Importance: There is limited information on infant drug exposure via breastfeeding by mothers who are receiving antiepileptic drug therapy. Objective: To provide direct, objective information on antiepileptic drug exposure through breast milk. Design, Setting, and Participants: This prospective cohort study was conducted between December 2012 to October 2016, with follow-up in children until 6 years of age at 20 sites across the United States. Data were collected via an observational multicenter investigation (Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs [MONEAD]) of outcomes in pregnant mothers with epilepsy and their children. Pregnant women with epilepsy who were aged 14 to 45 years, had pregnancies that had progressed to less than 20 weeks' gestational age, and had measured IQ scores of more than 70 points were enrolled and followed up through pregnancy and 9 postpartum months. Their infants were enrolled at birth. Data were analyzed from May 2014 to August 2019. Exposures: Antiepileptic drug exposure in infants who were breastfed. Main Outcomes and Measures: The percentage of infant-to-mother concentration of antiepileptic drugs. Antiepileptic drug concentrations were quantified from blood samples collected from infants and mothers at the same visit, 5 to 20 weeks after birth. Concentrations of antiepileptic drugs in infants at less than the lower limit of quantification were assessed as half of the lower limit. Additional measures collected were the total duration of all daily breastfeeding sessions and/or the volume of pumped breast milk ingested from a bottle. Results: A total of 351 women (of 865 screened and 503 eligible individuals) were enrolled, along with their 345 infants (179 female children [51.9%]; median [range] age, 13 [5-20] weeks). Of the 345 infants, 222 (64.3%) were breastfed; the data collection yielded 164 matching infant-mother concentration pairs from 138 infants. Approximately 49% of all antiepileptic drug concentrations in nursing infants were less than the lower limit of quantification. The median percentage of infant-to-mother concentration for all 7 antiepileptic drugs and 1 metabolite (carbamazepine, carbamazepine-10,11-epoxide, levetiracetam, lamotrigine, oxcarbazepine, topiramate, valproate, and zonisamide) ranged from 0.3% (range, 0.2%-0.9%) to 44.2% (range, 35.2%-125.3%). In multiple linear regression models, maternal concentration was a significant factor associated with lamotrigine concentration in infants (Pearson correlation coefficient, 0.58; P <.001) but not levetiracetam concentration in infants. Conclusions and Relevance: Overall, antiepileptic drug concentrations in blood samples of infants who were breastfed were substantially lower than maternal blood concentrations. Given the well-known benefits of breastfeeding and the prior studies demonstrating no ill effects when the mother was receiving antiepileptic drugs, these findings support the breastfeeding of infants by mothers with epilepsy who are taking antiepileptic drug therapy.
Bibliographical noteFunding Information:
received research support from the National Institutes of Health, Epilepsy Foundation, Supernus Pharmaceuticals, and Veloxis Pharmaceuticals and is also a coinventor of a patent for intravenous carbamazepine (Lundbeck Pharmaceuticals). Dr Meador has received research support from the National Institutes of Health and Sunovion Pharmaceuticals and travel support from UCB Pharma; the Epilepsy Study Consortium pays Dr Meador’s university for his research consultant time for Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB Pharma, and Vivus Pharmaceuticals. Dr Gerard received research support from Sage Pharmaceuticals and Sunovion Pharmaceuticals and received speaker and travel funds from UCB Pharma. Dr Penovich has served on speakers’ bureaus for Eisai, Sunovian, GW Pharmaceuticals, Aquestive Therapeutics, and UCB. Dr Cavitt received research support from the National Institute of Neurological Disorders and Stroke and GW Pharmaceuticals. Dr Pack received royalties for the website UpToDate. Dr Miller has received grant and research support from the National Institutes of Health, Medtronic, the US Centers for Disease Control and Prevention, SK Biopharmaceuticals, Eisai, and Xenon Pharma and has a financial relationship with Therma Neurosciences Inc involving advisory board participation and patents. Dr Pennell has received research support from the National Institutes of Health and the Epilepsy Foundation and honoraria and travel support from American Epilepsy Society, American Academy of Neurology, Epilepsy Foundation, National Institutes of Health, and academic institutions for continuing medical education lectures. No other disclosures were reported.
Funding/Support: This work was supported by National Institute of Neurological Disorders and Stroke and National Institute of Child Health and Development (grants U01-NS038455 [Drs Meador and Pennell]), U01-NS050659 [Dr May], and 2U01-NS038455 [Drs Meador, Pennell, and May]).
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