ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Thyroid Endocrinology
First-Trimester Thyroid Reference Intervals in Twin Pregnancy: Establishment, Diagnostic Utility, and Association with Adverse Outcomes
Provisionally accepted
- 1Shanghai Jiao Tong University School of Medicine Affiliated International Peace Maternal and Child Health Hospital, Shanghai, China
- 2Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Objective: This large retrospective study aims to establish twin pregnancy-specific reference intervals for serum TSH and FT4 in early gestation and evaluate their clinical utility. Methods: This study analyzed TSH and FT4 levels in early pregnancy among 46,474 singleton and 1,183 twin pregnancies at a tertiary hospital. Local gestation-specific reference intervals for TSH and FT4 were established by calculating the 2.5th to 97.5th percentiles. Chi-square tests were used to compare abnormal detection rates, univariate regression analyzed differences in thyroid dysfunction prevalence, and multivariate regression assessed their predictive value for adverse pregnancy outcomes. Stratified, interaction, and marginal analyses were performed to evaluate the consistency and clinical relevance of the association. Results: Twin pregnancies showed lower median TSH (0.62 vs. 1.17 mIU/L) and higher FT4 (15.40 vs. 14.80 pmol/L) than singletons. Twin-specific intervals can reduce abnormal TSH/FT4 detection (P<0.001). Based on the twin-specific intervals, low TSH was significantly associated with preeclampsia, whereas low FT4 was linked to SGA, LGA, emergency cesarean delivery, and fetal distress (P<0.05). Multivariable logistic regression confirmed that reduced FT4 independently predicted risks of SGA and LGA. Interaction analyses showed the FT4–growth abnormality association was consistent across different maternal characteristics. Marginal value analysis showed that FT4 levels between P2.5 and P5 did not significantly increase risks of SGA or LGA, supporting the clinical validity of the current reference range. Conclusion: Twin-specific thyroid reference intervals in early pregnancy can improve the accuracy of high-risk pregnancy identification and show strong potential for clinical application.
Keywords: pregnancy outcomes, Twin, Thyroid function, Free thyroxine, Thyroid stimulating hormone
Received: 07 Sep 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Dong, Lin, Han and Meng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mi Han, hanmi880905@alumni.sjtu.edu.cn
Yu Meng, mengyu_1224@126.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.