggests that the birth rates are much lower,” Dr. Harden said in an interview.

“It’s really the first solid evidence, and it’s nice because in a sea of bad news for women when it comes to family planning and achieving pregnancy and pregnancy outcomes, I think this was very positive to say that their ability to achieve pregnancy was no different than what was reported by a control population without epilepsy,” Dr. Katherine Noe, an epilepsy specialist at the Mayo Clinic in Scottsdale, Ariz., said when asked to comment on the study.

“There was certainly reason to be concerned,” said Dr. Noe, who was not involved in the study. “We have a lot of data saying that babies exposed to antiepileptic drugs are more likely to have malformations, and so you could have a baby that already early in pregnancy has severe malformations that would be more likely to end in spontaneous abortion.”

Dr. Noe said that pregnancy registry data indicate that women with epilepsy may be more likely to have a pregnancy that ends in a miscarriage. Investigators for several studies published in 2015 reported that women with epilepsy face greater risk for morbidity and adverse outcomes at the time of delivery and during pregnancy than women without epilepsy (JAMA Neurol. 2015;72[9]:981-8 and Lancet. 2016;386[10006]:1845–52). Women with epilepsy also have been thought to be more prone to infertility for various reasons, including menstrual irregularities, polycystic ovarian syndrome related to antiepileptic medications, and early menopause, she said.

Three previous studies had reported that women with epilepsy had birth rates as low as only one-quarter to one-third that of women without epilepsy. There have been many reasons reported for why that might be the case, including lower marriage rates, sexual dysfunction, lower libido (in both men and women with epilepsy), and increased number of anovulatory cycles, or greater choice to not become pregnant, Dr. Pennell said.

The WEPOD study enrolled 89 women with epilepsy and 109 healthy controls who were seeking to become pregnant and had stopped using contraception within 6 months of enrollment or were about to stop using it. The investigators excluded women with infertility, polycystic ovarian syndrome, endometriosis, endocrine disorder, and heavy smoking, or who were not in an exclusive heterosexual relationship with a significant other or spouse.

Participants received iPod touch devices with an app with which they tracked menses and intercourse, as well as antiepileptic drug use and seizures in women with epilepsy. “This was a particularly novel part of the study,” Dr. Harden said. It allowed the investigators to track adherence very well. Participants logged about 87% of their days in the app, and the investigators could see when the entries were made.

Women in both groups had a mean age of about 31 years and mean body mass index of about 25 kg/m². Overall, 52%-58% had undergone a prior pregnancy. Women with epilepsy, compared with controls, were less often Asian (17% vs. 6%) or African American (16% vs. 1%). The education level of participants was “fairly similar” between the groups, and slightly more women with epilepsy were unemployed (21% vs. 10%). Women with epilepsy also were more often married than were controls (89% vs. 75%).

During the study, 36% of women with epilepsy were still having seizures. At enrollment, most of the women’s seizure types were generalized (30%) or focal only (63%). Dr. Pennell noted that the antiseizure medications that the women were taking were typical for women of reproductive age: lamotrigine monotherapy (44%), levetiracetam monotherapy (28%), monotherapy with a strong enzyme-inducing drug (12%), other polytherapy (10%), polytherapy with a strong enzyme-inducing drug (6%), other monotherapy (3%), or no antiseizure medication (2%). A few women either added or stopped drugs during the study. A total of 18 women with epilepsy and 15 healthy controls dropped out.

As expected, age affected the likelihood of becoming pregnant, as well as number of prior pregnancies. Body mass index did not affect the likelihood of becoming pregnant, while white race and being married increased the likelihood.

In future analyses, the investigators are planning on checking whether ovulatory rates, frequency of intercourse, and time of intercourse had any impact on pregnancy, and in women with epilepsy, they will check the effect of the type of antiseizure medication and seizure-related factors.

“I think our findings will stand with future analyses.” Dr. Harden said. “The most interesting future findings may come from within the epilepsy group,” she said, noting that older antiepileptic medications have been previously associated with difficulty conceiving.

The WEPOD study was funded by the Milken Family Foundation, the Epilepsy Therapy Project, and the Epilepsy Foundation.

[email protected]

VANCOUVER – Women with epilepsy have fertility rates comparable with healthy women in the general population, according to results from the first prospective observational cohort study to make the comparison.

During the year-long Women With Epilepsy: Pregnancy Outcomes and Deliveries (WEPOD) study, 70% of women with epilepsy and 67% of healthy control women became pregnant, and there was no significant difference in the mean time to pregnancy between those with and without epilepsy (6 months vs. 9 months, respectively), Dr. Page Pennell reported at the annual meeting of the American Academy of Neurology.

