Abstract
Objective: Thyroid hormones are essential for neurodevelopment in early life. However, the impact of mild alterations in neonatal thyroid hormones on infant neurodevelopment and its sex dimorphism is unclear. We aimed to assess whether mild variations in neonatal thyroid hormones of term-born newborns with maternal euthyroid are related to neurodevelopment in 2-year-old boys and girls.Methods: This study used data from 452 singleton term-born infants of mothers with normal thyroid function in Shanghai, China, and their follow-up measure at the age of 2 years. Cord serum concentrations of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were measured by chemiluminescent microparticle immunoassays and classified into three groups: the low (1st, Q1), middle (2nd−4th, Q2–Q4), and high (5th, Q5) quintiles. Neurodevelopment indices were assessed using the Ages and Stages Questionnaire, third edition (ASQ-3), at 24 months of age.Results: Compared to infants with thyroid hormones in the middle (Q2–Q4), boys with FT4 in the lowest quintile had 5.08 (95% CI: 1.37, 8.78) points lower scores in the communication domain, 3.25 (0.25,6.25) points lower scores in the fine motor domain, and 3.84 (0.04, 7.64) points lower scores in the personal-social domain, respectively. Boys with FT3 in the highest quintile had 4.46 (0.81, 8.11) points increase in the personal-social domain. These associations were not observed in girls. No associations were observed between cord blood serum TSH and ASQ-assessed neurodevelopment in the boys or the girls.Conclusions: Mild alterations in thyroid hormones of newborns were associated adversely with neurodevelopment in boys, suggesting the importance of optimal thyroid hormone status for neurodevelopment in early life.
Highlights
An adequate supply of thyroid hormones is essential for healthy neurodevelopment in utero and during infancy [1, 2]
Fetal thyroid hormones are of maternal origin, and from mid gestation onward, fetal thyroid gland begins to secrete thyroxine (T4) and triiodothyronine (T3) under the control of the hypothalamic-pituitary-thyroid axis, and the thyroid hormone axis becomes fully functional around the time of term birth [3]
Studies in recent decades have showed that variations in the lower and higher ranges of neonatal thyroid hormone levels may be associated with neurodevelopment, but data are limited and contradictory [7]
Summary
An adequate supply of thyroid hormones is essential for healthy neurodevelopment in utero and during infancy (the first 2 years of postnatal life) [1, 2]. The developing brain may be susceptible to even mild thyroid hormone deficiency [4] It is unclear whether mild variations in neonatal thyroid hormones may affect subsequent neurodevelopment during infancy. There are several randomized controlled trials (RCTs) addressing the effect of thyroid hormone supplementation during infancy on neurodevelopment and reporting that T4 supplementation does not improve mental or motor development in preterm infants [23] and in infants with Down syndrome [24]. It remains unclear whether mild variations in neonatal thyroid hormones, within normal ranges, may affect neurodevelopment during infancy. The brain undergoes substantial organization and sexual differentiation during infancy [25], and it is unclear whether sex has an impact on the association between neonatal thyroid hormones and neurodevelopment
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