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

¹ Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado
² Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway
³ Department of Preventive Medicine & Biometrics, University of Colorado Health Sciences Center, Denver, Colorado
⁴ Department of Human Genetics, Roche Molecular Systems, Alameda, California

Address correspondence and reprint requests to Marian Rewers, MD, PhD, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East 9th Ave., Box B-140, Denver, CO 80262. E-mail: marian.rewers{at}uchsc.edu

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.

Abbreviations: GADA, autoantibodies to GAD₆₅ • IAA, insulin autoantibody

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