Live births occurred in 82% of pregnancies of women with epilepsy and 80% of controls, while miscarriages occurred in 13% and 20%, respectively. Both of those rates are very similar to the general population. Another 5% of pregnancies in women with epilepsy were ectopic, terminated due to chromosomal abnormality, or lost to follow-up.

“These findings should reassure women with epilepsy and clinicians when counseling women with epilepsy who are planning pregnancy,” said Dr. Pennell, director of research for the division of epilepsy in the department of neurology at Brigham and Women’s Hospital in Boston. She is a primary investigator of the study along with Dr. Jacqueline French, professor of neurology at NYU Langone Medical Center and Dr. Cynthia Harden, system director of epilepsy services at Mount Sinai Beth Israel, both in New York.

“I think overall the findings are more in the light of myth busting. ... We don’t necessarily see a lot of problems with fertility, yet the literature suggests that the birth rates are much lower,” Dr. Harden said in an interview.

“It’s really the first solid evidence, and it’s nice because in a sea of bad news for women when it comes to family planning and achieving pregnancy and pregnancy outcomes, I think this was very positive to say that their ability to achieve pregnancy was no different than what was reported by a control population without epilepsy,” Dr. Katherine Noe, an epilepsy specialist at the Mayo Clinic in Scottsdale, Ariz., said when asked to comment on the study.

“There was certainly reason to be concerned,” said Dr. Noe, who was not involved in the study. “We have a lot of data saying that babies exposed to antiepileptic drugs are more likely to have malformations, and so you could have a baby that already early in pregnancy has severe malformations that would be more likely to end in spontaneous abortion.”

Dr. Noe said that pregnancy registry data indicate that women with epilepsy may be more likely to have a pregnancy that ends in a miscarriage. Investigators for several studies published in 2015 reported that women with epilepsy face greater risk for morbidity and adverse outcomes at the time of delivery and during pregnancy than women without epilepsy (JAMA Neurol. 2015;72[9]:981-8 and Lancet. 2016;386[10006]:1845–52). Women with epilepsy also have been thought to be more prone to infertility for various reasons, including menstrual irregularities, polycystic ovarian syndrome related to antiepileptic medications, and early menopause, she said.

Three previous studies had reported that women with epilepsy had birth rates as low as only one-quarter to one-third that of women without epilepsy. There have been many reasons reported for why that might be the case, including lower marriage rates, sexual dysfunction, lower libido (in both men and women with epilepsy), and increased number of anovulatory cycles, or greater choice to not become pregnant, Dr. Pennell said.

The WEPOD study enrolled 89 women with epilepsy and 109 healthy controls who were seeking to become pregnant and had stopped using contraception within 6 months of enrollment or were about to stop using it. The investigators excluded women with infertility, polycystic ovarian syndrome, endometriosis, endocrine disorder, and heavy smoking, or who were not in an exclusive heterosexual relationship with a significant other or spouse.

Participants received iPod touch devices with an app with which they tracked menses and intercourse, as well as antiepileptic drug use and seizures in women with epilepsy. “This was a particularly novel part of the study,” Dr. Harden said. It allowed the investigators to track adherence very well. Participants logged about 87% of their days in the app, and the investigators could see when the entries were made.

Women in both groups had a mean age of about 31 years and mean body mass index of about 25 kg/m². Overall, 52%-58% had undergone a prior pregnancy. Women with epilepsy, compared with controls, were less often Asian (17% vs. 6%) or African American (16% vs. 1%). The education level of participants was “fairly similar” between the groups, and slightly more women with epilepsy were unemployed (21% vs. 10%). Women with epilepsy also were more often married than were controls (89% vs. 75%).

During the study, 36% of women with epilepsy were still having seizures. At enrollment, most of the women’s seizure types were generalized (30%) or focal only (63%). Dr. Pennell noted that the antiseizure medications that the women were taking were typical for women of reproductive age: lamotrigine monotherapy (44%), levetiracetam monotherapy (28%), monotherapy with a strong enzyme-inducing drug (12%), other polytherapy (10%), polytherapy with a strong enzyme-inducing drug (6%), other monotherapy (3%), or no antiseizure medication (2%). A few women either added or stopped drugs during the study. A total of 18 women with epilepsy and 15 healthy controls dropped out.

As expected, age affected the likelihood of becoming pregnant, as well as number of prior pregnancies. Body mass index did not affect the likelihood of becoming pregnant, while white race and being married increased the likelihood.

