甲状腺自身抗体与复发性流产

摘要：甲状腺自身抗体是一种以自身甲状腺组织作为靶抗原的自身抗体,主要包括抗甲状腺过氧化物酶抗体、甲状腺球蛋白抗体及促甲状腺激素受体抗体,三者均是反映自身免疫性甲状腺疾病的特异指标。甲状腺自身抗体的存在可能与复发性流产有相关性,应对高危人群进行甲状腺自身抗体的筛查、早期诊断并及时给予治疗,可有效降低妊娠不良结局的发生。     

甲状腺自身抗体与复发性流产关系的初步探讨

目的 研究抗甲状腺球蛋白抗体和抗甲状腺过氧化物酶抗体与复发性流产（RSA）之间的关系。方法 2004-08—2005—10选取山东省立医院妇产科门诊100例有复发性流产史非妊娠妇女为研究组，其中原发性RSA62例（原发性RSA组），继发性RSA38例（继发性RSA组），100例有正常妊娠史非孕健康妇女为对照组，化学发光免疫法测两组血清中的抗甲状腺抗体。结果 研究组血清中抗甲状腺球蛋白抗体和抗甲状腺过氧化物酶抗体的阳性率分别为：24％和28％，明显高于对照组的4％和6％（P〈0、05）。原发性与继发性RSA患者血清中抗体阳性率差异无显著性（P〉0、05）。结论 在复发性流产患者中，甲状腺自身抗体的阳性率增高，需进一步研究治疗后对妊娠结局的影响。     

甲状腺自身抗体与复发性流产相关性的研究

目的:探讨甲状腺自身抗体(ATA)与复发性流产的相关性。方法:收集2013年8月—2014年4月于我院产科进行孕前检查,并符合入组条件的非妊娠期妇女,其中有复发性流产病史妇女92例,夫妻双方染色体检查未见异常,凝血功能相关检查无异常,为研究组;无复发性流产病史妇女226例,为对照组。检测2组对象甲状腺球蛋白抗体(Tg Ab)和甲状腺过氧化物酶抗体(TPOAb)的阳性率,Tg Ab(+)和(或)TPOAb(+)为ATA阳性。结果:1研究组中,年龄≥35岁及<35岁者的ATA阳性率分别为39.29%(11/28)和26.56%(17/64),差异无统计学意义(P>0.05);在对照组中则分别为25.00%(10/40)和18.28%(34/186),差异也无统计学意义(P>0.05),说明ATA在不同年龄阶段的状况相近。2研究组ATA阳性率为30.43%(28/92),高于对照组的19.47%(44/226),差异有统计学意义(P<0.05)。研究组TPOAb阳性率为30.43%(28/92),高于对照组的11.95%(27/226),差异有统计学意义(P<0.05)。研究组Tg Ab阳性率为7.61%(7/92),与对照组的7.52%(17/226)比较差异无统计学意义(P>0.05)。结论:ATA与复发性流产有关,尤其与TPOAb关系密切。     

甲状腺自身抗体与稽留流产关系的初步研究

目的探讨甲状腺自身抗体与稽留流产的关系。方法选择2013年1月至2014年12月于青岛市海慈医疗集团确诊为早期稽留流产的100例女性作为研究组,同期正常的100例早孕女性作为对照组,检测并比较两组患者血清中甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(Tg Ab)水平,分析其与早期稽留流产的关系。结果研究组TPOAb阳性率、Tg Ab阳性率均高于对照组(P0.05)。经对数转化后,研究组女性血清中TPOAb水平[(0.91±0.65)U/ml]高于对照组[(0.72±0.26)U/ml](P0.01),而研究组女性血清中Tg Ab水平与对照组比较,差异无统计学意义(P0.05)。经多因素Logistic分析,研究组女性TPOAb阳性率是对照组的4.129倍。结论甲状腺自身抗体阳性可能与稽留流产有关,TPOAb阳性为稽留流产的独立危险因素。     

