Evaluating the progression to abnormal thyrotropin in euthyroid preconception women: a population-based study

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Abstract
Background: Abnormal preconception thyrotropin levels were associated with fecundability and adverse fetomaternal outcomes, however, little is known regarding the natural change of serum thyrotropin in euthyroid preconception women. Thus, we performed a population-based study to evaluate the progression to abnormal thyrotropin in euthyroid preconception women. Methods: This retrospective cohort study used data from the National Free Prepregnancy Checkups Project (NFPCP) collected between 2010 and 2020. Female Han Chinese participants aged 20–49 years who had two repeated NFPCP participations with a time interval of 1.5–3.0 years, confirmed non-pregnant status within this duration, and normal thyrotropin levels during their first participation were included for the analysis of thyrotropin abnormalities during the second NFPCP examination. Data were analyzed between June 1 and October 1, 2023. Results: This study included 186,095 euthyroid women of reproductive age (mean ± SD, 26.72 ± 4.70 years) whose preconception thyrotropin levels were between 0.37 and 4.87 mIU/L. The median follow-up time was 2.13 (IQR, 1.85–2.54) years. A total of 8,497 (4.57%) women developed abnormal thyrotropin, including 4,118 (2.21%) subnormal thyrotropin and 4,379 (2.35%) supranormal thyrotropin. Compared with the reference group (thyrotropin 1.01–2.00 mIU/L), the lower baseline thyrotropin group had greater risk of developing subnormal thyrotropin, and the higher baseline thyrotropin group had greater risk of developing supranormal thyrotropin. Moreover, the restricted cubic spline analysis revealed a U-shaped dose–response association of baseline thyrotropin levels or thyrotropin multiples of the median (MOM) levels against risk of subnormal thyrotropin in the follow-up, and a J-shaped dose–response association against risk of supranormal thyrotropin levels in the follow-up. We further found that baseline thyrotropin outside of 1.43–1.93 mIU/L or baseline thyrotropin MOM outside 0.59–1.36 would hava a higher risk of developing of abnormal thyrotropin. Conclusions: Both low and high baseline thyrotropin were associated with a significantly increased risk of developing abnormal thyrotropin outcomes. The optimal preconception baseline thyrotropin levels may be between 1.43 mIU/L and 1.93 mIU/L or baseline thyrotropin MoM between 0.59 and 1.36 to minimize progression toward abnormal thyrotropin after 1.5–3.0 years. These findings may help with counseling of preconception thyroid function monitoring.
Funding Information
  • National Key Research and Development Program of China (2016YFC1000307)
  • Chinese Academy of Medical Sciences Innovation Fund (2018-I2M-1-004)

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