孕母患自身免疫性甲状腺疾病对婴儿甲状腺功能影响的多因素分析
|
摘要
研究背景
自身免疫性甲状腺疾病如Graves病或慢性淋巴细胞性甲状腺炎，好发于妊娠期妇女，发病率为0.2％。孕母患自身免疫性甲状腺疾病如处理不当除了引起围产期并发症增多外，还可使新生儿甲状腺功能异常的发病率增加。新生儿甲状腺功能异常如未能及时发现，重者引起死亡、轻者引起智能发育障碍和生长迟缓。
在过去的十年中，人们陆续发现自身免疫性甲状腺疾病孕母的新生儿发生原发性甲状腺功能低下、垂体性甲低、甲状腺功能亢进和高TSH血症，并在有些新生儿体内测到了高浓度的促甲状腺素受体(?)体(TRAb)，因此推测这些新生儿甲状腺功能异常可能与TRAb有关。但以往的研究只是考虑单个因素的作用，其实影响婴儿甲状腺功能的因素是多方面的。孕母妊娠期服药、孕母妊娠期甲状腺功能状态、孕母所患的甲状腺疾病种类、孕母选择的治疗方案等等对婴儿甲状腺功能有无影响?影响有多大?这些问题有待于进一步研究。
研究目的
孕母患自身免疫性甲状腺疾病对婴儿甲状腺功能有影响。但影响有多大，哪些因素与之有关目前仍不明确。本课题通过浙江省新生儿疾病筛查的网络系统，采用病例对照研究的方法，在国内首次在全省范围内开展对母亲患自身免疫性甲状腺疾病的婴儿甲状腺功能的跟踪调查，研究这些婴儿甲状腺功能情况以及甲状
2004年浙江大学硕士学位论文
腺功能异常的发病率，探讨孕母患自身免疫性甲状腺疾病对婴儿甲状腺功能的影
响因素。
研究对象
2001年7月1日至2003年6月30日在浙江省(除宁波市外)各县、市、
省级医院产科分娩的孕母患自身免疫性甲状腺疾病(符合纳入标准)的婴儿，且
无产时窒息史的足月儿作为研究对象。对照组:为同期在浙江省(除宁波市外)
各县、市、省级医院产科分娩的无甲状腺疾病孕母的婴儿。
纳入标准:对妊娠前或妊娠期间曾在省、市级医院检查有甲状腺功能减退且
伴有抗微粒体抗体或抗甲状腺过氧化物酶抗体、抗甲状腺球蛋白抗体增高者为慢
性淋巴细胞性甲状腺炎孕母;有甲状腺功能亢进且甲状腺B超或甲状腺ECT扫
描或甲状腺细针穿刺病理检查证实、并排除高功能腺瘤及多发性结节者为Graves
病孕母。
研究方法
对生后满3天的新生儿由各产科医院采足跟血，标本干燥后送浙江省新生儿
疾病筛查中心，用滤纸血斑时间分辨荧光法检测促甲状腺素(TSH)。对
TSH>9 mU/L者于结果报告后1一3天立即召回母亲及新生儿(健康孕母者只召回
新生儿)，对TSH正常者于分娩后28一35天召回医院。记录孕母所患的甲状腺
疾病种类、病程、妊娠期甲状腺功能状态、服药史、母亲妊娠年龄、胎龄及新生
儿出生体重，复查婴儿及母亲的甲状腺功能，并留母亲及婴儿的血清测定抗过氧
化物酶抗体(TPOAb)、抗甲状腺球蛋白抗体(TGAb)，促甲状腺激素受体抗体
(TRAb)、甲状腺素刺激抗体(TSAb)。用化学发光免疫法检测T3、几、TSH、
FT3、FT4、Tp0Ab，采用美国nPC公司的Immulite化学发光仪检测，用放射免
疫法测定TGAb(药合由北京原子能研究所提供)，采用EUSA法测定母亲及婴
儿体内的促甲状腺激素受体抗体(TRAb)、甲状腺素刺激抗体(TSAb)。TRAb
2004年浙江大学硕士学位论文
药盒为德国汉堡nLn oesel一sehan仙Diagnosti恤und medi‘nisehe Gerate mbH生
产，TSAb药盒为天津医科大学生物实验厂提供。对确诊先天性甲状腺功能低
下(TsH增高伴T4下降)的新生儿进行优甲乐治疗，对高TSH血症者(滤纸片
法TSH>9闪u/ml或血清TsH>4.4 mlu/L，而其它指标均正常)，每月一次复查甲
状腺功能直至TSH恢复正常。所有数据由SSPSS10.0软件处理，以p<0.05为有
显著差异。健康孕母的婴儿与自身免疫性甲状腺疾病孕母的婴儿，其甲状腺功
能异常的发病率比较采用两百分率比较的u检验。母婴体内的抗甲状腺抗体分析
采用双变量相关分析，两组之间的比较采用独立样本t检验，婴儿甲状腺功能异
常的危险因素分析，采用非条件多元loglstic回归分析。
结果
1.孕母患自身免疫性甲状腺疾病对婴儿甲状腺功能的影响78例自身免
疫性甲状腺疾病孕母的婴儿，确诊先天性原发性甲低7例，占9.0%(7/78)高
