Risk of Congenital Ocular Anomaly After Prenatal Exposure to Medications: A EUROmediCAT Study

Background: In Europe, the prevalence of congenital ocular anomaly (COA) is estimated at 3.7 per 10,000 births. While certain COAs have a genetic origin, the cause for most patients remains unknown. The role of medications administered during pregnancy in COA genesis in humans is unclear. Objective: To investigate any association between fetal exposure in the first trimester of pregnancy to medications and the occurrence of COA. Methods: We conducted a case-malformed-control study using data on 298,351 cases registered as having congenital anomalies (CA) from 19 registries and one healthcare database in 13 European countries. Two analyses were performed: (i) A signal confirmation analysis of signals from the literature, examining associations between COA and specific medications (nitrofurantoin, NSAIDs, opioids, alprazolam, antihypertensives, asthma medications, pyridoxine, and hydroxyethylrutoside). (ii) A signal detection analysis of all medications reported in the database. Results: We identified 4185 COA cases and 232,718 nongenetic and 38,409 genetic controls. We confirmed the association between prenatal opioid exposure and COA (aROR: 2.66, 95% CI: 1.18, 6.02, and 3.22, 95% CI: 1.35, 7.69, for nongenetic and genetic controls, respectively). Signal detection analysis revealed consistent associations for antiglaucoma preparations and miotics (p < 0.01) related to COA. Other associations included congenital cataracts and lens anomalies with desloratadine, congenital glaucoma with antiepileptics, and eyelid malformations with dermatological hydrocortisone. Conclusions: This pharmacoepidemiological study in Europe analyzing COA following fetal medication exposure confirmed reported signals regarding opioids and COA and identified new associations. Validation in independent datasets is necessary to consolidate these findings.