甲减和亚临床甲减对妊娠及其结局的影响
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摘要
背景与目的
甲状腺功能减退症和亚临床甲状腺功能减退症是常见的内分泌疾病,而育龄妇女是这种疾病的高发人群。孕妇合并甲减和亚临床甲减可增加妊娠不良结局和并发症的发生,是妊娠的高危因素。由于甲减和亚临床甲减起病隐匿,临床表现缺乏特异性,容易忽略,故对高危妇女进行早期筛查、诊断并及时给予足量甲状腺素补充治疗,可有效降低不良妊娠结局的发生,所以应提高对妊娠女性中甲减和亚临床甲减的认识和关注。
本研究旨在动态观察妊娠期间甲状腺功能对孕妇妊娠结局和产科并发症发生情况的影响,为评估孕妇甲减和甲减对妊娠及其结局的影响提供理论依据。
研究方法
通过前瞻性的分析2008年3月-2008年12月间,在山西医科大学第一医院妇产科筛查、治疗和随访妊娠女性共149例。
初诊时进行甲状腺功能筛查,应用化学发光法(CIA)法测定血清游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)水平、抗甲状腺过氧化物酶抗体(TPOAb)。依据甲状腺功能筛查结果,按甲状腺功能分组:甲状腺功能减退症组、亚临床甲状腺功能减退组、正常对照组。
首先关注在整个研究人群中甲状腺功能减退症和亚临床甲状腺功能减退症的总体患病率。其次在甲状腺功能减退症组、亚临床甲状腺功能减退组和正常对照组,根据妊娠的不同时期、孕妇年龄、既往有无甲状腺病史和危险因素进一步分组研究,对于亚临床甲减患者还根据严格定义的各种组成成分以及TSH不同水平分组,对于以上各个亚组研究其筛查时的甲状腺功能水平。
达到甲状腺功能减退症和亚临床甲状腺功能减退诊断标准者,参照美国甲状腺学会推荐的方案给予及时干预治疗和随访。分析、观察各组孕妇出现流产、早产、死胎以及各种产科并发症(如胎儿窘迫、胎儿宫内发育迟缓、妊高症和妊娠糖代谢异常等)的比率,评估甲状腺疾病对妊娠结局的影响及干预治疗的效果。
研究结果
①本研究中,妊娠女性甲减的患病率为2.68%(4/149),和国内外的文献数据比较接近,而亚临床甲减的发病率为23.49%(35/149),远远高于以往文献的结果。
②亚临床甲状腺功能减退组患者包含四种组成,其中单纯TSH升高和单纯FT4降低患者比例较高。
③甲状腺功能减退症和亚临床甲状腺功能减退组在筛查时TSH的水平出现明显的升高,与正常对照组相比均有统计学差异(P＜0.01)。但FT3、FT4降低程度不明显,与正常对照组相比,无统计学差异(P＞0.05)。经过药物干预,甲状腺功能减退症组和亚临床甲状腺功能减退组患者甲状腺功能指标基本控制在参考范围内,与正常对照组相比差异无统计学意义(P＞0.05)。
④既往有甲状腺病史组的TPOAb阳性率明显高于既往甲状腺病史阴性组,差异有统计学意义(P＜0.01)。
⑤甲状腺功能减退症和亚临床甲状腺功能减退症组与正常对照组相比,妊娠不良结局发生率明显升高,差异有统计学意义(P＜0.01)。既往甲状腺病史阳性组与阴性组相比较,前者不良结局和并发症发生率均明显增高,差异有统计学意义(P＜0.01)。
⑥按不同的TSH水平分组,TSH＞10 uIU/ml组的不良结局及并发症发生率最高,与TSH 2.5—4.2 uIU/ml组和TSH 4.2-10 uIU/ml组相比,差异有统计学意义(P＜0.01):TSH4.2-10 uIU/ml组的不良结局及并发症的发生率,较TSH2.5-4.2 uIU/ml组升高,差异有统计学意义(P＜0.01)。
⑦妊娠晚期甲减和亚临床甲减的发生率明显升高。
⑧在不同年龄组妊娠女性中,21-25岁组亚临床甲减的发生率明显升高。结论:
甲状腺功能减退症和亚临床甲状腺功能减退症对妊娠有不良的影响,增加妊娠的风险。但是,通过及时、适当的治疗,保证甲状腺功能水平维持在正常范围,可将并发症等风险降低,达到满意的妊娠结果。所以,对高危人群进行筛查,妊娠期严密的监测甲状腺功能水平,及时诊断和治疗对于保护孕妇健康具有十分重要的意义。
Background and objective:
Subclinical hypothyroidism is common in the population and especially in reproductive women.It is noticed that maternal thyroid dysfunction during pregnancy such as hypothyroidism can lead to both obstetrical complications and adverse reproductive outcomes. Not only overt,but also subclinical thyroid disorders are high risk for pregnancy. Hypothroidism is a chronic but progressive disease,without overt clinical characteristics,so thyroid function screening in high-risk women is necessary and treatment should be caught out in time.Subclinical hypothyroidism is moving with a result of overt hypothyroidism, which is related to the increased level of TSH,as well as the positive thyroid peroxidase antibody(TPOAb).Hyperthyroidism can lead to severe complications on both mother and offspring,which is only next to gestational diabetes.However the adverse effect is minor if mothers get treatment during pregnancy.
