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, according to a study published online ahead of print Dec. 30, 2019, in JAMA Neurology. The results may explain why previous research failed to find adverse neurodevelopmental effects of breastfeeding in infants whose mothers are undergoing AED treatment, said the authors.
“The results of this study add support to the general safety of breastfeeding by mothers with epilepsy who take AEDs,” wrote Angela K. Birnbaum, PhD, professor of experimental and clinical pharmacology at the University of Minnesota in Minneapolis, and colleagues.
Investigators measured infants’ blood AED concentrations
To date, medical consensus about the safety of breastfeeding while the mother is taking AEDs has been elusive. Researchers have investigated breast milk concentrations of AEDs as surrogate markers of AED concentrations in children. Breast milk concentrations, however, do not account for differences in infant pharmacokinetic processes and thus could misrepresent AED exposure in children through breastfeeding.
Dr. Birnbaum and colleagues sought to measure blood concentrations of AEDs in mothers with epilepsy and the infants that they breastfed to achieve an objective measure of AED exposure through breastfeeding. They examined data collected from December 2012 to October 2016 in the prospective Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study. Eligible participants were pregnant women with epilepsy between the ages of 14 and 45 years whose pregnancies had progressed to fewer than 20 weeks’ gestational age and who had IQ scores greater than 70 points. Participants were followed up throughout pregnancy and for 9 months post partum. Children were enrolled at birth.
The investigators collected blood samples from mothers and infants who were breastfed at the same visit, which occurred at between 5 and 20 weeks after birth. The volume of ingested breast milk delivered through graduated feeding bottles each day and the total duration of all daily breastfeeding sessions were recorded. For infants, blood samples were collected from the plantar surface of the heel and stored as dried blood spots on filter paper. The study’s primary endpoint was the percentage of infant-to-mother concentration of AEDs. Concentrations of AEDs in infants at less than the lower limit of quantification were assessed as half of the lower limit.
Exposure in utero may be greater than exposure through breast milk
In all, the researchers enrolled 351 pregnant women with epilepsy into the study and collected data on 345 infants. Two hundred twenty-two (64.3%) of the infants were breastfed, and 146 (42.3%) had AED concentrations available. After excluding outliers and mothers with missing concentration data, Dr. Birnbaum and colleagues included 164 matching infant-mother concentration pairs in their analysis (i.e., of 135 mothers and 138 infants). Approximately 52% of the infants were female, and their median age at blood collection was 13 weeks. The mothers’ median age was 32 years. About 82% of mothers were receiving monotherapy. The investigators found no demographic differences between groups of mothers taking various AEDs.
Sixty-eight infants (49.3%) had AED concentrations that were less than the lower limit of quantification. AED concentration was not greater than the lower limit of quantification for any infants breastfed by mothers taking carbamazepine, oxcarbazepine, valproic acid, or topiramate. Most levetiracetam (71.4%) and zonisamide (60.0%) concentrations in infants were less than the lower limit of quantification. Most lamotrigine concentrations in infants (88.6%) were greater than the lower limit of quantification.
The median percentage of infant-to-mother concentration was 28.9% for lamotrigine, 5.3% for levetiracetam, 44.2% for zonisamide, 5.7% for carbamazepine, 5.4% for carbamazepine epoxide, 0.3% for oxcarbazepine, 17.2% for topiramate, and 21.4% for valproic acid. Multiple linear regression models indicated that maternal concentration was significantly associated with lamotrigine concentration in infants, but not levetiracetam concentration in infants.
“Prior studies at delivery demonstrated that umbilical-cord concentrations were nearly equal to maternal concentrations, suggesting extensive placental passage to the fetus,” wrote Dr. Birnbaum and colleagues. “Therefore, the amount of AED exposure via breast milk is likely substantially lower than fetal exposure during pregnancy and appears unlikely to confer any additional risks beyond those that might be associated with exposure in pregnancy, especially given prior studies showing no adverse neurodevelopmental effects of breastfeeding while taking AEDs.”
The investigators acknowledged several limitations of their research, including the observational design of the MONEAD study. The amount of AED in participants’ breast milk is unknown, and the investigators could not calculate relative infant dosages. Only one blood sample was taken per infant, thus the results may not reflect infants’ total exposure over time.
The National Institute of Neurological Disorders and Stroke and the National Institute of Child Health and Development funded the research. The authors reported receiving research support from various pharmaceutical companies.
SOURCE: Birnbaum AK et al. JAMA Neurol. 2019 Dec 30. doi: 10.1001/jamaneurol.2019.4443.
