(303) Prevalence of major congenital malformations in France between 2010 and 2021: estimates among the 9 millions children and foetuses of the EPI-MERES register and relevance for perinatal pharmacoepidemiology

Background: Major congenital malformations (MCMs) concern ~3% of births and are a major cause of death and disability. Local registers are the main source of information on MCMs, in France (6 registers covering < 20% of the population) and in Europe (EUROCAT network). The French National Health Data System (SNDS), which contains comprehensive reimbursements and hospitalisations data for almost 100% of the population, provides a potentially relevant tool to study the impact of prenatal drug exposures on MCM risk.

Objectives: To measure the frequency of MCMs based on comprehensive data of the mother-child EPI-MERES register, built from the SNDS and including all pregnancies in France since 2010.

Methods: All children and fœtuses (except same-sex twins) deriving from a delivery or a pregnancy termination after 22 weeks of amenorrhea between 2010 and 2021 were included. 77 MCMs (grouped into 13 groups) of the Eurocat list were identified, using hospital diagnoses and medical acts between birth and 1 year of age (or 2 years for 3 MCMs). MCM prevalence was assessed for all 77 MCMs among livebirths, and for 11 severe MCMs detectable by prenatal diagnosis among stillbirths and fœtuses deriving from pregnancy termination.

Results: 8,995,077 children/foetuses were included (8,910,047 livebirths, 47,519 stillbirths and 37,511 foetuses deriving from pregnancy termination). Overall, 165,550 children/fœtuses, i.e. 184 per 10,000 births, were identified with at least one MCM. Among livebirths, this prevalence was 181 cases per 10,000 births (vs. 204 in Eurocat). Congenital heart defects (CHD) were the most frequent MCMs (31% of all cases), followed by limb (16%), urinary (14%) and genital malformations (13%). The overall MCM prevalence increased from 168 in 2010-2012 to 189 in 2019-2021 (vs. from 202 to 204 in Eurocat). The highest increase was found for CHD (from 48.4 in 2010-12 to 61.9 in 2019-2021), followed by limb (from 26.0 to 30.3), urinary (from 22.1 to 25.8), digestive (from 10.6 to 11.8), nervous malformations (from 9.8 to 13.5) and chromosomal anomalies (from 7.2 to 8.4). The prevalence of each specific MCM was generally of the same order of magnitude as that reported by Eurocat among livebirths (median relative difference: -3%), but lower among stillbirths and fœtuses deriving from pregnancy termination (-96%).

Conclusions: The EPI-MERES register constitutes a reliable source of information on most MCMs among livebirths in France. Thanks to the large number of MCM cases included –almost 166,000–, to the availability of information on maternal drug consumption during pregnancy and to the linkage between information of mothers and children, it constitutes a highly powerful tool for improving knowledge on drug teratogenicity.