ARTICLE IN BRIEF
An analysis of data from the Neurodevelopmental Effects of Antiepileptic Drugs study found that the children who were breastfed had higher IQ scores and higher verbal index scores at age 6 than those who were not breastfed.
Does breastfeeding in mothers who take antiepileptic drugs (AEDs) affect cognitive outcomes in their children?
Not according to a new analysis by investigators who reported their findings at the American Epilepsy Society annual meeting earlier this month. The investigators found that the children who had been breastfed by women taking AEDs did not have worse cognitive outcomes at 6 years of age.
The study — which used data collected from the NEAD (Neurodevelopmental Effects of Antiepileptic Drugs) study, an observational, multicenter study in the US and UK — found that the children who were breastfed actually had higher IQ scores and higher verbal index scores at age 6 than those who were not breastfed. [See “Data on Breastfeeding and AEDs.”]
The study was a follow-up on the cognitive outcomes of children whose mothers had taken carbamazepine, lamotrigine, phenytoin, or valproate while they were pregnant. It's the only cohort in which breastfed children of mothers on AEDs have been compared with the children of mothers who did not take AEDs while breastfeeding.
Despite the well-known benefits of breastfeeding on the development of children, there is still some consternation about women breastfeeding while they're taking AEDs, said study author Kimford Meador, MD, professor of neurology at Stanford University, who was at Emory at the time of the study.
“I have women all the time coming into the clinic stating a doctor or nurse told them, ‘Never breastfeed,’ a conclusion based solely on a theoretical risk without any data,” Dr. Meador said. “But the data doesn't seem to support that concern.”
The researchers previously showed that there were no adverse effects on IQ at age 3 years from breastfeeding while mothers were taking AEDs. But IQ at age 6 is more predictive of how children will perform in school and of their intelligence as adults.
And at age 6, the overall IQ for the children who were breastfed was 108, while the IQ for those who weren't breastfed was 104. Those are figures after adjustment for the IQ of the mother, AED group, AED dose, and preconceptual folate level.
As seen in previous studies, the IQs for the children of mothers who were taking valproate the lowest among the four drugs, with an IQ at age 6 of 105 for those who were breastfed and 94 for those who were not breastfed.
Other cognitive domains — including Verbal Index, Non-verbal Index, Memory Index, and Executive Index — were assessed at age 6 as well. But only Verbal Index showed a higher value for those who were breastfed, compared to those who were not (p=.03).
Dr. Meador said the results should be reason for doctors to encourage women on AEDs to breastfeed their children if they want to, since there seems to be nothing adverse about doing so.
“Even if you don't think that the positive IQ effect here is real, there's certainly no indication of a negative cognitive effect, and there are other known positive effects of breastfeeding,” he said. “That's why I think if women want to breastfeed, I think it's fine. That's the general take-home message for women that I follow.”
He stressed that the findings only apply to women who have already been on AEDs while pregnant, and not the unusual cases of women who might have had to start taking AEDs after delivering a baby.
Dr. Meador said that one explanation of the findings is that perhaps it's the peak dose that matters, and not the duration of the exposure, as has been found in animal studies.
“The peak levels are going to be much less in the children being breastfed than they're going to be in children in the womb — the level's going to be the same in the womb as it is for the mother,” he said. But in breastfed children, “how much is secreted in the milk? How much do they take in? How fast does the child metabolize the drug? All these other factors come into play.”
It might be a matter of, “If they're going to have a problem, they've already taken the hit in utero,” he said.
It's better to “take the known benefit rather than the theoretical risk,” he added.
He acknowledged that the “quantification of breastfeeding is not as good as I would like and we did not measure AED levels in the child.” He is leading an ongoing new study with women on AEDs in which the exposure will be quantified, and the level of the drugs in the children's blood will be measured.
W. Allen Hauser, MD, professor of neurology and epidemiology at the College of Physicians and Surgeons and Mailman School of Public Health at Columbia University, said that the study might help turn around common perceptions that might lessen the likelihood of breastfeeding while on AEDs.
“I think the general perception is if you're taking drugs of any sort, you probably shouldn't breastfeed because there's some likelihood of transmission to the child,” he said. “What this study shows is that, at least in terms of cognitive effects, the levels that are transmitted are not great enough to cause any cognitive problems.... This provides hard evidence that some of the concerns that people might have are not there.”
In the end, he said, these are findings that can have immediate clinical impact. “It's quite useful for any physician who's trying to consult women with epilepsy who want to have children or want to have a child,” he said.
Cynthia Harden, MD, chief of the Division of Epilepsy and Electroencephalography at Hofstra-North Shore LIJ School of Medicine, said the most surprising finding was that the valproate group's IQ increased by 10 points, into a normal range, in the breastfeeding group.
“Environmental factors were well-controlled for across the groups, therefore, these results raise the question as to whether breast-feeding can help mitigate the cognitive teratogenesis of valproate exposure during development,” she said.
She added, though, that “the mechanism of the possible beneficial effect of breastfeeding in the setting of valproate exposure is unknown and somewhat mysterious.”
DATA ON BREASTFEEDING AND AEDS
- Analysis included 181 children born to women with epilepsy of childbearing age who were enrolled in the NEAD study from 1999 to 2004 and who were on AED monotherapy during pregnancy and after delivery.
- At age 6, children for whom there was also data on breastfeeding were assessed using the Differential Abilities Scales. Other cognitive domains were tested as well, including verbal index, non-verbal index, and executive index.
- 43 percent of the children were breastfed, for an average duration of six months.
- AEDs were carbamazepine, lamotrigine, phenytoin, and valproate.
- No cognitive deficits were found in those who were breastfed. IQ was higher in the breastfed group.