In future analyses, the investigators are planning on checking whether ovulatory rates, frequency of intercourse, and time of intercourse had any impact on pregnancy, and in women with epilepsy, they will check the effect of the type of antiseizure medication and seizure-related factors.

“I think our findings will stand with future analyses.” Dr. Harden said. “The most interesting future findings may come from within the epilepsy group,” she said, noting that older antiepileptic medications have been previously associated with difficulty conceiving.

The WEPOD study was funded by the Milken Family Foundation, the Epilepsy Therapy Project, and the Epilepsy Foundation.

[email protected]

Breastfeeding during the first 27 weeks of life had a risk-specific effect on reducing respiratory symptoms in healthy term infants, based on data from a prospective cohort study of 436 children in Switzerland.

“Breastfeeding is generally accepted to be protective against respiratory symptoms in early life,” but most published studies on this topic are cross-sectional and more likely biased, wrote Dr. Olga Gorlanova of the University of Basel (Switzerland) and her colleagues.

©Jupiterimages/ thinkstockphotos.com

The researchers studied infants enrolled in the Bern-Basel Infant Lung Development cohort via weekly telephone interviews during the first year of life. In addition, weekly measurements of environmental particulate matter were collected from local monitoring stations. Risk factors included maternal history of atopy, vaginal vs. cesarean delivery, parents’ level of education, smoking during and after pregnancy, number of older siblings, child care attendance, and housing conditions.

Overall, infants breastfed during the first 27 weeks of life had significantly reduced respiratory symptoms, compared with nonbreastfed infants (risk ratio, .70)

The study “suggests that breastfeeding attenuates the effects of risk factors such as sex, age, gestational age, cesarean delivery, and prenatal maternal tobacco smoking in healthy term infants,” Dr. Gorlanova and her associates wrote. No significant interaction was noted between breastfeeding and child care attendance, number of older siblings, maternal atopy, or environmental particulate matter.

Read the full study here (J Pediatr. 2016. doi: 10.1016/j.jpeds.2016.03.041).

Breastfeeding during the first 27 weeks of life had a risk-specific effect on reducing respiratory symptoms in healthy term infants, based on data from a prospective cohort study of 436 children in Switzerland.

“Breastfeeding is generally accepted to be protective against respiratory symptoms in early life,” but most published studies on this topic are cross-sectional and more likely biased, wrote Dr. Olga Gorlanova of the University of Basel (Switzerland) and her colleagues.

©Jupiterimages/ thinkstockphotos.com

The researchers studied infants enrolled in the Bern-Basel Infant Lung Development cohort via weekly telephone interviews during the first year of life. In addition, weekly measurements of environmental particulate matter were collected from local monitoring stations. Risk factors included maternal history of atopy, vaginal vs. cesarean delivery, parents’ level of education, smoking during and after pregnancy, number of older siblings, child care attendance, and housing conditions.

Overall, infants breastfed during the first 27 weeks of life had significantly reduced respiratory symptoms, compared with nonbreastfed infants (risk ratio, .70)

The study “suggests that breastfeeding attenuates the effects of risk factors such as sex, age, gestational age, cesarean delivery, and prenatal maternal tobacco smoking in healthy term infants,” Dr. Gorlanova and her associates wrote. No significant interaction was noted between breastfeeding and child care attendance, number of older siblings, maternal atopy, or environmental particulate matter.

Read the full study here (J Pediatr. 2016. doi: 10.1016/j.jpeds.2016.03.041).

Breastfeeding during the first 27 weeks of life had a risk-specific effect on reducing respiratory symptoms in healthy term infants, based on data from a prospective cohort study of 436 children in Switzerland.

“Breastfeeding is generally accepted to be protective against respiratory symptoms in early life,” but most published studies on this topic are cross-sectional and more likely biased, wrote Dr. Olga Gorlanova of the University of Basel (Switzerland) and her colleagues.

©Jupiterimages/ thinkstockphotos.com

The researchers studied infants enrolled in the Bern-Basel Infant Lung Development cohort via weekly telephone interviews during the first year of life. In addition, weekly measurements of environmental particulate matter were collected from local monitoring stations. Risk factors included maternal history of atopy, vaginal vs. cesarean delivery, parents’ level of education, smoking during and after pregnancy, number of older siblings, child care attendance, and housing conditions.

Overall, infants breastfed during the first 27 weeks of life had significantly reduced respiratory symptoms, compared with nonbreastfed infants (risk ratio, .70)

The study “suggests that breastfeeding attenuates the effects of risk factors such as sex, age, gestational age, cesarean delivery, and prenatal maternal tobacco smoking in healthy term infants,” Dr. Gorlanova and her associates wrote. No significant interaction was noted between breastfeeding and child care attendance, number of older siblings, maternal atopy, or environmental particulate matter.

