Laura Saint-Lary 1, Anna-Belle Beau 2 3, Agnès Sommet 2 3, Valériane Leroy 2, Maria Loane 4, Clara Cavero-Carbonell 5, Ester Garne 6, Jonathan Hoareau 7, Anna Latos Bielenska 8, Isabelle Monier 9, Vera Nelen 10, Amanda J Neville 11, Mary O'Mahony 12, Isabelle Perthus 13, Anna Pierini 14, Anke Rissmann 15, Florence Rouget 16, Joanna Sichitiu 17, David Tucker 18, Helen Dolk 19, Christine Damase-Michel 2 3Affiliations Expand

• PMID: 40011239
• PMCID: PMC12003615
• DOI: 10.1007/s00228-025-03814-w

AbstractPurpose: Antiretroviral drugs are recommended during pregnancy to achieve HIV viral suppression and reduce mother-to-child transmission. Congenital anomaly signals were reported after fetal exposure to antiretroviral drugs in several studies warranting further investigation. We aimed to evaluate the risk of congenital anomalies after fetal exposure to antiretroviral drugs using the European congenital anomaly registry data.Methods: A case/non-case study was performed, using the EUROmediCAT central database. All the congenital anomalies, exposed to any antiretroviral drugs, were included from 1995 to 2019. We explored each signal identified from the literature for associations between congenital anomalies and specific antiretroviral exposures. We compared antiretroviral exposure between the signal anomalies (cases) and all other malformed registrations (controls). Reporting odds ratio (ROR) and their 95% confidence intervals were estimated and adjusted for registry and maternal age.Results: Between 1995 and 2019, 173 cases of congenital anomalies were observed after any exposure to antiretroviral drugs. The signal previously identified in the literature between congenital heart defects and exposure to zidovudine was confirmed in the main analysis (aROR 3.66 [1.63-8.23]). Other signals identified in the literature were not confirmed, although two cases of hypospadias and two cases of limb defects were reported after zidovudine and atazanavir exposure, respectively. The signal detection analysis did not reveal any new signal after applying the Bonferroni correction.Conclusions: Our study does not reveal new signals but confirms the previously identified signal between congenital heart defects and fetal exposure to zidovudine. The physio-pathological hypothesis induced by zidovudine exposure should be explored in future studies.Keywords: Antiretroviral drug; Congenital anomalies; First trimester exposure; HIV; Pregnancy.© 2025. The Author(s).