Interpretation of the association between thyroid peroxidase antibodies and thyroid function during pregnancy: An individual participant data meta-analysis

IF 6.8 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity Pub Date : 2025-12-01 Epub Date: 2025-10-10 DOI:10.1016/j.jaut.2025.103491

Yindi Liu , Joris A.J. Osinga , Ulla Feldt-Rasmussen , Tanja G.M. Vrijkotte , Peter N. Taylor , Ashraf Aminorroaya , Ghalia Ashoor , Sofie Bliddal , Liang-Miao Chen , Bijay Vaidya , Glenn E. Palomaki , Farkhanda Ghafoor , Abel López-Bermejo , Victor J.M. Pop , Sachiko Itoh , Fang-biao Tao , Lorena Mosso , Tuija Männistö , Kris G. Poppe , Elizabeth N. Pearce , Tim I.M. Korevaar

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引用次数: 0

Abstract

Background

Thyroid peroxidase antibody (TPOAb) positivity is the most important risk factor for hypothyroidism and determines thyroid function follow-up during pregnancy. TPOAb positivity is usually defined by manufacturer cut-offs which typically derived from non-pregnant populations. However, as a state of immune tolerance, pregnancy can affect TPOAb concentrations. To improve the understanding of clinical relevance of TPOAb concentrations during pregnancy, we investigated the association of TPOAbs with maternal thyroid function.

Methods

We performed an individual participant data meta-analysis embedded in the Consortium on Thyroid and Pregnancy. Participants with multiple gestations, pre-existing thyroid disease, thyroid (interfering) medication usage, or conception by in vitro fertilization were excluded. We used mixed effects regression models to assess the association of TPOAb percentiles calculated in each cohort with maternal thyroid function.

Results

The study population comprised 62,634 pregnant women from 24 cohorts. As compared to TPOAb percentiles ≤80, there were progressively higher mean thyroid stimulating hormone (TSH) concentrations across TPOAb percentiles ≥89, with corresponding mean differences ranging from +0.11 SD (95 % confidence interval [CI] +0.04 SD, +0.19 SD) at the 89th percentile to +1.04 SD (95 % CI + 0.96 SD, 1.11 SD) at the 100th percentile. Higher TPOAb percentiles were associated with progressively lower mean free thyroxine (FT4) concentrations across TPOAb percentiles ≥91, with corresponding mean differences ranging from −0.08 SD (95 % CI -0.16 SD, −0.01 SD) at the 91st percentile to −0.48 SD (95 % CI -0.56 SD, −0.4 SD) at the 100th percentile. From the 89th TPOAb percentile upwards, there were progressively higher risks of TSH >4.0 mU/L, with absolute risks of 2.4 %, 4.0 %, and 28.1 % in cases of ≤80th, 89th, and 100th TPOAb percentiles, respectively. Higher TPOAb percentiles were also associated with lower thyroidal response to human chorionic gonadotropin stimulation and higher risks of overt and subclinical hypothyroidism. In 19 of the included cohorts, there were 0.4–6.3 % of pregnant women with TPOAb concentrations lower than the positivity cut-offs but larger than or equal to the 89th-percentile concentrations. The associations of TPOAbs with TSH and with FT4 were most apparent during early pregnancy (P for interaction <0.001 for both TSH and FT4).

Conclusions

During pregnancy, TPOAbs were dose-dependently associated with TSH, FT4, and the risk of abnormal thyroid function. With concentrations below currently used positivity cut-offs, TPOAbs could be associated with lower maternal thyroid function, which indicates clinically relevant thyroid autoimmunity. These findings implicates that high normal TPOAb concentrations upon first assessment in pregnancy may warrant active follow-up.

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解释孕期甲状腺过氧化物酶抗体与甲状腺功能之间的关系：个体参与者数据荟萃分析

背景甲状腺过氧化物酶抗体（TPOAb）阳性是甲状腺功能减退最重要的危险因素，决定了妊娠期间甲状腺功能的随访。TPOAb阳性通常由制造商的截止值来定义，这些截止值通常来自非怀孕人群。然而，作为一种免疫耐受状态，妊娠可影响TPOAb浓度。为了提高对妊娠期间TPOAb浓度的临床相关性的理解，我们研究了TPOAb与母亲甲状腺功能的关系。方法：我们在甲状腺和妊娠联盟中进行了个体参与者数据荟萃分析。多胎妊娠、既往甲状腺疾病、甲状腺（干扰）药物使用或体外受精受孕的参与者被排除在外。我们使用混合效应回归模型来评估每个队列中计算的TPOAb百分位数与母亲甲状腺功能的关系。结果研究人群包括来自24个队列的62,634名孕妇。与TPOAb百分位数≤80相比，TPOAb百分位数≥89时，促甲状腺激素（TSH）的平均浓度逐渐升高，相应的平均差异范围从第89百分位数的+0.11 SD（95%置信区间[CI] +0.04 SD, +0.19 SD）到第100百分位数的+1.04 SD （95% CI + 0.96 SD, 1.11 SD）。TPOAb百分位数越高，TPOAb百分位数≥91的平均游离甲状腺素（FT4）浓度越低，相应的平均差异范围从第91百分位数的- 0.08 SD （95% CI -0.16 SD, - 0.01 SD）到第100百分位数的- 0.48 SD （95% CI -0.56 SD, - 0.4 SD）。从TPOAb第89百分位开始，TSH 4.0 mU/L的风险逐渐增加，TPOAb≤80、89和100百分位的绝对风险分别为2.4%、4.0%和28.1%。较高的TPOAb百分位数也与甲状腺对人绒毛膜促性腺激素刺激的反应较低以及明显和亚临床甲状腺功能减退的风险较高有关。在纳入的19个队列中，有0.4 - 6.3%的孕妇TPOAb浓度低于阳性临界值，但大于或等于第89百分位浓度。tpoab与TSH和FT4的相关性在妊娠早期最为明显（TSH和FT4的相互作用P值为0.001）。结论妊娠期tpoab与TSH、FT4及甲状腺功能异常风险呈剂量依赖性相关。当浓度低于目前使用的阳性临界值时，tpoab可能与母亲甲状腺功能低下有关，这表明临床相关的甲状腺自身免疫。这些发现表明，妊娠期首次评估时TPOAb浓度偏高可能需要积极随访。

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来源期刊

Journal of autoimmunity 医学-免疫学

CiteScore

27.90

自引率

1.60%

发文量

117

审稿时长

17 days

期刊介绍： The Journal of Autoimmunity serves as the primary publication for research on various facets of autoimmunity. These include topics such as the mechanism of self-recognition, regulation of autoimmune responses, experimental autoimmune diseases, diagnostic tests for autoantibodies, as well as the epidemiology, pathophysiology, and treatment of autoimmune diseases. While the journal covers a wide range of subjects, it emphasizes papers exploring the genetic, molecular biology, and cellular aspects of the field. The Journal of Translational Autoimmunity, on the other hand, is a subsidiary journal of the Journal of Autoimmunity. It focuses specifically on translating scientific discoveries in autoimmunity into clinical applications and practical solutions. By highlighting research that bridges the gap between basic science and clinical practice, the Journal of Translational Autoimmunity aims to advance the understanding and treatment of autoimmune diseases.