TSH血症33例，占42.3%(33/78)，甲状腺功能亢进1例，占1 .3%(1/78)，而
同期浙江省新生儿疾病筛查中心(除宁波市外)共筛查新生儿424665例，确诊
先天性原发性甲状腺功能低下305例，占0.7%。，暂时性TSH增高1 993例，占
4.7%0，甲亢O例，二者比较有显著差异(U甲低=28.996，尸<0.01，UTsH增高=53.628，
P<0 .01)o
2.母婴体内抗甲状腺自身抗体的关系对分娩后25~35天的母亲及婴儿
测定体内抗甲状腺自身抗体:TPOAb、TGAb、TRAb、TSAb，经双变量相关
分析，speannan相关系数分别为0.636、0.574、0.619、0.473，尸均(0.01。甲
状腺功能异常的婴儿，其体内TRAb、TPOAb分别为5.53士1.20(IU/L)、41.65
士2.89(Iu/L)明显高于甲状腺功能正常的婴儿夏4.12士1.41(Iu几)24.27士3.03
(Iu几)}，而ToAb、TSAb两组之间则无差异。
3.婴儿甲状腺功能异常的危险因素分析经单因素logistic回归分析，筛选
2004年浙江大学硕士学位论文
It was well documented that women in pregnancy were trend to suffer from autoimmune thyroid disease such as Graves or Hashimoto thyroiditis with a prevalence of 0.2% and has been shown to affect neonatal thyroid function as well as other outcomes such as spontaneous abortion, intrauterine growth retardation, still birth, premature labor and congenital malformation if they were not appropriately treated. Neonatal thyroid dysfunction without therapy will lead to mental and physical retardation, and some times even result in death.
In the last decade, neonates born to mothers with autoimmune thyroid disease were in succession to be found to have primary hypothyroidism, pituitary hypothyroidism, hyperthyroidism or hyperthyrotropinemia, and some were found to have high anti-TSH receptor antibody (TRAb). Previous researches about neonatal thyroid dysfunction were concerned in single factor, very little data were available from early infancy . their mothers and environment based studies on the risk factors for early infantile thyroid dysfunction. While factors such as the state of maternal thyroid function during pregnancy, maternal medical treatment or therapy program during pregnancy and the type of maternal thyroid disease will affect neonatal thyroid function and how widely will they contribute to?
