The objective of this study was to test whether maternal age at delivery, child’s birth order, cesarean section, complicated delivery, maternal smoking during pregnancy, or neonatal jaundice predict islet autoimmunity in children at genetically increased risk of type 1 diabetes in a birth cohort with blood draws at ages 9, 15, and 24 months and yearly thereafter. Newborns with diabetes-associated human leukocyte antigen genotypes (n=938) and offspring or siblings of persons with type 1 diabetes (n=428) from the Denver, Colorado, metropolitan area were examined from January 1994 to February 2003. Information on perinatal factors was collected by using questionnaires soon after the birth. Islet autoimmunity was defined as positivity for ≥1 autoantibody to glutamic acid decarboxylase65, insulin, or protein tyrosine phosphatase-2/ICA512 at ≥2 consecutive visits (n=52; mean follow-up, 3.9 years). Complicated delivery (breech, forceps, vacuum extraction) predicted a higher risk of islet autoimmunity (hazard ratio=2.10, 95% confidence interval: 1.09, 4.05). Increasing maternal age was related to risk of islet autoimmunity among first-degree relatives of persons with type 1 diabetes (hazard ratios=3.96 and 8.88 for maternal ages 25–34 and ≥35 years, respectively, compared with <25 years; p for trend=0.008. Other factors evaluated were not related to risk of islet autoimmunity. In conclusion, influences in utero or during delivery may affect the fetal immune system.