The aim of this study was to monitor the change of thyroid function and antibody during the course of pregnancy in those who suffer from various thyroid disorders and normal control.We evaluate the consequences of pregnancy outcomes and determine management and therapeutic intervention in relation to pregnancy outcomes,providing to clinical obstetrician as a theoretically proof.
Method:
A descriptive analysis involving 149 pregnant women who visited and delivered in the first hospital of Shanxi Province from March 2008 to December 2008.
Firstly,with high-sensitive chemical irradiance assay(CIA) technique,we analyzed the concentrations of thyroid stimulating hormone(TSH),free triiodo-thyroxine(FT3),free thyroxine(FT4) and TPOAb in pregnant women during their antenatal visit.According to the results of thyroid function tests assessed by standard laboratory reference ranges,we classified them into four different groups:overt hypothyroidism,subclinical hypothyroidism, normal and other thyroid dysfunction.The last group is excluded in this study.
We pay attention to the prevalence of overt hypothyroidism & subclinical hypothyroidism as a whole.Then according to the stages of pregnancy,age of pregnant women,history of thyroid disease and other risk factors,we divide the groups above into several subgroups.We divided the pregnant women into groups according to different components of subclinical hypothyroidism and different levels of TSH.Then we can analyze the thyroid function without therapy.
We intervene the patients with hypothyroidism and subclinical hypothyroidism.After several months of observation & follow-up,we got the final data of pregnant women with miscarriage,abortion and other complications to evaluate the effect of hypothyroidism and subclinical hypothyroidism on pregnancy.
Results:
①In this study,the prevalence of hypothyroidism is 2.68%(4/149),similar to the data of published articles,while the prevalence of subclinical hypothyroidism is 23.49%(35/149), much higher than the results having been reported.
②There are four components of subclinical hypothyroidism,and in them groups of patients with simple TSH elevation & simple FT4 decreasing have higher ratios.
③The levels of TSH in groups of patients with hypothyroidism & subclinical hypothyroidism are higher than those of the normal groups during the screening(P＜0.01) while decreasing of FT3 & FT4 is not obvious(P＞0.05).Thyroid function in controlled hypothyroidism group is in the reference range,and no significant difference is showed compared to the normal group(P＞0.05).
④The ratio of positive TPOAb in a high-risk group was significantly higher than those without a past history of thyroid disease(P＜0.01).
⑤We observed that significantly higher incidences of adverse obstetrical outcomes and complications in uncontrolled hypothyroidism group and subclinical hypothyroidism group compared with normal group(P＜0.01).The incidences of adverse outcomes is obviously increased in women who have a high risk than those without a past history of thyroid disease(P＜0.01).
⑥According to the TSH level,we divide the study women into four groups,as TSH＞10 uIU/ml,TSH4.2-10 uIU/ml,TSH2.5-4.2 uIU/ml and TSH＜2.5 uIU/ml group.Following the raising of TSH level,the incidences of adverse outcomes and complications were increased.
⑦The prevalence of hypothyroidism & subclinical hypothyroidism is much higher in the 3rd trimester.
⑧The prevalence of subclinical hypothyroidism is much higher in the group of 21-25 years old pregnant women.
Conclusion:
Presence of clinical & subclinical thyroid disorders can negatively affect the pregnancy. However,if mothers with thyroid disease get adequate treatment in time and remain thyroid function normal,the adverse influence maybe reduced to the least.So serial monitoring and therapeutic intervention maybe necessary for the prevention of undesirable obstetric outcomes.
