Exposition in-utéro aux antibiotiques et risque de malformations congénitales majeures : analyse à partir du Système National des Données de Santé (SNDS)

Bacterial infections and the subsequent need for antibiotic use are frequent during pregnancy, yet the evidence regarding the fetal risks of certain antibiotic classes remains inconclusive. Leveraging medico-administrative databases is crucial for improving our knowledge about the use and safety of antibiotics during pregnancy. This thesis used data derived from the French health insurance databases. In the first part, out of nearly 9.8 million pregnancies ending in live and non-live births, from 2010 to 2019, 3,501,294 (35.8%) were exposed to at least one antibiotic at some stage during pregnancy. A reduction in antibiotic prescriptions during pregnancy compared to one year earlier and substantial changes in prescribed antibiotic agents were observed. Pregnant women residing in specific regions, those with smoking disorders, and those with chronic diseases were more likely to receive antibiotics. In the second part, we evaluated the risks of 42 different major congenital malformations (MCMs) in live-born infants among 140,708 pregnancies exposed to macrolides during the first trimester, from 2010 to 2020, compared with 592,652 exposed to amoxicillin. Increased risks of syndactyly (aRR 1.68, 95%CI 1.08-2.61) and spina bifida (aRR 1.80, 95%CI 1.21-2.69) were observed, based on 31 and 36 affected infants in the macrolide exposure group, respectively. Despite similar results yielded in sensitivity analyses and null findings in negative control analyses, independent studies are needed to confirm these associations. Overall, this thesis contributed to examining thoroughly antibiotic exposure during pregnancy in France and exploring the potential risks of MCMs associated with first-trimester macrolide exposure.