Background: Early life exposure to per- and polyfluoroalkyl substances (PFAS) has been hypothesized as a risk factor for celiac disease development. We aimed to examine this putative association in two longitudinal studies.
Methods: Participants were included from the Odense Child Cohort (OCC) for a cohort study and from the Danish National Birth Cohort (DNBC) for a nested case-control study. In both studies the concentrations of five PFAS were measured in maternal blood during first trimester of pregnancy. Celiac autoimmunity was assessed in the OCC children at age 7-9 years (antibody screening) and in DNBC at age 15-21 years (antibody screening and biopsy, questionnaires and registry data). In the DNBC sub-study, controls were matched for HLA-type (HLA-DQ2/-DQ8) and sex. Both populations were analyzed by logistic regression and results expressed as odds ratios (OR). Results for OCC were unadjusted; in DNBC adjusted for the matching factors HLA-type, sex and duration of breastfeeding.
Results: Among the 523 eligible mother-child pairs in OCC, we identified 8 cases of celiac autoimmunity (1.5%). In DNBC, 26 cases with celiac disease and 6 additional cases with celiac autoimmunity were identified and 75 controls were selected. The prevalence of celiac disease was high among screened DNBC participants (2.1%). Median PFOS levels were highest in DNBC (approx. 13.4 ng/mL) compared to OCC (approx. 7.6 ng/mL). High levels of prenatal perfluorooctane sulfonic acid (PFOS) exposure were associated with celiac autoimmunity in the OCC (OR per 1 ng/mL exposure increase: 1.31, 95%CI: 1.13 ; 1.52, p<0.001), despite the small sample size. No other PFAS were statistically significantly associated with celiac autoimmunity in either cohort.
Conclusion: Higher prenatal PFOS exposure may contribute to the development of celiac autoimmunity, but given the small sample size and the lack of reproducibility between the two studies the results should be interpreted cautiously.