甲状腺功能减退症和亚临床甲状腺功能减退症是常见的内分泌疾病,而育龄妇女是这种疾病的高发人群。孕妇合并甲减和亚临床甲减可增加妊娠不良结局和并发症的发生,是妊娠的高危因素。由于甲减和亚临床甲减起病隐匿,临床表现缺乏特异性,容易忽略,故对高危妇女进行早期筛查、诊断并及时给予足量甲状腺素补充治疗,可有效降低不良妊娠结局的发生,所以应提高对妊娠女性中甲减和亚临床甲减的认识和关注。
本研究旨在动态观察妊娠期间甲状腺功能对孕妇妊娠结局和产科并发症发生情况的影响,为评估孕妇甲减和甲减对妊娠及其结局的影响提供理论依据。
研究方法
通过前瞻性的分析2008年3月-2008年12月间,在山西医科大学第一医院妇产科筛查、治疗和随访妊娠女性共149例。
初诊时进行甲状腺功能筛查,应用化学发光法(CIA)法测定血清游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)水平、抗甲状腺过氧化物酶抗体(TPOAb)。依据甲状腺功能筛查结果,按甲状腺功能分组:甲状腺功能减退症组、亚临床甲状腺功能减退组、正常对照组。
首先关注在整个研究人群中甲状腺功能减退症和亚临床甲状腺功能减退症的总体患病率。其次在甲状腺功能减退症组、亚临床甲状腺功能减退组和正常对照组,根据妊娠的不同时期、孕妇年龄、既往有无甲状腺病史和危险因素进一步分组研究,对于亚临床甲减患者还根据严格定义的各种组成成分以及TSH不同水平分组,对于以上各个亚组研究其筛查时的甲状腺功能水平。
达到甲状腺功能减退症和亚临床甲状腺功能减退诊断标准者,参照美国甲状腺学会推荐的方案给予及时干预治疗和随访。分析、观察各组孕妇出现流产、早产、死胎以及各种产科并发症(如胎儿窘迫、胎儿宫内发育迟缓、妊高症和妊娠糖代谢异常等)的比率,评估甲状腺疾病对妊娠结局的影响及干预治疗的效果。
研究结果
①本研究中,妊娠女性甲减的患病率为2.68%(4/149),和国内外的文献数据比较接近,而亚临床甲减的发病率为23.49%(35/149),远远高于以往文献的结果。
②亚临床甲状腺功能减退组患者包含四种组成,其中单纯TSH升高和单纯FT4降低患者比例较高。
③甲状腺功能减退症和亚临床甲状腺功能减退组在筛查时TSH的水平出现明显的升高,与正常对照组相比均有统计学差异(P＜0.01)。但FT3、FT4降低程度不明显,与正常对照组相比,无统计学差异(P＞0.05)。经过药物干预,甲状腺功能减退症组和亚临床甲状腺功能减退组患者甲状腺功能指标基本控制在参考范围内,与正常对照组相比差异无统计学意义(P＞0.05)。
④既往有甲状腺病史组的TPOAb阳性率明显高于既往甲状腺病史阴性组,差异有统计学意义(P＜0.01)。
⑤甲状腺功能减退症和亚临床甲状腺功能减退症组与正常对照组相比,妊娠不良结局发生率明显升高,差异有统计学意义(P＜0.01)。既往甲状腺病史阳性组与阴性组相比较,前者不良结局和并发症发生率均明显增高,差异有统计学意义(P＜0.01)。
⑥按不同的TSH水平分组,TSH＞10 uIU/ml组的不良结局及并发症发生率最高,与TSH 2.5—4.2 uIU/ml组和TSH 4.2-10 uIU/ml组相比,差异有统计学意义(P＜0.01):TSH4.2-10 uIU/ml组的不良结局及并发症的发生率,较TSH2.5-4.2 uIU/ml组升高,差异有统计学意义(P＜0.01)。
⑦妊娠晚期甲减和亚临床甲减的发生率明显升高。
⑧在不同年龄组妊娠女性中,21-25岁组亚临床甲减的发生率明显升高。结论:
甲状腺功能减退症和亚临床甲状腺功能减退症对妊娠有不良的影响,增加妊娠的风险。但是,通过及时、适当的治疗,保证甲状腺功能水平维持在正常范围,可将并发症等风险降低,达到满意的妊娠结果。所以,对高危人群进行筛查,妊娠期严密的监测甲状腺功能水平,及时诊断和治疗对于保护孕妇健康具有十分重要的意义。
Background and objective:
Subclinical hypothyroidism is common in the population and especially in reproductive women.It is noticed that maternal thyroid dysfunction during pregnancy such as hypothyroidism can lead to both obstetrical complications and adverse reproductive outcomes. Not only overt,but also subclinical thyroid disorders are high risk for pregnancy. Hypothroidism is a chronic but progressive disease,without overt clinical characteristics,so thyroid function screening in high-risk women is necessary and treatment should be caught out in time.Subclinical hypothyroidism is moving with a result of overt hypothyroidism, which is related to the increased level of TSH,as well as the positive thyroid peroxidase antibody(TPOAb).Hyperthyroidism can lead to severe complications on both mother and offspring,which is only next to gestational diabetes.However the adverse effect is minor if mothers get treatment during pregnancy.