Objective
In order to minimize complications and to improve maternal and neonatal outcomes, a cohort of 78 infants born to mothers with autoimmune thyroid disease was investigated to evaluate the impact of maternal thyroid dysfunction during pregnancy and postpartum on infant thyroid function and to identify the possible maternal, neonatal and /or environmental risk factors for causing early infantile thyroid dysfunction by Provincial Neonatal Disease Screening Network which covers nearly thirty seven thousand neonates a year in south east part of China Patients:
All the newborns delivered to mothers with autoimmune thyroid disease as defined by criteria from Zhejiang Province (except for Ningbo city) during July 1st of 2001 to June 30th of 2003 were investigated. Seventy eight term, non-asphyxiated neonates met the criteria were recruited into the study. Neonates born to healthy mothers at the same period were set as controls according to Provincial Neonatal Disease Screening Network.
The criteria for the diagnosis of Graves' disease or Hashimoto thyroiditis was as follows:
Graves disease in the mothers had been diagnosed by clinical and laboratory evidence of hyperthyroidism, increased TPOAb and TPOAb level and a diffuse goiter, excluding other common causes of thyrotoxicosis such as toxic multinodular goiter or toxic adenoma by thyroid ultrasonography or ECT scan or fine-needle biopsy of thyroid tissue.
Hashimoto thyroiditis was diagnosed by the presence of increased TPO-Ab and TGAb level, clinical and laboratory evidence of hypothyroidism at the time of
diagnosis, and decreased echogenicity of the thyroid gland. Some cases with lymphocytic infiltration were confirmed by a fine-needle biopsy of thyroid tissue. Methods:
Heel capillary blood was collected on 3-day newborn by obstetrician of local hospital. Samples of blood dried on filter paper were sent to Provincial Neonatal Disease Screening Center to be detected on TSH by Time difference fluorescent analysis (1420 type II, Wallac company, Finland). The neonate was called back immediately if his or her TSH was over 9 mU/L, and the others were called back at 28 to 35 days after birth. The data of mothers and newborns' status were recorded in detail including the type of maternal thyroid disease (Graves disease or Hashimoto thyroiditis), the maternal thyroid function during the pregnancy (three groups were divided: Group A: hyperthyroidism, Group B: hypothyroidism, Group C: euthyroidism based on the level of FT3 FT4 and TSH during pregnancy), the history of medication, the maternal age of pregnancy, the gestational age of baby and neonatal birth weight . The serum concentrations of T3, T4, TSH, FT3, FT4, TPOAb were m