, according to a study published online ahead of print Dec. 30, 2019, in JAMA Neurology. The results may explain why previous research failed to find adverse neurodevelopmental effects of breastfeeding in infants whose mothers are undergoing AED treatment, said the authors.
“The results of this study add support to the general safety of breastfeeding by mothers with epilepsy who take AEDs,” wrote Angela K. Birnbaum, PhD, professor of experimental and clinical pharmacology at the University of Minnesota in Minneapolis, and colleagues.
Investigators measured infants’ blood AED concentrations
To date, medical consensus about the safety of breastfeeding while the mother is taking AEDs has been elusive. Researchers have investigated breast milk concentrations of AEDs as surrogate markers of AED concentrations in children. Breast milk concentrations, however, do not account for differences in infant pharmacokinetic processes and thus could misrepresent AED exposure in children through breastfeeding.
Dr. Birnbaum and colleagues sought to measure blood concentrations of AEDs in mothers with epilepsy and the infants that they breastfed to achieve an objective measure of AED exposure through breastfeeding. They examined data collected from December 2012 to October 2016 in the prospective Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study. Eligible participants were pregnant women with epilepsy between the ages of 14 and 45 years whose pregnancies had progressed to fewer than 20 weeks’ gestational age and who had IQ scores greater than 70 points. Participants were followed up throughout pregnancy and for 9 months post partum. Children were enrolled at birth.
The investigators collected blood samples from mothers and infants who were breastfed at the same visit, which occurred at between 5 and 20 weeks after birth. The volume of ingested breast milk delivered through graduated feeding bottles each day and the total duration of all daily breastfeeding sessions were recorded. For infants, blood samples were collected from the plantar surface of the heel and stored as dried blood spots on filter paper. The study’s primary endpoint was the percentage of infant-to-mother concentration of AEDs. Concentrations of AEDs in infants at less than the lower limit of quantification were assessed as half of the lower limit.
Exposure in utero may be greater than exposure through breast milk
In all, the researchers enrolled 351 pregnant women with epilepsy into the study and collected data on 345 infants. Two hundred twenty-two (64.3%) of the infants were breastfed, and 146 (42.3%) had AED concentrations available. After excluding outliers and mothers with missing concentration data, Dr. Birnbaum and colleagues included 164 matching infant-mother concentration pairs in their analysis (i.e., of 135 mothers and 138 infants). Approximately 52% of the infants were female, and their median age at blood collection was 13 weeks. The mothers’ median age was 32 years. About 82% of mothers were receiving monotherapy. The investigators found no demographic differences between groups of mothers taking various AEDs.
Sixty-eight infants (49.3%) had AED concentrations that were less than the lower limit of quantification. AED concentration was not greater than the lower limit of quantification for any infants breastfed by mothers taking carbamazepine, oxcarbazepine, valproic acid, or topiramate. Most levetiracetam (71.4%) and zonisamide (60.0%) concentrations in infants were less than the lower limit of quantification. Most lamotrigine concentrations in infants (88.6%) were greater than the lower limit of quantification.
The median percentage of infant-to-mother concentration was 28.9% for lamotrigine, 5.3% for levetiracetam, 44.2% for zonisamide, 5.7% for carbamazepine, 5.4% for carbamazepine epoxide, 0.3% for oxcarbazepine, 17.2% for topiramate, and 21.4% for valproic acid. Multiple linear regression models indicated that maternal concentration was significantly associated with lamotrigine concentration in infants, but not levetiracetam concentration in infants.
“Prior studies at delivery demonstrated that umbilical-cord concentrations were nearly equal to maternal concentrations, suggesting extensive placental passage to the fetus,” wrote Dr. Birnbaum and colleagues. “Therefore, the amount of AED exposure via breast milk is likely substantially lower than fetal exposure during pregnancy and appears unlikely to confer any additional risks beyond those that might be associated with exposure in pregnancy, especially given prior studies showing no adverse neurodevelopmental effects of breastfeeding while taking AEDs.”
The investigators acknowledged several limitations of their research, including the observational design of the MONEAD study. The amount of AED in participants’ breast milk is unknown, and the investigators could not calculate relative infant dosages. Only one blood sample was taken per infant, thus the results may not reflect infants’ total exposure over time.
The National Institute of Neurological Disorders and Stroke and the National Institute of Child Health and Development funded the research. The authors reported receiving research support from various pharmaceutical companies.
SOURCE: Birnbaum AK et al. JAMA Neurol. 2019 Dec 30. doi: 10.1001/jamaneurol.2019.4443.