The aim of this study was to monitor the change of thyroid function and antibody during the course of pregnancy in those who suffer from various thyroid disorders and normal control.We evaluate the consequences of pregnancy outcomes and determine management and therapeutic intervention in relation to pregnancy outcomes,providing to clinical obstetrician as a theoretically proof.
Method:
A descriptive analysis involving 149 pregnant women who visited and delivered in the first hospital of Shanxi Province from March 2008 to December 2008.
Firstly,with high-sensitive chemical irradiance assay(CIA) technique,we analyzed the concentrations of thyroid stimulating hormone(TSH),free triiodo-thyroxine(FT3),free thyroxine(FT4) and TPOAb in pregnant women during their antenatal visit.According to the results of thyroid function tests assessed by standard laboratory reference ranges,we classified them into four different groups:overt hypothyroidism,subclinical hypothyroidism, normal and other thyroid dysfunction.The last group is excluded in this study.
We pay attention to the prevalence of overt hypothyroidism & subclinical hypothyroidism as a whole.Then according to the stages of pregnancy,age of pregnant women,history of thyroid disease and other risk factors,we divide the groups above into several subgroups.We divided the pregnant women into groups according to different components of subclinical hypothyroidism and different levels of TSH.Then we can analyze the thyroid function without therapy.
We intervene the patients with hypothyroidism and subclinical hypothyroidism.After several months of observation & follow-up,we got the final data of pregnant women with miscarriage,abortion and other complications to evaluate the effect of hypothyroidism and subclinical hypothyroidism on pregnancy.
Results:
①In this study,the prevalence of hypothyroidism is 2.68%(4/149),similar to the data of published articles,while the prevalence of subclinical hypothyroidism is 23.49%(35/149), much higher than the results having been reported.
②There are four components of subclinical hypothyroidism,and in them groups of patients with simple TSH elevation & simple FT4 decreasing have higher ratios.
③The levels of TSH in groups of patients with hypothyroidism & subclinical hypothyroidism are higher than those of the normal groups during the screening(P＜0.01) while decreasing of FT3 & FT4 is not obvious(P＞0.05).Thyroid function in controlled hypothyroidism group is in the reference range,and no significant difference is showed compared to the normal group(P＞0.05).
④The ratio of positive TPOAb in a high-risk group was significantly higher than those without a past history of thyroid disease(P＜0.01).
⑤We observed that significantly higher incidences of adverse obstetrical outcomes and complications in uncontrolled hypothyroidism group and subclinical hypothyroidism group compared with normal group(P＜0.01).The incidences of adverse outcomes is obviously increased in women who have a high risk than those without a past history of thyroid disease(P＜0.01).
⑥According to the TSH level,we divide the study women into four groups,as TSH＞10 uIU/ml,TSH4.2-10 uIU/ml,TSH2.5-4.2 uIU/ml and TSH＜2.5 uIU/ml group.Following the raising of TSH level,the incidences of adverse outcomes and complications were increased.
⑦The prevalence of hypothyroidism & subclinical hypothyroidism is much higher in the 3rd trimester.
⑧The prevalence of subclinical hypothyroidism is much higher in the group of 21-25 years old pregnant women.