Read the full study here (J Pediatr. 2016. doi: 10.1016/j.jpeds.2016.03.041).

An increased risk of acute lymphoblastic leukemia (ALL) was seen in young children born by prelabor cesarean delivery, in a pooled analysis of 13 case-control studies from nine countries.

The odds ratio was significant at 1.23 for an association between prelabor cesarean delivery and ALL (P = .018); there was not a significant association between ALL and all indications of cesarean delivery nor was there an association with emergency cesarean delivery. Further, the risk for childhood AML was not associated with cesarean delivery, prelabor cesarean delivery, or emergency cesarean delivery, reported Erin L. Marcotte, Ph.D., of the University of Minnesota, Minneapolis, and her associates.

VashiDonsk/Creative Commons/CC ASA 3.0

The association between ALL and prelabor cesarean delivery is based on 13 case-control studies from the Childhood Leukemia International Consortium. Birth delivery method was known for 97%-99% of 8,780 ALL cases, 1,332 AML cases, and 23,459 controls in those studies. In four of the studies, the indications for cesarean delivery were known for 1,061 of 4,313 ALL cases, 138 of 664 AML cases, and 1,401 of 5,884 controls. The multivariable logistic regression models used for the analysis were adjusted for birth weight, sex, age, ethnic origin, parental education, maternal age, and study.

If the association proves to be causal, “maladaptive immune activation due to an absence of stress response before birth in children born by prelabor caesarean delivery could be considered as a potential mechanism,” the researchers wrote (Lancet Haematol. 2016;3[4]:e176–e185).

ALL involves genetic and developmental aberrations that are probably modified by exposure and response to infectious agents. Early exposure to a variety of infections seems to decrease risk, and a vigorous response to infections (quantified by physician visits for infections) increases risk. During vaginal birth, the newborn is exposed to commensal bacteria that modulate immune development, Joseph Weimels, Ph.D., of the University of California at San Francisco, and Xiaomei Ma, Ph.D., of the Yale School of Public Health, New Haven, Conn., wrote in an editorial published in the same issue of The Lancet Haematology. Children delivered vaginally have different gut microbiomes and T-cell reactivity persisting up to age 2 years compared with children born by cesarean, they wrote.

The National Cancer Institute funded the study. The researchers had no relevant disclosures.

[email protected]

On Twitter @maryjodales

An increased risk of acute lymphoblastic leukemia (ALL) was seen in young children born by prelabor cesarean delivery, in a pooled analysis of 13 case-control studies from nine countries.

The odds ratio was significant at 1.23 for an association between prelabor cesarean delivery and ALL (P = .018); there was not a significant association between ALL and all indications of cesarean delivery nor was there an association with emergency cesarean delivery. Further, the risk for childhood AML was not associated with cesarean delivery, prelabor cesarean delivery, or emergency cesarean delivery, reported Erin L. Marcotte, Ph.D., of the University of Minnesota, Minneapolis, and her associates.

VashiDonsk/Creative Commons/CC ASA 3.0

The association between ALL and prelabor cesarean delivery is based on 13 case-control studies from the Childhood Leukemia International Consortium. Birth delivery method was known for 97%-99% of 8,780 ALL cases, 1,332 AML cases, and 23,459 controls in those studies. In four of the studies, the indications for cesarean delivery were known for 1,061 of 4,313 ALL cases, 138 of 664 AML cases, and 1,401 of 5,884 controls. The multivariable logistic regression models used for the analysis were adjusted for birth weight, sex, age, ethnic origin, parental education, maternal age, and study.

If the association proves to be causal, “maladaptive immune activation due to an absence of stress response before birth in children born by prelabor caesarean delivery could be considered as a potential mechanism,” the researchers wrote (Lancet Haematol. 2016;3[4]:e176–e185).

ALL involves genetic and developmental aberrations that are probably modified by exposure and response to infectious agents. Early exposure to a variety of infections seems to decrease risk, and a vigorous response to infections (quantified by physician visits for infections) increases risk. During vaginal birth, the newborn is exposed to commensal bacteria that modulate immune development, Joseph Weimels, Ph.D., of the University of California at San Francisco, and Xiaomei Ma, Ph.D., of the Yale School of Public Health, New Haven, Conn., wrote in an editorial published in the same issue of The Lancet Haematology. Children delivered vaginally have different gut microbiomes and T-cell reactivity persisting up to age 2 years compared with children born by cesarean, they wrote.

The National Cancer Institute funded the study. The researchers had no relevant disclosures.

