Thyroid-Stimulating Hormone (TSH) Serum Levels and Risk of Spontaneous Abortion

A Prospective Population-Based Cohort Study

Maryam Kianpour; Ashraf Aminorroaya; Massoud Amini; Awat Feizi; Sima Aminorroaya Yamini; Mohsen Janghorbani

Disclosures

Clin Endocrinol. 2019;91(1):163-169. 

In This Article

Abstract and Introduction

Abstract

Objective: Thyroid dysfunction, a common complication of pregnancy, is associated with adverse obstetric and neonatal consequences. This study aimed to determine the effect of TSH levels on early pregnancy outcome in a prospective population-based cohort study.

Design and methods: The serum TSH, free thyroxine, free triiodothyronine, thyroid peroxidase antibody levels and urinary iodine concentration of 418 pregnant women in their first trimester of pregnancy were measured. According to the American Thyroid Association (ATA) and the local reference ranges for TSH, women were divided into two groups of 0.1-2.5, >2.5 mIU/L and 0.2-4.6, >4.6 mIU/L. The risk of spontaneous abortion (SA) was calculated for each group.

Results: Spontaneous abortion was detected in 7.2% (n = 30) of total 418 pregnancies. Women with TSH levels > 2.5 mIU/L had an increased risk of SA, compared to women with TSH levels of 0.1-2.5 mIU/L (relative risk [RR] 3.719, 95% confidence interval [CI]:1.713-8.074). The risk of SA was increased in women with TSH levels > 4.6 mIU/L (RR 5.939, 95% CI: 1.711-20.620). The rate of SA was increased by 78% for every unit increase in standard deviation of TSH concentration (RR 1.35, 95% CI: 1.09-1.70). The rate of miscarriages in the treated group by levothyroxine was 9.8% (n = 6) compared to 28.6% (n = 8) in the untreated group (P = 0.024).

Conclusions: Our finding suggests that the upper limit for the TSH normal range should be redefined to <2.5 mIU/L during the first trimester of gestation. The local upper limit was 4.6 mIU/L, consistent with 4.0 mIU/L cut-off value recommended by the ATA.

Introduction

Pregnancy is associated with significant physiological changes in the thyroid gland, inducing changes in its economy, leading to hormonal and metabolic variations in relation to pregnancy.[1] The reduced level of thyroid-stimulating hormone (TSH) during pregnancy, specifically in the first trimester, is correlated with the increased human chorionic gonadotropin hormone (hCG). This decrease might have been originated from the weak stimulating effects of hCG on the TSH receptors of the thyroid gland, that would occur due to the molecular similarity of the alpha—subunit of hCG and TSH.[2] Therefore, when the hCG level is at the highest, the TSH level is at the lowest during pregnancy. HCG level increases until weeks 8th-11th of pregnancy; then remains roughly constant and decreases following the increment in the TSH level.[1] Such changes indicate the need for specific reference ranges during pregnancy to prevent misdiagnosis.[3] Considering the effect of geographic and ethnic variation on the reference ranges of TSH during pregnancy, the American Thyroid Association (ATA)[4] and the European Thyroid Association (ETA)[3] have recommended that the reference ranges during pregnancy should be established for each trimester, separately for different regions. The latest guideline of the ATA has recommended an upper limit of 2.5 mIU/L for TSH during the first trimester and 3.0 mIU/L during the second and third trimester in American and European pregnant women.[5] Previous studies reported the reference range of TSH in Brazilian, Swiss and Indian pregnant women during the first trimester as 0.14-3.68 mIU/L, 0.0878-2.829 mIU/L and 0.09-6.65 mIU/L, respectively.[6,7] In two separate studies conducted in Iran,[9,10] the reference range of TSH for first trimester was reported as 0.2-3.9 mIU/L and 0.2-4.6 mIU/L, which are wider and higher than the recommended ranges by the ATA.[5]

Failure in compatibility with the physiologic changes during pregnancy causes thyroid dysfunction and leads to adverse maternal-foetal complications.[11] Several studies have reported consequences for thyroid dysfunction during pregnancy and prenatal period, including spontaneous abortion,[12,13] foetal death, preterm delivery,[14] decreased head circumference and low birthweight.[15] A systematic review reported increased pregnancy complications including preeclampsia, prenatal death and abortion in pregnant women with subclinical hypothyroidism and positive thyroid auto-antibodies.[16] The increased risk of spontaneous abortion and foetal death was also reported in women with mild hypothyroidism.[17] Subclinical hypothyroidism in the presence or absence of thyroid antibodies is also suggested to be considered as a threat to fertility, pregnancy outcomes and foetal development.[18]

Considering the differences in the reference ranges of TSH in various studies, recommendations for the use of specific pregnancy reference ranges in different geographic regions and reported occurrence of adverse pregnancy complications in relation to TSH level during pregnancy, the present study aimed to determine the relationship between maternal TSH level and spontaneous abortion during the first trimester of pregnancy based on two specific reference range of TSH recommended by the ATA (0.1-2.5 mIU/L)[5] and a previous local study (0.2-4.6 mIU/L).[10] These data were driven from a cohort study conducted on pregnant women who were receiving prenatal care in public and private care centres in Isfahan, Iran.

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