Early Maternal Thyroid Function During Gestation Is Associated With Fetal Growth, Particularly in Male Newborns

Abstract

Background: Intrauterine growth patterns are influenced by maternal thyroid function during gestation and by fetal sex. It is unknown, however, whether the relationships between maternal thyrotropin (TSH) and free thyroxine (fT4) levels in early pregnancy and fetal growth outcomes are modified by fetal sex. Design: Data were obtained from a community-based cohort study of pregnant women living in Amsterdam (Amsterdam Born Children and Their Development study). TSH and fT4 levels were determined during the first prenatal screening at median 13 weeks (interquartile range, 12 to 14). Women with live-born singletons and no overt thyroid dysfunction were included (N = 3988). Associations between these maternal hormones and birth weight, small for gestational age (SGA), and large for gestational age (LGA) were analyzed separately for each sex. Results: After adjustments, 1 pmol/L increase in maternal fT4 levels was associated with a reduction in birth weight of 33.7 g (P < 0.001) in male newborns and 16.1 g (P < 0.05) in female newborns. Increased maternal fT4 was not associated with increased odds for SGA, but was associated with a decreased odds for LGA in boys [per 1 pmol/L; odds ratio (OR), 0.79; 95% confidence interval (CI), 0.69 to 0.90]. Maternal subclinical hypothyroidism in early pregnancy (TSH > 2.5 mU/L, 7.3%) was associated with increased odds for LGA in male newborns (OR, 1.95; 95% CI, 1.22 to 3.11). Conclusion: Maternal fT4 in early pregnancy was observed to be inversely associated with birth weight, with a stronger relationship in males. Male infants also had increased odds for LGA in mothers with subclinical hypothyroidism. Sexual dimorphism appears to be present in the relationship between maternal thyroid metabolism and fetal intrauterine growth, with stronger associations in male infants.