Abstracts

Rationale: Breastfeeding provides benefits to the mother and child and is strongly recommended by the American Academy of Pediatrics. However, women on anti-epileptic drugs (AEDs) may be discouraged from breastfeeding due to concerns of possible adverse effects of continued exposure to AEDs in the developing infant. We measured the blood concentrations of several AEDs in breastfed infants from mothers with epilepsy to provide objective information for decision making by clinicians and patients. Methods: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational multi-center investigation of pregnancy outcomes for both the mother and child. The MONEAD study enrolled pregnant women with epilepsy (PWWE) from 20 clinical sites, and two other control groups, not pertinent to this analysis. Enrollment of PWWE occurred up to 20 weeks gestational age and they were followed until 9 months postpartum. At birth, the children were enrolled in the MONEAD study. Dried blood spot (DBS) samples were collected for AED measurements from a free flowing drop of blood from the plantar surface of the baby's warmed heel in breastfeeding infants between 6 weeks and 3 months of age. All AED measurements were measured in a CLIA/CAP-certified laboratory and based on calculated whole blood to plasma ratios in adults. All samples were run within one week of collection. The plasma equivalent lower limits of quantification (LLoQ) were reported as follows in ug/ml: lamotrigine (0.1), levetiracetam (1.8), carbamazepine (0.7), and oxcarbazepine (0.1). Results: The MONEAD study enrolled 351 PWWE, who have given birth to 338 infants thus far. As of June 1, 2016, AED concentrations have been measured in DBS from 121 breastfeeding infants. The higher total number of AEDs assayed reflects polytherapy in some women. The number of infants who had levels below LLoQ reported over the total number of infants with DBS measurements, were as follows for each of the AEDs: lamotrigine (6/64), levetiracetam (40/54), carbamazepine (9/9), and oxcarbazepine (7/7). The mean concentrations in breastfed infants with detectable amounts were as follows: lamotrigine (2.2 ug/ml), and levetiracetam (2.6 ug/ml). Conclusions: Nearly half of the infant AED concentrations measured to date via DBS as whole blood were below the respective AED LLoQ. Of the measureable AED concentrations, values were below the therapeutic ranges used for epilepsy treatment. Our findings may explain why prior studies have found no adverse neurodevelopment effects of breastfeeding while taking an AED. The children in the MONEAD study will be followed with neuropsychometric testing until age 6 years to determine if this finding extends to other AEDs in mono- and polytherapy. Future analyses will include paired maternal drug concentrations, maternal dosing, proximity to sample collection, and effects of exclusive versus partial breastfeeding to provide calculations that can be extrapolated to other mother-child pairs in clinical practice. Funding: NINDS U01-NS038455