Women with antibodies against the enzyme thyroid peroxidase [TPO-Ab; formerly microsomal antibodies (MsAb)] are at particular risk for developing postpartum thyroid dysfunction; the latter is significantly associated with postpartum depression. Although the negative effect of postpartum maternal depression on child development is well documented, the consequences of elevated titers of TPO-Ab during pregnancy and subsequent postpartum thyroid dysfunction on child development are not known. In a prospective study of a cohort of 293 pregnant women, the occurrence of TPO-Ab during gestation, thyroid dysfunction, and depression was investigated. Five years after delivery, child development was assessed in 230 children of the original cohort using the Dutch translation of the McCarthy Scales of Children's Abilities. Children of women with TPO-Ab during late gestation (n = 19, with normal thyroid function) had significantly lower scores (by t test) on the McCarthy Scales of Children's Abilities than antibody-negative women. The difference on the General Cognitive Scale, which reflects IQ scores, was substantial (10.5 points; t = 2.8; P = 0.005). After correction for possibly confounding variables, maternal TPO-Ab during gestation was found to be the most important factor related to the scores on the General Cognitive Scale (odds ratio = 10.5; 95% confidence interval = 3-34; P = 0.003). We conclude that children of pregnant women who had elevated titers of TPO-Ab but normal thyroid function are at risk for impaired development.