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Prenatal valproate exposure and adverse neurodevelopmental outcomes: Does sex matter?

Eliza Honybun1, Rebecca Thwaites2, Charles B Malpas1,3,4

  • 1Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia.

Epilepsia
|February 6, 2021
PubMed

Insights

Prenatal exposure to valproic acid (VPA) may alter autism spectrum disorder (ASD) risk, particularly in females. This study found VPA exposure negated the typical male predominance in ASD symptoms.

Area of Science:

  • Neuroscience
  • Developmental Psychology
  • Pharmacology

Background:

  • Prenatal exposure to antiepileptic drugs (AEDs), specifically valproic acid (VPA), is linked to neurodevelopmental issues like autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD).
  • The influence of sex and VPA dosage on these outcomes requires further investigation.

Purpose of the Study:

  • To investigate how sex and VPA dosage affect the association between prenatal VPA exposure and postnatal behavioral outcomes.
  • To explore the potential of VPA as a behavioral teratogen, considering sex-specific effects.

Main Methods:

  • Utilized data from the Australian Pregnancy Register of AEDs for children aged 4-11 years.
  • Assessed child behavior using the Autism Spectrum Quotient-Children's Version and the Vanderbilt Assessment Scale for ADHD.
  • Employed general linear mixed-effects models to analyze demographic and psychometric data.

Main Results:

  • Males exhibited higher ASD scores than females overall.
  • VPA exposure appeared to neutralize the typical male predisposition to ASD symptoms.
  • No significant dose-response relationship was found between VPA exposure levels and ASD symptoms.
  • Males had higher ADHD scores, but VPA exposure was not linked to ADHD symptoms.

Conclusions:

  • Prenatal VPA exposure may mitigate the sex-based differences typically observed in ASD incidence, suggesting females may be more sensitive to VPA's effects.
  • VPA's role as a behavioral teratogen is complex and sex-influenced.
  • The study's findings on VPA dosage were inconclusive, potentially due to the relatively low doses administered.
Abstract

Keywords:
antiepileptic drugsattention-deficit/hyperactivity disorderautism spectrum disorderepilepsyneurodevelopment

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