Identification of Major Congenital Malformations based on Healthcare Databases in France: a Proof-of-Concept Study using the EPI-MERES Nationwide Mother-Child Register

AimBesides registries, healthcare databases can provide useful information for assessing major congenital malformations (MCMs) frequency and investigating their risk factors, particularly medications exposures. This study aimed to assess the validity of MCMs identification based on French national, comprehensive healthcare databases. MethodsUsing information on hospital discharge diagnoses, medical procedures (e.g. surgery) and death causes from the EPI-MERES register nested in the French National Health Data System, 72 specific MCMs grouped in 11 organ groups were assessed among all births occurred after 22 weeks of amenorrhea in France between 2010 and 2023. MCMs prevalence rates were estimated and compared to those from EUROCAT, and associations with prenatal exposure to valproate were assessed. ResultsAmong 10.5 million births, 213,153 live born infants with at least one MCM, i.e. 203.0 cases per 10,000 births, were identified. MCMs prevalence rates among live births were close to those reported in EUROCAT overall (difference: -1.76 per 10,000 births [-1%]), for each organ group (differences ranging from -9.10 [-13%] to +3.44 [+16%] per 10,000 births), and for the 72 specific MCMs (median prevalence difference: 1%). Prenatal exposure to valproate was significantly associated with increased risks of any MCM (adjusted odds ratio (aOR) 2.82, 95% CI [2.33-3.41]) and of 15 specific MCMs including spina bifida (aOR 17.88 [7.88-40.53]). ConclusionThis study supports the validity of MCMs identification based on data of the EPI-MERES register. The EPI-MERES register provides a highly powerful, reactive and operational tool complementing MCMs registries for improving real-life knowledge on drug teratogenicity. Plain language summaryMajor congenital malformations are serious structural abnormalities present at birth that can have lasting consequences on childrens health. Better understanding their risk factors, particularly medication exposures during pregnancy, is crucial. Population-based registries are today the primary source of information on malformations, but healthcare databases could offer a faster and broader alternative. This study tested whether the EPI-MERES register, built upon the French National Health Data System (SNDS), could accurately identify 72 specific malformations across 10.5 million births between 2010 and 2023. Prevalence estimates closely matched those from the European EUROCAT registry, confirming good data accuracy. As expected, valproate (a known teratogen) was associated with an increased risk of various malformations, including spina bifida, EPI-MERES thus constitutes a promising tool for studying medication risks during pregnancy.