Supplementary file 1_Isolated ventricular septal defect is not a risk factor for celiac disease: evidence from a large real-world data cohort of 493,382 children.docx

BackgroundVentricular septal defect (VSD) is one of the most common congenital heart defects in children. Celiac disease (CD) is known to cluster with autoimmune conditions and chromosomal syndromes, but it remains unclear whether isolated VSD is independently associated with CD.
MethodsWe performed a population-based retrospective cohort study using electronic records from Clalit Health Services. Children aged 0–10 years were followed for up to 10 years to identify incident cases of CD. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 97.5% confidence intervals (CIs) for the association between VSD and CD. The models were adjusted for age, sex, type 1 diabetes mellitus, autoimmune diseases, immunodeficiency, and chromosomal anomalies.
ResultsThe Cox model included 493,382 children. VSD was not independently associated with an increased risk of CD (HR 1.25, 97.5% CI 0.85–1.82). In contrast, established comorbidities showed strong associations with CD: type 1 diabetes mellitus (HR 10.26, 97.5% CI 8.15–12.91), chromosomal anomalies (HR 5.20, 97.5% CI 3.67–7.37), and autoimmune diseases (HR 2.07, 97.5% CI 1.39–3.10).
ConclusionIn this large real-world data, isolated VSD was not an independent risk factor for CD, whereas type 1 diabetes mellitus, chromosomal anomalies, and other autoimmune diseases were strongly associated with CD. These findings do not support routine CD screening based solely on the presence of VSD in children.