宁夏2007—2010年新生儿先天性甲状腺功能减低症和苯丙酮尿症筛查情况分析

目的分析宁夏新生儿先天性甲状腺功能减低症(CH)和苯丙酮尿症(PKU)的筛查和治疗情况。方法 2007年8月至2010年12月宁夏新生儿疾病筛查中心对新生儿采用时间分辨荧光免疫法测定促甲状腺素浓度,采用荧光免疫法测定苯丙氨酸浓度。回顾性分析CH和PKU检出率和治疗情况。结果 2007—2010年共筛查新生儿70491名,每年筛查的新生儿数分别为2154、9496、10841、47680名。共确诊CH17例,治疗13例,患病率0.24‰,治疗率76.5%;确诊PKU23例,治疗20例,患病率0.33‰,治疗率87.0%。结论宁夏新生儿疾病筛查工作近几年发展较快,筛查人数逐年增加,新生儿疾病筛查可使患儿得到早期诊治。     

南京地区1998-2009年新生儿先天性甲状腺功能减低症筛查及治疗随访结果分析

目的 总结并分析1998年1月- 2009年12月南京地区新生儿先天性甲状腺功能减低症(CH)的筛查结果.方法 采集出生72 h新生儿442 454例的足跟血滴于滤纸上,采用时间分辨免疫法测定滤纸血斑促甲状腺激素(TSH),阳性者召回进一步测定静脉血TSH、三碘甲状腺原氨酸(T3)、四碘甲状腺原氨酸(T4)、游离T3(FT3)、游离T4(FT4)以明确诊断.确诊者立即开始予左旋甲状腺素片(4.3～12.0μg·kg-1·d-1)替代治疗,定期监测其甲状腺功能,测量其身高、体质量,其中68例患儿子智力测试,以评估疗效.结果 12 a共筛查442 454人,确诊CH 183例,发病率为0.41‰,对117例进行随访.初始治疗时间的中位数为18 d(7～67d),初始左旋甲状腺素的平均剂量为7.35 μg·kg-1·d-1.CH患儿的身高、体质量结果基本达到正常参照标准.盖泽尔婴幼儿发展量表(GESELL)测试结果显示1例智能发育落后,8例智能发育迟缓.T4、FT4的治疗前水平与患儿的GESELL测试总分、适应性及精细运动均呈正相关(Pa＜0.05).结论 经筛查确诊的CH患儿,应尽可能早地进行激素替代治疗,可有效改善其预后.因此新生儿筛查及随访治疗工作值得推广和完善.     

湖南省9万例新生儿先天性甲状腺功能减低症筛查

目的　先天性甲状腺功能减低症 (CH)是一种严重危害儿童健康、但早期诊治可以有效防治的疾病 ,1 996年以来 ,该院开展了新生儿CH筛查工作 ,现总结 7年来筛查结果 ,以了解湖南省新生儿CH的发生情况。方法　对 91 375例新生儿在生后 72h后或母乳喂养 2 4h后采足跟血 ,采用时间分辨荧光免疫法测定足跟血TSH浓度进行初筛 ,并用化学发光法检测初筛阳性患儿血清中TSH、FT3、FT4以确诊。确诊为CH者立即给予口服甲状腺素片治疗并定期随访。结果　TSH初筛 2 80例阳性 ,初筛阳性率为 1 /32 9,确诊先天性甲低 5 6例 ,发病率为1 /1 6 32。经治疗的患儿智能体格发育均正常。结论　新生儿筛查是早期发现、及时诊断和治疗CH的重要措施 ,能有效地改变患儿的预后     

内分泌系统疾病

020569湖南省斯生儿先天性甲状腺功能减低症和苯丙酮尿症的筛查分析/黄定梅…//中国现代医学杂志.一2001,11(8)一44一45 目的:了解湖南省新生儿先夭性甲状腺功能减低症(CH)和苯丙酮尿症(PKU)的发病情况,早期诊断和治疗。方法:采用时间分辨荧光免疫法(DELFIA)测定促甲状腺素(TSH)浓度,使用盖塞利细菌抑制法或荧光法测定血苯丙氨酸(Phe)浓度。对TSH)20拼u/L或Phe)0.26mmol/以Zm以dl)者,进行确诊检查,确诊后给予治疗并随访。结果:湖南省部分地区46 323例新生儿,确诊为CH28例(包括3例TSH延期上升型CH),PKU患儿1例。经治疗随访患者…     

