(318) The occurrence of specific congenital anomalies associated with maternal Systemic Lupus Erythematosus: A ConcePTION Case-malformed control study in EUROmediCAT

Tuesday, August 27, 2024

8:00 AM – 6:00 PM CEST

Location: Convention Hall II

Presenting Author(s)

Sudip Karki

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

Co-Author(s)

MB

Marie Beslay, PhD

Post-doctorant
CERPOP, Inserm U1295, Université de Toulouse Paul Sabatier, Service de Pharmacologie Clinique, CHU de Toulouse, France
EC

Erika Cifuentes-Castro

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

Anna-Belle Beau, PhD

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

Justine Bénévent

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

Marie-Claude Addor

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

Ingeborg Barisic

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

Dieuwke Broekstra

Department of Genetics, EUROCAT Registration Nothern Netherlands, University of Groningen, University of Groningen Medical Center
Groningen, Netherlands
CC

Clara Cavero-Carbonell

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

Ester Garne

Paediatric Department, Hospital Lillebaelt, Kolding, Denmark, Denmark
MG

Miriam Gatt

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

Jonathan Hoareau

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

Elly Den Hond

Provincial Institute of Hygiene, Antwerp, Belgium, Belgium
AL

Anna Latos-Bielenska

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

Nathalie Lelong

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

Anke Rissmann

Malformation Monitoring Centre Saxony-Anhalt, Germany, Germany
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
JM

Joan K. Morris

Professor
Population Health Research Institute, St George’s, University of London, UK, United Kingdom
CD

Christine Damase-Michel

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

Background: The prevalence of Systemic Lupus Erythematosus (SLE) is 0.024% in the general population, and it is more common among women of reproductive age. However, little is known about its association with adverse pregnancy outcomes.

Objectives: To assess the risk of Congenital Anomalies (CA) associated with a maternal diagnosis of SLE.

Methods: A case-malformed control study was performed using data from the EUROmediCAT central database including livebirths, fetal deaths from 20 weeks gestational age, and terminations of pregnancy for fetal anomaly. For registrants in each specific EUROCAT subgroup of non-genetic anomalies (cases), the odds of having a maternal SLE diagnosis (ICD-9/10-CM codes: M32.1, M32.8, M32.9, and 710) were compared with the odds of having a maternal SLE diagnosis in the remaining non-genetic anomalies or genetic conditions (malformed controls). Subgroups with ≥ 3 exposed cases were analyzed. Reporting odds ratios (ROR) with 95% Confidence Intervals (95% CI) were estimated using a logistic regression method. P-values were adjusted for multiple testing using the false discovery rate (FDR) method.

Results: Data included 254,146 registrants with CA in 12 European countries from 1995–2020. Fifty-four registrants (44 non-genetic and 10 genetic) had a mother with an SLE diagnosis. An increased reporting of maternal SLE diagnosis was associated with spina bifida [(ROR 3.57, 95% CI 1.14-12.27; 3 exposed cases) compared with non-genetic controls and compared with genetic controls (ROR 4.21, 95% CI 1.06-16.59)] and abdominal wall defects [(ROR 3.94, 95% CI 1.21-12.80; 3 exposed cases) compared with non-genetic control and compared with genetic control (ROR 5.39, 95% CI 1.39-20.87). When adjustment for multiple testing was made, these associations were no longer statistically significant. After excluding registries with 20% of the missing values in maternal illness variable, increase reporting of maternal SLE among spina bifida (ROR 4.66, 95% CI 1.39-15.57 compared to non-genetic control and ROR 8.15, 95% CI 1.68-39.42 compared to genetic control) and abdominal wall defects (ROR 5.19, 95% CI 1.56-17.20 compared to non-genetic control and ROR 10.44, 95% CI 2.24-48.68 compared to genetic control) were significant.

Conclusions: This study suggests an increasing reporting of maternal SLE among the spina bifida and abdominal wall defects CA subgroups. However, the number of cases of specific CA were very few in EUROmediCAT. Considering the small number of exposed cases, results should be interpreted with caution. Further, the findings can serve as a safety signals that need further research to establish a causal relation..