In utero antiseizure med exposure may not affect early neurodevelopment in children

Exposure to antiseizure medications during pregnancy does not appear to affect neurodevelopmental outcomes in offspring at age 3 years, according to results of the MONEAD* study presented at AAN 2021.

“[O]ur study results are reassuring to women with epilepsy who may be considering pregnancy as we found no neurodevelopmental or neuropsychological problems in 3-year-old children linked to antiseizure medications,” said study author Professor Kimford Meador from Stanford University Medical Center, Stanford, California, US.

Researchers of this prospective, multicentre, observational study enrolled 275 pregnant women with epilepsy and 77 healthy pregnant women to assess the outcome of exposure to antiseizure medications in their children at age 3 years (289 and 89 children, respectively). The outcome examined was Verbal Index score which was calculated based on the average of Differential Ability Scales-II (DAS-II) Naming Vocabulary and Verbal Comprehension subtests, Preschool Language Scale-5 Expressive Communication and Auditory Comprehension subscales, and Peabody Picture Vocabulary Test-4.

At enrolment, 74 percent of the pregnant women with epilepsy were on monotherapy, which was mainly lamotrigine (43 percent) or levetiracetam (37 percent). Twenty-two percent of women with epilepsy were on multiple therapies, 44 percent of whom were on a lamotrigine-levetiracetam combination. The remaining 4 percent were not on any antiseizure medications.

After adjusting for maternal education and IQ, Verbal Index scores at age 3 years were comparable between children born to women with epilepsy (least squares [LS] mean 103.4, 95 percent confidence interval [CI], 102.1–104.6) and those born to healthy women (LS mean, 102.7, 95 percent CI, 100.2–105.1). [AAN 2021, programme number S1.001]

Among 251 women whose maximum blood levels of antiseizure medication in the third trimester were assessed, levels of said medications did not appear to affect neurodevelopment in their children (adjusted parameter estimate, -1.2, 95 percent CI, -6.2 to 3.8).

Secondary analysis showed that children born to women with epilepsy and healthy women did not differ with regard to DAS-II Non-Verbal Index and General Conceptual Ability scores, with no exposure-dependent effects of antiseizure medication observed in children born to women with epilepsy.

Meador pointed out certain factors that affected the outcomes in children. For example, higher maternal IQ or educational level was associated with a better outcome in children, while postpartum anxiety was associated with a worse outcome.

“Having a seizure during pregnancy may not only harm the mother but possibly the baby as well, so seizure control is an important part of prenatal care,” noted Meador.

“Yet, antiseizure drugs are known to cause birth defects or neurobehavioural problems, but these effects vary widely with some having very low risks but others having substantial risks. While the risks for some medications are known, and careful planning can result in healthy pregnancies, there are some newer medications for which the longer-term effects are still not fully known.”

“When a woman of childbearing potential receives an antiseizure medication, she should be advised by her physician to determine the best medication to control seizures and minimize any risks to the baby,” said Meador.

The authors cautioned that these outcomes at age 3 years may not be predictive of those in adolescence and adulthood. Furthermore, a majority of the current study population were on lamotrigine or levetiracetam which may differ from that of other populations.

Despite the positive findings, further research is warranted, said Meador. He referred to an upcoming analysis of this population when the children are age 4–6 years, where the primary outcome will be cognitive outcomes at age 6 years which may be more predictive of school performance and adult cognitive abilities.