联合检测促甲状腺素及游离甲状腺素筛查新生儿先天性甲状腺功能减低症

目的初步探讨联合检测干血滤纸片中促甲状腺素(TSH)及游离甲状腺素(FT4)水平筛查新生儿先天性甲状腺功能减低症(CH)的临床意义。方法对2013年6月至2013年12月出生的活产新生儿,采用时间分辨荧光免疫分析法联合检测干血滤纸片中TSH及FT4水平;对筛查阳性者再采血检测血清TSH及FT4水平,并与干血滤纸片法结果进行比较。结果共筛查新生儿31 199例,确诊CH 12例,发生率1/2 600,高TSH血症4例,未检测到垂体性甲状腺功能减低症。筛查确诊CH新生儿的血清TSH及FT4的检测结果与干血滤纸片检测结果一致,差异无统计学意义(P0.05)。结论联合检测干血滤纸片中TSH及FT4水平可用于新生儿CH筛查,并有助于早期诊断与治疗,以及对中枢性CH的筛查。     

中山市先天性甲状腺功能减低症筛查及治疗效果分析

目的总结先天性甲状腺功能减低症(CH)筛查状况,并分析替代治疗疗效。方法采用时间分辨荧光免疫法测定新生儿滤纸干血片标本的促甲状腺激素(TSH)水平,阳性者召回并采用化学发光法检测静脉血TSH、游离甲状腺素以确诊。选取经确诊CH并规范治疗2年的永久性CH患儿54例(CH组)及正常健康儿童120例(对照组),两组均长期监测体格发育,并于6月龄、24月龄时采用Gesell婴幼儿发育量表及儿童气质量表分别评估神经运动发育水平及气质特征。结果共筛查新生儿285242例,确诊140例,CH发病率1/2037。CH组及对照组的年龄别身高Z评分(LAZ)及年龄别体质量Z评分(WAZ)差异无统计学意义(P均0.05);6月龄、24月龄时CH组Gesell总发育商与对照组差异无统计学意义(P均0.05),但大运动发育商均落后于对照组,差异有统计学意义(P均0.05);6月龄、24月龄时,CH组和对照组气质类型的分布差异有统计学意义(P均0.05);相比对照组,CH组中难养型及中间偏难养型的比例较高。CH组与对照组在活动水平、适应性、反应强度及坚持性四个维度的得分差异有统计学意义(P均0.05)。结论 CH患儿经早期替代治疗后体格生长及神经运动发育基本正常,但尚需关注其心理行为问题。     

广州市18年新生儿先天性甲低苯丙酮尿症和葡萄糖-6-磷酸脱氢酶缺乏症筛查

目的 探讨广州市新生儿先天性甲低、苯丙酮尿症和葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症筛查方法及其对遗传代谢缺陷病的控制作用.方法 收集广州市新生儿出生3 d时的足跟血滤纸干血斑标本,检测促甲状腺素(TSH)筛查先天性甲状腺功能减低症(CH);检测苯丙氨酸(Phe)检出持续性高苯丙氨酸血症(PHPA),筛查苯丙酮尿症(PKU)和四氢生物蝶呤缺乏症(BH4D);检测红细胞G6PD活性筛查G6PD缺乏症.凡筛查阳性者按疾病诊疗常规进行确诊和治疗,将检出的CH和PHPA作为筛查干预组.将未经过新生儿筛查出现症状才就诊、临床诊断CH和PKU的患儿做为对照组.结果 1989年4月至2007年6月共筛查新生儿945 372名,检出CH 331例,PHPA 29例,G6PD缺乏症39 700例.结果 显示CH发病率为1∶2 856, PHPA为1∶32 599,G6PD缺乏症达1∶23.81.总发病率为4.24%.CH和PHPA共360例,治疗随访357例,治疗率99.2%.PHPA全部免费治疗.平均开始治疗日龄20 d,4～6岁时IQ或0～3岁DQ测定智能正常(IQ或DQ≥90)者320例(89.6%),低于正常(70≤IQ或DQ<90)者36例(10.1%), 智能残疾 (IQ或DQ<70)者1例(0.3%).对照组开始治疗年龄平均3岁,智能残疾26例,筛查组的智能发育明显好于对照组.结论 新生儿代谢病筛查是遗传代谢缺陷病的一种早期诊断和早期防治方法,对检出的CH、PKU进行早期有效治疗,可保持脑和智能发育正常,预防智能性残疾.     

