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

E-A Cifuentes¹, A Beau¹, A Caillet¹, F Frémont^{2

3}, A J Neville⁴, E Ballardini⁵, H Dolk⁶, M Loane⁷, E Garne⁸, B Khoshnood⁹, N Lelong⁹, A Rissmann¹⁰, M O'Mahony¹¹, A Pierini¹², M Gatt¹³, J E H Bergman¹⁴, M R Krawczynski¹⁵, A Latos Bielenska¹⁵, L-J Echevarría González de Garibay¹⁶, C Cavero Carbonell¹⁷, M-C Addor¹⁸, D Tucker¹⁹, S Jordan²⁰, E Den Hond²¹, V Nelen²¹, I Barisic²², F Rouget²³, H Randrianaivo²⁴, J Hoareau²⁴, I Perthus²⁵, M Courtade-Saïdi^{26

27}, C Damase-Michel¹, C Dubucs^{1

26

27}

Affiliations

¹ Unité de Pharmacoépidémiologie, UMR CERPOP, INSERM, Université de Toulouse, Toulouse, France.
² Service d'ophtalmologie, Hôpital Pierre-Paul Riquet, CHU Toulouse-Purpan, Toulouse, France.
³ Clinique Honoré Cave, Montauban, France.
⁴ Centre for Clinical and Epidemiological Research, University of Ferrara and Azienda, Ospedaliero Universitario di Ferrara, Ferrara, Italy.
⁵ Neonatal Intensive Care Unit, University Hospital of Ferrara, IMER Registry (Emilia Romagna Registry of Birth Defects), Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
⁶ School of Medicine, Ulster University, Coleraine, UK.
⁷ Institute of Nursing and Health Research, Ulster University, Belfast, UK.
⁸ Department of Paediatrics and Adolescent Medicine, Lillebaelt Hospital, University Hospital of Southern Denmark, Kolding, Denmark.
⁹ Obstetrical Perinatal and Pediatric Epidemiology Research Team (EPOPé), INSERM, INRA, Université Paris Cité Centre of Research in Epidemiology and StatisticS (CRESS), Paris, France.
¹⁰ Malformation Monitoring Centre Saxony-Anhalt, Medical Faculty Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
¹¹ Health Service Executive, Department of Public Health, St. Finbarr's Hospital, Cork, Ireland.
¹² Unit of Epidemiology of Rare Diseases and Congenital Anomalies, Institute of Clinical Physiology-National Research Council, Pisa, Italy.
¹³ Malta CA Register, Directorate for Health Information and Research, Malta.
¹⁴ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹⁵ Department of Medical Genetics, Poznan University of Medical Science, Poznan, Poland.
¹⁶ Department of Health of the Basque Government, Vitoria-Gasteiz, Spain.
¹⁷ Rare Diseases Research Unit, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, Valencia, Spain.
¹⁸ Department of Woman-Mother-Child, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
¹⁹ Public Health Wales, Public Health Knowledge and Research, Singleton Hospital, Swansea, Wales, UK.
²⁰ Faculty of Medicine, Health and Life Science, Swansea University, Wales, UK.
²¹ Provincial Institute of Hygiene, Antwerp, Belgium.
²² Centre of Excellence for Reproductive and Regenerative Medicine, Medical School University of Zagreb, Zagreb, Croatia.
²³ Brittany Registry of Congenital Anomalies, CHU Rennes, Université de Rennes, INSERM, EHESP, Irset (Institut de recherche en santé, environnement et travail)-UMR_S, Rennes, France.
²⁴ REMACOR, Register of Reunion Island CHU LA REUNION, La Reunion, France.
²⁵ Centre d'Etude Des Malformations Congénitales en Auvergne, Génétique médicale, CHU Estaing, Clermont-Ferrand, France.
²⁶ Département d'Anatomie et Cytologie Pathologiques, IUCT-Oncopole, Toulouse, France.
²⁷ Faculté de Santé, Département MMP, Toulouse, France.

PMID: 39890450
DOI: 10.1002/bdr2.2435

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

E-A Cifuentes et al. Birth Defects Res. 2025 Feb.

. 2025 Feb;117(2):e2435.

doi: 10.1002/bdr2.2435.

Authors

Affiliations

¹ Unité de Pharmacoépidémiologie, UMR CERPOP, INSERM, Université de Toulouse, Toulouse, France.
² Service d'ophtalmologie, Hôpital Pierre-Paul Riquet, CHU Toulouse-Purpan, Toulouse, France.
³ Clinique Honoré Cave, Montauban, France.
⁴ Centre for Clinical and Epidemiological Research, University of Ferrara and Azienda, Ospedaliero Universitario di Ferrara, Ferrara, Italy.
⁵ Neonatal Intensive Care Unit, University Hospital of Ferrara, IMER Registry (Emilia Romagna Registry of Birth Defects), Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
⁶ School of Medicine, Ulster University, Coleraine, UK.
⁷ Institute of Nursing and Health Research, Ulster University, Belfast, UK.
⁸ Department of Paediatrics and Adolescent Medicine, Lillebaelt Hospital, University Hospital of Southern Denmark, Kolding, Denmark.
⁹ Obstetrical Perinatal and Pediatric Epidemiology Research Team (EPOPé), INSERM, INRA, Université Paris Cité Centre of Research in Epidemiology and StatisticS (CRESS), Paris, France.
¹⁰ Malformation Monitoring Centre Saxony-Anhalt, Medical Faculty Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
¹¹ Health Service Executive, Department of Public Health, St. Finbarr's Hospital, Cork, Ireland.
¹² Unit of Epidemiology of Rare Diseases and Congenital Anomalies, Institute of Clinical Physiology-National Research Council, Pisa, Italy.
¹³ Malta CA Register, Directorate for Health Information and Research, Malta.
¹⁴ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹⁵ Department of Medical Genetics, Poznan University of Medical Science, Poznan, Poland.
¹⁶ Department of Health of the Basque Government, Vitoria-Gasteiz, Spain.
¹⁷ Rare Diseases Research Unit, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, Valencia, Spain.
¹⁸ Department of Woman-Mother-Child, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
¹⁹ Public Health Wales, Public Health Knowledge and Research, Singleton Hospital, Swansea, Wales, UK.
²⁰ Faculty of Medicine, Health and Life Science, Swansea University, Wales, UK.
²¹ Provincial Institute of Hygiene, Antwerp, Belgium.
²² Centre of Excellence for Reproductive and Regenerative Medicine, Medical School University of Zagreb, Zagreb, Croatia.
²³ Brittany Registry of Congenital Anomalies, CHU Rennes, Université de Rennes, INSERM, EHESP, Irset (Institut de recherche en santé, environnement et travail)-UMR_S, Rennes, France.
²⁴ REMACOR, Register of Reunion Island CHU LA REUNION, La Reunion, France.
²⁵ Centre d'Etude Des Malformations Congénitales en Auvergne, Génétique médicale, CHU Estaing, Clermont-Ferrand, France.
²⁶ Département d'Anatomie et Cytologie Pathologiques, IUCT-Oncopole, Toulouse, France.
²⁷ Faculté de Santé, Département MMP, Toulouse, France.

PMID: 39890450
DOI: 10.1002/bdr2.2435

Abstract

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.

Keywords: congenital ocular anomaly; in utero exposure; medications; pharmacology; pregnancy.

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References

1. Al‐Damri, A., and H. M. Alotaibi. 2023. “Congenital Cataracts in Preterm Infants: A Review.” Cureus 15, no. 6: e40378.
1. Andersson, N. W., H. E. Poulsen, and J. T. Andersen. 2020. “Desloratadine Use During Pregnancy and Risk of Adverse Fetal Outcomes: A Nationwide Cohort Study.” Journal of Allergy and Clinical Immunology. In Practice 8, no. 5: 1598–1605.
1. Angra, S. K. 1983. “Congenital Cataract and Maternal Ingestion of Corticosteroids.” Indian Journal of Ophthalmology 31: 844–846.
1. Arbabi, A., X. Bao, W. S. Shalaby, and R. Razeghinejad. 2022. “Systemic Side Effects of Glaucoma Medications.” Clinical & Experimental Optometry 105, no. 2: 157–165.
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Risk of Congenital Ocular Anomaly After Prenatal Exposure to Medications: A EUROmediCAT Study

Affiliations

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

Authors

Affiliations

Abstract

References

MeSH terms

Substances

LinkOut - more resources

Full Text Sources