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72h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1745998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CH482例,发病率1：3622;PKU192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。     

Povidone-iodine in umbilical cord care interferes with neonatal screening for hypothyroidism

Out of 1346 newborns screened for congenital hypothyroidism, 31 non-hypothyroid infants were summoned because of a thyroid stimulating hormone (TSH) level above 10 U/ml. False-positive TSH levels were significantly more frequent in the babies treated with povidone-iodine (4.6%) than in those treated with either alcohol or triple dye (0.7%).Conclusion Iodine containing solutions should be avoided in umbilical cord care of the newborn     

Screening for congenital hypothyroidism in Turkey

Abstract A pilot study was performed to determine the incidence of congenital hypothyroidism (CH) in Turkey and to build a model for nationwide screening. From December 1991 to December 1992, 30097 newborns were screened for CH using a primary measurement of thyroid stimulating hormone in capillary blood on days 3–5 of life. Samples were obtained in collaboration with the ongoing nationwide phenylketonuria screening programme. Eleven cases of primary CH were detected giving the incidence of 12736. Recall rate was 2.3%. Replacement therapy withl-thyroxine was started after the confirmation of diagnosis. The median age at the initiation of replacement therapy was 23 days (range 7–35 days).Conclusion The incidence of CH is notably higher in Turkey than reported in most other countries. Iodine deficiency and/or dyshormonogenesis might contribute to this high incidence. This result emphasizes the necessity of a nationwide screening programme.     

Screening for congenital hypothyroidism in France

Misdiagnosed cases of congenital-hypothyroidism (CH) during the first 9 years of the French screening program were analysed. A total of 50 cases were missed (3% of total diagnosed) which represents a severe failure of the system. Failures were caused by technical errors of sample collection or TSH assay (n=27) or due to normal TSH (n=22) or T₄ (n=1) concentrations in the newborn blood specimens. We conclude that screening methods should be improved and that physicians should remain alert to clinical signs of hypothyroidism.     

Treatment variables as predictors of intellectual outcome in children with congenital hypothyroidism

The purpose of this study was to assess how much of the variance in intellectual outcome at 2 and 6 years of age could be attributed to treatment variables in children with congenital hypothyroidism, and which of the parameters used for monitoring treatment predicted later development. Forty-five children, early treated according to general recommendations, were studied. Linear multiple regression analysis was used, controlling for socio-economic status and the pretreatment serum thyroxine concentration. At 2 years of age, 19% of the variance in Mental Development Index (Bayley Scales of Infant Development) was attributed to treatment variables: combinations of serum thyroxine and serum TSH during the 1st year and bone age at mean age 1.5 years (meanz-scores). At 6 years of age, 35% of the variance in Verbal IQ (Wechsler Preschool and Primary Scale of Intelligence) was attributed to treatment variables: 13% to the mean serum thyroxine concentration during the 1st year, 12% to the initiall-thyroxine dose per kilogram body weight per day, and 10% to a combined measure for serum thyroxine and serum TSH during the 2nd year (meanz-score).Conclusion Both the initiall-thyroxine dosage and treatment variables during the 1st and the 2nd year (serum thyroxine, serum TSH and bone age) predicted later intellectual outcome in children with congenital hypothyroidism.     

Hypothalamo-pituitary hypothyroidism detected by neonatal screening for congenital hypothyroidism using measurement of thyroid-stimulating hormone and thyroxine

The optimal strategy in neonatal screening for congenital hypothyroidism is still a subject of controversy. In Kanagawa Prefecture in Japan, simultaneous thyroid-stimulating hormone (TSH) and T4/fT4 determination has been used, while the results of our program may provide valuable information. Cumulative findings were analysed to determine the type and frequency of thyroid disorders in infants detected by simultaneous TSH and T4/fT4 determination, and the TSH and T4/fT4 screening strategy was validated. A total of 1284130 neonates were screened between October 1979 and September 1997 and infants followed because of low T4/fT4 without elevated TSH (T4 < 51.5 nmol/L or fT4 < 9 pmol/L and TSH < 15 mU/L) were retrospectively analysed. The first survey was carried out within 6 mo of birth and the second in 1998; 258 infants were diagnosed with congenital hypothyroidism at the first medical evaluation, 15 of them with hypothalamo-pituitary hypothyroidism. However, in the second survey, only 8 children were confirmed as having hypothalamo-pituitary hypothyroidism, therefore the incidence detected by the present strategy was 1/160516. Of 8 children with hypothalamo-pituitary hypothyroidism, mental retardation was prevented in 3 owing to early treatment. CONCLUSIONS: Simultaneous measurement of TSH and T4/fT4 is a useful strategy for detecting hypothalamo-pituitary hypothyroidism, but more studies are needed to show the cost-benefits of using this strategy.     

