(10) The Medikeye Project: The First European Study on in Utero Medicine Exposure and Congenital Anomalies of Eyes

Publication Number: 684

Background: The prevalence of congenital anomalies of eyes (COA) ranges between 2.4 and 7.5 per 10,000 births. Some have a genetic origin; however most are still unexplained. Research on the impact of prenatal medication exposure on COA genesis is sparse in humans. Several medicines taken during pregnancy are reported to be associated with human COA and around 30 are associated with COA in animal models. Some of these are commonly prescribed to pregnant women.

Objectives: The aim of the Medikeye project is (Part 1) to describe COA across Europe, and (Part 2) to investigate any potential associations between first trimester exposure to medication and the occurrence of a COA. The study is ongoing. Part 1 will be presented here.

Methods: This study is a European collaboration within the EUROmediCAT network, which brings together 18 population-based registries of congenital anomalies from 13 European countries covering more than 11 million births, 1995-2018. Part 1 is a descriptive study of the “Eye anomaly subgroup” defined by the EUROCAT Guide 1.4 according to the international classification ICD-10 (Q10, Q11, Q12, Q13, Q14, and Q15). Minor eye anomalies are excluded. Cases include livebirths, stillbirths, fetal deaths from 20 weeks and terminations of pregnancy for fetal anomaly.

Results: We identified 4 433 cases of COA. The prevalence was 3.47/ 10 000 births, and was stable over time . Prevalence ranged from 1.26-13.74 / 10 000 depending on location of registry. Congenital lens anomalies were the most frequent eye anomalies (30 %), of which over half (54.2%) were isolated. Microphthalmia was the second most frequent eye anomaly (26 %) of which 74.5% were syndromic forms . 22% of liveborn cases have a fetal weight < 5th percentile. Known genetic determinants of COA explained only 3 to 25% of COA depending on the type of anomaly. The three ATC classes most frequently prescribed or dispensed to women during the first trimester of pregnancy were B (Blood and blood forming organs ), A (Alimentary tract and metabolism), and N (Nervous system). Among women who used medications, the mean [SD] number of medicines per woman was 1.82.

Conclusions: This is the first European epidemiological descriptive study reporting COA. This is a first step toward exploring possible associations between prenatal medication exposure and COA.