Signal detection in EUROmediCAT: Identification and evaluation of medication-congenital anomaly associations and use of VigiBase as a complementary source of reference.

A Cavadino, L Sandberg , I Öhman, T Bergvall , K Star, Helen Dolk, Maria Loane

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
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Introduction: Knowledge on the safety of medication use during pregnancy is often sparse. Pregnant women are generally excluded from clinical trials, and there is a dependence on post-marketing surveillance to identify teratogenic medications. Aims: This study aimed to identify signals of potentially teratogenic medications using EUROmediCAT registry data on medication exposure in pregnancies with a congenital anomaly, and to investigate the use of VigiBase reports of adverse events of medications in the evaluation of these signals. Methods: Signals of medication–congenital anomaly associations were identified in EUROmediCAT (21,636 congenital anomaly cases with 32,619 medication exposures), then investigated in a subset of VigiBase (45,749 cases and 165,121 exposures), by reviewing statistical reporting patterns and VigiBase case reports. Evidence from the literature and quantitative and qualitative aspects of both datasets were considered before recommending signals as warranting further independent investigation. Results: EUROmediCAT analysis identified 49 signals of medication–congenital anomaly associations. Incorporating investigation in VigiBase and the literature, these were categorised as follows: four non-specific medications; 11 likely due to maternal disease; 11 well-established teratogens; two reviewed in previous EUROmediCAT studies with limited additional evidence; and 13 with insufficient basis for recommending follow-up. Independent investigations are recommended for eight signals: pregnen (4) derivatives with limb reduction; nitrofuran derivatives with cleft palate and patent ductus arteriosus; salicylic acid and derivatives with atresia or stenosis of other parts of the small intestine and tetralogy of Fallot; carbamazepine with atrioventricular septal defect and severe congenital heart defect; and selective beta-2-adrenoreceptor agonists with posterior urethral valve and/or prune belly. Conclusion: EUROmediCAT data should continue to be used for signal detection, accompanied by information from VigiBase and review of the existing literature to prioritise signals for further independent evaluation.

Original languageEnglish
Pages (from-to)765-785
Number of pages21
JournalDrug Safety
Issue number7
Early online date9 May 2021
Publication statusPublished (in print/issue) - 31 Jul 2021

Bibliographical note

Funding Information:
The authors sincerely thank all the people throughout Europe who have been involved in providing and processing information for both EUROCAT and EUROmediCAT, including affected families, clinicians, health professionals, medical record clerks and registry staff. EUROCAT registries are funded as fully described in Paper 6 of Report 9 'EUROCAT Member Registries: Organization and Activities' available at We would also like to thank Catherine Lynch and Carmel Mullaney for providing anonymised South East Ireland registry data for this study. Similarly, we are indebted to the national centres which make up the WHO Programme for International Drug Monitoring and provide reports to VigiBase. However, the opinions and conclusions of this study are not necessarily those of the various centres, nor of the WHO. We would also like to express our gratitude to Pia Caduff-Janosa for reviewing a previous version of the manuscript and providing valuable input.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.


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