[email protected]

On Twitter @maryjodales

An increased risk of acute lymphoblastic leukemia (ALL) was seen in young children born by prelabor cesarean delivery, in a pooled analysis of 13 case-control studies from nine countries.

The odds ratio was significant at 1.23 for an association between prelabor cesarean delivery and ALL (P = .018); there was not a significant association between ALL and all indications of cesarean delivery nor was there an association with emergency cesarean delivery. Further, the risk for childhood AML was not associated with cesarean delivery, prelabor cesarean delivery, or emergency cesarean delivery, reported Erin L. Marcotte, Ph.D., of the University of Minnesota, Minneapolis, and her associates.

VashiDonsk/Creative Commons/CC ASA 3.0

The association between ALL and prelabor cesarean delivery is based on 13 case-control studies from the Childhood Leukemia International Consortium. Birth delivery method was known for 97%-99% of 8,780 ALL cases, 1,332 AML cases, and 23,459 controls in those studies. In four of the studies, the indications for cesarean delivery were known for 1,061 of 4,313 ALL cases, 138 of 664 AML cases, and 1,401 of 5,884 controls. The multivariable logistic regression models used for the analysis were adjusted for birth weight, sex, age, ethnic origin, parental education, maternal age, and study.

If the association proves to be causal, “maladaptive immune activation due to an absence of stress response before birth in children born by prelabor caesarean delivery could be considered as a potential mechanism,” the researchers wrote (Lancet Haematol. 2016;3[4]:e176–e185).

ALL involves genetic and developmental aberrations that are probably modified by exposure and response to infectious agents. Early exposure to a variety of infections seems to decrease risk, and a vigorous response to infections (quantified by physician visits for infections) increases risk. During vaginal birth, the newborn is exposed to commensal bacteria that modulate immune development, Joseph Weimels, Ph.D., of the University of California at San Francisco, and Xiaomei Ma, Ph.D., of the Yale School of Public Health, New Haven, Conn., wrote in an editorial published in the same issue of The Lancet Haematology. Children delivered vaginally have different gut microbiomes and T-cell reactivity persisting up to age 2 years compared with children born by cesarean, they wrote.

The National Cancer Institute funded the study. The researchers had no relevant disclosures.

[email protected]

On Twitter @maryjodales

BOSTON – A prospective cohort study of women with polycystic ovarian syndrome who developed gestational diabetes mellitus during pregnancy has implicated fasting blood glucose, non–high density lipoprotein, and sex hormone–binding globulin as significant predictive factors for the development of GDM.

“Polycystic ovarian syndrome [PCOS] is the most common reproductive disorder in women of reproductive age and is commonly associated with metabolic disorders including diabetes and obesity. In women with GDM, a history of PCOS is associated with higher incidence of complications and postpregnancy glucose intolerance. Risk factors during early pregnancy in women with PCOS for development of GDM have not been well characterized,” said Dr. Wenyu Huang of Northwestern University, Chicago.

To provide some clarity, Dr. Huang and his colleagues conducted a prospective cohort study. Inclusion criteria were age 18-45 years, diagnosis of PCOS prior to conception, singlet pregnancy, and enrollment during the first trimester. Preexisting chronic disease including diabetes, hypertension, and thyroid, kidney, or cardiovascular disease was grounds for exclusion. The findings were presented at the annual meeting of the Endocrine Society.

The 248 women with PCOS enrolled from 2011 to 2013 from a screened population of 25,000 pregnant women were followed from their first prenatal visit (before week 18) to delivery. Blood was collected at the first visit for analysis of metabolic hormones. A 75-g oral glucose tolerance test (OGTT) was carried out at week 24-28 and diagnosis of GDM was according to 2013 American Diabetes Association OGTT criteria.

Of the 248 women, 75 (30.2%) developed GDM, and 173 (69.8%) women had normal OGTT results. Examination over the same time period early in pregnancy revealed a higher incidence of GDM in women with PCOS.

In a univariate analysis, PCOS patients who developed GDM had higher fasting blood glucose (FBG), Homeostasis Model Assessment-Insulin resistance (HOMA-IR) score, total cholesterol, low-density lipoprotein cholesterol, non-HDL cholesterol, systolic and diastolic blood pressures, and free testosterone index. These patients also had lower levels of sex hormone–binding globulin (SHBG) and higher likelihood of family history of diabetes and earlier delivery.

Multiple logistic regression revealed associations between increased incidence of GDM and FBG greater than or equal to 4.86 mmol/L, non-HDL cholesterol greater than or equal to 2.84 mmol/L, and SHBG greater than or equal to 222 nmol/L. The predictive power of the three factors for the development of GDM in PCOS was relatively strong.