云南省部分地区新生儿先天性甲状腺功能减低症筛查结果分析

目的 总结并分析云南省部分州市先天性甲状腺功能减低症(CH)的筛查结果.方法 对2012 年7 月至2014 年4 月在云南省昭通市、曲靖市、丽江市和迪庆藏族自治州四地出生的活产婴儿236 218 例进行CH 筛查,其中男121 463 例,女114 755 例.初筛足跟血促甲状腺激素(TSH)≥ 8 μIU/L 者原血片重新复查,复查后仍为阳性者召回进一步测定静脉血TSH 和游离甲状腺素(FT4)以明确诊断.结果 236 218 名新生儿中,血片合格率为96.67%,不合格血片补采率为81.75%,初筛阳性召回率为73.02%.确诊CH 66 例,其中男性36 例,女性30 例(P>0.05).CH 发病率为1: 3 579,显著低于全国平均发病水平(1/2 034,P<0.01).患儿出生胎龄多为37~42 周,>42 周者只占3%;大部分患儿出生体重在正常范围;出生身长<50 cm 者占32%.结论 云南地区CH 发病率低于全国平均水平;CH 患儿临床特征无特异性;云南地区新生儿疾病筛查工作质量还需要进一步提高.     

Congenital hypothyroidism and neonatal withdrawal syndrome

We describe a neonate born of drug dependent parents. This observation documents the variability of expression in the neonatal abstinence syndrome and the interaction with an additional disease.     

Intellectual outcome, motor skills and BMI of children with congenital hypothyroidism: a population-based study

AIM: To evaluate intellectual outcome, motor skills and anthropometric data of children with congenital hypothyroidism (CH). METHODS: Children with permanent CH who were born in 1999 in Bavaria were eligible for this prospective, population-based study. Cognitive performance was evaluated by the Kaufman Assessment Battery for Children and motor skills were assessed by the motor test, Motoriktest für vier-bis sechsjahrige Kinder (MOT) 4-6. RESULTS: Eighteen of 21 eligible children participated (86%). Median age of the children was 5.5 years (range 4.9-5.8). Treatment with levothyroxine was started after a median of 7.2 days (range 4-15) with a median dose of 12.0 microg/kg (range 7.2-17.0). Mean intelligence quotient (IQ) of the children was 100.4 (standard deviation [SD] 10.1): no children had IQ values below the normal range. Reactivity and speed of movement were significantly reduced in children with CH. Children with an initial thyroid-stimulating hormone (TSH) value of >200 mU/L performed significantly worse than children with TSH value of 相似文献   

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。     

Neonatal screening for congenital hypothyroidism in the Federation of Bosnia and Herzegovina: eight years’ experience

This report demonstrates the prevalence of primary congenital hypothyroidism (CH) in the Federation of Bosnia and Herzegovina and summarizes the laboratory data. Neonatal thyroid-stimulating hormone (TSH) was measured in whole blood drawn between the 3rd and 5th days of life and spotted on filter paper using the fluorometric assay. Among the 87,061 neonates, 22 had CH, 13 dysgenetic forms, and nine with thyroids in situ. No differences were found between the two types in terms of TSH and total T4 concentrations. However, thyroglobulin was significantly lower in patients with dysgenetic thyroid tissue (p = 0.0023). We conclude that the prevalence of CH in the Federation of Bosnia and Herzegovina is 1:3,957 newborns.     

Neonatal screening for congenital hypothyroidism and phenylketonuria in China

Background  Neonatal screening is helpful to prevent serious disabitily and sufferings caused by congenital or inherited disease. This study was to review the status of neonatal screening for congenital hypothyroidism (CH) and phenylketonuria (PKU) in China. Methods  We analyzed data of neonatal screening for CH and PKU in the past two decades which were obtained from the national network of neonatal screening centers collected by the National Center for Clinical Laboratory. Results  Of 18.8 million newborns screened from 1985 to 2007, 9198 were identified with CH, giving a prevalence of 1/2047. In 19.0 million newborns screened in the same period, 1638 had PKU, with a prevalence of 1/11 572. An increasing number of neonates have been subjected to neonatal screening in China annually during this period. Data from Zhejiang Neonatal Screening Center showed that the recall rate of neonates suspected with CH and PKU was 95.52% in 2007. Confirmatory tests were performed and treatments were initiated in most of the neonates with CH and PKU within a month after birth. Conclusions  More governmental support at different levels is needed to make neonatal screening more efficient. The screening should be improved with a satisfactory control system including shorter time of report and a higher recall rate.     

Manifestations of congenital hypothyroidism during the 1st week of life

Congenital hypothyroidism (CHT) produces few and vague clinical signs during the first few weeks of life, when it is still possible to prevent irreparable brain damage. In the Finnish national screening programme for CHT, treatment is started at a median age of 6 days. According to multiple logistic regression analysis based on 102 cases, the main manifestations of CHT at this age are retardation of skeletal maturation and growth in lenght, icterus, large tongue, abdominal distension, skin mottling, muscle hypotonia and probably increased head size. The presence of other signs did not increase the probability of CHT. All signs are non-specific and some of the hypothyroid infants did not have any of them. Control of other confusing perinatal problems improved the diagnostic scoring but this did not increase the accuracy of prediction acceptably.Abbreviations T4 thyroxine - TSH thyroid stimulating hormone - CHT congenital hypothyroidism - FEH height of distal femoral epiphyses     

The screening programme for congenital hypothyroidism in Greece: evidence of iodine deficiency in some areas of the country

Newborn screening for Congenital Hypothyroidism, using TSH measurement in dried blood spots, was started in Greece in 1979. A total of 1,274,000 neonates have been screened and 377 cases of Congenital Hypothyroidism were detected, for an incidence of 1:3370. Employing a cut-off point of 30mU/L of TSH in whole blood, 0.3% of the infants were recalled for repeat examination. The sensitivity of the screening test was 0.99 and the predictive value of a positive test 0.1. The frequency of "false positive" cases in the different geographic regions of Greece showed wide variation between the south and the north areas of the country. We suggest that these differences reflect the degree of iodine deficiency in the population and may be used as an epidemiological indicator of this deficiency.     

