Thyroid Hormone Status in Umbilical Cord Serum Is Positively Associated with Male Anogenital Distance

Abstract

CONTEXT: In human adults and adolescents, thyroid function affects sex hormones and male reproductive functions. Little is known about the thyroid function effects on the gonadal development in human infants. OBJECTIVE: The aim was to examine the association between thyroid hormones (THs) and sexually dimorphic genital development or fetal growth. DESIGN: This is a birth cohort study. PARTICIPANTS: A total of 616 mothers and newborns were analyzed from two local hospitals. MAIN OUTCOME MEASURES: TSH, free T3 (FT3), and free T4 (FT4) levels in cord blood serum, anogenital distance (AGD), birth weight, birth length, birth body mass index, and head circumference in neonates. RESULTS: Longer AGD in male newborns was observed with higher cord serum FT3 (β, 1.36 mm [95% confidence interval (CI), 0.58-2.13] for 1 pmol/L FT3), FT4 (β, 0.12 mm [95% CI, 0.00-0.25] for 1 pmol/L FT4), and TSH (β, 3.14 mm [95% CI, 0.65-5.63] for a 10-fold TSH increase), and with a lower FT4/FT3 ratio (β, -0.11 mm [95% CI, -0.20 to -0.02] for doubling FT4/FT3 ratio). The relationships between TSH, birth weight, and birth length were different by secondhand smoke exposure. Secondhand smoke exposure had an effect modification, with interaction P value .039 and .010, respectively. Secondhand smoke exposure also had an effect modification on the relation between FT4 and head circumference with interaction P value .020. CONCLUSIONS: In the absence of overt thyroid dysfunction, THs are positively associated with AGD in male newborns. TH effects on body size and head circumference may be modified by maternal secondhand smoke exposure.