北京市20年新生儿疾病筛查回顾性分析

目的 分析北京市1989-2009年新生儿先天性甲状腺功能减退症(CH)和苯丙酮尿症(PKU)的筛查结果,为进一步提高新生儿疾病筛查的管理水平及干预措施提供依据.方法 采集出生72 h后、正常哺乳的新生儿足跟血于特定滤纸上,进行CH及PKU筛查.PKU筛查检测指标为血苯丙氨酸(Phe)浓度,分别采用细菌抑制法(1989-2003年)和荧光法(2004-2009年);CH筛查检测指标为血促甲状腺激素(TSH)水平,分别采用放免法(1989-2003年)及时间分辨荧光免疫分析法(DELFIA)(2003-2009年).结果 1989-2009年,北京市共筛查新生儿1745 998名,筛查率由1989年的14.01%提高到2009年98.16%,可疑患儿复诊率由1991年的65.85%提高到2009年的92.18%,共确诊CH 482例,发病率1:3622;PKU 192例,发病率1:9094.结论 新生儿疾病筛查是包括管理、筛查、随访、诊治、评估、教育等多个环节的系统服务工程,各部门的协调配合是提高筛查管理质量的有效措施,完善的新生儿疾病筛查工作可有效降低残疾儿的发生.     

深圳地区先天性甲状腺功能减退症的治疗及远期随访

目的 探讨先天性甲状腺功能减退症(CH)患儿早期治疗效果和对生长发育的影响.方法 对2005年9月-2006年12月深圳市出生的新生儿进行足底血片促甲状腺激素(TSH)筛查,筛查阳性儿童召回,行血清促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)检测.确诊CH 68例.平均27.1 d开始治疗,口服左旋甲状腺素钠片.定期检测患儿TSH、FT3、FT4,并根据临床表现调整药物剂量使FT4维持在正常高值水平.监测患儿体格发育如头围、身高和体质量.采用贝利婴幼儿发育量表方法进行智力发育评价.采用SPSS 12.0软件进行数据分析.结果 确诊患儿治疗1个月后临床症状完全消失,TSH、FT4维持正常水平.身高、体质量、头围等体格发育指标均在正常范围,均值50%,贝利婴幼儿发育量表测试中运动发育指数测定均在冲等水平,智力发育指数测定均基本达到同龄健康儿童.结论 早期诊治CH能明显改善预后,降低脑损害、智力低下的发生率.新生儿筛查是早期诊断CH的有效方法.     

2008-2012年陕西省新生儿疾病筛查中心筛查结果分析

目的 分析陕西省新生儿疾病筛查中心筛查结果,探讨当地苯丙酮尿症（PKU）及先天性甲状腺功能减低症（CH）的发病情况.方法 2008-2012年陕西省新生儿疾病筛查中心对新生儿采用荧光分析法检测滤纸干血斑中苯丙氨酸（Phe）浓度;采用时间分辨免疫荧光分析法（Tr-FIA）检测滤纸干血斑中促甲状腺激素（TSH）的浓度.回顾分析PKU及CH检出情况、发病率及治疗随访情况.结果 2008-2012年共筛查新生儿213 392名,每年筛查的新生儿数分别为34 656、47 670、47 485、45 443、38 138名.初筛阳性可疑PKU 1003例,CH 2179例;召回复查,5年间PKU复查率由79.0％上升至96.1％;CH由91.5％上升至99.4％.经筛查共确诊PKU 29例,发病率1∶7358;确诊CH 80例,发病率1∶2667.结论 通过新生儿疾病筛查可以做到早诊断、早治疗,避免因PKU、CH导致终生残疾,有利于提高出生人口质量.     

