Screening Program For Congenital Hypothyroidism Research Articles

Evidence or enthusiasm? Why yields from UK newborn screening programmes for congenital hypothyroidism are increasing

Newborn screening for congenital hypothyroidism (CHT) is generally regarded as a highly successful public health measure. It was officially added to the UK newborn screening programme for phenylketonuria in 19811...

Newborn screening for congenital hypothyroidism in Henan province, China

BackgroundCongenital hypothyroidism is the most common congenital endocrine disorder. The study aimed to determine the congenital hypothyroidism incidence by newborn screening programs in Henan Province, China. MethodsThe screening programs for congenital hypothyroidism are based on the measurement of TSH in dried blood spots. The TSH concentration was measured in the dry blood spot specimen using a DELFIA fluoroimmunoassay. The TSH cutoff concentration was 8mU/l. ResultsThe total coverage and the incidence of congenital hypothyroidism were 24.85% (5,142,148/20,694,441) and 0.37‰ (1992/5,142,148), respectively. The coverage and the incidence of CH were only 0.58% (4526/784,580) and 0.22‰ (1/4526) in 1997, respectively. However, the coverage and the incidence of CH were increased to 74.67% (1,203,278/1,611,582) and 0.32‰ (389/1,203,278). There were no significant differences in the number of congenital hypothyroidism between males and females (P>0.05). The number of congenital hypothyroidism was increased year after year. ConclusionsThe newborn screening program for CH is successful and quite effective.

Congenital Hypothyroidism: An Audit and Study of Different Cord Blood Screening TSH Values in a Tertiary Medical Centre in Malaysia

Mothers are often discharged within 24 hours in most Asian countries. Therefore, our screening programs for congenital hypothyroidism (CH) must consider the value of cord blood TSH. Our objectives were to compare the incidence of CH, positive predictive values, and recall rates using different cord blood TSH values. We also reviewed the results of the second-screening program for premature babies. 99.7% (n=25,757) of all newborns were screened from 1st January 2009 to 31st December 2013. Babies with cord blood TSH > 25 mIU/L or 20–25 mIU/L and FT4<20 pmol/L were recalled for a repeat venous TSH and FT4 on days 3–5 of life to confirm CH. Twenty-two babies were confirmed to have CH, an incidence of 1:1170. Five were premature. Eleven term babies had cord blood TSH>30 mIU/L and six had values 25.1–30 mIU/L. Lowering the recall cut-off value to 20 mIU/L would double the recall rate from 0.63% (n=163) to 1.3% (n=340) with no additional cases detected, whereas using 30 mIU/L would have missed 35% of cases. The incidence of CH was similar, 1:1515, when using either cut-off 20 mIU/L or cut-off 25 mIU/L but lower, 1:2380, when using 30 mIU/L. We recommend the screening cord blood TSH cut-off should be 25 mIU/L and screening for premature babies should be continued.

No Association Between Transient Hypothyroxinemia of Prematurity and Neurodevelopmental Outcome in Young Adulthood.

Transient hypothyroxinemia of prematurity (THoP) has been associated with neurodevelopmental impairment in infancy and childhood. It is not known whether these relations persist into adulthood. The objective was to examine whether there is an effect of THoP on intelligence quotient (IQ) score and motor functioning at a young adult age. This study was part of the 19-year follow-up of the Project On Preterm and Small-for-gestational-age birth (POPS) cohort, which included infants born very preterm (ie, <32 wk) and/or with a very low birth weight (ie, <1500 g). This was a multicenter study. There were 398 19-year-old participants of the POPS cohort, of whom 120 had THoP. T4 concentrations were obtained through the national neonatal screening program for congenital hypothyroidism. THoP was defined as a total T4 concentration < -3 SD of the daily mean (approximately 60 nmol/L). Main outcome measures were IQ and motor functioning, measured with the digital Multicultural Capacities Test-Intermediate Level and a revised version of Touwen's examination of minor neurological dysfunction, respectively. THoP was not associated with IQ score (mean difference, 0 [95% confidence interval, -3.8 to 3.8] points) or motor function (mean difference, 0.6 [95% confidence interval, -1.3 to 2.5] points) after adjustment for demographic and perinatal characteristics. No associations between THoP and neurodevelopmental outcome at age 19 years were found.

Tamizaje nacional unificado de hipotiroidismo congénito en el Perú: un programa inexistente

Congenital hypothyroidism (CH) is the most important cause of preventable mental retardation. The prevalence of CH varies by geographic region, race and ethnicity. In the countries of the Northern hemisphere, the prevalence has been reported as 1:4,000 live newborns. The prevalence is remarkably different among the countries of Latin America not only because of their different races and ethnicities but also because of the heterogeneous social-economic development. The prevalence of CH in 1984 in Peru was reported as 1:1250. In 2007, the reported incidence by the Instituto Nacional Materno Perinatal was 1:1638. A recent retrospective study performed by the Instituto Nacional de Salud del Niño in Lima, Peru described the average age of diagnosis of CH as 5,9 months +/- 5,28. This late age of CH diagnosis certainly suggests the poor efficiency of the current neonatal CH screening programs in Peru. Every Peruvian infant deserves a timely newborn screening and treatment for CH. The Peruvian government is responsible for ensuring this mandatory goal is achieved promptly.

