Liu Xueying, Zhang Chen, Lin Zhongliang, Zhu Kejing, He Renke, Jiang Zhaoying, Wu Haiyan, Yu Jiaen, Luo Qinyu, Sheng Jianzhong, Fan Jianxia, Pan Jiexue, Huang Hefeng
International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Obstetrics and Gynecology, Center for Reproductive Medicine, The Fourth Affiliated Hospital of School of Medicine, International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China; Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China.
Am J Obstet Gynecol. 2025 May;232(5):480.e1-480.e19. doi: 10.1016/j.ajog.2024.08.047. Epub 2024 Aug 30.
Mild hypothyroidism, including subclinical hypothyroidism and isolated maternal hypothyroxinemia, is fairly common in pregnant women, but its impact on pregnancy outcomes is less clear, especially mild hypothyroidism in late pregnancy.
To evaluate the impact of subclinical hypothyroidism and isolated maternal hypothyroxinemia in the first and third trimesters, respectively, on obstetric and perinatal outcomes.
This large prospective study was conducted at the International Peace Maternity and Child Health Hospital in Shanghai; 52,027 pregnant women who underwent the first-trimester antenatal screening at International Peace Maternity and Child Health Hospital were consecutively enrolled from January 2013 to December 2016. To evaluate the impact of maternal subclinical hypothyroidism and isolated maternal hypothyroxinemia in the first trimester on pregnancy outcomes, participants were divided into 3 groups according to thyroid function in the first trimester: first-trimester euthyroidism group (n=33,130), first-trimester subclinical hypothyroidism group (n=884), and first-trimester isolated maternal hypothyroxinemia group (n=846). Then, to evaluate the impact of maternal subclinical hypothyroidism and isolated maternal hypothyroxinemia in the third trimester on pregnancy outcomes, the first-trimester euthyroidism group was subdivided into 3 groups according to thyroid function in the third trimester: third-trimester euthyroidism group (n=30,776), third-trimester subclinical hypothyroidism group (n=562), and third-trimester isolated maternal hypothyroxinemia group (n=578). Obstetric and perinatal outcomes, including preterm birth, preeclampsia, gestational hypertension, gestational diabetes mellitus, large for gestational age, small for gestational age, macrosomia, cesarean delivery, and fetal demise were measured and compared between those in either subclinical hypothyroidism/isolated maternal hypothyroxinemia group and euthyroid group. Binary logistic regression was used to assess the association of subclinical hypothyroidism or isolated maternal hypothyroxinemia with these outcomes.
Thirty-four thousand eight hundred sixty pregnant women who had first (weeks 8-14) and third trimester (weeks 30-35) thyrotropin and free thyroxine concentrations available were included in the final analysis. Maternal subclinical hypothyroidism in the first trimester was linked to a lower risk of gestational diabetes mellitus (adjusted odds ratio 0.64, 95% confidence interval 0.50-0.82) compared with the euthyroid group. However, third-trimester subclinical hypothyroidism is associated with heightened rates of preterm birth (adjusted odds ratio 1.56, 95% confidence interval 1.10-2.20), preeclampsia (adjusted odds ratio 2.23, 95% confidence interval 1.44-3.45), and fetal demise (adjusted odds ratio 7.00, 95% confidence interval 2.07-23.66) compared with the euthyroid group. Isolated maternal hypothyroxinemia in the first trimester increased risks of preeclampsia (adjusted odds ratio 2.14, 95% confidence interval 1.53-3.02), gestational diabetes mellitus (adjusted odds ratio 1.45, 95% confidence interval 1.21-1.73), large for gestational age (adjusted odds ratio 1.64, 95% confidence interval 1.41-1.91), macrosomia (adjusted odds ratio 1.85, 95% confidence interval 1.49-2.31), and cesarean delivery (adjusted odds ratio 1.35, 95% confidence interval 1.06-1.74), while isolated maternal hypothyroxinemia in the third trimester increased risks of preeclampsia (adjusted odds ratio 2.85, 95% confidence interval 1.97-4.12), large for gestational age (adjusted odds ratio 1.49, 95% confidence interval 1.23-1.81), and macrosomia (adjusted odds ratio 1.60, 95% confidence interval 1.20-2.13) compared with the euthyroid group.
