Antiepileptic use during breastfeeding not associated with adverse cognitive outcomes

1. At 6 years old, children of breastfeeding mothers on antiepileptics had, on average. a 4 point higher IQ than children of epileptic mothers who were bottlefed. 

2. Breastfed children scored 4 points higher on verbal abilities compared with bottle-fed counterparts.  

Evidence Rating Level: 2 (Good)

Study Rundown: Antiepileptic drugs (AEDs) have been shown to cause widespread neuronal apoptosis in the immature brain, which can lead to future cognitive disabilities in children who are exposed in utero. It is biologically plausible that exposure in infancy, when the brain is still developing, might also cause cognitive dysfunction down the line, such that exposure to maternal AEDs in infancy via breastmilk might represent an especially vulnerable exposure. But with so many known benefits of breastfeeding—a more robust immune system, lower rates of obesity and diabetes, and even potentially improved cognition— mothers are left with a dilemma.

In a previous investigation, researchers used data from the Neurodevelopmental Effects of Antiepileptic Drugs study, a longitudinal study assessing AED exposure and cognitive development, to assess for differences in early developmental outcomes among infants of mothers on AEDs. Among children born to mothers on antiepileptic drugs, researchers found no significant difference in the IQ at 3 years of age between those who were breastfed and those who were not. In the present work, researchers expanded on current knowledge by evaluating longer-term outcomes and found that at 6 years of age, breast milk exposure to AEDs was not associated with adverse outcomes and in fact was associated with an average 4 point increase in IQ compared to infants who were bottlefed. Strengths of this study include multi-national cohort, prospective design and sufficient power to stratify analysis by AED type. Limitations include small sample size, selection bias and lack of an unexposed control group (all cohort members had previously been exposed to AEDs in utero). Furthermore, there was no adjustment for AED dosage during breastfeeding or amount of breastfeeding. Future studies might include a control group of breastfed children who were not exposed to AEDs in utero, to better understand whether breastfeeding is simply not harmful, or might correct for cognitive deficits obtained from in utero exposure to AEDs. Additionally, the similarity of IQ and verbal ability scores between groups calls for additional investigation into whether statistical significance confers clinical significance.

Click to read the study in JAMA Pediatrics

Click to read an accompanying editorial in JAMA Pediatrics

Relevant Reading: Effects of breastfeeding in children of women taking antiepileptic drugs

In-Depth [prospective cohort]: Researchers in the United States and the United Kingdom enrolled pregnant women with epilepsy receiving monotherapy (carbamazepine, lamotrigine, phenytoin, or valproate) and compared breastfed infants with those who were not. The primary outcome was IQ at age 6. Secondary outcomes included verbal, nonverbal, memory, and executive functions.

Of the 177 mothers and 181 children, 42.9% were breastfed for a mean of 7.2 months, with no significant difference between AED type on either parameter. Among children born to mothers on antiepileptic drugs, children who were breastfed had a higher IQ than those who were not (108 vs. 104, p=0.04). Verbal abilities were also higher in breastfed infants (105 vs. 102, p=.03), but there was no significant difference found for other cognitive domains.

Image: PD 

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