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Children exposed to valproate in utero--population based evaluation of risks and confounding factors for long-term
Kai Eriksson1, Katriina Viinikainen, Anne Mönkkönen
1Pediatric Research Centre, University of Tampere and Tampere University Hospital, Pediatric Neurology Unit, POB 2000, 33521 Tampere, Finland. kai.eriksson@uta.fi
Insights
Children exposed to valproate in utero showed higher rates of low intelligence and minor neurological dysfunctions compared to controls. Further research is needed to understand long-term effects.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Pharmacology
Background:
- Prenatal exposure to antiepileptic drugs (AEDs) can impact neurodevelopment.
- Valproate (VPA) is commonly used for epilepsy and bipolar disorder during pregnancy.
- Understanding the long-term neurological and cognitive effects of in utero VPA exposure is crucial.
Purpose of the Study:
- To assess neurological and cognitive functioning in school-aged children exposed to valproate monotherapy during pregnancy.
- To compare outcomes in VPA-exposed children with those exposed to carbamazepine (CBZ) and unexposed children of mothers with epilepsy.
Main Methods:
- A population-based, evaluator-blinded, controlled study.
- Included 39 children (aged 6.6-13.4 years) and their mothers.
- Evaluations included neurological examinations, maternal and child intelligence quotients (IQ), and child neuropsychological assessments (NEPSY).
Main Results:
- 19% of VPA-exposed children had low intelligence (FIQ<80), and 10% had exceptionally low intelligence (FIQ<70).
- Children exposed to CBZ or unexposed had at least low average intelligence.
- 21% of VPA-exposed children exhibited minor neurological dysfunctions.
Conclusions:
- In utero valproate exposure is associated with an increased prevalence of neurocognitive symptoms.
- Inheritance and environmental factors may contribute to these outcomes.
- Concerns regarding the long-term effects of intrauterine valproate exposure persist.
Purpose:
To evaluate neurological and cognitive functioning of school-aged (> or =6 years) children exposed to valproate monotherapy in utero in a population based, evaluator-blinded, controlled study.
Methods:
Studied children (N=39, aged 6.6-13.4 years) and their mothers were identified through a population based pregnancy registry. Mothers with carbamazepine monotherapy and mothers with epilepsy but without antiepileptic drug (AED) treatment during pregnancy and their age and gender matched children served as controls. Hospital records were reviewed and neurological examination (Touwens test), intelligent quotients (IQ) of mothers (WAIS), and children (WISC-III) and neuropsychological assessment of children (NEPSY) were performed evaluator-blinded.
Results:
The prevalence of low intelligence (FIQ<80) was 19% (4/21) and the prevalence of exceptionally low intelligence (FIQ<70) 10% (2/21) in valproate (VPA) monotherapy exposed children. Children exposed to carbamazepine (CBZ) and children of women with epilepsy but without AED exposure during pregnancy had all at least low average intelligence. The mothers using valproate scored significantly lower (p<0.05) in FIQ, VIQ and PIQ tests and had also significantly lower (p=0.035) educational level. Altogether 21% (8/39) of the children had minor neurological dysfunctions.
Conclusions:
In a population based setting inheritance and cumulating environmental factors may partly explain the increased prevalence of neurocognitive symptoms in children exposed to valproate in utero although concern about the possible long-term effects of intrauterine valproate exposure does exist.