自身免疫性甲状腺疾病如Graves病或慢性淋巴细胞性甲状腺炎，好发于妊娠期妇女，发病率为0.2％。孕母患自身免疫性甲状腺疾病如处理不当除了引起围产期并发症增多外，还可使新生儿甲状腺功能异常的发病率增加。新生儿甲状腺功能异常如未能及时发现，重者引起死亡、轻者引起智能发育障碍和生长迟缓。
在过去的十年中，人们陆续发现自身免疫性甲状腺疾病孕母的新生儿发生原发性甲状腺功能低下、垂体性甲低、甲状腺功能亢进和高TSH血症，并在有些新生儿体内测到了高浓度的促甲状腺素受体(?)体(TRAb)，因此推测这些新生儿甲状腺功能异常可能与TRAb有关。但以往的研究只是考虑单个因素的作用，其实影响婴儿甲状腺功能的因素是多方面的。孕母妊娠期服药、孕母妊娠期甲状腺功能状态、孕母所患的甲状腺疾病种类、孕母选择的治疗方案等等对婴儿甲状腺功能有无影响?影响有多大?这些问题有待于进一步研究。
研究目的
孕母患自身免疫性甲状腺疾病对婴儿甲状腺功能有影响。但影响有多大，哪些因素与之有关目前仍不明确。本课题通过浙江省新生儿疾病筛查的网络系统，采用病例对照研究的方法，在国内首次在全省范围内开展对母亲患自身免疫性甲状腺疾病的婴儿甲状腺功能的跟踪调查，研究这些婴儿甲状腺功能情况以及甲状
2004年浙江大学硕士学位论文
腺功能异常的发病率，探讨孕母患自身免疫性甲状腺疾病对婴儿甲状腺功能的影
响因素。
研究对象
2001年7月1日至2003年6月30日在浙江省(除宁波市外)各县、市、
省级医院产科分娩的孕母患自身免疫性甲状腺疾病(符合纳入标准)的婴儿，且
无产时窒息史的足月儿作为研究对象。对照组:为同期在浙江省(除宁波市外)
各县、市、省级医院产科分娩的无甲状腺疾病孕母的婴儿。
纳入标准:对妊娠前或妊娠期间曾在省、市级医院检查有甲状腺功能减退且
伴有抗微粒体抗体或抗甲状腺过氧化物酶抗体、抗甲状腺球蛋白抗体增高者为慢
性淋巴细胞性甲状腺炎孕母;有甲状腺功能亢进且甲状腺B超或甲状腺ECT扫
描或甲状腺细针穿刺病理检查证实、并排除高功能腺瘤及多发性结节者为Graves
病孕母。
研究方法
对生后满3天的新生儿由各产科医院采足跟血，标本干燥后送浙江省新生儿
疾病筛查中心，用滤纸血斑时间分辨荧光法检测促甲状腺素(TSH)。对
TSH>9 mU/L者于结果报告后1一3天立即召回母亲及新生儿(健康孕母者只召回
新生儿)，对TSH正常者于分娩后28一35天召回医院。记录孕母所患的甲状腺
疾病种类、病程、妊娠期甲状腺功能状态、服药史、母亲妊娠年龄、胎龄及新生
儿出生体重，复查婴儿及母亲的甲状腺功能，并留母亲及婴儿的血清测定抗过氧
化物酶抗体(TPOAb)、抗甲状腺球蛋白抗体(TGAb)，促甲状腺激素受体抗体
(TRAb)、甲状腺素刺激抗体(TSAb)。用化学发光免疫法检测T3、几、TSH、
FT3、FT4、Tp0Ab，采用美国nPC公司的Immulite化学发光仪检测，用放射免
疫法测定TGAb(药合由北京原子能研究所提供)，采用EUSA法测定母亲及婴
儿体内的促甲状腺激素受体抗体(TRAb)、甲状腺素刺激抗体(TSAb)。TRAb
2004年浙江大学硕士学位论文
药盒为德国汉堡nLn oesel一sehan仙Diagnosti恤und medi‘nisehe Gerate mbH生
产，TSAb药盒为天津医科大学生物实验厂提供。对确诊先天性甲状腺功能低
下(TsH增高伴T4下降)的新生儿进行优甲乐治疗，对高TSH血症者(滤纸片
法TSH>9闪u/ml或血清TsH>4.4 mlu/L，而其它指标均正常)，每月一次复查甲
状腺功能直至TSH恢复正常。所有数据由SSPSS10.0软件处理，以p<0.05为有
显著差异。健康孕母的婴儿与自身免疫性甲状腺疾病孕母的婴儿，其甲状腺功
能异常的发病率比较采用两百分率比较的u检验。母婴体内的抗甲状腺抗体分析
采用双变量相关分析，两组之间的比较采用独立样本t检验，婴儿甲状腺功能异
常的危险因素分析，采用非条件多元loglstic回归分析。
结果
1.孕母患自身免疫性甲状腺疾病对婴儿甲状腺功能的影响78例自身免
疫性甲状腺疾病孕母的婴儿，确诊先天性原发性甲低7例，占9.0%(7/78)高
TSH血症33例，占42.3%(33/78)，甲状腺功能亢进1例，占1 .3%(1/78)，而
同期浙江省新生儿疾病筛查中心(除宁波市外)共筛查新生儿424665例，确诊
先天性原发性甲状腺功能低下305例，占0.7%。，暂时性TSH增高1 993例，占
4.7%0，甲亢O例，二者比较有显著差异(U甲低=28.996，尸<0.01，UTsH增高=53.628，
P<0 .01)o
2.母婴体内抗甲状腺自身抗体的关系对分娩后25~35天的母亲及婴儿
测定体内抗甲状腺自身抗体:TPOAb、TGAb、TRAb、TSAb，经双变量相关
分析，speannan相关系数分别为0.636、0.574、0.619、0.473，尸均(0.01。甲
状腺功能异常的婴儿，其体内TRAb、TPOAb分别为5.53士1.20(IU/L)、41.65
士2.89(Iu/L)明显高于甲状腺功能正常的婴儿夏4.12士1.41(Iu几)24.27士3.03
(Iu几)}，而ToAb、TSAb两组之间则无差异。
3.婴儿甲状腺功能异常的危险因素分析经单因素logistic回归分析，筛选
2004年浙江大学硕士学位论文
It was well documented that women in pregnancy were trend to suffer from autoimmune thyroid disease such as Graves or Hashimoto thyroiditis with a prevalence of 0.2% and has been shown to affect neonatal thyroid function as well as other outcomes such as spontaneous abortion, intrauterine growth retardation, still birth, premature labor and congenital malformation if they were not appropriately treated. Neonatal thyroid dysfunction without therapy will lead to mental and physical retardation, and some times even result in death.
