In 2013, a prospective cohort study completed by Gyri Veiby’s scientific team was published in JAMA NEUROLOGY, Vol. 70, No. 11. The study was designed to determine whether children with a history of embryonic antiepileptic drug exposure showed signs of impaired development in the first month of life and to explore whether mothers taking antiepileptic drugs while breastfeeding had potential adverse effects on their infants. The study found that embryonic antiepileptic drug exposure, especially co-exposure to multiple antiepileptic drugs, was associated with impairment in fine motor skills that manifested by 6 months of age; however, no harmful effects were seen with concurrent antiepileptic drug administration while breastfeeding. Therefore, the authors concluded that mothers with epilepsy who are being treated with antiepileptic drugs should be encouraged to breastfeed their children. In response to these studies, Professor Meador of the Department of Neurology and Neuroscience at Stanford University School of Medicine published a mini-review and recommendations. The full text is translated as follows: The effects of antiepileptic drugs (AEDs) during development are poorly understood; the association between embryonic AED exposure and congenital malformations was first reported in the 1960s; by the early 1980s, the first reports of a specific AED causing a specific congenital malformation (e.g., valproic acid causing cleft lip and palate) were published. Only recently has attention been paid to the risk of congenital malformations, mental retardation, and behavioral disorders resulting from various embryonic AED exposures. Concerns about the effects of AEDs on cognitive and behavioral abilities exist not only in the case of embryonic exposures (in the case of AEDs) but also in the case of exposures occurring through breast milk. Because of the risks associated with epileptic seizures (e.g., maternal respiratory arrest due to epileptic seizures, which can deprive the fetus of oxygen in utero), women with epilepsy generally cannot discontinue AEDs during pregnancy. In this context, the morphologic and behavioral teratogenic risks associated with effective AEDs should be central to the clinical decision making process In the postpartum period, the absence of breastfeeding allows the infant to avoid additional exposure to AEDs. However, the risks associated with the administration of AEDs while breastfeeding remain theoretical due to the lack of research data to support them. In contrast, there is a wealth of information supporting the idea that breastfeeding is beneficial for both mother and child. The benefits of breastfeeding for children include reduced risk of severe lower respiratory infections, allergic dermatitis, asthma, acute otitis media, non-specific gastroenteritis, obesity, type 1 and type 2 diabetes, childhood leukemia, sudden infant death syndrome, and necrotizing enterocolitis; and a possible positive effect on cognitive performance in young children. The benefits of breastfeeding for mothers include reduced risk of type 2 diabetes, breast cancer, ovarian cancer, and postpartum depression. (After administration of AEDs) Many AEDs are detectable in breast milk to varying degrees, but the long-term effects of AED exposure occurring through breast milk on neurodevelopment remain uncertain. In the study mentioned above, Gyri Veiby et al. reported comparative results on developmental outcomes of breastfed and non-breastfed children in the presence of maternal administration of AEDs. The main outcome variable of the study was the mother’s rating of the toddler’s developmental and behavioral abilities according to a standardized scale. The AEDs most commonly applied by mothers in the study were carbamazepine, lamotrigine, and valproic acid. The investigators found no statistical difference between the breastfeeding and non-breastfeeding groups (when mothers applied AEDs); and, children in the breastfeeding group tended to have fewer developmental abnormalities. The study had the following advantages: prospective design, evaluated women with and without AEDs during pregnancy, included fathers with epilepsy (a factor), a large reference group, and evaluated many potential confounding variables. The weaknesses of the study were: reliance on self-report for epilepsy diagnosis; lack of information on epilepsy classification, seizure severity, maternal dose/in vivo levels of AEDs applied, maternal intelligence level, and maternal socioeconomic status; lack of levels of AEDs in young children receiving breastfeeding; small number of cases in each subgroup of AEDs; failure to apply blinding when mothers performed developmental assessments for young children; retention rate at 36 months of age 60.2%; and other potential confounding factors. Only 1 previously published study has evaluated the effects of mothers taking AEDs while breastfeeding on the neurodevelopment of young children. The study, Neurodevelopmental Effects of Antiepileptic Drugs (NEAD), is a multicenter prospective study of the neuropsychiatric effects of embryonic AED exposure in women with epilepsy in early pregnancy (with carbamazepine, lamotrigine, phenytoin sodium, or triazine, phenytoin sodium, or valproic acid monotherapy). Children in the breastfeeding and non-breastfeeding groups were assessed at 3 years of age (the assessor was unaware of the subject’s medication and feeding status), and adjusted intelligence quotient (IQ) scores did not differ between the two groups. Thus, 2 prospective, well-controlled studies confirmed the absence of any adverse effects on cognitive function with concomitant breastfeeding on AEDs. Similar to ethanol, some AEDs induce apoptosis and dysfunction of viable neuronal cells in the immature brain. This effect is dose-dependent and can occur with a single exposure, while its magnitude depends on the peak concentration of AEDs. The level of AEDs in breastfed children depends on the amount of AEDs in breast milk, the amount of breast milk consumed and absorbed, and the clearance rate of AEDs. Although data on AED serum levels in breastfed infants are lacking, it is likely that for most AEDs, the levels of AEDs in breastfed infants who are exposed are lower than the levels of AEDs in fetuses who are exposed in utero. Since the in vivo AED levels are lower with breast milk exposure than with intrauterine exposure, breastfeeding may not add any adverse effects. The Veiby et al. study also found that young children exposed to AEDs during embryonic life showed a higher risk of impaired fine motor skills at 6 months of age (11.5% vs. 4.8% in controls). The team previously reported data at 18 months of age and 36 months of age. There were no significant differences in young children whose mothers had epilepsy but were not medicated or whose fathers had epilepsy compared with controls. Embryonic AED-exposed toddlers had significant abnormalities in gross motor scores (7.5% vs. 3.3%), intact utterance skills (11.2% vs. 4.8%), and autistic tendencies (6.0% vs. 1.5%) at 36 months of age compared to controls. Although all subgroups were small, all 3 major AEDs (carbamazepine, lamotrigine, and valproic acid) were able to cause impairment. In contrast, the previously mentioned NEAD study recently reported greater cognitive and behavioral impairment in 6-year-olds with a history of valproic acid exposure compared with 6-year-olds with a history of exposure to other AEDs when the mother had epilepsy and was taking AEDs (carbamazepine, lamotrigine, phenytoin sodium, and valproic acid). The difference in results between the two studies may be related to the use of a blinded method for formal cognitive function assessment and control for maternal intelligence in the NEAD study. Although more information is needed to fully characterize the risks and benefits, the positive effects of breastfeeding are well established, whereas the risks associated with breastfeeding while taking AEDs are only theoretical; this theoretical risk has also not been confirmed by the 2 prospective clinical studies mentioned above. In addition, there is speculation that the adverse effects of embryonic AED exposure may not be superimposed by lactational AED exposure. In summary, it is more important to inform female patients in detail about the known benefits and potential risks of the act of breastfeeding than to inform them in general terms that it is unsafe to take AEDs while breastfeeding. Furthermore, based on the available information, it is reasonable to provide mothers who have been on AEDs during pregnancy with recommendations to encourage breastfeeding. Additional precautions should be communicated to women who started AEDs only after delivery; especially those AEDs that are known to be associated with adverse effects in the immature brain (and should be more preached to).