妊娠早期单纯甲状腺自身抗体阳性孕妇妊娠结局分析

目的观察妊娠早期单纯甲状腺自身抗体阳性孕妇妊娠晚期甲状腺功能(甲功)变化及妊娠结局,了解甲状腺自身抗体对妊娠的影响。方法选择妊娠早期127例甲功正常、甲状腺过氧化物酶抗体(TPOAb)或(和)甲状腺球蛋白抗体(TG-Ab)阳性孕妇为研究组,223例甲功正常、TPO-Ab和TG-Ab阴性妊娠早期孕妇为对照组,随访妊娠结局。结果研究组28.35%(36/127)的孕妇妊娠晚期出现甲功紊乱,其中11.81%(15/127)为亚临床甲状腺功能减退(甲减),7.87%(10/127)为临床甲减;对照组10.31%(23/223)的孕妇出现甲功紊乱,其中2.69%(6/223)为亚临床甲减,2.24%(5/223)为临床甲减,两组比较,差异有统计学意义(P0.05)。研究组流产率(18.90%,24/127)、早产率(22.83%,29/127)及胎儿窘迫率(7.87%,10/127)与对照组流产率(9.42%,21/223;8.52%,19/223;2.69%,6/223)比较,差异均有统计学意义(P0.05);两组单纯低T4血症、死胎、胎儿畸形及低出生体质量儿发生率比较,差异均无统计学意义(P0.05);研究组产后甲状腺炎发生率(40.16%,51/127)显著高于对照组(10.17%,18/177)(P0.05)。结论妊娠早期单纯甲状腺自身抗体阳性孕妇妊娠晚期发生甲功紊乱及不良妊娠结局风险明显增高,加强妊娠早期甲功筛查有意义。     

妊娠期TPO-Ab阳性亚临床甲状腺功能减退症对妊娠结局的影响

甲状腺激素是胚胎期胎儿大脑发育所必需.妊娠期亚临床甲状腺功能减退症(简称:亚甲减)可能导致流产、早产、胎盘早剥、低出生体重儿、妊娠期糖尿病等不良妊娠结局,重度亚甲减患者发展为甲状腺功能减退症的风险较高.甲状腺过氧化酶抗体(TPO-Ab)是反映自身免疫性甲状腺疾病的特异指标,通过激活补体、抗体依赖细胞介导的细胞毒性作用和...     

甲状腺自身抗体对甲状腺功能正常女性生殖与妊娠的影响

自身免疫性甲状腺疾病出现甲状腺自身抗体异常并导致甲状腺功能紊乱,可引起女性不孕、自然流产、早产、死胎、子痫前期、低出生体重儿和胎儿智力发育缺陷等生殖与不良妊娠结局.但甲状腺自身抗体对甲状腺功能正常的育龄妇女的生殖与妊娠有无影响尚有一定的争议,大多数研究认为有影响.其发病机制尚不清楚.对甲状腺自身抗体阳性而甲状腺功能正常的妇女应用静脉注射免疫球蛋白,泼尼松和阿司匹林联合治疗,左旋甲状腺素或在应用左旋甲状腺素基础上加硒治疗等治疗方案可提高妊娠率,降低流产、早产和死胎等不良妊娠风险.     

L-T_4治疗妊娠合并甲状腺过氧化物酶抗体阴性的亚临床甲状腺功能减退症的临床观察

目的:观察左旋甲状腺激素(L-T_4)治疗甲状腺过氧化物酶(TPOAb)阴性的妊娠合并亚临床甲状腺功能减退症(SCH)对妊娠结局的影响。方法:回顾分析2018年1月至2019年1月在广东省妇幼保健院行妊娠早期甲状腺激素筛查且有妊娠结局记录的867例孕产妇的临床资料。867例孕产妇中,甲状腺功能正常(N)+TPOAb(-)者584例(对照组),SCH+TPOAb(-)者283例,其中112例未接受左旋甲状腺治疗(观察组),171例接受左旋甲状腺素治疗(治疗组)。比较3组孕妇的妊娠结局及产科并发症情况。结果:观察组孕妇的流产率、妊娠期糖尿病发生率、早产率、出生低体质量儿发生率高于对照组、治疗组,差异均有统计学意义(P0.05)。观察组中3.4%最终发展为临床甲减。结论:妊娠早期合并SCH患者,TPOAb阴性者亦应及时给予L-T_4治疗;L-T_4治疗能有效改善妊娠合并TPOAb阴性的L-T_4患者不良妊娠结局。     