In the last decade, neonates born to mothers with autoimmune thyroid disease were in succession to be found to have primary hypothyroidism, pituitary hypothyroidism, hyperthyroidism or hyperthyrotropinemia, and some were found to have high anti-TSH receptor antibody (TRAb). Previous researches about neonatal thyroid dysfunction were concerned in single factor, very little data were available from early infancy . their mothers and environment based studies on the risk factors for early infantile thyroid dysfunction. While factors such as the state of maternal thyroid function during pregnancy, maternal medical treatment or therapy program during pregnancy and the type of maternal thyroid disease will affect neonatal thyroid function and how widely will they contribute to?
Objective
In order to minimize complications and to improve maternal and neonatal outcomes, a cohort of 78 infants born to mothers with autoimmune thyroid disease was investigated to evaluate the impact of maternal thyroid dysfunction during pregnancy and postpartum on infant thyroid function and to identify the possible maternal, neonatal and /or environmental risk factors for causing early infantile thyroid dysfunction by Provincial Neonatal Disease Screening Network which covers nearly thirty seven thousand neonates a year in south east part of China Patients:
All the newborns delivered to mothers with autoimmune thyroid disease as defined by criteria from Zhejiang Province (except for Ningbo city) during July 1st of 2001 to June 30th of 2003 were investigated. Seventy eight term, non-asphyxiated neonates met the criteria were recruited into the study. Neonates born to healthy mothers at the same period were set as controls according to Provincial Neonatal Disease Screening Network.
The criteria for the diagnosis of Graves' disease or Hashimoto thyroiditis was as follows:
Graves disease in the mothers had been diagnosed by clinical and laboratory evidence of hyperthyroidism, increased TPOAb and TPOAb level and a diffuse goiter, excluding other common causes of thyrotoxicosis such as toxic multinodular goiter or toxic adenoma by thyroid ultrasonography or ECT scan or fine-needle biopsy of thyroid tissue.
Hashimoto thyroiditis was diagnosed by the presence of increased TPO-Ab and TGAb level, clinical and laboratory evidence of hypothyroidism at the time of
diagnosis, and decreased echogenicity of the thyroid gland. Some cases with lymphocytic infiltration were confirmed by a fine-needle biopsy of thyroid tissue. Methods:
Heel capillary blood was collected on 3-day newborn by obstetrician of local hospital. Samples of blood dried on filter paper were sent to Provincial Neonatal Disease Screening Center to be detected on TSH by Time difference fluorescent analysis (1420 type II, Wallac company, Finland). The neonate was called back immediately if his or her TSH was over 9 mU/L, and the others were called back at 28 to 35 days after birth. The data of mothers and newborns' status were recorded in detail including the type of maternal thyroid disease (Graves disease or Hashimoto thyroiditis), the maternal thyroid function during the pregnancy (three groups were divided: Group A: hyperthyroidism, Group B: hypothyroidism, Group C: euthyroidism based on the level of FT3 FT4 and TSH during pregnancy), the history of medication, the maternal age of pregnancy, the gestational age of baby and neonatal birth weight . The serum concentrations of T3, T4, TSH, FT3, FT4, TPOAb were m
引文
1. Polak M. Hyperthyroidism in early infancy: pathogenesis, clinical features and diagnosis with a focus on neonatal hyperthyroidism. Thyroid, 1998,(8): 1174-1177
2. Lieutaud H. Pregnancy and the thyroid gland. Ann Med Interne. 1999, 150(5): 397-407
3. Corssmit EP, Wiersinga WM, Boer K, et al. Pregnancy(conception) in hyper-hypothyroidism. Ned Tijdschr Geneeska,.2001,145(15):727-731.
