Levothyroxine treatment in pregnant women with thyroid stimulating hormone levels ranging between 2.5 and 10 mIU/L: A propensity score matched analysis

Shen Gao; Xueran Wang; Rong Zhao; Yuchen Cui; Shaofei Su; Enjie Zhang; Jianhui Liu; Shuanghua Xie; Yue Zhang; Yuxi Yang; Kaikun Huang; Minhui Hu; Wentao Yue; Ruixia Liu; Chenghong Yin

doi:10.1089/thy.2023.0662

Levothyroxine treatment in pregnant women with thyroid stimulating hormone levels ranging between 2.5 and 10 mIU/L: A propensity score matched analysis

Thyroid. 2024 Apr 26. doi: 10.1089/thy.2023.0662. Online ahead of print.

Authors

Shen Gao¹, Xueran Wang², Rong Zhao³, Yuchen Cui⁴, Shaofei Su⁵, Enjie Zhang⁶, Jianhui Liu⁷, Shuanghua Xie⁸, Yue Zhang⁹, Yuxi Yang¹⁰, Kaikun Huang¹¹, Minhui Hu¹², Wentao Yue¹³, Ruixia Liu¹⁴, Chenghong Yin¹⁵

Affiliations

¹ Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Department of Central Laboratory, Beijing, China; shengao@mail.ccmu.edu.cn.
² Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Department of Central Laboratory, 251 Yaojiayuan Road, Chaoyang District, Beijing 100026, China, Beijing, --- Select One ---, China, 100026; wangxueran@mail.ccmu.edu.cn.
³ Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Beijing, China; zhaorong051@ccmu.edu.cn.
⁴ Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Beijing, China; cycwx@mail.ccmu.edu.cn.
⁵ Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Department of Central Laboratory, Beijing, China; movingsu@mail.ccmu.edu.cn.
⁶ Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Department of Central Laboratory, Beijing, China; zhangenjie@mail.ccmu.edu.cn.
⁷ Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Beijing, China; jianhuiliu@mail.ccmu.edu.cn.
⁸ Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Department of Central Laboratory, Beijing, China; xiesh2021@mail.ccmu.edu.cn.
⁹ Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Department of Research Management, Beijing, China; zhangyue0517@ccmu.edu.cn.
¹⁰ Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, 251 Yaojiayuan Road, Chaoyang District, Beijing, Beijing, China, 100006; yangyuxi1031@mail.ccmu.edu.cn.
¹¹ Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Department of Central Laboratory, Beijing, China; kaikunhuang@mail.ccmu.edu.cn.
¹² Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Beijing, China; huminhui@mail.ccmu.edu.cn.
¹³ Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Beijing, China; yuewt@ccmu.edu.cn.
¹⁴ Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Department of Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, 251 Yaojiayuan Road, Chaoyang District, Beijing, China, Beijing, Beijing, China, 100026; liuruixia@ccmu.edu.cn.
¹⁵ Capital Medical University Beijing Obstetrics and Gynecology Hospital, 105762, Department of Central Laboratory, No.251, Yaojiayuan Rd, Beijing, China, 100026; yinchh@ccmu.edu.cn.

PMID: 38666684
DOI: 10.1089/thy.2023.0662

Abstract

Objective: To clarify the association between levothyroxine (LT-4) treatment and various adverse pregnancy outcomes in pregnant women with thyroid stimulating hormone (TSH) levels ranging between 2.5 to 10.0 mIU/L in the first trimester, stratified according to thyroid peroxidase antibody (TPOAb) positivity and TSH level.

Methods: This retrospective analysis of retrospectively and prospectively collected cohort data included Chinese pregnant women with TSH levels of 2.5-10 mIU/L and normal free thyroxine levels (11.8-18.4 pmol/L) in the first trimester. All participants were followed up until the completion of pregnancy, and information on LT-4 treatment, pregnancy complications, and pregnancy outcomes was recorded. A 1:1 nearest-neighbor propensity score matching (PSM) between the LT-4-treated and -untreated groups with a caliper distance of 0.02 was performed using a multivariable logistic regression model. Multivariable-adjusted modified Poisson regression was used to estimate the relative risk (RR) and 95% confidence interval (CI) of LT-4 treatment for adverse pregnancy outcomes. Subgroup analyses were also performed in four subgroups simultaneously stratified by TPOAb status (negative or positive) and TSH levels (2.5-4.0 mIU/L as high-normal group and 4.0-10.0 mIU/L as SCH group). The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100047394).

Results: Among the 4,370 pregnant women in the study, 1,342 received LT-4 treatment, and 3,028 did not. The 1:1 PSM yielded 668 pairs of individuals and revealed that LT-4 treatment was significantly associated with a decreased risk of pregnancy loss (RR=0.528, 95% CI: 0.344-0.812) and an increased risk of small-for-gestational-age infants (RR=1.595, 95% CI: 1.023-2.485). Subgroup analyses suggested that the above effects of LT-4 treatment were mainly from TPOAb-negative participants. LT-4 treatment was associated with an increased risk of preterm birth (RR=2.214, 95% CI: 1.016-4.825) in TPOAb-positive pregnant women with high-normal TSH levels.

Conclusion: LT-4 treatment was significantly associated with a lower risk of pregnancy loss and a higher risk of small-for-gestational-age infants in pregnant women with TSH levels of 2.5-10 mIU/L. An increased risk of preterm birth was observed in the LT-4-treated group among TPOAb-positive participants with TSH levels of 2.5-4.0 mIU/L.