Aim

Besides 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.

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.