Objective Small prospective studies have identified that children exposed to valproate in utero have poorer scores on cognitive testing. We wanted to identify whether children exposed to antiepileptic drugs (AEDs) in utero have poorer school performance.
Methods We used anonymised, linked, routinely collected healthcare records to identify children born to mothers with epilepsy. We linked these children to their national attainment Key Stage 1 (KS1) tests in mathematics, language and science at the age of 7 and compared them with matched children born to mothers without epilepsy, and with the national KS1 results. We used the core subject indicator (CSI) as an outcome measure (the proportion of children achieving a minimum standard in all subjects) and the results in individual subjects.
Results We identified 440 children born to mothers with epilepsy with available KS1 results. Compared with a matched control group, fewer children with mothers being prescribed sodium valproate during pregnancy achieved the national minimum standard in CSI (−12.7% less than the control group), mathematics (−12.1%), language (−10.4%) and in science (−12.2%). Even fewer children with mothers being prescribed multiple AEDs during pregnancy achieved a national minimum standard: CSI (by −20.7% less than the control group), mathematics (−21.9%), language (−19.3%) and science (−19.4%). We did not observe any significant difference in children whose mothers were prescribed carbamazepine or were not taking an AED when compared with the control group.
Conclusions In utero exposure to AEDs in combination, or sodium valproate alone, is associated with a significant decrease in attainment in national educational tests for 7-year-old children compared with both a matched control group and the all-Wales national average. These results give further support to the cognitive and developmental effects of in utero exposure to sodium valproate as well as multiple AEDs, which should be balanced against the need for effective seizure control for women during pregnancy.
- educational attainment
- antiepileptic drugs
- case-control study
- clinical decision support
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Contributors Conceived and designed the study: ASL, WOP, RHT, CPW, MPK and MIR. Performed the study: ASL. Performed statistical analysis: ASL. Wrote the paper: ASL. Critical revision of the manuscript: ASL, WOP, RHT, CPW, MPK and MIR.
Funding This research was funded by the Health and Social Care Research Wales via the Brain Repair and Intracranial Neurotherapeutics (BRAIN) unit.
Competing interests WOP is supported by Health and Social Care Research Wales in the form of a WCAT clinical lectureship. RHT is supported by Health and Social Care Research Wales in the form of a WCAT clinical lectureship; receives/has received research support from Epilepsy Research UK, Action Medical Research, Epilepsy Action and the Dravet Society; is an associate editor of Practical Neurology and web editor of Seizure ; and has received honoraria from Eisai, Sanofi and UCB. The authors confirm that they have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Ethics approval This study was approved by SAIL’s independent information governance review panel (project 0228). The National Research Ethics Service has confirmed that SAIL projects using anonymised data do not require specific NHS research ethics committee approval.
Provenance and peer review Not commissioned; externally peer reviewed.
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