Supplementary Material for: Maternal use of fertility treatments and the risk for celiac disease in the offspring

ABSTRACT
Background: Fertility treatments affect the maternal hormonal and immunological milieu, which also support the developing fetus. Given that celiac disease is an immune-mediated disorder, it has been hypothesized that fertility treatments may influence immune programming in utero and potentially increase the risk of immune-related conditions in the offspring, such as celiac disease.
Objective: We sought to investigate whether offspring conceived following fertility treatments are at increased risk of developing celiac disease during childhood.
Study design: A large population-based cohort study was conducted, including all singleton deliveries at a tertiary medical center between the years 1991 and 2021. The risk of developing celiac disease was compared between offspring (followed up to the age of 18) of women who conceived using fertility treatments - including ovulation induction and in vitro fertilization - and those born following spontaneous conception. Data regarding celiac disease diagnoses were extracted from community-based clinics and hospitalization records of the offspring. Kaplan–Meier survival analysis was used to compare the cumulative incidence of celiac disease between the study groups. A Cox proportional hazards model was applied to control for potential confounders.
Results: A total of 356,356 singleton deliveries were included in the study, of which 7,711 (2.2%) were conceived using fertility treatments. Offspring born following fertility treatments had a comparable rate of celiac disease to those born after spontaneous conception (0.6% vs. 0.5%, p = 0.477). Kaplan–Meier survival analysis demonstrated similar cumulative incidence of celiac disease between the groups (log-rank test, p= 0.285). In a Cox proportional hazards model, adjusted for maternal age and gestational age, fertility treatments were not associated with an increased risk of celiac disease in the offspring (adjusted hazard ratio [aHR]=1.13, 95% confidence interval [CI] 0.84 - 1.52, p=0.392).
Limitations: Follow-up was limited to age 18, and cases diagnosed later in life could not be captured.
Conclusion: In our large cohort with long-term follow up, fertility treatments were not associated with an increased risk of celiac disease in the offspring.