Identification of major congenital malformations based on healthcare databases in France: A proof‐of‐concept study using the epi‐meres nationwide mother–child register

AIM: Besides registries, healthcare databases can provide useful information for assessing the frequency of major congenital malformations (MCMs) and investigating their risk factors, particularly medication exposures. This study aimed to assess the validity of MCMs identification based on French national, comprehensive healthcare databases. METHODS: Using 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 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. RESULTS: Among a total of 10.5 million births, 213 153 live-born infants MCM (203.0 per 10 000 births) with at least one MCM were identified. Almost half (47%) of MCMs cases were identified based on a medical procedure code. MCM prevalence rate increased by 16% between 2010-2012 and 2022-2023, from 181.2 to 211.2 cases per 10 000 births. MCMs prevalence rates among live births were close to those reported in EUROCAT (overall 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]). CONCLUSION: This 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.