Abstract: Background Thyroid hormones are crucial for metabolism，growth，and development in the human body，especially playing a pivotal role in fetal development during early pregnancy. Currently，research on thyroid hormone reference ranges for twin pregnancies remains inconsistent，and most studies on thyroid dysfunction and pregnancy outcomes in twin pregnancies still use singleton pregnancy reference ranges as a benchmark. Objective To establish reference intervals for thyroid stimulating hormone（TSH）and free thyroxine（FT4）in early pregnancy among women with twin pregnancies，compare the incidence of thyroid dysfunction diagnosed based on singleton versus twin standards，and compare pregnancy outcomes for different thyroid function statuses under the two standards. Methods Twin pregnant women who visited Beijing Obstetrics and Gynecology Hospital，Capital Medical University，from October 2015 to February 2021 and met the inclusion and exclusion criteria were enrolled. We used chemiluminescence to detect TSH and FT4 in early pregnancy，and determined the reference range based on bilateral limits of P2.5-P97.5. The reference interval for thyroid function in the first trimester of single pregnancy in our hospital is TSH 0.59-3.54 mIU/L and FT4 11.8-18.4 pmol/L，respectively. Thyroid function results in early pregnancy for twin pregnancies were classified using both singleton and twin reference standards，including normal thyroid function，subclinical hypothyroidism，hypothyroidism，subclinical hyperthyroidism，and hyperthyroidism. Differences in pregnancy outcomes for thyroid dysfunction diagnosed using different reference standards were analyzed. Results A total of 1 724 twin pregnant women were enrolled，of which 254 met the inclusion and exclusion criteria for establishing reference intervals for thyroid function in early twin pregnancies. The TSH range for twin pregnancies in early pregnancy was 0.11-3.16 mIU/L，and the FT4 range was 2.45-28.56 pmol/L. Using the single reference standard for classification，2 cases（0.1%）of clinical hypothyroidism were diagnosed，33 cases（1.9%）of subclinical hypothyroidism，860 cases（49.9%）of normal，363 cases（21.1%）of subclinical hyperthyroidism，366 cases（21.2%）of clinical hyperthyroidism，and 100 cases（5.8%）of other. Using the twin reference standard for classification，3 cases（0.2%）of clinical hypothyroidism were diagnosed，47 cases（2.7%）of subclinical hypothyroidism，1 609 cases（93.3%）of normal，3 cases（0.2%）of subclinical hyperthyroidism，3 cases（0.2%）of clinical hyperthyroidism，and 59 cases（3.4%）of other. Using different reference standards for thyroid function in the first trimester of pregnancy for singleton and twin pregnancies，there was a statistically significant difference in the classification of thyroid function in the first trimester of twin pregnancy（P<0.001）. Among pregnant women with normal thyroid function，the pre-pregnancy BMI and early pregnancy TSH in the singleton reference standard were higher than those in the twin reference standard，while the early pregnancy FT4 was lower than that in the twin reference standard（P<0.05）. Among pregnant women with hypothyroidism，the early pregnancy TSH in the singleton reference standard was higher than that in the twin reference standard（P<0.05）. Among pregnant women with hyperthyroidism，the early pregnancy TSH，total weight gain during pregnancy，and neonatal birth weight in the singleton reference standard were higher than those in the twin reference standard，while the early pregnancy FT4 was lower than that in the twin reference standard（P<0.05）. The results of regression analysis showed that among pregnant women with hyperthyroidism，different reference standards for thyroid function were associated with gestational weight gain and neonatal birth weight（P<0.05）. Conclusion The TSH reference range for early twin pregnancies at our center is 0.11-3.16 mIU/L，and the FT4 reference range is 2.45-28.56 pmol/L. The number of cases of subclinical hyperthyroidism and hyperthyroidism diagnosed using the twin reference standard is significantly lower than that using the single reference standard. In pregnant women with hyperthyroidism，the reference standards for thyroid function are related to weight gain during pregnancy and the birth weight of the newborn.

Key words: Twin pregnancy, Thyroid function, Reference intervals, Pregnancy outcomes

摘要： 背景 甲状腺激素对机体新陈代谢、生长发育至关重要，尤其在孕早期对胎儿发育有关键作用。目前关于双胎妊娠甲状腺激素参考范围的研究尚不统一，大多数关于双胎妊娠甲状腺功能（简称甲功）异常与妊娠结局的研究仍以单胎妊娠的参考范围作为基准。目的 建立双胎妊娠女性孕早期促甲状腺激素（TSH）及游离甲状腺素（FT4）参考区间，比较基于单胎标准与双胎标准诊断的甲功异常发生率的差异，并比较两组标准下不同甲功状态的妊娠结局。方法 纳入2015年10月—2021年2月就诊首都医科大学附属北京妇产医院且符合纳入与排除标准的双胎孕妇，采用化学发光法检测孕早期TSH和FT4，按双侧限制P2.5~P97.5 确定参考区间。分别参考本院单胎妊娠孕早期甲功参考区间（TSH为0.59~3.54mIU/L，FT4 为11.8~18.4pmol/L）和本研究建立的双胎妊娠孕早期甲功参考区间为标准对双胎妊娠孕早期甲功结果进行分类，包括正常、亚临床甲状腺功能减退症（简称亚临床甲减）、临床甲状腺功能减退症（简称临床甲减）、亚临床甲状腺功能亢进（简称亚临床甲亢）和临床甲状腺功能亢进（简称临床甲亢），分析使用不同参考标准诊断的甲功异常的妊娠结局的差异。结果 本研究共纳入1 724例双胎妊娠孕妇，其中254例符合建立双胎妊娠孕早期甲功参考区间的纳排标准。本研究建立的双胎妊娠孕早期甲功参考区间为：TSH为0.11~3.16mIU/L，FT4 为2.45~28.56 pmol/L。使用单胎参考标准进行分类，诊断临床甲减2例（0.1%）、亚临床甲减33例（1.9%）、正常860例（49.9%）、亚临床甲亢363例（21.1%）、临床甲亢366例（21.2%）、其他100例（5.8%）。使用双胎参考标准进行分类，诊断临床甲减3例（0.2%）、亚临床甲减47例（2.7%）、正常1 609例（93.3%）、亚临床甲亢3例（0.2%）、临床甲亢3例（0.2%）、其他59例（3.4%）。使用单胎和双胎不同的孕早期甲功参考标准对双胎妊娠孕早期甲功进行分类，差异有统计学意义（P<0.001）。在甲功正常的孕妇中，单胎参考标准孕前BMI、孕早期TSH高于双胎参考标准，孕早期FT4 低于双胎参考标准（P<0.05）；在甲减的孕妇中，单胎参考标准孕早期TSH高于双胎参考标准（P<0.05）；在甲亢的孕妇中，单胎参考标准孕早期TSH、妊娠期总增重、新生儿出生体质量高于双胎参考标准，孕早期FT4 低于双胎参考标准（P<0.05）。回归分析结果显示，在甲亢的孕妇中，甲功参考标准不同与妊娠期增重和新生儿出生体质量相关（P<0.05）。结论 本中心双胎妊娠孕早期TSH参考范围为0.11~3.16 mIU/L，FT4 参考范围为2.45~28.56 pmol/L，使用双胎参考标准诊断的亚临床甲亢和甲亢例数少于单胎参考标准。在甲亢的孕妇中，甲功参考标准不同与妊娠期增重和新生儿出生体质量有关。

关键词: 双胎妊娠, 甲状腺功能, 参考标准, 妊娠结局