Neurodevelopmental outcomes in children and adults with Fetal Valproate Spectrum Disorder: A contribution from the ConcePTION project

Neurotoxicol Teratol. 2023 Nov-Dec:100:107292. doi: 10.1016/j.ntt.2023.107292. Epub 2023 Sep 4.

Abstract

Aim: To describe the neurodevelopmental phenotype of older children and adults with a diagnosis of Fetal Valproate Spectrum Disorder (FVSD).

Methods: In this cross-sectional study, 90 caregivers were recruited and completed a series of questionnaires regarding the neurodevelopmental outcomes of 146 individuals aged 7-37 years (M = 18.1), including individuals with a formal diagnosis of FVSD (n = 99), individuals exposed to Valproate but without an FVSD diagnosis (n = 24), and individuals not exposed to Valproate (N = 23). The mean dose of valproate exposure for individuals with an FVSD diagnosis was 1470 mg/day.

Results: Individuals with a diagnosis of FVSD showed significantly higher levels of moderate (43.4%) and severe (14.4%) cognitive impairment than other groups (p = 0.003), high levels of required formal educational support (77.6%), and poorer academic competence than individuals not exposed to Valproate (p = 0.001). Overall psychosocial problems (p = 0.02), internalising problems (p = 0.05) and attention problems (p = 0.001), but not externalising problems, were elevated in individuals with a diagnosis of FVSD. Rates of neurodevelopmental disorders, particularly autistic spectrum disorders (62.9%) and sensory problems (80.6%) are particularly central to the FVSD phenotype. There was no evidence of a statistical dose-dependent effect, possibly due to the high mean dose of exposure having a uniformly negative impact across the sample. Individuals with FVSD had required a significant number of health and child development services.

Interpretation: Children and young adults with a diagnosis of FVSD are at an increased risk of a range of altered neurodevelopmental outcomes, highlighting the need for a multidisciplinary approach to clinical management across the lifespan.

Keywords: Cognition; Epilepsy; Fetal Valproate Spectrum Disorder; Neurodevelopment; Sodium Valproate; Teratology.

MeSH terms

  • Adolescent
  • Anticonvulsants
  • Child
  • Cross-Sectional Studies
  • Epilepsy* / chemically induced
  • Epilepsy* / drug therapy
  • Humans
  • Valproic Acid* / adverse effects
  • Young Adult

Substances

  • Valproic Acid
  • Anticonvulsants

Supplementary concepts

  • Valproic acid antenatal infection