Conclusion:
Presence of clinical & subclinical thyroid disorders can negatively affect the pregnancy. However,if mothers with thyroid disease get adequate treatment in time and remain thyroid function normal,the adverse influence maybe reduced to the least.So serial monitoring and therapeutic intervention maybe necessary for the prevention of undesirable obstetric outcomes.
引文
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[29].Lazarus JH.Thyroid disease in pregnancy and childhood.Minerva Endoerinol,2005,30:71-87.
[30].Meeacei F,Parretti E,Cioni R,et al.Thyroid autoimmunity and its association With no-organ-specific antibodies and subclinical alterations of thyroid function in women with a history of pregnancy loss or preeclampsia[J].J Reprod Immunol,2000,46:39-50.
[31].Kutteh WH,Yetman DL,Carr AC,et al.Increased prevalence of antithyroid antibodies identified in women with recurrent pregnancy loss but not in women undergoing assisted reproduction[J].Fertil Steril,1999,71:843-848.
[32].Roti E,Uberti E.Post-partum thyroiditis-a clinical update.Eur J Endoerinol,2002,146:275-279.
[33].Ghafoor F,Mansoor M,Malik T,et al.Role of thyroid peroxidase antibodies in the outcome of pregnancy.J Coll Physicians Surg Pak,2006,16:468-471.
[34].Hollowell JG,LaFranehi SH,Smallridge RC,et al.2004 where do we go from here?—Summary of working group discussions on thyroid function and gestational outcomes.Thyroid,2005,15:72-76.
[35].Consensus Statement #2 Ameriean Thyroid Association statement on early maternal thyroidal insufficiency:recognition,clinical management and research directions.Thyroid,2005,15:77-79.
[36].Casey BM.Subclinical hypothyroidism and pregnancy.Obstet Gyneeol Stiry,2006,61:415-420.
[1]Surks MI,Ortiz E,Daniels GH.Subclinical thyroid diseas;scientific review and guidelines for diagnosis and management[J].JAMA,2004,291(2):228-238
[2]滕卫平 妊娠亚临床甲状腺功能减退症的筛查和干预 2007年全国内分泌学学术会议
[3]Burrow G.N.,Fisher D.A.,Larsen P.R.,et al:Maternal and fetal thyroid function.N Engl J Med 331.1072-1078.1994;
[4]Glinoer D.,Delange F.:The potential repercussions of maternal,fetal,and neonatal hypothyroxinemia on the progeny.Thyroid 10.(10):871-887.2000;
[5]Glinoer D.:Potential consequences of maternal hypothyroidism on the offspring:evidence and implications.[Review][17 refs][Journal Article.Review]Horm Res 55.(3):109-114.2001;
[6]Madhuri Devdhar,MD et al:Hypothyroidism.Endocrinology and Metabolism Clinics-Volume 36,Issue 3(September 2007)
[7]Haddow J.E.,Palomaki G.E.,Allan W.C.,et al:Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child.N Engl J Med 341.549-555.1999;
[8]Vanderpump M.P.:The epidemiology of thyroid diseases.In:Braverman L.E.,Utiger R.D.,ed.The thyroid:a fundamental and clinical text,9th edition Lippincott Williams and Wilkins Philadelphia2004:398-406.
[9]Thorpe-Beeston J.G.,et al:Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus.N Engl J Med 324.532-536.1991;
[10]Glinoer D.:Management of hypo- and hyperthyroidism during pregnancy.Growth Horm IGF Res 13.(Suppl A):S45-S54.2003;
[11]Kasatkina E.P.,Samsonova L.N.,Ivakhnenko V.N.,et al:Gestational hypothyroxinemia and cognitive function in offspring.Neurosci Behav Physiol 36.(6):619-624.2006;
[12]郭敏 亚临床甲状腺功能减退与妊娠 国外医学计划生育/生殖健康分册 2007年26 卷2期100-103
[13]Negro R.,Formoso G.,Mangieri T.,et al:Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease:effects on obstetrical complications.J Clin Endocrinol Metab 91.(7):2587-2591.2006;
[14]Marcos Abalovich,Nobuyuki Amino,Linda A.Barbour,et al:CLINICAL PRACTICE GUIDLINE Management of Thyroid Dysfunction during Pregnancy and Postpartum:An Endocrine Society Clinical Practice Guideline The Journal of Clinical Endocrinology Metabolism 92(8) (Supplement):S1-S4723
[3].Casey BM,Dashe JS,Wells CE,et al.Subclinical hypothyroidism and pregnancy outcomes.obstet Gynecol,2005,105:239-245.
