Characterization of neurodevelopmental disorders in children exposed or unexposed in utero to valproate and/or other antiepileptic drugs with long-term follow-up: retrospective study of multiple European data sources (AVALON)

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/105976
• EU PAS number:
  EUPAS103711
• Study ID:
  105976
• Official title and acronym:
  Characterization of neurodevelopmental disorders in children exposed or unexposed in utero to valproate and/or other antiepileptic drugs with long-term follow-up: retrospective study of multiple European data sources (AVALON)
• DARWIN EU® study:
  No
• Study countries:
  Denmark

  Finland

  France

  Italy

  Netherlands

  Norway

  Sweden

  United Kingdom
• Study description:
  This is a population-based retrospective cohort study conducted using secondary data from multiple databases with mother-to-child linkage from recording longitudinal medical data including registries within Norway, Sweden, Finland, Denmark, the Netherlands, England, Wales, France and Italy. It aims at comparing the risk of Neurodevelopmental Disorders (NDD) up to 17 years of age in children exposed in utero to valproate (VPA) and in those with in utero exposure to other AEDs. A further aim is to investigate incidence and characteristics of minor congenital malformations (mCMs) in children exposed to valproate in utero. NDD will be defined as a composite outcome and separately by NDD sub-types (ASD, ADHD, ID, CD, DPD, MD)). Primary objective will consider VPA/other AEDs in monotherapy while secondary objective will evaluate exposure in polytherapy. In exploratory objectives, NDD risk, disease course and clinical pathway in children exposed in utero to VPA (mono and polytherapy) will be compared with those with exposure to each one of 13 AEDs and with no exposure to AEDs. Finally, exploratory objectives will also address the risk of minor congenital malformations in children exposed in utero to VPA.
• Study status:
  Planned

Research institution and networks

Institutions

IQVIA

United Kingdom

Study timelines

Date when funding contract was signed

Planned: 09/10/2018

Study start date

Planned: 01/08/2023

Date of final study report

Planned: 01/08/2026

Sources of funding

Pharmaceutical company and other private sector 

More details on funding

A Consortium of Marketing Authorization Holders for valproate and related substances

Regulatory

• Was the study required by a regulatory body?:
  Yes
• Is the study required by a Risk Management Plan (RMP)?:
  EU RMP category 1 (imposed as condition of marketing authorisation)
• Regulatory procedure number:
  EMEA/H/N/PSP/J/0094