4. Phoojaroenchanachai M, Sriussadaporn S, Peerapatdit T, et al. Effect of maternal hyperthyroidism during late pregnancy on the risk of neonatal low birth weight. Clin Endocrinol (Oxf). 2001,54(3):365-370.
5. Blazer S, Moreh-Waterman Y, Miller-Lotan R, Maternal hypothyroidism may affect fetal growth and neonatal thyroid function. Obstet Gynecol. 2003,102(2):232-241.
6. Cedergren MI, Selbing AJ, Kallen BA. Risk factors for cardiovascular malformation-a study based on prospectively collected data. Scand J Work Environ Health. 2002,28(1): 12-17.
7. Barwell J, Fox GF, Round J, et al. Choanal atresia: the result of maternal thyrotoxicosis or fetal carbimazole? Am J Med Genet. 2002,111(1):55-56;
8. Smit BJ, Kok JH, Vulsma T, Neurologic development of the newborn and young child in relation to maternal thyroid function. Acta Paediatr. 2000,89(3):291-295.
9. Nicaise C, Gire C, Bremond V, Neonatal hyperthyroidism in a premature infant born to a mother with Grave's disease Arch Pediatr. 2000,7(5):505-508.
10. Pacaud D, Huot C, Gattereau A, et al. Outcome in three siblings with
antibody-mediated transient congenital hypothyroidism. J Pediatr. 1995,127(2): 275-7.
11. Wada K, Kazukawa I, Someya T, et al. Maternal hypothyroidism in autoimmune thyroiditis and the prognosis of infants. Endocr J. 2000, 47 Suppl: S 133-5.
12. Dussault JH, Fisher DA. Thyroid function in mothers of hypothyroid newborns. Obstet Gynecol. 1999;93(1): 15-20.
13. Brown RS, Bellisario RL, Botero D, et al. Incidence of transient congenital hypothyroidism due to maternal thyrotropin receptor-blocking antibodies in over one million babies. J Clin Endocrinol Metab. 1996, 81(3): 1147-51.
14. Peleg D, Cada S, Peleg A, et al. The relationship between maternal serum thyroid-stimulating immunoglobulin and fetal and neonatal thyrotoxicosis. Obstet Gynecol. 2002,99(6): 1040-1043.
15. LaFranchi S. Congenital hypothyroidism: etiologies, diagnosis, and management. Thyroid. 1999,9(7): 735-40.
16. Rink T, Wieg C, Schroth HJ, et al. Hyperthyroidism in a premature infant due to transplacental passage of maternal thyrotropin receptor antibodies Nuklearmedizin. 1999,38(5): 156-159.
17. Radetti G, Persani L, Moroder W, et al. Transplacental passage of anti-thyroid auto-antibodies in a pregnant woman with auto-immune thyoid disease. Prenat Diagn, 1999, 19(5):468-471.