, according to a study published online ahead of print Dec. 30, 2019, in JAMA Neurology. The results may explain why previous research failed to find adverse neurodevelopmental effects of breastfeeding in infants whose mothers are undergoing AED treatment, said the authors.
“The results of this study add support to the general safety of breastfeeding by mothers with epilepsy who take AEDs,” wrote Angela K. Birnbaum, PhD, professor of experimental and clinical pharmacology at the University of Minnesota in Minneapolis, and colleagues.
Investigators measured infants’ blood AED concentrations
To date, medical consensus about the safety of breastfeeding while the mother is taking AEDs has been elusive. Researchers have investigated breast milk concentrations of AEDs as surrogate markers of AED concentrations in children. Breast milk concentrations, however, do not account for differences in infant pharmacokinetic processes and thus could misrepresent AED exposure in children through breastfeeding.
Dr. Birnbaum and colleagues sought to measure blood concentrations of AEDs in mothers with epilepsy and the infants that they breastfed to achieve an objective measure of AED exposure through breastfeeding. They examined data collected from December 2012 to October 2016 in the prospective Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study. Eligible participants were pregnant women with epilepsy between the ages of 14 and 45 years whose pregnancies had progressed to fewer than 20 weeks’ gestational age and who had IQ scores greater than 70 points. Participants were followed up throughout pregnancy and for 9 months post partum. Children were enrolled at birth.
The investigators collected blood samples from mothers and infants who were breastfed at the same visit, which occurred at between 5 and 20 weeks after birth. The volume of ingested breast milk delivered through graduated feeding bottles each day and the total duration of all daily breastfeeding sessions were recorded. For infants, blood samples were collected from the plantar surface of the heel and stored as dried blood spots on filter paper. The study’s primary endpoint was the percentage of infant-to-mother concentration of AEDs. Concentrations of AEDs in infants at less than the lower limit of quantification were assessed as half of the lower limit.
Exposure in utero may be greater than exposure through breast milk
In all, the researchers enrolled 351 pregnant women with epilepsy into the study and collected data on 345 infants. Two hundred twenty-two (64.3%) of the infants were breastfed, and 146 (42.3%) had AED concentrations available. After excluding outliers and mothers with missing concentration data, Dr. Birnbaum and colleagues included 164 matching infant-mother concentration pairs in their analysis (i.e., of 135 mothers and 138 infants). Approximately 52% of the infants were female, and their median age at blood collection was 13 weeks. The mothers’ median age was 32 years. About 82% of mothers were receiving monotherapy. The investigators found no demographic differences between groups of mothers taking various AEDs.
Sixty-eight infants (49.3%) had AED concentrations that were less than the lower limit of quantification. AED concentration was not greater than the lower limit of quantification for any infants breastfed by mothers taking carbamazepine, oxcarbazepine, valproic acid, or topiramate. Most levetiracetam (71.4%) and zonisamide (60.0%) concentrations in infants were less than the lower limit of quantification. Most lamotrigine concentrations in infants (88.6%) were greater than the lower limit of quantification.
The median percentage of infant-to-mother concentration was 28.9% for lamotrigine, 5.3% for levetiracetam, 44.2% for zonisamide, 5.7% for carbamazepine, 5.4% for carbamazepine epoxide, 0.3% for oxcarbazepine, 17.2% for topiramate, and 21.4% for valproic acid. Multiple linear regression models indicated that maternal concentration was significantly associated with lamotrigine concentration in infants, but not levetiracetam concentration in infants.
“Prior studies at delivery demonstrated that umbilical-cord concentrations were nearly equal to maternal concentrations, suggesting extensive placental passage to the fetus,” wrote Dr. Birnbaum and colleagues. “Therefore, the amount of AED exposure via breast milk is likely substantially lower than fetal exposure during pregnancy and appears unlikely to confer any additional risks beyond those that might be associated with exposure in pregnancy, especially given prior studies showing no adverse neurodevelopmental effects of breastfeeding while taking AEDs.”
The investigators acknowledged several limitations of their research, including the observational design of the MONEAD study. The amount of AED in participants’ breast milk is unknown, and the investigators could not calculate relative infant dosages. Only one blood sample was taken per infant, thus the results may not reflect infants’ total exposure over time.
The National Institute of Neurological Disorders and Stroke and the National Institute of Child Health and Development funded the research. The authors reported receiving research support from various pharmaceutical companies.
SOURCE: Birnbaum AK et al. JAMA Neurol. 2019 Dec 30. doi: 10.1001/jamaneurol.2019.4443.
FROM JAMA NEUROLOGY