Association Between Maternal Thyroid Function in Early Pregnanc and Stillbirth: A Multicenter Prospective Cohort Study in China

AbstractContext: The association between maternal levels of thyroid stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase antibody (TPOAb) status and stillbirth has not been clearly established.Objective: We aimed to confirm the association of thyroid function in early pregnancy with stillbirth.Methods: The study was designed as a multicenter prospective cohort study, nested within the China Birth Cohort Study (CBCS). A total of 140,245 pregnant women were enrolled from 9 tertiary maternal and child health care hospitals across China between February 12, 2018 and December 31, 2022.Results: The final analysis included 91,673 pregnant women, and the overall incidence of stillbirth was 0.45%. The results showed that FT4 exhibited a significant positive association with stillbirth risk (aOR = 1.04, 95%CI: 1.01–1.07, P = 0.003), with significant linearity (overall P = 0.025, nonlinear P = 0.397). TSH, TPOAb positivity (>60 IU/L), free triiodothyronine (FT3), total triiodothyronine (TT3), total thyroxine (TT4) showed no significant associations with stillbirth. Overt hyperthyroidism was associated with a 2.13-fold higher stillbirth risk compared to euthyroidism (aOR = 2.13, 95%CI: 1.09–4.14, P = 0.026), and the results revealed significant associations between early pregnancy FT4 levels and stillbirths attributed to umbilical cord and maternal causes using the ReCode classification.Conclusions: Maternal FT4 level in early pregnancy is significantly associated with stillbirth risk, even within the clinically defined normal range. Additionally, overt hyperthyroidism is associated with a 2.13-fold increased risk of stillbirth.