Background: Two ongoing intervention trials were designed to investigate if early gluten intervention strategies prevent or delay celiac disease autoimmunity (CDA) and celiac disease (CD) in children at genetic risk.
Methods: Newborns carrying HLA-DQ2/DQ2 and HLA-DQ2/X were randomized to normal gluten-containing diets or to a gluten-free diet in the PreCiSe (NCT03562221), or to gluten-reduced in GRaIn (NCT04593888) studies, until age 3 years. Participants were followed annually with tissue transglutaminase autoantibody (tTGA) screening from age 6 months to age 7 years. Enrollment is now complete with 220 infants enrolled in PreCiSe and 1,141 infants enrolled in GRaIn, respectively. The primary outcome was CDA, defined as being tTGA positive in two consecutive samples. The secondary outcome was CD confirmed by intestinal biopsy. Detailed environmental information and compliance with intervention diets are obtained regularly. The daily intake of gluten was estimated from repeated 3-day food records every 3-6 months.
Results: In PreCiSe, CDA occurred in 34 (23.3%) children on a normal diet versus 9 (12.2%) on a gluten-free diet (Relative Risk [RR]=0.52, 95%CI=0.26-1.03; p=0.05). CD developed in 27 (18.5%) children at mean age 3.1 years (SD=1.5) versus 8 (10.8%), at mean age 5.6 years (SD 1.0), respectively (RR=0.58, 95%CI=0.28-1.22; p=0.14). In GRaIn, CDA occurred in 29 (5.2%) children on a normal diet versus 18 (3.1%) on a gluten-reduced diet (RR=0.59, 95%CI=0.33-1.05; p=0.06). CD was diagnosed in 23 (4.1%) at mean age 3.0 years (SD=0.6) versus 8 (1.4%) at mean age 4.0 years (SD=1.0), respectively (RR=0.33, 95%CI=0.15-0.73; p=0.006).
Conclusion: Preliminary interim analyses from these two ongoing randomized intervention trials indicate that gluten-free or gluten-reduced diets in early childhood may lower the risk of CDA and CD in genetically at-risk children. A significant reduction in CD was observed in the GRaIn study, while similar trends in PreCiSe were not statistically significant.