Safety assessments
Effect of delayed gluten introduction
on celiac disease–associated tTGCAs. By
the age of 3 years, eight children in the
control group and three children in the
late-exposure group developed persistent
tTGCAs. The cumulative risk of developing
tTGCAs at age 3 years was 14% (95%
CI 4.2–23.8) in the control group and 4%
(0.1–9.9; P = 0.1) in the late-exposure
group (Fig. 3A). An additional six children
developed tTGCAs after age 3 years
(two children in the control group and
four in the late-exposure group). Three
of the tTGCA-positive children of the
control group underwent a biopsy, and
celiac disease was diagnosed in two of
them. In the late-exposure group, four
children had a biopsy and all had celiac
disease.
Effect of delayed gluten introduction
on growth. The development of height
and weight during the first 3 years of life
did not differ between the control and
late-exposure groups (Fig. 3B). Weight
gain during the first year of life (control
group: 5,630 g vs. late-exposure group:
5,640 g; P = 0.6) and from age 12 to 48
months (control group: 7,070 g vs. lateexposure
group 7,230 g; P = 0.9) was
comparable between groups. The prevalence
of overweight (BMI percentile $90
as determined by the German reference
system [16]) was similar between groups
(age 2 years: 4 of 56 children in the control
group vs. 4 of 49 children in the lateexposure
group; P = 1.0; data not shown).
Effect of delayed gluten introduction
on islet autoimmunity outcome and type
1 diabetes: intention-to-treat analysis. A
total of 16 children developed islet autoantibodies
during the first 3 years, including
8 in the control group and 8 in the
late-exposure group; 11 of 16 children
developed more than one islet autoantibody
(6 in the control group and 5 in the
late-exposure group). An additional eight
children developed islet autoantibodies
after the age of 3 years (five children in the
late-exposure group). Six children developed
autoantibodies prior to their first
reported gluten exposure. The probability
of developing any islet autoantibody
(IAAs, GAD antibodies, and/or IA-2As) by
the age of 3 years in the total cohort was
12% (95% CI 6.1–17.9) and was 12% in
the control (4.2–19.8) and 13% in the
late-exposure (5.2–20.8; P = 0.6) groups
(Fig. 4A). The probability of developing
multiple islet autoantibodies also was
similar between groups (control group:
9.0% by age 3 years; late-exposure group