Data from: Verbal abilities in children of mothers with epilepsy: association to maternal folate status

Objective: 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.
Methods: Children of mothers with and without epilepsy enrolled 1999-2008 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 week 17-19 and immediately after birth, respectively. Language development at 18 and 36 months was evaluated by the Ages and Stages Questionnaires.
Results: 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 OR for language delay in AED exposed children compared to the controls at 18 months was 3.9 (CI 1.9-7.8, p<0.001) and at 36 months 4.7 (CI 2.0-10.6, p<0.001). When folic supplementation was used, the corresponding ORs for language delay were 1.7 (CI 1.2-2.6, p=0.01) and 1.7 (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 only significant when supplement was used in the period from four weeks before the pregnancy and until the end of the first trimester.
Conclusion: Folic acid use early in pregnancy may have a preventative effect on language delay associated with in utero AED exposure.

研究目的：探讨母亲叶酸补充情况、母体血浆叶酸水平及抗癫痫药物（antiepileptic drug, AED）浓度，对罹患癫痫的母亲所产下的、宫内暴露于抗癫痫药物的儿童的语言发育迟缓的影响。
研究方法：纳入1999年至2008年于挪威母婴队列研究（Norwegian Mother and Child Cohort study）中入组的、母亲罹患或未罹患癫痫的儿童。通过家长填写的调查问卷收集孕期既往病史、抗癫痫药物使用情况及叶酸补充相关信息。分别于妊娠17~19周采集母体血液样本、产后即刻采集脐带血样本，以检测母体血浆叶酸水平、母体血浆及脐带血中的抗癫痫药物浓度。采用年龄与发育进程问卷（Ages and Stages Questionnaires）评估儿童在18月龄及36月龄时的语言发育水平。
研究结果：本研究共纳入335名母亲罹患癫痫且胎儿暴露于抗癫痫药物的儿童，以及104222名母亲未罹患癫痫的儿童。在未接受围孕期叶酸补充的亚组中，经完全校正混杂因素后，18月龄时暴露于抗癫痫药物的儿童相较于对照组的语言发育迟缓比值比（odds ratio, OR）为3.9（95%置信区间1.9~7.8，p<0.001），36月龄时该比值比为4.7（95%置信区间2.0~10.6，p<0.001）。若母亲使用叶酸补充剂，则上述对应的语言发育迟缓比值比分别为1.7（95%置信区间1.2~2.6，p=0.01）及1.7（95%置信区间0.9~3.2，p=0.13）。仅当叶酸补充始于孕前4周且持续至妊娠首孕期末时，叶酸补充对暴露于抗癫痫药物的儿童的语言发育迟缓才具有显著的改善作用。
研究结论：妊娠早期使用叶酸补充剂，可能对宫内暴露于抗癫痫药物的儿童所出现的语言发育迟缓具有预防作用。