Maternal Thyroid Hormone Parameters during Early Pregnancy and Birth Weight: The Generation R Study

Context: Maternal hyperthyroidism during pregnancy is associated with an increased risk of low birth weight, predisposing to neonatal morbidity and mortality. However, the effects of variation in maternal serum thyroid parameters within the normal range on birth weight are largely unknown. Objective: The aim was to study the effects of early pregnancy maternal serum thyroid parameters within the normal range on birth weight, as well as the relation between umbilical cord thyroid parameters and birth weight. Design, Setting, and Participants: In early pregnancy, serum TSH, FT4 (free T-4), and thyroid peroxidase antibody levels were determined in 4464 pregnant women. Cord serum TSH and FT4 levels were determined in 2724 newborns. Small size for gestational age at birth (SGA) was defined as a gestational age-adjusted birth weight below the 2.5th percentile. The associations between normal-range maternal and cord thyroid parameters, birth weight, and SGA were studied using regression analyses. Results: In mothers with normal-range FT4 and TSH levels, higher maternal FT4 levels were associated with lower birth weight [beta = -15.4 (3.6) g/pmol . liter, mean (SE); P = 1.6 x 10(-5)], as well as with an increased risk of SGA newborns [odds ratio (95% confidence interval) = 1.09 (1.01-1.17); P = 0.03]. Birth weight was positively associated with both cord TSH [beta = 4.1 (1.4) g/mU . liter; P = 0.007] and FT4 levels [beta = 23.0 (3.2) g/pmol . liter; P = 9.2 x 10(-13)]. Conclusions: We show that maternal high-normal FT4 levels in early pregnancy are associated with lower birth weight and an increased risk of SGA newborns. Additionally, birth weight is positively associated with cord TSH and FT4 levels. These data demonstrate that even mild variation in thyroid function within the normal range can have important fetal consequences. (J Clin Endocrinol Metab 98: 59-66, 2013)