Women who take epilepsy drugs while they are pregnant may have a lower risk of having a child with delays in language skills if they take folic acid supplements before and early in pregnancy, according to a study published in the August 1, 2018, online issue of Neurology.
The study found that among children whose mothers took epilepsy drugs while they were pregnant, those whose mothers did not take folic acid supplements were four times more likely to have delays in their language skills when they were 18 months old compared to children of mothers without epilepsy whose mothers did not take folic acid supplements. By three years old, those whose mothers took no supplements were nearly five times as likely to have language delays compared to children of mothers without epilepsy.
The study was conducted in Norway, where the government does not require foods to be fortified with folic acid, which is required in the United States. Even with folic acid added to foods, taking additional supplements is recommended for pregnant women in the United States.
“These results are important for women with epilepsy all over the world because many epilepsy drugs interact with the way folate is metabolized by the body, so we are still learning how much folic acid is needed for women with epilepsy and how it benefits their children,” said study author Elisabeth Synnøve Nilsen Husebye, MD, of the University of Bergen in Bergen, Norway.
The study involved 335 children of mothers with epilepsy who took epilepsy drugs while they were pregnant and 104,222 children of mothers without epilepsy. Maintaining effective epilepsy treatment during pregnancy is important because seizures may cause harm to the fetus and the mother.
Researchers collected information on use of epilepsy drugs and folic acid supplements. Parents filled out surveys about their children’s language development at 18 months and three years.
Among the children whose mothers did not take folic acid, 34 percent of the children of mothers with epilepsy had delayed language skills at 18 months, compared to 11 percent of the children whose mothers did not have epilepsy. At three years old, 24 percent of the children of mothers with epilepsy had a delay in expressive language skills, compared to 6 percent of those with mothers without epilepsy.
Among the children whose mothers did take folic acid, 17 percent of children of mothers with epilepsy had language delay at 18 months, compared to 11 percent in the control group.
The results remained the same after researchers controlled for other factors that could affect language skills, such as education level of the parents, smoking and alcohol use during pregnancy and gestational age.
Husebye also noted that the mothers of children exposed to epilepsy drugs with language delays started taking folic acid later in pregnancy, with the average starting at week 6.5 of pregnancy for those with language delay at 18 months. Mothers with children exposed to epilepsy drugs with no delays in language skills most often started taking folic acid three weeks before they conceived.
“The apparently protective effect of taking folic acid supplements was striking,” Husebye said. “Half of the risk of having language delays at 18 months could be attributed to the lack of folic acid in children exposed to epilepsy drugs, while in children of mothers without epilepsy only 6 percent of the risk was attributed to the lack of supplements.”
Husebye also noted that the critical period for supplementation to prevent language delays was from four weeks before the start of pregnancy until the end of the first trimester.
A limitation of the study was that the children’s language skills were not assessed by a researcher but provided by the parents.
Funding: The study was supported by Norwegian Ministry of Health and Care Services and Ministry of Education and Research and the US National Institutes of Health, National Institute of Environmental Health Sciences and National Institute of Neurological Disorders and Stroke.
Source: Renee Tessman – ANN
Publisher: Organized by NeuroscienceNews.com.
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Original Research: Abstract for “Verbal abilities in children of mothers with epilepsy: Association to maternal folate status” by Elisabeth Synnøve Nilsen Husebye, Nils Erik Gilhus, Bettina Riedel, Olav Spigset, Anne Kjersti Daltveit, Marte Helene Bjørk in Neurology. Published August 16 2018.
Verbal abilities in children of mothers with epilepsy: Association to maternal folate status
To examine the effect of maternal folic acid supplementation and maternal plasma folate and antiepileptic drug (AED) concentrations on language delay in AED-exposed children of mothers with epilepsy.
Children of mothers with and without epilepsy enrolled from 1999 to 2008 in the Norwegian Mother and Child Cohort study were included. Information on medical history, AED use, and folic acid supplementation during pregnancy was collected from parent-completed questionnaires. Maternal plasma folate and maternal plasma and umbilical cord AED concentrations were measured in blood samples from gestational weeks 17 to 19 and immediately after birth, respectively. Language development at 18 and 36 months was evaluated by the Ages and Stages Questionnaires.
A total of 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy were surveyed. For those with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratio (OR) for language delay in AED-exposed children compared to the controls at 18 months was 3.9 (95% confidence interval [CI] 1.9–7.8, p < 0.001) and at 36 months was 4.7 (95% CI 2.0–10.6, p < 0.001). When folic supplementation was used, the corresponding ORs for language delay were 1.7 (95% CI 1.2–2.6, p = 0.01) and 1.7 (95% CI 0.9–3.2, p = 0.13), respectively. The positive effect of folic acid supplement use on language delay in AED-exposed children was significant only when supplement was used in the period from 4 weeks before the pregnancy and until the end of the first trimester.
Folic acid use early in pregnancy may have a preventive effect on language delay associated with in utero AED exposure.