甲状腺功能异常与稽留流产的相关性研究

目的:探讨甲状腺功能异常与稽留流产的相关性。方法:选取妊娠12周内的95例稽留流产患者为研究对象(观察组),并选择同期正常妊娠的92例妇女作为对照组,应用化学发光法检测2组患者血清中促甲状腺素(TSH)、游离甲状腺素(FT4)、甲状腺过氧化物酶抗体(TPOAb)水平。结果:2组甲状腺功能亢进、甲状腺功能减退、低T4血症发生率差异无统计学意义(均P>0.05);观察组亚临床甲状腺功能减退、TPOAb(+)发生率均高于对照组,差异有统计学意义(P<0.05),与稽留流产有弱相关性(列联系数分别为0.21和0.22)。结论:甲状腺功能异常中的亚临床甲状腺功能减退、TPOAb(+)与稽留流产有一定的关系,提示开展妊娠早期甲状腺功能相关检查对降低稽留流产的发生率有一定临床意义。     

妊娠晚期妇女甲状腺疾病特点及甲状腺自身抗体变化的研究

目的 探讨妊娠晚期妇女甲状腺疾病的患病率、患病特点和甲状腺自身抗体的变化.方法 选择664例妊娠晚期妇女为妊娠组,276例非妊娠育龄妇女作为对照组.应用固相化学发光酶免疫法测定两组妇女的血清促甲状腺激素（TSH）和抗甲状腺过氧化物酶抗体（TPOAb）水平;TSH水平检测异常者加测游离甲状腺素（FT4）和游离三碘甲状腺原氨酸（FT3）,同时测定尿碘水平.按如下标准确定诊断：TSH＜0.3 mU/L,FT4和（或）FT3水平升高者诊断为临床甲状腺功能亢进症（甲亢）;TSH＜0.3 mU/L,而FT4和FT3水平正常者诊断为亚临床甲亢;TSH＞4.8 mU/L,FT4水平降低者诊断为临床甲状腺功能减退症（甲减）;TSH＞4.8 mU/L,而FT4和FT3水平正常者诊断为亚临床甲减.TPOAb＞5 kU/L为阳性.结果 （1）妊娠组妇女尿碘平均水平为201.5μg/L,对照组妇女尿碘平均水平为196.0μg/L,均为碘充足水平.两组比较,差异无统计学意义（P＞0.05）.（2）妊娠组妇女甲状腺疾病总患病率为7.8%（52/664）,对照组妇女甲状腺疾病总患病率为6.9%（19/276）.两组比较,差异无统计学意义（P＞0.05）.（3）两组妇女的甲状腺患病类型有明显不同,妊娠组妇女甲亢患病率为1.1%（7/664）,甲减患病率为6.8%（45/664）,妊娠组妇女甲亢患病率明显低于甲减,两者比较,差异有统计学意义（P＜0.01）;对照组甲亢患病率为4.7%（13/276）,甲减患病率为2.2%（6/276）,两者比较,差异无统计学意义（P＞0.05）.妊娠组与对照组妇女的甲亢或甲减患病率分别比较,差异均有统计学意义（P＜0.01）.（4）妊娠组非患病妇女的TSH水平显著高于对照组,分别为2.50 mU/L及1.54 mU/L,差异有统计学意义（P＜0.01）;妊娠组妇女TPOAb阳性率显著低于对照组,分别为3.3%（22/664）及9.4%（26/276）,差异有统计学意义（P＜0.01）.结论 妊娠晚期妇女甲状腺疾病的特点是甲减的患病率高,同时甲状腺自身免疫功能受到抑制.     

