近日，荷兰甲状腺与妊娠联合会早产研究小组，探讨了甲状腺功能异常和甲状腺自身免疫与早产（37周前分娩）的关系。 2019年8月20日，国际知名学术期刊《美国医学会杂志》发表了这一成果。

这项前瞻性队列研究包括甲状腺功能测试（促甲状腺激素TSH和游离甲状腺素FT4浓度）或甲状腺过氧化物酶（TPO）抗体测量以及婴儿出生胎龄。由2名独立评审员进行资格审查，采用混合效应模型进行分析。

研究人群包括47045名孕妇，平均年龄为29岁，抽血时平均孕周为12.9周，其中1234名（3.1%）为亚临床甲状腺功能减退（TSH浓度增加，FT4浓度正常），904名（2.2%）为孤立性低甲状腺素血症（FT4浓度降低，TSH浓度正常），3043名 （7.5%）TPO抗体阳性。共有2357名（5.0%）孕妇早产。

亚临床甲状腺功能减退妇女的早产风险为6.1%，孤立性低甲状腺素血症妇女的早产风险为7.1%，均高于甲状腺功能正常妇女（5.0%）。在连续分析中，母体TSH浓度每升高1-SD，早产的风险就更高。TPO抗体阳性妇女的早产风险为6.6%，高于TPO抗体阴性的妇女（4.9%）。

在无明显甲状腺疾病的孕妇中，亚临床甲状腺功能减退症、孤立性甲状腺功能减退症和TPO抗体阳性与早产风险显著相关。 这些结果为优化临床决策提供了依据，以权衡孕期是否适宜进行左甲状腺素治疗。

据了解，母体甲状腺功能减退和甲状腺功能亢进是早产的危险因素。轻度甲状腺功能测试异常和甲状腺自身免疫更为普遍，但这些是否与早产有关仍存在争议。 

附：英文原文

Title: Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth

Author: The Consortium on Thyroid and Pregnancy—Study Group on Preterm Birth

Issue&Volume: Vol 322 No 7

Abstract:

Importance  Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth.

Objective  To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth.

Data Sources and Study Selection  Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT₄] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded.

Data Extraction and Synthesis  The primary authors provided individual participant data that were analyzed using mixed-effects models.

Main Outcomes and Measures  The primary outcome was preterm birth (<37 weeks’ gestational age).

Results  From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47?045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT₄ concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT₄ concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody–positive women had a higher risk of preterm birth vs TPO antibody–negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]).

Conclusions and Relevance  Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

DOI: 10.1001/jama.2019.10931

Source: https://jamanetwork.com/journals/jama/article-abstract/2748509