Abstract
Background: In Europe, the prevalence of congenital ocular anomaly (COA) was estimated at 3.7 per 10.000 births. While certain COAs have a genetic origin, the cause for most patients remains unknown. Overall, the role of medicines administered during pregnancy in COA genesis in humans is unclear, but some medicines (e.g. Mycophenolate mofetil) are associated with COAs.
Objectives: To assess the risk of congenital ocular anomalies after prenatal exposure to drugs during the first trimester of pregnancy in the EUROmediCAT database for the period between 1995 and 2019
Methods: We conducted a case-malformed-control study using data on 298.351 children registered as having congenital anomalies (CA) from 19 registries and 1 healthcare database, in 13 European countries (covering live births, stillbirths, and terminations of pregnancy for fetal anomaly). Cases were babies or fetuses with COA, and controls were registrants with other CAs (whether genetic or not). Two analyses were performed: 1. Evaluation of the signals found in the literature. For this purpose, associations between COA and specific medicines (nitrofurantoin, NSAIDs, alprazolam, antihypertensives—asa class-, asthma medications, pyridoxine, hydroxyethylrutoside and opioids) were tested. 2. Exploratory analysis of the other medications reported in the database. Adjusted Reporting Odds Ratios (aROR) with 95% confidence intervals were estimated, accounting for multiple testing.
Results: 4.185 COA cases and 232.720 non-genetic and 38.409 genetic controls were identified. We confirmed the association between opioids and COA (aROR: 2.66 (1.18, 6.02) and 3.22 (1.35, 7.69) for non-genetic and genetic control groups). In the exploratory analysis, consistent associations were found in both control groups for specific anatomical levels of the ATC classification system: Dermatological (p < 0.01), Nervous System (p< 0.01), and Sensory Organs (p < 0.01) related to COA. Moreover, specific associations were identified: congenital glaucoma and antiepileptics -asa class-were associated in both non-genetic (p = 0.040) and genetic (p = 0.035) control groups and malformations of the eyelids were associated with hydrocortisone in both control groups (p < 0.01).
Conclusions: This study confirmed the reported signal regarding opioids and COA. In addition, we identified new potential associations. Studies in independent, databanks with prescription linkage are necessary to validate and consolidate these findings.
Objectives: To assess the risk of congenital ocular anomalies after prenatal exposure to drugs during the first trimester of pregnancy in the EUROmediCAT database for the period between 1995 and 2019
Methods: We conducted a case-malformed-control study using data on 298.351 children registered as having congenital anomalies (CA) from 19 registries and 1 healthcare database, in 13 European countries (covering live births, stillbirths, and terminations of pregnancy for fetal anomaly). Cases were babies or fetuses with COA, and controls were registrants with other CAs (whether genetic or not). Two analyses were performed: 1. Evaluation of the signals found in the literature. For this purpose, associations between COA and specific medicines (nitrofurantoin, NSAIDs, alprazolam, antihypertensives—asa class-, asthma medications, pyridoxine, hydroxyethylrutoside and opioids) were tested. 2. Exploratory analysis of the other medications reported in the database. Adjusted Reporting Odds Ratios (aROR) with 95% confidence intervals were estimated, accounting for multiple testing.
Results: 4.185 COA cases and 232.720 non-genetic and 38.409 genetic controls were identified. We confirmed the association between opioids and COA (aROR: 2.66 (1.18, 6.02) and 3.22 (1.35, 7.69) for non-genetic and genetic control groups). In the exploratory analysis, consistent associations were found in both control groups for specific anatomical levels of the ATC classification system: Dermatological (p < 0.01), Nervous System (p< 0.01), and Sensory Organs (p < 0.01) related to COA. Moreover, specific associations were identified: congenital glaucoma and antiepileptics -asa class-were associated in both non-genetic (p = 0.040) and genetic (p = 0.035) control groups and malformations of the eyelids were associated with hydrocortisone in both control groups (p < 0.01).
Conclusions: This study confirmed the reported signal regarding opioids and COA. In addition, we identified new potential associations. Studies in independent, databanks with prescription linkage are necessary to validate and consolidate these findings.
Original language | English |
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DOIs | |
Publication status | Published online - 19 Nov 2024 |
Event | 2024 ISPE Annual Meeting, Berlin, Germany - Berlin, Berlin, Germany Duration: 24 Aug 2024 → 28 Aug 2024 |
Conference
Conference | 2024 ISPE Annual Meeting, Berlin, Germany |
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Country/Territory | Germany |
City | Berlin |
Period | 24/08/24 → 28/08/24 |