复发性流产患者妊娠早期边缘性亚临床甲状腺功能减退症的研究

Borderline subclinical hypothyroidism during first trimester of pregnancy in euthyroid patients with recurrent spontaneous abortion

目的探讨甲状腺功能正常的复发性流产患者妊娠早期发生边缘性亚临床甲状腺功能减退症(亚甲减)的危险因素。方法选取2017年7月至2019年7月于中国医科大学附属盛京医院第六产科门诊就诊患者3794例,系统病因学筛查排除具有诊断明确的解剖、凝血、遗传异常及感染因素的患者后,选取孕前甲状腺功能正常的复发性流产患者302例,再排除其中孕前促甲状腺激素(TSH)高于2.5 mIU/L的患者62例,最终纳入240例。本研究将妊娠早期边缘性亚甲减定义为妊娠13周+6天前2.5 mIU/L<TSH<妊娠特异参考值上限。妊娠早期发生边缘性亚甲减患者84例,未发生者156例。分析2组患者病史、临床及实验室检查结果,进行单因素、多因素logistic回归分析,分析边缘性亚甲减的高危因素,并进行共线性诊断、相关性分析。结果单因素分析提示,受孕方式、孕前TSH水平、抗核抗体(ANA)阳性、狼疮抗凝物(LAC)阳性、抗β2糖蛋白1(β2GP1)抗体阳性为潜在高危因素(P<0.1)。多因素logistic回归分析发现,孕前TSH水平>1.5 mIU/L(OR=5.241,95%CI 2.659~10.330)、ANA阳性(OR=3.614,95%CI 1.866~7.000)、抗β2GP1抗体阳性(OR=3.415,95%CI 1.176~9.917)、LAC阳性(OR=2.785,95%CI 1.024~7.573)与妊娠早期边缘性亚甲减发生有关(P<0.05或P<0.01)。共线性诊断未发现各因素间存在明显共线性关系。甲状腺过氧化物酶抗体、甲状腺球蛋白抗体间存在相关性(P<0.01),其余非组织特异性自身免疫抗体、甲状腺自身抗体间未发现相关性。结论孕前TSH水平、非组织特异性自身免疫抗体异常是复发性流产患者妊娠早期边缘性亚甲减发生的最主要危险因素。

Objective To explore the risk factors of borderline subclinical hypothyroidism during first trimester of pregnancy in euthyroid patients with recurrent spontaneous abortion history.Methods Among the 3794 outpatients in the Sixth Obstetric Clinic of Shengjing Hospital of China Medical University from July 2017 to July 2019,302 patients with recurrent spontaneous abortion and euthyroid function before pregnancy were selected after excluding those with abnormality in anatomy,coagulation,genetics,endocrine,infection,and immunology aspects through a systematic etiological screen.Exclusion of 62 patients with pre-pregnancy thyroid stimulating hormone(TSH)above 2.5 mIU/L,240 recurrent spontaneous abortion patients were finally included.Borderline subclinical hypothyroidism is defined as the level of TSH higher than 2.5 mIU/L but less than the upper limit of pregnancy specific reference range during the first trimester.Among these 240 recurrent spontaneous abortion patients,84 had borderline subclinical hypothyroidism and 156 were not.After analyzing the history,clinical and laboratory examination results of the two groups of patients,univariate analysis and multivariate logistic regression analysis were applied,to analyze and screen the high-risk factors of borderline subclinical hypothyroidism.Collinear diagnosis of regression analysis and correlation analysis were used to find out the if further relationships among the high-risk factors existed.Results Univariate analysis suggested that conception method,pre-pregnancy TSH level,anti-nuclear antibody(ANA),lupus anticoagulant(LAC),and anti-β2 glycoprotein 1(β2GP1)antibody were the potential high-risk factors(P<0.1).Multivariate logistic regression analysis showed that pre-pregnancy TSH level>1.5 mIU/L(OR=5.241,95%CI 2.659-10.330),ANA positive(OR=3.614,95%CI 1.866-7.000),anti-β2GP1 antibody positive(OR=3.415,95%CI 1.176-9.917),and LAC positive(OR=2.785,95%CI 1.024-7.573)were independent risk factors of borderline subclinical hypothyroidism(P<0.05 or P<0.01).No significant collinearity was found among the factors in the collinearity diagnosis.Except for the thyroid peroxidase antibody and thyroglobulin antibody(P<0.01),no significant correlation was found among the non-organ-specific antibodies(NOSAs)and antithyroid antibodies.Conclusion The level of pre-pregnancy TSH and NOSAs before pregnancy are the most important risk factors of borderline subclinical hypothyroidism during first trimester of pregnancy of euthyroid patients with recurrent spontaneous abortion history.