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Original Investigation
December 30, 2019

Antiepileptic Drug Exposure in Infants of Breastfeeding Mothers With Epilepsy

Author Affiliations
  • 1Experimental & Clinical Pharmacology, University of Minnesota, Minneapolis
  • 2Department of Neurology & Neurological Sciences, Stanford University, Stanford, California
  • 3The Emmes Corporation, Rockville, Maryland
  • 4Department of Neurology, Northwestern University, Chicago, Illinois
  • 5Department of Neurology, Emory University, Atlanta, Georgia
  • 6Minnesota Epilepsy Group, Saint Paul
  • 7Department of Neurology, University of Southern California, Los Angeles
  • 8University of Cincinnati, Cincinnati, Ohio
  • 9Neurology, Columbia University, New York, New York
  • 10Department of Neurology, University of Washington, Seattle
  • 11Department of Psychiatry, University of Wisconsin at Madison, Madison
  • 12Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 13Department of Neurological Surgery, University of Washington, Seattle
JAMA Neurol. Published online December 30, 2019. doi:10.1001/jamaneurol.2019.4443
Key Points

Question  What is the extent of drug exposure via breastfeeding in infants whose mothers are receiving antiepileptic drug therapy?

Findings  In this prospective cohort study, the median percentage of infant-to-mother concentration for 7 antiepileptic drugs ranged from 0.3% to 44.2% in 164 infant-mother concentration pairs. For infants with mothers receiving lamotrigine therapy, infant concentrations were associated with maternal concentrations.

Meaning  In this study, the overall drug exposure was low in infants who were breastfed by mothers with epilepsy who were receiving antiepileptic drug therapy, and the findings add further support to breastfeeding by these mothers.


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.

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