早期治疗对先天性甲状腺功能减低症患儿智力及体格发育的影响

目的：比较治疗开始时间不同的先天性甲状腺功能减低症（congenital hypothyroidism, CH）患儿治疗后智力发育、体格发育水平的不同,以寻求改善患儿预后的最佳治疗时间。方法：对2008年9月至2011年9月经新生儿疾病筛查确诊为CH,并在出生后3个月内开始应用甲状腺激素治疗的CH患儿49名,按开始治疗时间分为两组：生后1个月内治疗组（n=26）及1～3个月治疗组（n=23）。分别于6个月、1岁、2岁时,检测两组患儿体格发育情况,应用Gessell 发育量表评估智力发育商（DQ）及采用免疫荧光法测定甲状腺功能。结果：两组经甲状腺激素长期治疗,6个月、1岁、2岁时游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）及促甲状腺素（TSH）水平差异无统计学意义（P>0.05）,但1个月内治疗组患儿的身长、体重均明显高于1～3个月治疗组,差异有统计学意义（P0.05）。结论：CH开始治疗时间影响患儿智力发育和体格发育;生后1个月内开始治疗者,智力及体格发育优于1～3个月开始治疗者。     

云南省部分地区先天性甲状腺功能减低症治疗效果分析

目的观察不同初始治疗剂量和治疗时机对先天性甲状腺功能减低症(CH)的疗效影响。方法以云南省4个地区新生儿筛查提示TSH异常、最终确诊并治疗随访的98例CH患儿为研究对象,予左旋甲状腺素钠治疗,按初始治疗剂量分为标准剂量组(每日10~15μg/kg)和小剂量组(每日10μg/kg),按照治疗起始时间又分为2月龄内治疗组和2月龄后治疗组。监测治疗前及治疗后多时点的甲状腺功能以及体格和神经发育情况。结果治疗后2周,标准剂量组的TSH低于小剂量组,FT4高于小剂量组,差异有统计学意义(P0.05),治疗后其他时间点的TSH、FT4差异均无统计学意义(P0.05);两组在治疗前以及治疗后各个时间点体格和神经发育的差异无统计学意义(P0.05)。不同治疗时机组,治疗后各个不同时间点的TSH和FT4及体格发育的差异均无统计学意义(P0.05);2月龄内开始治疗的患儿在6月龄时适应性行为、大运动、精细动作能区评分,12月龄时大运动能区评分,18月龄时精细动作能区评分,以及24月龄时语言能区评分均较高,差异具有统计学意义(P0.05)。结论标准剂量组疗效优于小剂量组,但需注意治疗后甲亢表现;治疗时机对CH患儿神经发育影响大,一经确诊,应尽早开始治疗。     

Thyroid function in children with Down's syndrome]

The aim of the present study was to evaluate thyroid function in 45 Down's syndrome patients in order to verify the hypothesis of an increased risk of thyroid disorders associated with trisomy 21. A patient with subclinical hypothyroidism (TSH 16.6 microU/ml; T4 6.4 micrograms/dl) was diagnosed in a group of 28 subjects with Down's syndrome studied at a mean age of 6 years and 5 months using T3, T4, FT3, FT4, TSH assays and clinical examination. T4 and TSH values were also measured in 10 of these children at the neonatal screening. One infant presented transient neonatal hyperthyrotropinemia but later became euthyroid. The analysis of thyroid hormone values at the neonatal screening of other 17 subjects with Down's syndrome did not reveal other cases with thyroid function disorders. The results of this study highlight that altered thyroid functions are evident in children with trisomy 21 associated with heart anomalies. A careful clinico-endocrinological follow-up of patients with Down's syndrome is recommended in order to ensure an early diagnosis of thyroid function disorders and/or autoimmune diseases which might complicate the evolution of trisomy and negatively affect outcome.     