Clinical controversies in screening women for thyroid disorders during pregnancy

Subclinical hypothyroidism and/or the presence of thyroid peroxidase antibodies (TPOAb) may be associated with subfertility, infertility, spontaneous abortion, placental abruption, preterm delivery, gestational hypertension, preeclampsia, postpartum thyroid dysfunction, depression (including postpartum depression), and impaired cognitive and psychomotor child development. In November 2002, the American Association of Clinical Endocrinologists (AACE) released new guidelines for clinical practice for the diagnosis and treatment of hyperthyroidism and hypothyroidism, which includes a new thyroid-stimulating hormone (TSH) reference range of 0.3 to 3.0 mIU/L. Recently, the AACE recommended screening all women considering conception and/or all gravid women in the first trimester for thyroid dysfunction. However, the American College of Obstetricians and Gynecologists (ACOG) and the United States Preventive Services Task Force (USPSTF) have not endorsed these recommendations. This article reviews the evidence regarding screening women during pregnancy for subclinical hypothyroidism and/or the presence of thyroid peroxidase antibodies.     

The usefulness of a thyrotropin-releasing hormone stimulation test in subfertile female patients

Background. The thyrotropin-releasing hormone (TRH) stimulation test is widely used as a screening procedure in subfertile patients to identify subclinical hypothyroidism. However, its usefulness in daily clinical practice has not been proven, despite more than 30 years of use.

Material and methods. We analyzed data from a cohort of 371 consecutive female subfertility patients, who were screened with an intravenous TRH test when they came for the first evaluation. All patients with positive thyroid peroxidase antibodies, basal TSH <1.5 mU/l, known thyroid disease or actual thyroid medication were not screened and excluded from the analysis.

Results. We found a good correlation between basal and stimulated levels of thyroid-stimulating hormone (TSH). Basal TSH and the difference between stimulated and basal TSH did not correlate with prolactin levels. Definition of a positive TRH test (difference of 15 or 20 mU/l) did not have sufficient sensitivity and specificity, as confirmed by analysis of receiver operating characteristic curves, to identify subclinical hypothyroidism.

Conclusion. TRH stimulation testing is not helpful to identify patients with subclinical hypothyroidism and should not be part of initial screening in this group.     

妊娠期亚临床甲状腺功能异常的研究

目的通过检测孕妇妊娠期甲状腺功能,探讨妊娠期亚临床甲状腺功能异常的患病情况及甲状腺过氧化物酶抗体(TPOAb)与甲状腺功能的关系。方法选择2010年10月至2011年7月在北京市海淀妇幼保健院进行常规产前检查的1978例单胎孕妇,并采用系统抽样方法从中抽取TPOAb水平正常(0～9U/ml)的120例妊娠早期(≤12周)和120例妊娠中期(13～24周)孕妇,留取空腹静脉血,检测甲状腺功能及甲状腺自身抗体水平,并对孕妇进行产后随访。结果建立了妊娠早、中期孕妇的促甲状腺激素(TSH)、总甲状腺素(TT4)和游离甲状腺素(FT4)的正常值参考范围。并以此参考值为标准筛出亚临床甲状腺功能减退者82例,单纯低T4血症38例,单纯TPOAb阳性158例,检出率分别为4.15%(82/1978)、1.92%(38/1978)和7.99%(158/1978)。TPOAb阳性组中TSH异常(15.17%)的比例显著高于TPOAb阴性组(6.73%;P<0.001),TPOAb阳性组FT4异常率(7.58%)与TPOAb阴性组(4.98%)比较,差异无统计学意义(P>0.05)。TSH与TPOAb水平呈正相关(r=0.06,P<0.01),但FT4与TPOAb水平无明显相关关系(r=-0.02,P>0.05)。结论 TPOAb阳性与甲状腺功能异常有一定关系,建议妊娠期TPOAb阳性者产后及时复查,监测甲状腺功能的变化。     

The impact of thyroid abnormalities during pregnancy on subsequent neuropsychological development of the offspring: a meta-analysis

Objective: To investigate the relationship between specific thyroid abnormalities in women during pregnancy and the subsequent neuropsychological development of their offspring.

Methods: A systematic literature search of PubMed, Embase and Web of Science was conducted. Eligible studies were case-control or cohort study that explored this association with euthyroid thyroid abnormalities during pregnancy. The outcomes included intelligence scores and motor scores. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated and heterogeneity was assessed with Cochrane Q chi-square test and I² statistics. A fixed-effects or random-effects model was used to pool the estimates according to the heterogeneity among the included studies.

