Association of Isolated Hypothyroxinemia and Subclinical Hypothyroidism With Birthweight: A Cohort Study in Japan

Akiko Sankoda; Naoko Arata; Shiori Sato; Nagayoshi Umehara; Naho Morisaki; Yushi Ito; Haruhiko Sago; Yuichiro Yano; Reiko Horikawa

doi:10.1210/jendso/bvad045

Association of Isolated Hypothyroxinemia and Subclinical Hypothyroidism With Birthweight: A Cohort Study in Japan

J Endocr Soc. 2023 Apr 11;7(5):bvad045. doi: 10.1210/jendso/bvad045. eCollection 2023 Mar 6.

Authors

Akiko Sankoda¹, Naoko Arata¹, Shiori Sato¹, Nagayoshi Umehara¹, Naho Morisaki², Yushi Ito¹, Haruhiko Sago¹, Yuichiro Yano³, Reiko Horikawa⁴

Affiliations

¹ Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo 157-0074, Japan.
² Department of Social Medicine, National Research Institute for Child Health and Development, Tokyo 157-0074, Japan.
³ Noncommunicable Disease Epidemiology Research Center, Shiga University of Medical Science, Otsu 520-2192, Japan.
⁴ Division of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo 157-0074, Japan.

Abstract

Context: Isolated hypothyroxinemia (low maternal free thyroxine [FT4] in the absence of thyroid-stimulating hormone [TSH] elevation) and subclinical hypothyroidism (high TSH in the absence of FT4 elevation) during early pregnancy are common. However, there are limited data regarding pregnancy outcomes, particularly their association with birthweight.

Objective: We assessed the association between isolated hypothyroxinemia and subclinical hypothyroidism during the first trimester and birthweight.

Methods: Analyses were conducted using a database of pregnant women (n = 1105; median age, 35 years) who delivered at the National Center for Child Health and Development, a tertiary hospital in Tokyo. The primary outcomes included the rates of small for gestational age (SGA), large for gestational age (LGA), and low birth weight.

Results: Of the 1105 pregnant women, 981 were classified into the euthyroidism group, 25 into the isolated hypothyroxinemia group, and 26 into the subclinical hypothyroidism group during the first trimester. The prevalence of SGA was significantly higher in isolated hypothyroxinemia and subclinical hypothyroidism groups than the euthyroidism group (28.0% and 19.2%, respectively, vs 5.7%; P < .01). The odds ratio with 95% CI for SGA was 12.51 (4.41-35.53) for isolated hypothyroxinemia and 4.44 (1.57-12.56) for subclinical hypothyroidism in a multivariable adjustment model. Isolated hypothyroxinemia and subclinical hypothyroidism were not significantly associated with LGA and low birth weight.

Conclusion: Pregnant women with isolated hypothyroxinemia and subclinical hypothyroidism in the first trimester have an increased likelihood of SGA. Screening and careful perinatal checkups for isolated hypothyroxinemia and subclinical hypothyroidism may help identify pregnant women at high risk for SGA.

Keywords: isolated hypothyroxinemia; pregnancy outcome; small for gestational age; subclinical hypothyroidism; thyroid hormones.