Preconception Thyrotropin Levels and Risk of Adverse Pregnancy Outcomes in Chinese Women Aged 20 to 49 Years

IMPORTANCE: Maternal thyrotropin levels during gestation have a profound effect on pregnancy outcomes; however, few studies to date have evaluated the importance of preconception thyrotropin levels. OBJECTIVE: To investigate the associations between preconception thyrotropin levels and pregnancy outcomes. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study enrolled Chinese women aged 20 to 49 years from the National Free Prepregnancy Checkups Project in China. Participants conceived within 6 months after the thyrotropin examination and completed follow-up for pregnancy outcomes between January 1, 2013, and December 31, 2017. Data were analyzed between May 1, 2019, and March 31, 2020. EXPOSURES: Levels of thyrotropin within 6 months before pregnancy, measured as less than 0.10 mIU/L, 0.10 to 0.36 mIU/L, 0.37 to 2.49 mIU/L, 2.50 to 4.87 mIU/L, 4.88 to 9.99 mIU/L, and 10.00 mIU/L or greater. MAIN OUTCOMES AND MEASURES: The association of maternal preconception thyrotropin levels with the 4 primary adverse pregnancy outcomes was assessed, including preterm birth (PTB), small for gestational age (SGA), birth defect, and perinatal infant death. Logistic regression analyses were used to evaluate the association between preconception maternal thyrotropin levels and risk of adverse pregnancy outcomes. The dose-response associations were assessed using restricted cubic spline regression. RESULTS: This study enrolled 5 840 894 women (mean [SD] age, 26.30 [4.10] years) in the primary analysis. The median (interquartile range [IQR]) thyrotropin level was 1.60 (1.06-2.37) mIU/L. The cumulative incidences for the adverse pregnancy outcomes were as follows: PTB, 6.56%; SGA, 7.21%; birth defect, 0.02%; and perinatal infant death, 0.33%. Compared with the reference group (thyrotropin range, 0.37-2.49 mIU/L), both low (<0.10 mIU/L and 0.10-0.36 mIU/L) and high (4.88-9.99 mIU/L and ≥10.00 mIU/L) maternal preconception thyrotropin levels were associated with higher risk of PTB (low: odds ratio [OR], 1.23 [95% CI, 1.19-1.27] and OR, 1.15 [95% CI, 1.13-1.18] vs high: OR, 1.13 [95% CI, 1.10-1.15] and OR, 1.14 [95% CI, 1.08-1.20]), SGA (low: OR, 1.37 [95% CI, 1.33-1.40] and OR, 1.14 [95% CI, 1.12-1.17] vs high: OR, 1.05 [95% CI, 1.03-1.08] and OR, 1.17 [95% CI, 1.11-1.23]), and perinatal infant death (low: OR, 1.26 [95% CI, 1.10-1.43] and OR, 1.14 [95% CI, 1.05-1.24] vs high: OR, 1.31 [95% CI, 1.20-1.43] and OR, 1.47 [95% CI, 1.21-1.80]). J-shaped associations between preconception thyrotropin levels and PTB (χ(2) = 1033.45; nonlinear P < .001), SGA (χ(2) = 568.90; nonlinear P < .001), and perinatal infant death (χ(2) = 38.91; nonlinear P < .001) were identified. CONCLUSIONS AND RELEVANCE: In this cohort study, both low and high maternal thyrotropin levels were associated with a significantly increased risk of adverse pregnancy outcomes. Results suggest that the optimal preconception thyrotropin levels may be between 0.37 mIU/L and 2.50 mIU/L to prevent adverse pregnancy outcomes.