Elevated serum creatinine levels in infants with congenital hypothyroidism: reflection of decreased renal function?

The effects of hypothyroid status on renal function have been poorly studied in children. We assessed the renal function of hypothyroid infants detected during neonatal mass screening for congenital hypothyroidism (CH). Eighty hypothyroid infants and 20 age-matched normal infants for controls were enrolled. The 80 patients, aged 1 mo, were divided into two groups based on the initial thyroid stimulating hormone (TSH) and free thyroxine (FT4) values: a mild-moderately hypothyroid (MHT) group (n = 64, 31M and 33F) and a severely hypothyroid (SHT) group (n     

Newborn screening for congenital hypothyroidism

Most neonates born with congenital hypothyroidism (CH) have normal appearance and no detectable physical signs. Hypothyroidism in the newborn period is almost always overlooked and delayed diagnosis leads to the most severe outcome of CH, mental retardation, emphasizing the importance of neonatal screening. Blood spot T4 or TSH or both can be used in neonatal screening for CH. The latter, which is more sensitive, is not cost effective, so the first two are used in different programs in the world. TSH screening was shown to be more specific in the diagnosis of CH; T4 screening is more sensitive in detecting newborns especially with rare hypothalamic-pituitary hypothyroidism, but less specific with a high frequency of false positives mainly in low birth weight and premature infants. The time at which the sample is taken may vary between centers, with the majority taking blood from a heel prick after 24 hours of age to minimize the false positive high TSH due to the physiological neonatal TSH surge that elevates TSH levels and causes dynamic T4 and T3 changes in the first 1 or 2 days after birth. Early discharge of mothers postpartum has increased the ratio of false positive TSH elevations. Although transient hypothyroidism may occur frequently, all suspected infants should be treated as having CH for the first 3 years of life, taking into account the risks of mental retardation. A reevaluation after 3 years is needed in such patients. The goal of initial therapy in CH is to minimize neonatal central nervous system exposure to hypothyroidism by normalizing thyroid function, as reflected by T4 and TSH levels, as rapidly as possible. Iodine deficiency is the most important cause of CH worldwide. Iodine is essential for thyroid hormone synthesis and is present in soil, water and air. Prevention of iodine deficiency can be by iodized salt, iodized oil, iodized bread or iodine tablets.     

Three-year follow-up of borderline congenital hypothyroidism

The purpose of this study was to determine whether children with borderline hypothyroidism in the neonatal period had persistent hypothyroidism after 3 years of levothyroxine replacement therapy. Fourteen term infants with slightly abnormal newborn screening results (thyroxine <10th percentile, thyroid stimulating hormone ?TSH <40 microU/mL) were identified. The subsequent serum confirmatory TSH results of 12 subjects were modestly elevated (5.3 to 18.8 microU/mL, normal 0.6 to 4.6), whereas 2 subjects who had borderline confirmatory TSH (4.6 and 4.7 microU/mL) had abnormal TSH responses to thyrotropin releasing hormone testing. After 3 years of therapy, levothyroxine was discontinued in 13 patients, and repeat thyroid function tests were obtained 1 month later. Levothyroxine was not discontinued in one patient because he had an elevated random TSH (10 microU/mL) while receiving therapy. At 3 years of age, 13 patients had persistently abnormal thyroid function tests (TSH >4.6 microU/mL or a thyroid releasing hormone test result consistent with primary hypothyroidism), and levothyroxine was reinitiated. Only one patient had normal thyroid function studies. Although prospective studies are still lacking, we recommend levothyroxine replacement in newborns with borderline hypothyroidism.     

