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Thyroid Hormone Status in Umbilical Cord Serum Is Positively Associated with Male Anogenital Distance
Rongju Liu1, Xijin Xu1, Yuling Zhang1
1Laboratory of Environmental Medicine and Developmental Toxicology (R.L., X.X., Y.Z., X.Z., X.H.), and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Obstetrics and Gynecology (R.L.), The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics (X.X.), Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Environmental Health (S.S.K., K.N.D., S.-M.H., T.R., A.C.), College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; and School of Environment (X.H.), Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China.
Insights
Thyroid hormones in newborns are linked to genital development. Maternal secondhand smoke exposure may alter thyroid hormone effects on infant growth and head size.
Area of Science:
- Endocrinology
- Reproductive Biology
- Neonatal Development
Background:
- Thyroid function influences sex hormones and male reproductive health in adults.
- Limited data exists on thyroid function's impact on infant gonadal development.
Purpose of the Study:
- To investigate the association between thyroid hormones (THs) and sexually dimorphic genital development in neonates.
- To examine the relationship between THs and fetal growth parameters.
Main Methods:
- A birth cohort study involving 616 mothers and newborns.
- Analysis of cord blood serum for thyroid-stimulating hormone (TSH), free T3 (FT3), and free T4 (FT4).
- Measurement of anogenital distance (AGD), birth weight, length, body mass index, and head circumference.
Main Results:
- Higher cord serum FT3, FT4, and TSH levels were associated with longer AGD in male newborns.
- A lower FT4/FT3 ratio was also linked to longer AGD in males.
- Secondhand smoke exposure modified the relationships between TSH and birth size, and FT4 and head circumference.
Conclusions:
- In the absence of overt thyroid dysfunction, THs show a positive association with AGD in male newborns.
- Maternal secondhand smoke exposure may modify the effects of THs on infant body size and head circumference.
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.
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