The correct reference range for maternal thyroid function during pregnancy is essential for making an accurate diagnosis of thyroid disease and delivering proper interventions in pregnant women. But there is still no universal standard for this in women with a twin pregnancy.

To determine a rational reference range for maternal thyroid function during twin pregnancies.

Healthy pregnant women who underwent antenatal examination in Obstetric Clinic, Beijing Friendship Hospital, Capital Medical University from January 2009 to September 2019 were retrospectively selected, including 352 with a twin pregnancy (twin group) , and 988 with a singleton pregnancy (singleton group) . Clinical and laboratory data were collected. The lower and upper limits for determining normal maternal thyroid function during twin pregnancies were the 2.5 (P_2.5) and 97.5 (P_97.5) percentiles of TSH and FT₄. Clinical hyperthyroidism was defined as TSH<P_{2.5 (total TSH)} and FT₄>P_{97.5 (total FT4)} . Clinical hypothyroidism was defined as TSH>P_{97.5 (total TSH)} and FT₄<P_{2.5 (total FT4)} . Subclinical hypothyroidism was diagnosed by TSH>P_97.5 and P_2.5≤FT₄≤P_97.5. Low T₄ syndrome was diagnosed by P_{2.5 (total TSH)} ≤TSH≤P_{97.5 (total TSH)} and FT₄<P_{2.5 (total FT4)} . FT₄ and TSH levels in the early, middle and late pregnancy were compared between singleton and twin groups. Prevalence of thyroid function abnormalities in the early, middle and late pregnancy was in twin group was recorded and analyzed.

Three hundred and fifty-two pregnant women with a twin pregnancy and 988 with a singleton pregnancy were finally included. The average FT₄ level in the twin group was higher than that of the singleton group regardless of the stage of pregnancy (P<0.05) . The average TSH level in the twin group was lower in the early pregnancy, but was higher in late pregnancy compared with that of singleton group (P<0.05) . For maternal thyroid function during a twin pregnancy, the determined normal FT₄ in the early, middle and late pregnancy expressed as median and interquartile range M (P_2.5, P_97.5) was 〔11.84 (7.95, 26.73) 〕, 〔8.24 (5.53, 18.58) 〕, 〔8.37 (5.80, 15.79) 〕pmol/L, respectively, and the determined normal TSH in the three stages of pregnancy was〔0.67 (0.03, 3.99) 〕, 〔1.44 (0.06, 4.79) 〕, 〔2.43 (0.41, 6.92) 〕mU/L, respectively. In the twin group, the prevalence of hyperthyroidism, clinical hypothyroidism, subclinical hypothyroidism, and low T₄ syndrome was 0, 0.28% (1/352) , 4.83% (17/352) and 3.98% (14/352) , respectively, by the above-mentioned criteria for diagnosing thyroid disease in a twin pregnancy, and that of the four diseases was 8.24% (29/352) , 0, 15.91% (56/352) and 1.99% (7/352) , respectively, by the criteria for diagnosing thyroid disease in a singleton pregnancy.

In this study, the recommended reference ranges of FT₄ in the early, middle and late stages of pregnancy were 7.95-26.73, 5.53-18.58 and 5.80-15.79 pmol/L, respectively, and the reference ranges of TSH were 0.03-3.99, 0.06-4.79 and 0.41-6.92 mU/L, respectively. Based on the FT₄ and TSH standards of the pregnant women with twin pregnancies obtained in our laboratory as the reference standards, the incidence of thyroid dysfunction detected in the pregnant women with twin pregnancies is low, which is consistent with relevant literature reports. The FT₄ and TSH standard range of single pregnancy obtained in our laboratory may lead to overdiagnosis of hyperthyroidism and subclinical hypothyroidism in pregnant women of twin pregnancy. So it is necessary to establish specific reference intervals for pregnant women with twin pregnancies based on the FT₄ and TSH standard ranges obtained in our laboratory.

正确的甲状腺功能指标参考区间对于准确诊断和干预孕妇甲状腺疾病至关重要，但是目前国内外对于双胎妊娠孕妇的甲状腺功能指标参考区间仍无统一标准。

探讨双胎妊娠孕妇妊娠期甲状腺功能指标合理的参考区间。

回顾性选取2009年1月至2019年9月在首都医科大学附属北京友谊医院产科门诊行产前检查的双胎妊娠健康孕妇作为双胎组。选取同期在首都医科大学附属北京友谊医院产科门诊行产前检查的单胎妊娠健康孕妇作为单胎组。收集研究对象基本信息和实验室检查数据。本研究以双胎妊娠孕妇促甲状腺激素（TSH）和游离甲状腺素（FT₄）的第2.5百分位数（P_2.5）和第97.5百分位数（P_97.5）为确定甲状腺功能正常与否的下限和上限。TSH<P_{2.5（总TSH）}，FT₄>P_{97.5（总FT4）}则诊断为临床甲状腺功能亢进（简称甲亢）；TSH>P_{97.5（总TSH）}，FT₄<P_{2.5（总FT4）}则诊断为临床甲状腺功能减低（简称甲减）；TSH>P_{97.5（总TSH）}，P_{2.5（总FT4）}≤FT₄≤P_{97.5（总FT4）}则诊断为亚临床甲减；P_{2.5（总TSH）}≤TSH≤P_{97.5（总TSH）}，FT₄<P_{2.5（总FT4）}则诊断为低T₄血症。比较单胎组和双胎组妊娠早期、中期、晚期FT₄和TSH，记录并分析妊娠早期、中期、晚期双胎妊娠孕妇甲状腺功能异常的患病率。

双胎组最终纳入352例，单胎组最终纳入988例。双胎组孕妇妊娠早期、中期、晚期时FT₄均高于单胎组（P<0.05）；双胎组孕妇妊娠早期TSH低于单胎组，妊娠晚期TSH高于单胎组（P<0.05）。双胎妊娠孕妇妊娠早期、中期、晚期时FT₄的M（P_2.5，P_97.5）分别为〔11.84（7.95，26.73）〕、〔8.24（5.53，18.58）〕、〔8.37（5.80，15.79）〕pmol/L，TSH分别为〔0.67（0.03，3.99）〕、〔1.44（0.06，4.79）〕、〔2.43（0.41，6.92）〕mU/L。以双胎妊娠孕妇的数据为参考区间：双胎妊娠孕妇甲亢、甲减、亚临床甲减、低T₄血症的患病率分别为0、0.28%（1/352）、4.83%（17/352）、3.98%（14/352）；以单胎妊娠孕妇的数据为参考区间：双胎妊娠孕妇甲亢、甲减、亚临床甲减、低T₄血症的患病率分别为8.24%（29/352）、0、15.91%（56/352）、1.99%（7/352）。

本研究建议的双胎妊娠孕妇妊娠早期、中期、晚期时FT₄的参考范围分别为7.95~26.73、5.53~18.58、5.80~15.79 pmol/L，TSH的参考范围分别为0.03~3.99、0.06~4.79、0.41~6.92 mU/L。以本实验室所得的双胎妊娠孕妇的FT₄、TSH标准范围为参考标准，则检出的双胎妊娠孕妇甲状腺功能异常发生率较低，与相关文献报道相符合；而以本实验室所得的单胎妊娠孕妇的FT₄、TSH标准范围为参考标准，则可能造成双胎妊娠孕妇甲亢和亚临床甲减的过度诊断，因此建立各自实验室的特异性双胎妊娠孕妇甲状腺功能指标参考区间是必要的。