Gkolfi Dimitra, van Rijt-Weetink Yrea R J, Taavola-Gustafsson Henric, Sandberg Lovisa, Raemaekers Boukje C, van Hunsel Florence P A M, Passier Anneke L M, Bromley Rebecca L, Yates Laura M, van Puijenbroek Eugène P
Groningen Research Institute of Pharmacy, PharmacoTherapy, -Epidemiology and -Economics, University of Groningen, Groningen, The Netherlands.
Uppsala Monitoring Centre, Uppsala, Sweden.
Drug Saf. 2025 Jul 7. doi: 10.1007/s40264-025-01583-0.
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.
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.
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.
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.
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.
了解提交给药物警戒中心的报告数量和特征随时间的变化，对于准确解读与孕期暴露相关的安全信号至关重要。
我们旨在评估信号检测结果指标的时间变化，特别是关于母亲丙戊酸盐暴露与后代神经发育结局的报告不良事件的数量和聚集情况。
一项使用VigiBase的观察性研究分析了孕期丙戊酸盐暴露后与后代神经发育结局相关的报告数量和事件聚集的变化。使用VigiBase妊娠算法识别从VigiBase开始到2023年4月3日的报告。时间趋势图展示了报告行为的变化，特别关注主要科学出版物和监管决策的影响。通过vigiGroup方法识别的报告集群由三名合格的评审员进行随机化和独立评审，以确定其与神经发育结局、形态学障碍或其他实体的临床相关性。
随着时间的推移，报告中提及神经发育结局的数量有所增加，丙戊酸盐不良事件的模式也更加多样化。关键出版物和国际监管指南发布后报告数量有所增加。
我们的研究表明，在重要出版物和监管决策之后，随着时间的推移，孕期神经发育结局和丙戊酸盐暴露的报告及认知有所增加。然而，这些进展对观察到的增加有多大贡献仍不清楚。
