Perinatal Outcome of Children Born to Mothers with Thyroid Dysfunction or Antibodies: A Prospective Population-Based Cohort Study

Context: There are only a few large prospective studies involving evaluation of the effect of maternal thyroid dysfunction on offspring and observations are inconsistent. Objective: The objective of the study was to investigate the effects of thyroid dysfunction or antibody positivity on perinatal outcome. Setting and Participants: The study included prospective population-based Northern Finland Birth Cohort 1986 including 9247 singleton pregnancies. First-trimester maternal serum samples were analyzed for thyroid hormones [TSH, free T-4 (fT4)] and antibodies [thyroid-peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab)]. Mothers were classified by their hormone and antibody status into percentile categories based on laboratory data and compared accordingly. Main Outcomes: Outcomes were perinatal mortality, preterm delivery, absolute and gestational age-adjusted birth weight, and absolute and relative placental weight. Results: The offspring of TPO-Ab-and TG-Ab-positive mothers had higher perinatal mortality, which was not affected by thyroid hormone status. Unadjusted and adjusted (for maternal age and parity) risk for increased perinatal mortality was an odds ratio of 3.1 (95% confidence interval 1.4-7.1) and 3.2 (1.4-7.1) in TPO-Ab-and 2.6 (1.1-6.2) and 2.5 (1.1-5.9) in TG-Ab-positive mothers. TPO-Ab-positive mothers had more large-for-gestational age infants (2.4 vs. 0.8%, P = 0.017), as did mothers with low TSH and high fT4 concentrations vs. reference group (6.6 vs. 2.5%, P = 0.045). Significantly higher placental weights were observed among mothers with low TSH and high fT4 or high TSH and low fT4 levels as well as among TPO-Ab-positive mothers. Conclusions: First-trimester antibody positivity is a risk factor for perinatal death but not thyroid hormone status as such. Thyroid dysfunction early in pregnancy seems to affect fetal and placental growth. (J Clin Endocrinol Metab 94: 772-779, 2009)