Even in the era of congenital hypothyroidism screening mild and subclinical sensorineural hearing loss remains a relatively common complication of severe congenital hypothyroidism

Only few studies have focused on neurosensory hearing function of patients with congenital hypothyroidism (CH) identified by CH screening programs and treated early and, therefore, this issue remains still controversial.The aim of this study was to ascertain whether an early and adequate replacement treatment may be able to prevent sensorineural hearing loss in 32 screened children with CH and no associated risk factors for neuro-otologic alterations. These patients were recruited according to highly selective criteria aiming to preliminarily exclude the negative interference of both treatment variables and other underlying risk factors. All the selected patients underwent, at a median age of 15.4 years, an audiologic investigation, which evidenced a mild and subclinical hearing loss in 25% of them. The poorest hearing scores were recorded in the individuals with athyreosis and in those with absence of distal femur bony nucleus at CH diagnosis. The prevalence of hearing impairment was significantly higher in CH patients than in 32 age-matched control subjects with no CH (χ2 = 6.3, p < 0.025).In light of these findings, we concluded that: a) 25% of CH patients detected by CH screening may show, at a median age of 15.4 years, a mild and subclinical hearing impairment, despite early and adequate replacement treatment; b) the risk of hearing loss is higher in CH young patients than in age-matched control subjects without CH; c) the risk of hearing loss is closely associated with the severity of CH; d) this risk is particularly relevant in the children with pre-natal onset of hypothyroidism.

Loss-of-Function Variants in a Hungarian Cohort Reveal Structural Insights on TSH Receptor Maturation and Signaling.

Congenital hypothyroidism (CH) is one of the most common inborn endocrine disorders with genetic background. Despite the well-established newborn CH screening program in Hungary, no systematic examination of the underlying genetic alterations has been performed as yet. We aimed to explore TSH receptor (TSHR) mutations in a cohort of Hungarian patients with CH. Eighty-five unrelated patients with permanent primary CH, all diagnosed at newborn screening, were selected. Coding exons of the TSHR gene were sequenced and evaluated together with the thyroid-specific clinical parameters. Functional features of the novel mutations were experimentally examined, and their comparative molecular models were built. In four patients (one heterozygous and three compound heterozygous), seven TSHR mutations were identified. Among these, N432(1.50)D and P449(2.39)L are novel missense alterations. Importantly, the N432(1.50) residue is highly conserved among G protein-coupled receptors, and its function has not been examined yet in human glycoprotein hormone receptors. Our results indicate that the N432(1.50)D mutation disrupts important, architecture-stabilizing intramolecular interactions and ultimately leads to the complete intracellular retention of the receptor. On the other hand, P449(2.39) is located in the intracellular part of the receptor, which is important in G protein coupling. The P449(2.39)L mutation results in signaling impairment, with a more profound effect on the Gq/11 pathway. TSHR mutations are common among Hungarian patients with CH. The novel genetic alterations revealed an important structural role of the N432(1.50) and the P449(2.39) residues in receptor expression and signaling, respectively.

Incidence and Interrelated Factors in Patients With Congenital Hypothyroidism as Detected by Newborn Screening in Guangxi, China.

Background. A newborn screening program (NSP) for congenital hypothyroidism (CH) was carried out in Guangxi in order to understand the incidence of CH and the factors interrelated to major types of CH in this region of China. Methods. During 2009 to 2013, data from 930 612 newborns attending NSP in Guangxi were collected. Patients were classified with either permanent CH (PCH) or transient CH (TCH) after 2 years of progressive study. Results. A total of 1210 patients were confirmed with CH with an incidence of 1/769, including 68 PCH and 126 TCH cases with incidences of 1/6673 and 1/3385, respectively. The frequency of thyroid stimulating hormone values greater than 5 mIU/L was 7.2%, which, based on WHO guidelines, suggests that the population was mildly iodine deficient. Conclusions. The incidence of CH was high in Guangxi. Approximately two thirds of CH patients were TCH, which may be due to a deficiency in iodine within the population.

Indicators of newborn screening for congenital hypothyroidism in Sri Lanka: program challenges and way forward.

