Background: Numerous studies have found that subclinical hypothyroidism (SCH) may increase adverse pregnancy outcomes; however, the benefit of levothyroxine (LT4) treatment remains controversial. The 2017 guidelines of the American Thyroid Association weakly recommended LT4 therapy for serum antithyroid peroxidase antibody (TPOAb)-negative women with thyroid-stimulating hormone (TSH) concentrations greater than the pregnancy-specific reference range and below 10.0 mU/L. Therefore, the primary goal of this study was to investigate the correlation between thyroid autoantibody-negative SCH with or without LT4 treatment and adverse pregnancy outcomes.
Methods: We prospectively enrolled 1868 consecutive pregnant women. Finally, 1344 women were involved in the study according to the inclusion and exclusion criteria. Assays for TSH, free thyroxine (FT4), TPOAb, anti-thyroglobulin antibody, and laboratory indicators were performed. The participants were divided into the euthyroid (ET) group (n = 1250) and the SCH group(n = 94). The SCH group was further divided into LT4 group (n = 40) and non-LT4 group(n = 54). The laboratory indicators and pregnancy outcomes were evaluated during follow-ups.
Results: Maternal age, BMI, parity, and the history of spontaneous abortion did not differ significantly between the ET group and the different SCH groups. There were no significant differences in lipid profile and homocysteine levels between ET and SCH group in the first and third trimester of pregnancy. After adjusting the confounding factors, the non-LT4 group was a risk factor for spontaneous abortion (odds ratio: 3.141, 95% CI: 1.060-9.302). Survival analysis showed that the time of abortion was different between the ET group and SCH group (log-rank P= 0.042). The spontaneous abortion in SCH, especially in non-LT4, group mainly occurred in the first trimester of pregnancy.
Conclusions: Thyroid autoantibody negative-SCH seems to be associated with increased risk of spontaneous abortions during the first trimester of pregnancy. LT4 therapy in this patient population might be beneficial to reduce adverse pregnancy outcomes.
Keywords: levothyroxine; pregnancy outcomes; subclinical hypothyroidism.