Osinga Joris A J, Liu Yindi, Männistö Tuija, Vafeiadi Marina, Tao Fang-Biao, Vaidya Bijay, Vrijkotte Tanja G M, Mosso Lorena, Bassols Judit, López-Bermejo Abel, Boucai Laura, Aminorroaya Ashraf, Feldt-Rasmussen Ulla, Hisada Aya, Yoshinaga Jun, Broeren Maarten A C, Itoh Sachiko, Kishi Reiko, Ashoor Ghalia, Chen Liangmiao, Veltri Flora, Lu Xuemian, Taylor Peter N, Brown Suzanne J, Chatzi Leda, Popova Polina V, Grineva Elena N, Ghafoor Farkhanda, Pirzada Amna, Kianpour Maryam, Oken Emily, Suvanto Eila, Hattersley Andrew, Rebagliato Marisa, Riaño-Galán Isolina, Irizar Amaia, Vrijheid Martine, Delgado-Saborit Juana Maria, Fernández-Somoano Ana, Santa-Marina Loreto, Boelaert Kristien, Brenta Gabriela, Dhillon-Smith Rima, Dosiou Chrysoula, Eaton Jennifer L, Guan Haixia, Lee Sun Y, Maraka Spyridoula, Morris-Wiseman Lilah F, Nguyen Caroline T, Shan Zhongyan, Guxens Mònica, Pop Victor J M, Walsh John P, Nicolaides Kypros H, D'Alton Mary E, Visser W Edward, Carty David M, Delles Christian, Nelson Scott M, Alexander Erik K, Chaker Layal, Palomaki Glenn E, Peeters Robin P, Bliddal Sofie, Huang Kun, Poppe Kris G, Pearce Elizabeth N, Derakhshan Arash, Korevaar Tim I M
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.
Thyroid. 2024 May;34(5):646-658. doi: 10.1089/thy.2023.0646. Epub 2024 Mar 28.
International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; < 0.001). The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.
国际指南推荐进行针对性筛查以识别妊娠期甲状腺功能障碍。然而，目前使用的风险因素的鉴别能力存疑。我们对国际指南中目前使用的一部分风险因素导致甲状腺功能测试异常的风险进行了量化。我们纳入了前瞻性队列研究，这些研究包含妊娠期母亲甲状腺功能及潜在风险因素（母亲年龄、体重指数[BMI]、产次、吸烟状况、体外受精妊娠、双胎妊娠、孕周、母亲教育程度以及甲状腺过氧化物酶抗体[TPOAb]或甲状腺球蛋白抗体[TgAb]阳性）的数据。排除标准为既往存在的甲状腺疾病以及使用影响甲状腺功能的药物。我们使用混合效应回归模型分析个体参与者数据。主要结局为显性和亚临床甲状腺功能减退以及治疗指征（定义为显性甲状腺功能减退、促甲状腺素>10 mU/L的亚临床甲状腺功能减退或TPOAb阳性的亚临床甲状腺功能减退）。研究人群包括25个队列中的65559名参与者。使用目前推荐的风险因素（年龄>30岁、产次≥2、BMI≥40）的队列中的筛查率为58%，显性和亚临床甲状腺功能减退的检出率为59%。在整个年龄、BMI范围以及任何产次情况下，显性或亚临床甲状腺功能减退的绝对风险差异<2%。以母亲年龄、BMI、吸烟状况、产次以及采血时的孕周作为解释变量拟合的受试者工作特征曲线，主要结局的曲线下面积在0.58至0.63之间。TPOAbs/TgAbs阳性与显性甲状腺功能减退相关（抗体阴性的近似风险为0.1%，单纯TgAb阳性为2.4%，单纯TPOAb阳性为3.8%，抗体联合阳性为7.0%；<0.001），与亚临床甲状腺功能减退相关（抗体阴性的风险为2.2%，单纯TgAb阳性为8.1%，单纯TPOAb阳性为14.2%，抗体联合阳性为20.0%；<0.001）以及与治疗指征相关（抗体阴性的风险为0.2%，单纯TgAb阳性为2.2%，单纯TPOAb阳性为3.0%，抗体联合阳性为5.1%；<0.001）。双胎妊娠与显性甲状腺功能亢进的较高风险相关（5.6%对0.7%；<0.001）。本研究中评估的风险因素在检测甲状腺功能测试异常方面预测能力较差，质疑其在针对性筛查中的临床实用性。正如预期的那样，TPOAb阳性（用作基准）是（亚临床）甲状腺功能减退的一个相关风险因素。这些结果为妊娠期甲状腺功能障碍的不同风险因素提供了见解。