Future studies could aim to validate the prediction model and clarify the pathogenic basis of GDM in PCOS women, according to the researchers .

The study was funded by the Beijing Science Committee. Dr. Huang had no disclosures.

BOSTON – A prospective cohort study of women with polycystic ovarian syndrome who developed gestational diabetes mellitus during pregnancy has implicated fasting blood glucose, non–high density lipoprotein, and sex hormone–binding globulin as significant predictive factors for the development of GDM.

“Polycystic ovarian syndrome [PCOS] is the most common reproductive disorder in women of reproductive age and is commonly associated with metabolic disorders including diabetes and obesity. In women with GDM, a history of PCOS is associated with higher incidence of complications and postpregnancy glucose intolerance. Risk factors during early pregnancy in women with PCOS for development of GDM have not been well characterized,” said Dr. Wenyu Huang of Northwestern University, Chicago.

To provide some clarity, Dr. Huang and his colleagues conducted a prospective cohort study. Inclusion criteria were age 18-45 years, diagnosis of PCOS prior to conception, singlet pregnancy, and enrollment during the first trimester. Preexisting chronic disease including diabetes, hypertension, and thyroid, kidney, or cardiovascular disease was grounds for exclusion. The findings were presented at the annual meeting of the Endocrine Society.

The 248 women with PCOS enrolled from 2011 to 2013 from a screened population of 25,000 pregnant women were followed from their first prenatal visit (before week 18) to delivery. Blood was collected at the first visit for analysis of metabolic hormones. A 75-g oral glucose tolerance test (OGTT) was carried out at week 24-28 and diagnosis of GDM was according to 2013 American Diabetes Association OGTT criteria.

Of the 248 women, 75 (30.2%) developed GDM, and 173 (69.8%) women had normal OGTT results. Examination over the same time period early in pregnancy revealed a higher incidence of GDM in women with PCOS.

In a univariate analysis, PCOS patients who developed GDM had higher fasting blood glucose (FBG), Homeostasis Model Assessment-Insulin resistance (HOMA-IR) score, total cholesterol, low-density lipoprotein cholesterol, non-HDL cholesterol, systolic and diastolic blood pressures, and free testosterone index. These patients also had lower levels of sex hormone–binding globulin (SHBG) and higher likelihood of family history of diabetes and earlier delivery.

Multiple logistic regression revealed associations between increased incidence of GDM and FBG greater than or equal to 4.86 mmol/L, non-HDL cholesterol greater than or equal to 2.84 mmol/L, and SHBG greater than or equal to 222 nmol/L. The predictive power of the three factors for the development of GDM in PCOS was relatively strong.

Future studies could aim to validate the prediction model and clarify the pathogenic basis of GDM in PCOS women, according to the researchers .

The study was funded by the Beijing Science Committee. Dr. Huang had no disclosures.

BOSTON – A prospective cohort study of women with polycystic ovarian syndrome who developed gestational diabetes mellitus during pregnancy has implicated fasting blood glucose, non–high density lipoprotein, and sex hormone–binding globulin as significant predictive factors for the development of GDM.

“Polycystic ovarian syndrome [PCOS] is the most common reproductive disorder in women of reproductive age and is commonly associated with metabolic disorders including diabetes and obesity. In women with GDM, a history of PCOS is associated with higher incidence of complications and postpregnancy glucose intolerance. Risk factors during early pregnancy in women with PCOS for development of GDM have not been well characterized,” said Dr. Wenyu Huang of Northwestern University, Chicago.

To provide some clarity, Dr. Huang and his colleagues conducted a prospective cohort study. Inclusion criteria were age 18-45 years, diagnosis of PCOS prior to conception, singlet pregnancy, and enrollment during the first trimester. Preexisting chronic disease including diabetes, hypertension, and thyroid, kidney, or cardiovascular disease was grounds for exclusion. The findings were presented at the annual meeting of the Endocrine Society.

The 248 women with PCOS enrolled from 2011 to 2013 from a screened population of 25,000 pregnant women were followed from their first prenatal visit (before week 18) to delivery. Blood was collected at the first visit for analysis of metabolic hormones. A 75-g oral glucose tolerance test (OGTT) was carried out at week 24-28 and diagnosis of GDM was according to 2013 American Diabetes Association OGTT criteria.

Of the 248 women, 75 (30.2%) developed GDM, and 173 (69.8%) women had normal OGTT results. Examination over the same time period early in pregnancy revealed a higher incidence of GDM in women with PCOS.