Alterations of neonatal thyroid function

Grüters A, Krude H, Biebermann H, Liesenkötter KP, Schöneberg T, Gudermann T. Alterations of neonatal thyroid function. Acta Pædiatr 1999; Suppl 428: 17–22. Stockholm. ISSN 0803–5326
Recent progress has been made in understanding the pathogenesis of neonatal thyroid disorders. Autosomal recessive inheritance of mutations of the thyroid peroxidase and thyroglobulin genes has been described in some patients with congenital hypothyroidism (CH) and a family history of CH. Autosomal recessive inheritance of mutations of the thyrotrophin (TSH) receptor gene has also been reported in patients with CH and thyroid hypoplasia, and autosomal dominant mutations of the PAX8 gene have been described in patients with different forms of thyroid dysgenesis. These discoveries are important for patients with CH diagnosed by neonatal screening, as these patients will have normal fertility. The molecular genetic analysis of mutations of the TSH gene in patients with familial and sporadic cases of isolated central CH, who are missed by TSH screening programmes, now enables rapid diagnosis and appropriate therapy in the neonate. In newborn infants with severe non-autoimmune hyperthyroidism, autosomal dominant gain-of-function mutations in the TSH receptor gene have been demonstrated. In these patients, molecular genetic studies are extremely helpful in therapeutic decision making, as early thyroid ablation is the only effective treatment that avoids the sequelae of long-term hyperthyroidism. Molecular genetic studies are therefore useful in the diagnostic work-up of neonatal thyroid alterations. □ Congenital hypothyroidism, molecular pathogenesis, neonatal hyperthyroidism     

Alterations of neonatal thyroid function

Recent progress has been made in understanding the pathogenesis of neonatal thyroid disorders. Autosomal recessive inheritance of mutations of the thyroid peroxidase and thyroglobulin genes has been described in some patients with congenital hypothyroidism (CH) and a family history of CH. Autosomal recessive inheritance of mutations of the thyrotrophin (TSH) receptor gene has also been reported in patients with CH and thyroid hypoplasia, and autosomal dominant mutations of the PAX8 gene have been described in patients with different forms of thyroid dysgenesis. These discoveries are important for patients with CH diagnosed by neonatal screening, as these patients will have normal fertility. The molecular genetic analysis of mutations of the TSH gene in patients with familial and sporadic cases of isolated central CH, who are missed by TSH screening programmes, now enables rapid diagnosis and appropriate therapy in the neonate. In newborn infants with severe non-autoimmune hyperthyroidism, autosomal dominant gain-of-function mutations in the TSH receptor gene have been demonstrated. In these patients, molecular genetic studies are extremely helpful in therapeutic decision making, as early thyroid ablation is the only effective treatment that avoids the sequelae of long-term hyperthyroidism. Molecular genetic studies are therefore useful in the diagnostic work-up of neonatal thyroid alterations.     

Cord blood thyroxine and thyroid stimulating hormone screening for congenital hypothyroidism: how useful are they?

AIM: To determine and compare the usefulness of cord blood screening for free thyroxine (FT4) and thyroid stimulating hormone (TSH). BACKGROUND: There is a vast amount of literature on capillary heel prick screening tests, but relatively little on cord blood testing particularly FT4. For a decade all infants born at Tawam Hospital had cord blood FT4 and at Oasis Hospital cord TSH measured through the hospital-based screening programme. On January 1st 1998, the national screening programme (NSP) for congenital hypothyroidism (CH) in the United Arab Emirates (UAE) started using capillary TSH measurement (Delfia method). Since then newborns in both hospitals have been screened both ways, i.e. cord blood and capillary blood screening. METHODS: We reviewed retrospectively all infants born from January 1998 until the end of June 2004 with CH who had double screening: cord FT4 or TSH and 4th-5th day TSH screening. RESULTS: Thirteen infants (one in 1,778) had CH in Tawam Hospital. In six of these the cord blood FT4 was low (<9.1 pm/l) (0.73 ng/dl) and in seven the cord blood FT4 was normal, i.e., over half were missed. Eight infants (one in 1,198) had CH in the Oasis Hospital. Cord blood TSH was high in six of them (>13 IU/l) and two were normal. Cord FT4 detected the most severe cases, but missed most others. Cord TSH detected six out of eight cases, but there was a recall rate of one in 23. CONCLUSIONS AND RECOMMENDATIONS: Cord FT4 identifies only infants with severe CH. Cord TSH is more sensitive than cord FT4 screening. Capillary TSH dried blood spot testing on the 3rd-5th day is the most sensitive method.