Symptoms of Common Maternal Infections in Pregnancy and Risk of Islet Autoimmunity in Early Childhood

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Abstract
OBJECTIVE—The aim of this study was to test whether symptoms of maternal infections during pregnancy and indicators of postnatal infections predict development of islet autoimmunity in children at genetically increased risk of type 1 diabetes. RESEARCH DESIGN AND METHODS—A total of 871 children with type 1 diabetes-associated HLA genotypes born in Denver, Colorado, and 391 siblings or offspring of individuals with type 1 diabetes referred from clinics in the Denver metropolitan area were enrolled soon after birth and seen in the clinic at age ≤15 months. Information on indicators of infection was collected by structured interviews soon after birth and at ages 3–15 months. Clinic visits were scheduled at ages 9, 15, and 24 months, and yearly thereafter. The outcome was positivity for one or more islet autoantibodies (to GAD65, insulin, or IA-2/ICA512) at two or more consecutive visits. During a mean follow-up of 4.2 years, 52 children developed islet autoimmunity. RESULTS—Children whose mother reported at least one symptom of infection during pregnancy (mostly respiratory or gastrointestinal) had a significantly lower risk of islet autoimmunity compared with other children (hazard ratio 0.48; 95% CI 0.27–0.83). After stratification, the association appeared among girls (0.21; 0.09–0.48) but not among boys (1.09; 0.47–2.51) with a P value for interaction of 0.005. Symptoms of neonatal infections, early daycare attendance, exposure to cats or dogs, and household crowding were not related to islet autoimmunity. CONCLUSIONS—Symptoms of maternal infections in pregnancy predicted a significantly lower risk of islet autoimmunity in young girls, suggesting a protective effect of such infections.