In a univariate analysis, PCOS patients who developed GDM had higher fasting blood glucose (FBG), Homeostasis Model Assessment-Insulin resistance (HOMA-IR) score, total cholesterol, low-density lipoprotein cholesterol, non-HDL cholesterol, systolic and diastolic blood pressures, and free testosterone index. These patients also had lower levels of sex hormone–binding globulin (SHBG) and higher likelihood of family history of diabetes and earlier delivery.

Multiple logistic regression revealed associations between increased incidence of GDM and FBG greater than or equal to 4.86 mmol/L, non-HDL cholesterol greater than or equal to 2.84 mmol/L, and SHBG greater than or equal to 222 nmol/L. The predictive power of the three factors for the development of GDM in PCOS was relatively strong.

Future studies could aim to validate the prediction model and clarify the pathogenic basis of GDM in PCOS women, according to the researchers .

The study was funded by the Beijing Science Committee. Dr. Huang had no disclosures.

A new analysis of registry data from European countries does not support a risk of orofacial cleft and clubfoot with exposure to lamotrigine monotherapy, in contrast to signals from previous studies of the antiepileptic drug.

First author Helen Dolk, Dr.P.H., professor of epidemiology and health services research and the head of the center for maternal, fetal, and infant research at the University of Ulster in Coleraine, Northern Ireland, and her colleagues analyzed data from 10.1 million births exposed to antiepileptic drugs including lamotrigine (Lamictal) as a monotherapy during the first trimester between 1995 and 2011. The births were recorded in 21 population-based registries from 16 European countries. The outcomes of interest were major congenital malformations in general, as well as orofacial clefts and clubfoot (Neurology. 2016 April 6. doi: 10.1212/WNL.0000000000002540).

©KatarzynaBialasiewicz/thinkstockphotos.com

Assessment of all antiepileptic drug-exposed congenital malformation registrations revealed that 12% of pregnant registrants were exposed to lamotrigine monotherapy, with an additional 7% exposed to lamotrigine as part of polytherapy. A total of 77.1% of pregnant women exposed to lamotrigine monotherapy had records indicative of a diagnosis of epilepsy. The proportion of lamotrigine monotherapy exposures was observed to have increased over the study period, likely based on a movement away from the traditional use of valproate because of teratogenic concerns.

A total of 147 lamotrigine monotherapy-exposed babies with congenital malformations not attributable to chromosomal irregularities were identified from the total sample. The odds ratio for having a child with orofacial clefts after exposure to lamotrigine monotherapy was 1.31 (95% confidence interval, 0.73-2.33). Based on these data, the authors said they estimated exposure to lamotrigine would result in orofacial clefts in fewer than 1 in every 550 exposed babies.

The odds ratio for having a child with clubfoot after exposure to lamotrigine monotherapy was 1.83 (95% CI, 1.01-3.31). Although the study results confirmed the statistically significant signal for an overall excess of clubfoot risk found in a previous study conducted by this research team that analyzed births during 1995-2005, the investigators could not reproduce this result in an independent study population of 6.3 million births during 2005-2011(odds ratio, 1.43; 95% CI, 0.66-3.08). There were no significant differences in the risk for developing any other congenital malformations associated with lamotrigine monotherapy, the investigators said.

The authors said their results were in accord with those from several previous studies that did not detect an increased risk of orofacial clefts. In addition, they said statistically significant independent evidence of a clubfoot excess was not detected in the current study, despite findings from their previous study suggesting an increased risk.

The EUROCAT Central Database was funded by the EU Public Health Programme. GlaxoSmithKline, which markets lamotrigine, provided a grant for additional funding of this study. Dr. Dolk and her coauthors reported that their institutions received funding from GlaxoSmithKline for data or staff time contributed to this study.

A new analysis of registry data from European countries does not support a risk of orofacial cleft and clubfoot with exposure to lamotrigine monotherapy, in contrast to signals from previous studies of the antiepileptic drug.

First author Helen Dolk, Dr.P.H., professor of epidemiology and health services research and the head of the center for maternal, fetal, and infant research at the University of Ulster in Coleraine, Northern Ireland, and her colleagues analyzed data from 10.1 million births exposed to antiepileptic drugs including lamotrigine (Lamictal) as a monotherapy during the first trimester between 1995 and 2011. The births were recorded in 21 population-based registries from 16 European countries. The outcomes of interest were major congenital malformations in general, as well as orofacial clefts and clubfoot (Neurology. 2016 April 6. doi: 10.1212/WNL.0000000000002540).

