Temporal Changes in Reporting of Neurodevelopmental Outcomes After Maternal Exposure to Valproate: A Contribution of the ConcePTION Project.

Background: Understanding changes over time in the quantity and characteristics of reports submitted to pharmacovigilance centres is crucial for accurately interpreting safety signals associated with exposure during pregnancy.

Objective: We aimed to assess temporal changes in the outcome measures for signal detection, specifically the number and clustering of reported adverse events concerning maternal valproate exposure and neurodevelopmental outcomes in offspring.

Methods: An observational study using VigiBase analysed changes in the number of reports and event clustering related to neurodevelopmental outcomes in offspring following valproate exposure during pregnancy. Reports from the start of VigiBase till 3 April, 2023 were identified using the VigiBase pregnancy algorithm. Time trend graphs illustrated reporting behavioural changes, with particular focus on the impact of major scientific publications and regulatory decisions. Report clusters, identified by the vigiGroup method, were randomised and independently reviewed by three qualified reviewers for clinical relevance to neurodevelopmental outcomes, morphological disorders or other entities.

Results: Over time, an increase in reports mentioning neurodevelopmental outcomes and a more diverse pattern of adverse events for valproate has been reported. An increase in the number of reports following key publications and international regulatory guidelines was visible.

Conclusions: Our study revealed an increase over time in reporting and awareness of neurodevelopmental outcomes and valproate exposure during pregnancy, following important publications and regulatory decisions. However, the extent to which these developments contributed to the observed increase remains unclear.