[4].Gharib H,et al.Subclinical thyroid dysfunction:A joint statement on management from the American association of clinical endocrinologists,the American thyroid association,and the Endocrine society.J Clin Endoerinol Metab,2005,90:581-585.
[5].LaFranehi SH,et al.Is thyroid inadequacy during gestation a risk factor for adverse pregnancy and developmental outcomes?Thyroid,2005,15:60 — 71.
[6].Alexander EK,Marqusee E,Lawrence J,et al.Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism.N Engl J Med,2004,351:241-249.
[7].Surks Ml,Ortiz E,Daniels GH.Subclinical thyroid disease:scientific review and guidelines for diagnosis and management.JAMA,2004,291:228.
[8].Vaidya B,Anthony S,Bilous M,et al.Detection of thyroid dysfunction in early pregnancy:Universal screening or targeted high-risk case finding?2006 Oct 10.[EPub ahead of print].
[9].Andrade LJ,CruzT,Daltro C,et al.Detection of subclinical hypothyroidism in pregnant women with different gestational ages.Arq Bras Endoerinol Metabol,2005,49:923-929.
[10].Kalinin MI,et al.Prevalence of abnormal thyroid function tests during pregnancy.American association for clinical chemistry annual meeting.LosAngelos,California,USA.2004,July 25.
[ll].American thyroid association statement on early maternal thyroidal insufficiency:recognition,clinical management and research directions.Thyroid,2005,15:77-79.
[12].Burrow GN.,Fisher D.A.,Larsen P.R.,et al:Maternal and fetal thyroid function.N Engl J Med 331.1072-1078.1994;
[13].Glinoer D.,Delange E:The potential repercussions of maternal,fetal,and neonatal hypothyroxinemia on the progeny.Thyroid 10.(10):871-887.2000;
[14].Glinoer D.:Potential consequences of maternal hypothyroidism on the offspring:evidence and implications.[Review][17 refs][Journal Article.ReviewJHorm Res 55.(3):109-114.2001;
[15].J.Madhuri Devdhar,MD et al:Hypothyroidism.Endocrinology and Metabolism Clinics-Volume 36,Issue 3 (September 2007)
[16].Haddow J.E.,Palomaki GE.,Allan W.C,et al:Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child.N Engl J Med 341.549-555.1999;
[17].Negro R,Formoso G,Mangieri T,et al.Levothyroixine treatment in euthyroid pregnant women with autoimmune thyroid disease:effects on obstetrical complications.J Clin Endoerinol Metab,2006,91:2587-91.
[18].Glinoer D.Management of hypo-and hyperthyroidism during pregnancy.Growth Hormone &Igf Research,2003,13:545-554.
[19].Kato K,Mostafa MH,Mann K,et al.The human chronic gonadotropin molecule from patients with trophoblastic diseases has a high thyrotropic activity but is less active in the ovary.Gynecol Endoerinol,2004,18:269-277.
[20].Waseo EC,Martinez E,Grant KS,et al.Determinants of iodothyronine deiodinase activities in rodent uterus.Endocrinology,2003,144:4253-4261.
[21].Carvalho DP.Modulation of uterine iodothyronine deiodinases-A critical event for fetal development?Endocrinology,2003,144:4250-4252.
[22].ChanS,KachileleS,HobbsE,et al.Placental iodothyronine deiodinase expression in normal and growth-restricted human pregnancies.J Clin Endoerinol Metab,2003,88:4488-4495.
[23].Kurioka H,Takahashi K,Miyazaki K.Maternal thyroid function during pregnancy and puerperal period.Endocr J,2005,52:587-591.
[24].Wartofshy L,Dickey RA.The evidence for a narrower thyrotropin reference range is compelling.J Clin Endoerinol Metab,2005,90:5483-8.
[25].Surks MI,Goswami G,Daniels GH.The thyrotropin reference range should remain unchanged.J Clin Endoerinol Metab.2005,90:5489-96.
[26].Dashe JS,Casey BM,Wells CE,et al.Thyroid-stimulating hormone in singleton And twin pregnancy:importance of gestational age-specific reference ranges.Obstet Gynecol,2005,106:753-757.