©KatarzynaBialasiewicz/thinkstockphotos.com

Assessment of all antiepileptic drug-exposed congenital malformation registrations revealed that 12% of pregnant registrants were exposed to lamotrigine monotherapy, with an additional 7% exposed to lamotrigine as part of polytherapy. A total of 77.1% of pregnant women exposed to lamotrigine monotherapy had records indicative of a diagnosis of epilepsy. The proportion of lamotrigine monotherapy exposures was observed to have increased over the study period, likely based on a movement away from the traditional use of valproate because of teratogenic concerns.

A total of 147 lamotrigine monotherapy-exposed babies with congenital malformations not attributable to chromosomal irregularities were identified from the total sample. The odds ratio for having a child with orofacial clefts after exposure to lamotrigine monotherapy was 1.31 (95% confidence interval, 0.73-2.33). Based on these data, the authors said they estimated exposure to lamotrigine would result in orofacial clefts in fewer than 1 in every 550 exposed babies.

The odds ratio for having a child with clubfoot after exposure to lamotrigine monotherapy was 1.83 (95% CI, 1.01-3.31). Although the study results confirmed the statistically significant signal for an overall excess of clubfoot risk found in a previous study conducted by this research team that analyzed births during 1995-2005, the investigators could not reproduce this result in an independent study population of 6.3 million births during 2005-2011(odds ratio, 1.43; 95% CI, 0.66-3.08). There were no significant differences in the risk for developing any other congenital malformations associated with lamotrigine monotherapy, the investigators said.

The authors said their results were in accord with those from several previous studies that did not detect an increased risk of orofacial clefts. In addition, they said statistically significant independent evidence of a clubfoot excess was not detected in the current study, despite findings from their previous study suggesting an increased risk.

The EUROCAT Central Database was funded by the EU Public Health Programme. GlaxoSmithKline, which markets lamotrigine, provided a grant for additional funding of this study. Dr. Dolk and her coauthors reported that their institutions received funding from GlaxoSmithKline for data or staff time contributed to this study.

A new analysis of registry data from European countries does not support a risk of orofacial cleft and clubfoot with exposure to lamotrigine monotherapy, in contrast to signals from previous studies of the antiepileptic drug.

First author Helen Dolk, Dr.P.H., professor of epidemiology and health services research and the head of the center for maternal, fetal, and infant research at the University of Ulster in Coleraine, Northern Ireland, and her colleagues analyzed data from 10.1 million births exposed to antiepileptic drugs including lamotrigine (Lamictal) as a monotherapy during the first trimester between 1995 and 2011. The births were recorded in 21 population-based registries from 16 European countries. The outcomes of interest were major congenital malformations in general, as well as orofacial clefts and clubfoot (Neurology. 2016 April 6. doi: 10.1212/WNL.0000000000002540).

©KatarzynaBialasiewicz/thinkstockphotos.com

Assessment of all antiepileptic drug-exposed congenital malformation registrations revealed that 12% of pregnant registrants were exposed to lamotrigine monotherapy, with an additional 7% exposed to lamotrigine as part of polytherapy. A total of 77.1% of pregnant women exposed to lamotrigine monotherapy had records indicative of a diagnosis of epilepsy. The proportion of lamotrigine monotherapy exposures was observed to have increased over the study period, likely based on a movement away from the traditional use of valproate because of teratogenic concerns.

A total of 147 lamotrigine monotherapy-exposed babies with congenital malformations not attributable to chromosomal irregularities were identified from the total sample. The odds ratio for having a child with orofacial clefts after exposure to lamotrigine monotherapy was 1.31 (95% confidence interval, 0.73-2.33). Based on these data, the authors said they estimated exposure to lamotrigine would result in orofacial clefts in fewer than 1 in every 550 exposed babies.

The odds ratio for having a child with clubfoot after exposure to lamotrigine monotherapy was 1.83 (95% CI, 1.01-3.31). Although the study results confirmed the statistically significant signal for an overall excess of clubfoot risk found in a previous study conducted by this research team that analyzed births during 1995-2005, the investigators could not reproduce this result in an independent study population of 6.3 million births during 2005-2011(odds ratio, 1.43; 95% CI, 0.66-3.08). There were no significant differences in the risk for developing any other congenital malformations associated with lamotrigine monotherapy, the investigators said.

The authors said their results were in accord with those from several previous studies that did not detect an increased risk of orofacial clefts. In addition, they said statistically significant independent evidence of a clubfoot excess was not detected in the current study, despite findings from their previous study suggesting an increased risk.

The EUROCAT Central Database was funded by the EU Public Health Programme. GlaxoSmithKline, which markets lamotrigine, provided a grant for additional funding of this study. Dr. Dolk and her coauthors reported that their institutions received funding from GlaxoSmithKline for data or staff time contributed to this study.