This study indicates that while first-trimester subclinical hypothyroidism did not elevate the risk for adverse pregnancy outcomes, third-trimester subclinical hypothyroidism was linked to several adverse pregnancy outcomes. Isolated maternal hypothyroxinemia in the first and third trimesters was associated with adverse pregnancy outcomes, yet the impact varied by trimester. These results suggest the timing of mild hypothyroidism in pregnancy may be pivotal in determining its effects on adverse pregnancy outcomes and underscore the importance of trimester-specific evaluations of thyroid function.
轻度甲状腺功能减退，包括亚临床甲状腺功能减退和单纯孕妇甲状腺素血症，在孕妇中相当常见，但其对妊娠结局的影响尚不清楚，尤其是妊娠晚期的轻度甲状腺功能减退。
分别评估孕早期和孕晚期亚临床甲状腺功能减退和单纯孕妇甲状腺素血症对产科和围产期结局的影响。
这项大型前瞻性研究在上海国际和平妇幼保健院进行；2013年1月至2016年12月，连续纳入52027名在国际和平妇幼保健院接受孕早期产前筛查的孕妇。为了评估孕早期孕妇亚临床甲状腺功能减退和单纯孕妇甲状腺素血症对妊娠结局的影响，根据孕早期甲状腺功能将参与者分为3组：孕早期甲状腺功能正常组（n=33130）、孕早期亚临床甲状腺功能减退组（n=884）和孕早期单纯孕妇甲状腺素血症组（n=846）。然后，为了评估孕晚期孕妇亚临床甲状腺功能减退和单纯孕妇甲状腺素血症对妊娠结局的影响，根据孕晚期甲状腺功能将孕早期甲状腺功能正常组再分为3组：孕晚期甲状腺功能正常组（n=30776）、孕晚期亚临床甲状腺功能减退组（n=562）和孕晚期单纯孕妇甲状腺素血症组（n=578）。测量并比较亚临床甲状腺功能减退/单纯孕妇甲状腺素血症组和甲状腺功能正常组之间的产科和围产期结局，包括早产、子痫前期、妊娠期高血压、妊娠期糖尿病、大于胎龄儿、小于胎龄儿、巨大儿、剖宫产和胎儿死亡。采用二元逻辑回归评估亚临床甲状腺功能减退或单纯孕妇甲状腺素血症与这些结局的关联。
最终分析纳入了34860名在孕早期（第8 - 14周）和孕晚期（第30 - 35周）有促甲状腺激素和游离甲状腺素浓度数据的孕妇。与甲状腺功能正常组相比，孕早期孕妇亚临床甲状腺功能减退与妊娠期糖尿病风险降低相关（调整优势比0.64，95%置信区间0.50 - 0.82）。然而，与甲状腺功能正常组相比，孕晚期亚临床甲状腺功能减退与早产率升高（调整优势比1.56，95%置信区间1.10 - 2.20）、子痫前期（调整优势比2.23，95%置信区间1.44 - 3.45）和胎儿死亡（调整优势比7.00，95%置信区间2.07 - 23.66）相关。孕早期单纯孕妇甲状腺素血症增加了子痫前期（调整优势比2.14，95%置信区间1.53 - 3.02）、妊娠期糖尿病（调整优势比1.45，95%置信区间1.21 - 1.73）、大于胎龄儿（调整优势比1.64，95%置信区间1.41 - 1.91）、巨大儿（调整优势比1.85，95%置信区间1.49 - 2.31）和剖宫产（调整优势比1.35，95%置信区间1.06 - 1.74）的风险，而孕晚期单纯孕妇甲状腺素血症增加了子痫前期（调整优势比2.85，95%置信区间1.97 - 4.12）、大于胎龄儿（调整优势比1.49，95%置信区间1.23 - 1.81）和巨大儿（调整优势比1.60，95%置信区间1.20 - 2.13）的风险。
本研究表明，孕早期亚临床甲状腺功能减退并未增加不良妊娠结局的风险，而孕晚期亚临床甲状腺功能减退与多种不良妊娠结局相关。孕早期和孕晚期单纯孕妇甲状腺素血症均与不良妊娠结局相关，但影响因孕期不同而有所差异。这些结果表明，孕期轻度甲状腺功能减退的时间可能对其对不良妊娠结局的影响起关键作用，并强调了孕期特定阶段甲状腺功能评估的重要性。