Audit of neonatal screening programme for phenylketonuria and congenital hypothyroidism

The performance of the neonatal screening programme was audited against clinical standards in the Bath clinical area from 1 April 1994 to 31 March 1996. The standards and policy were agreed by local service provider representatives of the screening and were audited, using laboratory and child health computer systems and medical records. Two annual reports were produced with recommendations for improvement communicated to representatives of the service. Thus the first audit loop has been completed.  The audit shows that the coverage of the service is excellent, with all eligible babies being offered screening; those with congenital hypothyroidism or phenylketonuria receive appropriate treatment by the 28 day standard. The process works extremely well, although areas for improvement have been identified, to increase the efficiency of the service.  It is concluded that an effective and efficient audit cycle can be established, to monitor and improve the performance of the neonatal screening service.     

Improvement in screening performance and diagnosis of congenital hypothyroidism in Scotland 1979-2003

Aim

To assess the Scottish newborn screening programme for congenital hypothyroidism from 1994 to 2003 (period 2) for performance and compare with an initial audit covering 1979 to 1993 (period 1).

Design

Performance data—age at blood spot sampling, notification by screening laboratory, start of treatment, and the prevalence of late testing, notification or treatment—were compared, together with the incidence of congenital hypothyroidism.

Results

Comparing data for period 2 with period 1, the mean annual incidence of true congenital hypothyroidism was 1:3655 live births v 1:4363. Median age for Guthrie sampling (all referrals) was 6 v 7 days (p<0.0001). Late sampling (>10 days) had fallen from 10.7% to 7%. For infants requiring repeat sampling before notification, the median (range) interval between initial and final repeat samples was 11 (1 to 52) compared with 14 (3 to 73) days. Median age at notification for true congenital hypothyroidism was 10 v 12 days (p <0.0001). Late notification (>15 days) was justifiable (mild TSH elevation) in 10 of 13 patients in period 2. Median age at start of treatment for true congenital hypothyroidism had improved to 11 days from 13.5 days. For true congenital hypothyroidism, late treatment (>16 days) occurred in 7% of patients compared with 19% (p<0.0001).

Conclusions

There has been an improvement in performance measures for the congenital hypothyroidism screening programme in Scotland. However, late sampling, occurring primarily in inpatients and which is never justified, remains a problem, while the interval between initial and recall sampling is a further source of delay.     

先天性甲状腺功能减低症筛查及治疗效果分析

目的了解先天性甲状腺功能减低症(CH)的筛查及替代治疗结果。方法回顾性分析2003年7月—2015年7月采用时间分辨荧光免疫法测定新生儿促甲状腺激素(TSH)水平筛查CH的资料;阳性召回的可疑患儿采用化学免疫发光法测定血清甲状腺功能,确诊者予左旋甲状腺素钠替代治疗并定期随访。结果 12年来共筛查新生儿1 228 289例,确诊950例,CH发病率1/1 293。接受正规治疗、随访满2年及以上的635例CH患儿中,488例(76.85%)为永久性CH,147例(23.15%)为暂时性CH。CH患儿随访至1岁和3岁时,体格生长和发育商(DQ)无异常。结论新生儿筛查可早期诊断CH,早期实施替代治疗。     

Neonatal Hypothyroid Screening Using Enzymeimmunoassay of Thyrotropin — Comparison with Radioimmunoassay

In order to evaluate a new enzymeimmunoassay (EIA) of thyrotropin(TSH) for neonatal hypothyroidism, 6,100 blood samples on fdter paper, obtained through a neonatal hypothyroid screening program, were examined using a one-step sandwich EI A and a radioimmunoassay(RIA). Measured TSH values, numbers of cases and false-positives detected, and recall rates, were compared between the two methods. During this study two cases of congenital hypothyroidism were found by both EIA and RIA. However, a patient with hyperthyrotropinemia was detected only by the EIA. The reproducibility of the EIA was slightly better than that of the RIA. These results suggest that the EIA has same or higher sensitivity for detecting patients compared with the RIA. On the other hand, three cases with falsepositive elevation of TSH by EIA were found. High TSH values by the EIA were likely to be due to transplacental factors, probably immunoglobulin G. Because of high reproducibility of the EIA and false-positive cases found with it, recall rates of the screening program were slightly higher for the EIA than for the RIA. The recall rate of the EIA could have been decreased by setting a cut-off point at a higher percentile. Since the EIA is simple to use, this method is suitable for screening for congenital hypothyroidism.