18．钟一村，赵爱民，林其德．妊娠合并甲状腺功能亢进22例临床分析．上海医学2002，25(2)：105～107．
19．张斌，苏绮枫．妊娠合并甲状腺疾病的围产期结局．中国优生与遗传杂志2001，9(2)：60．
20．徐明娟，沙金燕，孔令山妊娠合并甲状腺功能亢进症40例的诊断和处理 第二军医大学学报 2001，22(1)80-82．
21．谭建平，张建平，王凌云 甲状腺功能亢进合并妊娠68例临床分析 实用医学杂志 2000 16(3)130-131．
22．李爱萍，徐玉霞，李敬等 孕妇患甲状腺功能亢进对其新生儿甲状腺功能的影响．大连医科大学学报．2002，24(2)：110～112．
23. Radetti G, Zavallone L, Gentili L, et al. Foetal and neonatal thyoid disorders. Minerva Pediatr, 2002,54(5):383-400.
24. Heithorn R, Hauffa BP, Reinwein D. Thyroid antibodies in children of mothers auto-immune thyroid disease. Eur J Pediatr, 1999,158(1) : 24-28.
25. Kohn LD, Suzuki K, Hoffman WH, et al. Characterization of monoclonal thyoid-stimulating and thyrotropin binding-inhibiting autoantibodies from a Hashimoto's patient whose children had intrauterine and neonatal thyroid disease. J Clin Endocrinol Metab,1997, 82(12):3998-4009.
26. Zimmerman D. Fetal and neonatal hyperthyroidism. Thyroid. 1999,9(7):727-33.
27．林艳丽，立彦，王自正．RRA法测定TSH受体抗体的临床应用价值．放射免疫杂志，2000，13(6)：377-379．
28. Pasquier S, Torresani T, Werder E, et al. Transitory neonatal hypothyroidism caused by transplacental transfer of anti-receptor antibodies of hypophyseal thyroid simulation. Case report and estimated incidence. Schweiz Med Wochenschr. 1997,127(44): 1824-8
29. Matsuura N, Harada S, Ohyama Y, et al. The mechanisms of transient hypothyroxinemia in infants born to mothers with Graves' disease. Pediatr Res. 1997,42(2): 214-8.
30. Higuchi K, Kumagai T, Kobayashi M, et al. Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease. Pediatrics, 2001, 107(4): E57.
31．乔文颖，朱本章．国外医学内分泌学分册2002，22(3)：90-93．
32. Mestman JH. Hyperthyroidism in pregnancy. Endocronol Metab Clin North Am.1998,27(1): 127-149.
2. Lieutaud H. Pregnancy and the thyroid gland. Ann Med Interne. 1999, 150(5): 397-407
3. Corssmit EP, Wiersinga WM, Boer K, et al. Pregnancy(conception) in hyper-hypothyroidism. Ned Tijdschr Geneeska,.2001,145(15):727-731.
4. Phoojaroenchanachai M, Sriussadaporn S, Peerapatdit T, et al. Effect of maternal hyperthyroidism during late pregnancy on the risk of neonatal low birth weight. Clin Endocrinol (Oxf). 2001,54(3):365-370.
5. Blazer S, Moreh-Waterman Y, Miller-Lotan R, Maternal hypothyroidism may affect fetal growth and neonatal thyroid function. Obstet Gynecol. 2003,102(2):232-241.
6. Cedergren MI, Selbing AJ, Kallen BA. Risk factors for cardiovascular malformation-a study based on prospectively collected data. Scand J Work Environ Health. 2002,28(1): 12-17.
7. Barwell J, Fox GF, Round J, et al. Choanal atresia: the result of maternal thyrotoxicosis or fetal carbimazole? Am J Med Genet. 2002,111(1):55-56;
8. Smit BJ, Kok JH, Vulsma T, Neurologic development of the newborn and young child in relation to maternal thyroid function. Acta Paediatr. 2000,89(3):291-295.
9. Nicaise C, Gire C, Bremond V, Neonatal hyperthyroidism in a premature infant born to a mother with Grave's disease Arch Pediatr. 2000,7(5):505-508.
10. Pacaud D, Huot C, Gattereau A, et al. Outcome in three siblings with
antibody-mediated transient congenital hypothyroidism. J Pediatr. 1995,127(2): 275-7.
