Poorer test results for children exposed to epilepsy drugs in the womb

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EpilepsyResearchers from the neurology research group in the Swansea University Medical School found that exposure to epilepsy drugs in the womb is linked to significantly poorer school test results among 7-year olds. The research recommends that mums-to-be need to be fully informed of the risks of treatment, but these should be weighed against the need for effective seizure control during pregnancy, say the researchers.

Women with epilepsy who need drugs to control their seizures are currently advised to continue taking them during pregnancy because convulsions can harm both mother and the unborn child.

Several studies indicate that epilepsy drugs, particularly sodium valproate, taken during pregnancy, are associated with neurodevelopmental disorders, but few of these studies have been based on real-life population circumstances (population data). To address this, the researchers from the research group in Swansea University Medical School used routinely-collected healthcare data from the Secure Anonymous Information Linkage (SAIL) databank and national school test (key stage 1) data to compare the academic performance of 7-year olds in Wales born to mothers with epilepsy. SAIL contains the anonymised primary care health records of 80% of Welsh family doctors, corresponding to around 77% of the Welsh population (2.3m people).

The Key Stage 1 (KS1) test assesses maths, language (English/Welsh) and science among 7-year olds, scoring them from levels 1 to 3. Test results were available for 440 children whose mums had been diagnosed with epilepsy before their pregnancy for 2003 through to 2008.

Prescription patterns were divided into five categories: treatment with one drug (carbamazepine, lamotrigine or sodium valproate); a combination of several drugs; and no drug treatment. Twenty (54%) of the 39 mums prescribed several drugs were taking sodium valproate, but there were 15 different drug combinations in all.

The results showed that children born to mums who had been prescribed carbamazepine or lamotrigine, or nothing, performed just as well as those born to mums of the same age and deprivation level, but without epilepsy (comparison group). But those whose mums had been prescribed sodium valproate during their pregnancy performed 10.5 – 13% less well on all KSI tests than those in the comparison group. Children born to mums who had been prescribed a combination of epilepsy drugs achieved worse results still. Their scores were 19-22% lower. Also, excluding children with epilepsy and whose mothers smoked from the analysis didn’t materially change the results.

The researchers acknowledge that they weren’t able to account for certain potentially influential factors, such as the mothers’ IQ, weight or alcohol consumption; the doses of epilepsy drugs prescribed; or intake of folic acid around conception.

But their results echo those of other independent studies, they point out.

Professor Mark Rees, professor of neurology and molecular neuroscience research said “While this study highlights the risk of cognitive effects in the children of mothers prescribed sodium valproate or multiple (anti-epilepsy drugs), it is important to acknowledge that some epilepsies are difficult to manage without these treatment regimens.”

Dr Owen Pickrell, leader of the SAIL neurology team added “Women with epilepsy should be informed of this risk and alternative treatment regimens should be discussed before their pregnancy with a physician that specialises in epilepsy.”

In a linked commentary of the study, Dr Richard Chin of the University of Edinburgh’s Muir Maxwell Epilepsy Centre, emphasises the importance of a study that is based on population data as this can be used to inform preventive/interventional strategies and help women to better understand the implications of epilepsy treatment while pregnant.
“By providing ‘functional’ outcome data from their study, the authors have now provided information that prospective parents may find readily tangible: it should be included in information given to women with epilepsy prior to pregnancy,” he advocates.

Abstract
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.

Authors
Arron S Lacey, William Owen Pickrell, Rhys H Thomas, Mike P Kerr, Cathy P White, Mark I Rees

Swansea University material
Journal of Neurosurgery: Neurology & Psychiatry abstract


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