Maternal Early Pregnancy and Newborn Thyroid Hormone Parameters: The Generation R Study

Abstract

Abnormal maternal thyroid parameters are associated with adverse pregnancy outcomes, with consequences for both mother and child. Although various studies have studied maternal thyroid parameters during the first half of pregnancy, little is known about their relations with thyroid parameters of the child. The objective was to study maternal thyroid parameters during the first half of pregnancy as well as their relations with cord thyroid parameters. Serum TSH, free T(4) (FT4), T(4), and thyroid peroxidase antibody (TPOAb) levels were determined once between gestational wk 9 and 18 in 5393 pregnant women from the population-based Generation R study. Cord serum TSH and FT4 levels were determined in 3036 newborns. Between gestational wk 9 and 18, the maternal TSH reference range (2.5th to 97.5th percentile) was 0.03-4.04 mU/liter. Gestational age was positively correlated with maternal TSH (r = 0.06, P = 6.3 × 10(-5)) and total T(4) (r = 0.21, P = 1.4 × 10(-44)) and negatively with FT4 (r = -0.27, P=7.3 × 10(-76)) and TPOAb-positivity (r=-0.04, P = 0.01). TPOAb positivity was associated with more subclinical (20.1 vs. 2.4%, P = 1.5 × 10(-39)) and overt hypothyroidism (3.3 vs. 0.1%, P = 1.4 × 10(-10)). Maternal and cord TSH were positively associated (β = 0.47 ± 0.15, P = 1.3 × 10(-5)) as well as maternal and cord FT4 (β = 0.11 ± 0.02, P = 4.5 × 10(-6)). We confirm correlations of maternal thyroid parameters with gestational age during the first half of pregnancy and show a substantially increased risk of (subclinical) hypothyroidism in TPOAb-positive mothers. A substantial part of the mothers had a TSH level above 2.5 mU/liter, underlining the importance of using population-specific reference ranges. Maternal and cord thyroid parameters were positively correlated, the exact biological basis of which remains to be determined.