11. Wada K, Kazukawa I, Someya T, et al. Maternal hypothyroidism in autoimmune thyroiditis and the prognosis of infants. Endocr J. 2000, 47 Suppl: S 133-5.
12. Dussault JH, Fisher DA. Thyroid function in mothers of hypothyroid newborns. Obstet Gynecol. 1999;93(1): 15-20.
13. Brown RS, Bellisario RL, Botero D, et al. Incidence of transient congenital hypothyroidism due to maternal thyrotropin receptor-blocking antibodies in over one million babies. J Clin Endocrinol Metab. 1996, 81(3): 1147-51.
14. Peleg D, Cada S, Peleg A, et al. The relationship between maternal serum thyroid-stimulating immunoglobulin and fetal and neonatal thyrotoxicosis. Obstet Gynecol. 2002,99(6): 1040-1043.
15. LaFranchi S. Congenital hypothyroidism: etiologies, diagnosis, and management. Thyroid. 1999,9(7): 735-40.
16. Rink T, Wieg C, Schroth HJ, et al. Hyperthyroidism in a premature infant due to transplacental passage of maternal thyrotropin receptor antibodies Nuklearmedizin. 1999,38(5): 156-159.
17. Radetti G, Persani L, Moroder W, et al. Transplacental passage of anti-thyroid auto-antibodies in a pregnant woman with auto-immune thyoid disease. Prenat Diagn, 1999, 19(5):468-471.
18．钟一村，赵爱民，林其德．妊娠合并甲状腺功能亢进22例临床分析．上海医学2002，25(2)：105～107．
19．张斌，苏绮枫．妊娠合并甲状腺疾病的围产期结局．中国优生与遗传杂志2001，9(2)：60．
20．徐明娟，沙金燕，孔令山妊娠合并甲状腺功能亢进症40例的诊断和处理 第二军医大学学报 2001，22(1)80-82．
21．谭建平，张建平，王凌云 甲状腺功能亢进合并妊娠68例临床分析 实用医学杂志 2000 16(3)130-131．
22．李爱萍，徐玉霞，李敬等 孕妇患甲状腺功能亢进对其新生儿甲状腺功能的影响．大连医科大学学报．2002，24(2)：110～112．
23. Radetti G, Zavallone L, Gentili L, et al. Foetal and neonatal thyoid disorders. Minerva Pediatr, 2002,54(5):383-400.
24. Heithorn R, Hauffa BP, Reinwein D. Thyroid antibodies in children of mothers auto-immune thyroid disease. Eur J Pediatr, 1999,158(1) : 24-28.
25. Kohn LD, Suzuki K, Hoffman WH, et al. Characterization of monoclonal thyoid-stimulating and thyrotropin binding-inhibiting autoantibodies from a Hashimoto's patient whose children had intrauterine and neonatal thyroid disease. J Clin Endocrinol Metab,1997, 82(12):3998-4009.
26. Zimmerman D. Fetal and neonatal hyperthyroidism. Thyroid. 1999,9(7):727-33.
27．林艳丽，立彦，王自正．RRA法测定TSH受体抗体的临床应用价值．放射免疫杂志，2000，13(6)：377-379．
28. Pasquier S, Torresani T, Werder E, et al. Transitory neonatal hypothyroidism caused by transplacental transfer of anti-receptor antibodies of hypophyseal thyroid simulation. Case report and estimated incidence. Schweiz Med Wochenschr. 1997,127(44): 1824-8
29. Matsuura N, Harada S, Ohyama Y, et al. The mechanisms of transient hypothyroxinemia in infants born to mothers with Graves' disease. Pediatr Res. 1997,42(2): 214-8.
30. Higuchi K, Kumagai T, Kobayashi M, et al. Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease. Pediatrics, 2001, 107(4): E57.
31．乔文颖，朱本章．国外医学内分泌学分册2002，22(3)：90-93．
32. Mestman JH. Hyperthyroidism in pregnancy. Endocronol Metab Clin North Am.1998,27(1): 127-149.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |