(310) Risk of congenital ocular anomaly in EUROmediCAT: Assessment of the Potential Risk of Taking Medications during Pregnancy in Europe.

Tuesday, August 27, 2024

8:00 AM – 6:00 PM CEST

Location: Convention Hall II

Presenting Author(s)

Erika A. Cifuentes Castro

Biostatistician
CERPOP, Inserm U1295, Université de Toulouse Paul Sabatier, Service de Pharmacologie Clinique, CHU de Toulouse, France

Co-Author(s)

AB

Anna-Belle Beau, PhD

Post-doctoral fellow
CERPOP, Inserm U1295, Université de Toulouse Paul Sabatier, Service de Pharmacologie Clinique, CHU de Toulouse, France
AC

Anthony Caillet

CERPOP, Inserm U1295, Université de Toulouse Paul Sabatier, Service de Pharmacologie Clinique, CHU de Toulouse, France
FF

Felix Fremont

Service d’ophtalmologie, Hôpital Pierre-Paul Riquet, CHU Toulouse-Purpan, France
AN

Amanda J. Neville

Department of Medical Sciences, Centre for Clinical and Epidemiological Research, Emilia Romagna Registry of Birth Defects, Ferrara University, Italy, Italy
EB

Elisa Ballardini

Neonatal Intensive Care Unit, University Hospital of Ferrara, IMER Registry (Emilia Romagna Registry of Birth Defects), Department of Medical Sciences, University of Ferrara, Italy, Italy
HD

Helen Dolk

School of Medicine, Ulster University, Belfast, United Kingdom, United Kingdom
ML

Maria Loane

Institute of Nursing and Health Research, Ulster University, United Kingdom
EG

Ester Garne

Paediatric Department, Hospital Lillebaelt, Kolding, Denmark, Denmark
BK

Babak Khoshnood

INSERM U953, Hopital Saint Vincent de Paul,Paris, France, France
NL

Nathalie Lelong

Paris Registry of Congenital Malformations, Obstetrical, Perinatal and Paediatric Epidemiology Research Team, INSERM, UMR 1153, France
AR

Anke Rissmann

Malformation Monitoring Centre Saxony-Anhalt, Germany, Germany
MO

Mary O’Mahony

Department of Public Health, Health Service Executive-South, Cork, Ireland, Ireland
AP

Anna Pierini

Unit of Epidemiology of Rare Diseases and Congenital Anomalies. Institute of Clinical Physiology-National Research Council, Italy
MG

Miriam Gatt

Malta Congenital Anomalies Registry, Directorate for Health Information and Research, Malta
AL

Anna Latos-Bielenska

Department of Medical Genetics, Poznan University of Medical Sciences, Poznań, Poland, Poland
LE

Luis Echevarria Gonzalez

Department of Health of the Basque Government, Vitoria-Gasteiz, Spain, Spain
CC

Clara Cavero-Carbonell

Rare Disease Research Unit, Foundation for Promotion of Health and Biomedical Research of Valencian Region (FISABIO), Valencia, Spain, Spain
MA

Marie-Claude Addor

Department of Woman-Mother-Child, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, Switzerland
DT

David Tucker

Public Health Wales, United Kingdom
SJ

Sue Jordan, MB.BCh., PhD. PGCE (FE),

professor
Faculty of Medicine, Health and Life Science, Swansea University, Wales, UK, United Kingdom
ED

Elly Den Hond

Provincial Institute of Hygiene, Antwerp, Belgium, Belgium
IB

Ingeborg Barisic

Children's Hospital Zagreb, Centre of Excellence for Reproductive and Regenerative Medicine, Medical School University of Zagreb, Zagreb, Croatia, Croatia
FR

Florence Rouget

Brittany Registry of congenital anomalies, CHU Rennes, Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Rennes, France, France
Hr

Hanitra randrianaivo

REMACOR /Register of Reunion Island CHU LA REUNION, France
JH

Jonathan Hoareau

Unit of congenital malformations, REMACOR- Medical School University of La Réunion St Pierre, France
Ip

Isabelle perthus

Centre d'Etude des Malformations Congénitales en Auvergne, Génétique médicale, CHU Estaing, France
MC

Monique Courtade-Saïdi

Département d’Anatomie et cytologie pathologiques, IUCT-oncopole, Toulouse, France et Faculté de Santé, Département MMP, Toulouse, France, France
CD

Christine Damase-Michel

CERPOP, Inserm U1295, Université de Toulouse Paul Sabatier, Service de Pharmacologie Clinique, CHU de Toulouse, France
CD

Charlotte Dubucs

CERPOP, Inserm U1295, Université de Toulouse Paul Sabatier, Service de Pharmacologie Clinique, CHU de Toulouse, France

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 EUROmediCATdatabase for the period between 1995-2019

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 - as a 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 -as a 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.