Tuesday, April 3, 2018

Prenatal valproate and polypharmacy exposure linked to lower school performance

Lacey AS, Pickrell WO, Thomas RH, Kerr MP, White CP, Rees MI. Educational attainment of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry. 2018 Mar 27. pii: jnnp-2017-317515. doi: 10.1136/jnnp-2017-317515. [Epub ahead of print]


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.

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.

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.

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.

Prenatal exposure to sodium valproate, or to multiple antiepileptic drugs (AEDs), is strongly linked to lower school performance in young children, new research confirms.

The new study supports previous research showing an association between prenatal exposure to valproate or combination AEDs and later adverse neurodevelopmental outcomes.

However, unlike previous research, this new study looked at "real life" educational tests, study author William Owen Pickrell, PhD, Wales Epilepsy Research Network, Swansea University, United Kingdom, told Medscape Medical News.

"We used compulsory tests that every child in Wales took during the study time period, so sort of real-world kind of tests, as opposed to the IQ tests that people used in the past," said Pickrell….
They divided mothers with epilepsy into groups according to prescribed AEDs. These included monotherapy with carbamazepine, lamotrigine or sodium valproate, multiple AEDs, and no AED prescription. About 54% In the polytherapy group were prescribed valproate.

The investigators found that compared with controls, children born to mothers prescribed valproate during pregnancy had a lower percentage of passes in KS1 tests across all indicators except language.

The differences were as follows: −12.7% (P = .035) for CSI, −12.1% (P = .011) for math, and −12.2% (P ≤ .004) for science. In the language category, the difference was −10.4% (P = .188)…

The study also found that compared with controls, children born to mothers with epilepsy who were prescribed multiple AEDs during pregnancy had a lower level of achievement across all indicators other than language. The differences here were −20.7% (P = .042) for CIS, −21.9% (P ≤ .007) for math, −19.4% (P = .010) for science, and −19.3% (P = .269) for language.

While the differences in language scores weren't statistically significant, "the trend is more or less the same" as for the other educational categories, noted Pickrell.

It's possible that the epilepsy itself leads to poorer school performance. Pickrell pointed out that it's generally women with more severe epilepsy who are receiving polytherapy during pregnancy.

"This might be due to a more severe underlying brain pathology, which is partly genetic and may be passed on to the child."…

The study results are useful and add to the existing literature, Kimford J. Meador, MD, professor of neurology and neurological sciences at Stanford University School of Medicine, Palo Alto, California, told Medscape Medical News. Meador has studied the effects of AEDs on offspring of women with epilepsy.

Among the strengths of the study were its large size, relatively long follow-up for school performance measures, and use of a cohort matched on several factors, said Meador.

But the study had weaknesses, he added. These included small numbers for polytherapy combinations and lack of information on maternal IQ, AED dosages, alcohol use during pregnancy, and maternal folate use.

"So there are some holes in the data in that regard."


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