Results: Six studies, involving 4449 participants, were included. Children of women with thyroid abnormalities had mean intelligence score of 6.27 points and motor score of 5.99 points lower than that of children of euthyroid women. Subgroup analysis suggested that, children of women with hypothyroxinaemia, subclinical hypothyroidism and positive TPOAb had mean intelligence scores of 5.69 points, 8.76 points and 10.55 points, and mean motor scores of 4.19 points, 9.98 points and 9.03 points lower than those of the controls, respectively.

Conclusions: The thyroid abnormalities in pregnant women may adversely affect neuropsychological development of their offspring.     

Assessment of thyroid functions and thyroid volume in normal pregnant Egyptian females

Abstract

The normal range of thyroid functions during pregnancy differs between ethnic groups. This study assessed the thyroid functions in normal pregnant Egyptian females. Thyroid peroxidase antibodies (TPO Abs) and thyroid volume were also assessed. The study included 150 normal pregnant Egyptian females, recruited from Cairo University Hospital Antenatal Care Clinic (50 in each trimester), with 40 age-matched non-pregnant females, as a control group. Serum thyroid stimulating hormone (TSH) and TPO Abs were measured. Thyroid volume was assessed by ultrasonography. TSH ranges were 0.21–1.7, 0.52–3.2 and 0.72–2.6 mIU/L during first, second and third trimesters, respectively. The mean TSH level in pregnant females was significantly lower than that of non-pregnant women (1.2?±?0.7 vs 2.7?±?0.9 mIU/L, p?<?.001). TPO Abs were significantly higher in the first trimester compared to both second and third trimesters (p?<?.001 for both). Thyroid volume of pregnant females was non-significantly higher than that of non-pregnant control subjects (p?=?.126). A significant positive correlation was found between thyroid volume and body mass index in pregnant females (p?<?0.001). Our study established trimester-specific reference ranges for thyroid functions in normal pregnant Egyptian females. A larger population-based study would help to confirm those ranges. Thyroid volume was non-significantly higher than that of non-pregnant control subjects.     

早孕期甲状腺过氧化物酶抗体阳性对甲状腺功能的影响

目的：探讨妊娠8~12周甲状腺过氧化物酶抗体(TPOAb)阳性对甲状腺功能的影响。方法：对2010年9月至2011年6月北京友谊医院产科门诊行产前检查的611例无甲状腺疾病高危因素的健康初产妇,于妊娠8~12周进行甲状腺功能[促甲状腺激素(TSH)、游离四碘甲状腺原氨酸(FT4)]和TPOAb的检测,通过制定早孕期甲状腺功能正常参考区间,分析TPOAb阳性切割值、阳性率及对TSH、FT4的影响。结果：(1)妊娠8~12周TPOAb中位数值及变化范围为38.9(6.4~>1300)mU/L。(2)通过建立妊娠8~12周人群特异参考标准,以第90百分位计算TPOAb阳性切割值为206.77 mU/L,TPOAb阳性率为10.8%(66/611)。(3)回归分析显示：TPOAb滴度与TSH呈正相关,与FT4呈负相关,P值均为0.000。妊娠8~12周TPOAb阳性妇女TSH中位数值较TPOAb阴性者升高0.4 mU/L,前者TSH异常升高的风险是后者的4.4倍。结论：妊娠8~12周TPOAb阳性率为10.8%,通过建立妊娠期人群特异甲状腺功能参考标准和TPOAb阳性切割值,可避免过高估计TPOAb的阳性率。TPOAb阳性孕妇发生TSH异常升高的风险明显增加。     

复发性流产合并甲状腺疾病的诊治

甲状腺疾病所致甲状腺功能异常是引起复发性流产的一个常见内分泌因素,近年来已成为内分泌学、生殖医学及围产医学领域研究和关注的热点之一。临床上常见的甲状腺疾病主要包括甲状腺功能亢进症、临床甲状腺功能减退症、亚临床甲状腺功能减退症及甲状腺自身免疫性疾病等。对于复发性流产合并甲状腺疾病的规范化诊治在业内尚未达成共识,故普遍存在诊断标准不一、用药不规范等现象。文章就复发性流产患者合并甲状腺疾病的诊治作一阐述。