[27].Mandel SJ,Spencer CA,Hollowell JG Are detection and treatment of thyroid Insufficiency in pregnancy feasible?Thyroid,2005,15:44-53
[28].Sapin R,D'Herbomez M,Schlienger JL.Free thyroxine measured with equilibrium dialysis and nine immunoassays decreases in late pregnancy.Clin Lab,2004,50:581-584.
[29].Lazarus JH.Thyroid disease in pregnancy and childhood.Minerva Endoerinol,2005,30:71-87.
[30].Meeacei F,Parretti E,Cioni R,et al.Thyroid autoimmunity and its association With no-organ-specific antibodies and subclinical alterations of thyroid function in women with a history of pregnancy loss or preeclampsia[J].J Reprod Immunol,2000,46:39-50.
[31].Kutteh WH,Yetman DL,Carr AC,et al.Increased prevalence of antithyroid antibodies identified in women with recurrent pregnancy loss but not in women undergoing assisted reproduction[J].Fertil Steril,1999,71:843-848.
[32].Roti E,Uberti E.Post-partum thyroiditis-a clinical update.Eur J Endoerinol,2002,146:275-279.
[33].Ghafoor F,Mansoor M,Malik T,et al.Role of thyroid peroxidase antibodies in the outcome of pregnancy.J Coll Physicians Surg Pak,2006,16:468-471.
[34].Hollowell JG,LaFranehi SH,Smallridge RC,et al.2004 where do we go from here?—Summary of working group discussions on thyroid function and gestational outcomes.Thyroid,2005,15:72-76.
[35].Consensus Statement #2 Ameriean Thyroid Association statement on early maternal thyroidal insufficiency:recognition,clinical management and research directions.Thyroid,2005,15:77-79.
[36].Casey BM.Subclinical hypothyroidism and pregnancy.Obstet Gyneeol Stiry,2006,61:415-420.
[1]Surks MI,Ortiz E,Daniels GH.Subclinical thyroid diseas;scientific review and guidelines for diagnosis and management[J].JAMA,2004,291(2):228-238
[2]滕卫平 妊娠亚临床甲状腺功能减退症的筛查和干预 2007年全国内分泌学学术会议
[3]Burrow G.N.,Fisher D.A.,Larsen P.R.,et al:Maternal and fetal thyroid function.N Engl J Med 331.1072-1078.1994;
[4]Glinoer D.,Delange F.:The potential repercussions of maternal,fetal,and neonatal hypothyroxinemia on the progeny.Thyroid 10.(10):871-887.2000;
[5]Glinoer D.:Potential consequences of maternal hypothyroidism on the offspring:evidence and implications.[Review][17 refs][Journal Article.Review]Horm Res 55.(3):109-114.2001;
[6]Madhuri Devdhar,MD et al:Hypothyroidism.Endocrinology and Metabolism Clinics-Volume 36,Issue 3(September 2007)
[7]Haddow J.E.,Palomaki G.E.,Allan W.C.,et al:Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child.N Engl J Med 341.549-555.1999;
[8]Vanderpump M.P.:The epidemiology of thyroid diseases.In:Braverman L.E.,Utiger R.D.,ed.The thyroid:a fundamental and clinical text,9th edition Lippincott Williams and Wilkins Philadelphia2004:398-406.
[9]Thorpe-Beeston J.G.,et al:Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus.N Engl J Med 324.532-536.1991;
[10]Glinoer D.:Management of hypo- and hyperthyroidism during pregnancy.Growth Horm IGF Res 13.(Suppl A):S45-S54.2003;
[11]Kasatkina E.P.,Samsonova L.N.,Ivakhnenko V.N.,et al:Gestational hypothyroxinemia and cognitive function in offspring.Neurosci Behav Physiol 36.(6):619-624.2006;
[12]郭敏 亚临床甲状腺功能减退与妊娠 国外医学计划生育/生殖健康分册 2007年26 卷2期100-103
[13]Negro R.,Formoso G.,Mangieri T.,et al:Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease:effects on obstetrical complications.J Clin Endocrinol Metab 91.(7):2587-2591.2006;
[14]Marcos Abalovich,Nobuyuki Amino,Linda A.Barbour,et al:CLINICAL PRACTICE GUIDLINE Management of Thyroid Dysfunction during Pregnancy and Postpartum:An Endocrine Society Clinical Practice Guideline The Journal of Clinical Endocrinology Metabolism 92(8) (Supplement):S1-S4723