Results from a large, population-based study from Swedish researchers show that children of mothers who took antiepileptics while pregnant could face developmental problems into their teenage years. In fact, such children had a nearly threefold greater chance of not receiving a grade at the end of their required education at age 16, which in Sweden usually means the child had been attending a special school for those with intellectual disabilities.

Interestingly, the study, led by Lisa Forsberg, MD, Karolinska Institute, Stockholm, found no association between antiepileptic monotheraphy and not receiving a grade.

"Our results support the current recommendations on pharmacologic polytherapy of women with epilepsy; namely, that if adequate seizure control can be obtained, it should be replaced with monotherapy during pregnancy in order to reduce the risk of poor cognitive outcomes," wrote the authors in Epilepsia, citing 2009 guidelines from the American Academy of Neurology and the American Epilepsy Society.

National registries and a single Stockholm hospital study were used to identify 1,235 children from 1973 to 1986 so they could look at long-term neurodevelopmental outcomes of children who were born to mothers who had epilepsy during pregnancy. Medical records were reviewed to quantify antiepileptic use. Educational outcomes for these children were compared to those of roughly 1.3 million children born during the same period to mothers without epilepsy.

Of mothers who had epilepsy, 641 were on monotherapy during pregnancy and 429 were on polytherapy. No record of antiepileptic use was available for 165 mothers with epilepsy, which the researchers point out doesn’t necessarily mean they were not on such therapy.

Forsberg and colleagues found that children whose mothers had epilepsy had a greater chance of not receiving a final grad from a compulsory school than those in the control group, regardless of antiepileptic exposure and after adjusting for year of birth, maternal age, parity, and maternal education level. After excluding children with congenital malformation, findings remained similar.

Along with the link between overall academic achievement and antiepileptic therapy, the team also looked at success in mathematics, Swedish, English, and sports among children without malformations. Increased odds of not passing and decreased odds of passing with excellence were seen in all four areas for children of mothers with epilepsy. Further, a lower chance of passing with excellence in math, English, and Swedish was seen among children who were exposed to carbamazepine monotherapy compared to those exposed to phenytoin monotherapy.

Based on the limited analysis allowed by the use of registry data in the current study, further research should control for such factors as socioeconomic factors, maternal IQ, maternal antiepileptic dose and blood levels during pregnancy, number of seizures during pregnancy, maternal comorbidities, and medical history of the children.

Questions for neurologists

What will you tell your female epileptic patients of childbearing age based on the results of this study? Should such patients be warned of the potential in utero harm of antiepileptics? If they desire to become pregnant but are at high risk for having seizures, what other options do they have for treatment aside from antiepileptic agents?

Questions for pediatricians

Have you ever thought to look at parental history of epilepsy in patients with learning disabilities? How would such knowledge help you treat these patients.