BackgroundMany of the countries in the Asia Pacific Region are just initiating newborn screening programs for selected metabolic and other congenital disorders. The present study is aimed at evaluating the congenital hypothyroidism screening program in the Southern region of Sri Lanka in terms of coverage, effectiveness of detecting and managing the cases.MethodsThe Newborn Screening System Database of Sri Lanka was reviewed from January 2011 to December 2012. The data of 47 babies who tested positive for hypothyroidism were analyzed.ResultsTotal of 78,167 babies (99.0% of live births) were screened. Of them, 5.8% (n = 4,472) were discharged within 12 hrs of delivery where as 58.1% (n = 44969) were discharged afterwards but within next 12 hrs (i.e., day 1). The positive predictive value for congenital hypothyroidism (CH) was 9.0%. The incidences of primary CH among screened infants were 1:1682. False positive rate among screened infants was maintained below 0.70%. Mean age of serum confirmation was 23.8 (±8) days.ConclusionsIn the light of the present findings, we would suggest direct communication systems, linking newborn screening program to the family unit. This would enhance timely follow-up for screen-positive infants and facilitate information sharing. Establishing a program with, public-private sector partnership should be considered. Costs could be contained if the specimen collection, its transportation and communication are carried out by this partnership and the laboratory tests are conducted by a non-profit organization such as a University in order to achieve the goal of universal coverage.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6963-14-385) contains supplementary material, which is available to authorized users.

Central hypothyroidism in children.

Central congenital hypothyroidism (CCH) is an underdiagnosed disorder poorly described in childhood and adolescence. Congenital defects in thyroid-stimulating hormone (TSH) synthesis, secretion or bioactivity may lead to a state of 'regulatory' hypothyroidism expressed through aberrantly low or normal TSH levels and low thyroxine (T4), a hormonal pattern undetectable by TSH-based neonatal screening programs for congenital hypothyroidism (CH) implemented in most countries worldwide. CCH is more prevalent than previously thought, reaching 1 in 16,000 neonates in countries consistently identifying CCH through T4-based CH screening strategies. Neonatal detection and early treatment of CCH would prevent the risk of developing mental retardation secondary to late diagnosis of infantile hypothyroidism. CCH is frequently associated with other pituitary defects causing life-threatening situations (like e.g. adrenocorticotropic hormone deficiency) which could benefit from the early detection of CCH, avoiding considerable morbidity and mortality. CCH is not easy to identify clinically, and therefore few children are investigated for the disorder. The current knowledge on the genetic bases of CCH is also scarce. At the hypothalamic level no gene defects causing CCH have yet been identified in humans, but pituitary (thyrotrope)-selective genes encoding the TSH-releasing hormone (TRH) receptor (TRHR), the TSH β-subunit (TSHB) and, recently, the immunoglobulin superfamily factor 1 (IGSF1) are genes involved in isolated central hypothyroidism. Moreover, central hypothyroidism is a complex condition where many regulatory signals are implicated and converge to finely modulate the activity of the hypothalamic-pituitary-thyroid axis. This review focuses on novel pathogenic mechanisms and their implications to understand human CCH and improve the identification and the therapeutic handling of this elusive disease in the pediatric age.

Neonatal screening for congenital hypothyroidism.

The possibility of measuring thyroid hormones from blood dried on filter paper opened the way to identifying neonates with congenital hypothyroidism (CH) already in the first days of life. Consequently the early initiation of adequate replacement therapy opened the way to an effective prevention of mental retardation. Timely and complete specimen collection, transport logistics, rapid analysis and communication of results are key points for the organization of a CH newborn screening program. Close collaboration between laboratory and treating specialists is necessary to ensure an adequate treatment and follow-up of babies identified by CH screening programs. Topics for further investigations remain in the fields of which forms of CH should be identified by screening (only severe or also very mild forms) and on the long-term outcome of the individuals identified by CH screening.

Etiology of congenital hypothyroidism in Isfahan: Does it different?

Background:Considering the higher prevalence of congenital hypothyroidism (CH) in Iran and the importance of determination of the etiology of CH for assessing appropriate treatment strategies, understanding the pathogenesis of CH and the implications of its inheritance and prognosis, the aim of this study was to determine the etiology of CH 7 years after initiation of the program in Isfahan province.Materials and Methods:In this cross-sectional study, children with a primary diagnosis of CH studied. They clinically examined and their medical files were reviewed by a Pediatric Endocrinologist. Considering screening and follow-up lab data and radiologic findings the etiology of CH was determined. Screening properties of different etiologies of CH was compared.Results:In this study, 437 patients with permanent CH (PCH) were studied. Etiology of PCH in 316 (72.3%) and 121 (27.7%) of cases was thyroid dyshormonogenesis and thyroid dysgenesis, respectively. Prevalence of agenesis, ectopia, hypoplasia and hemiagenesis in thyroid dysgenetic patients was 13.3%, 6.4%, 4.3% and 3.7% respectively. Mean of thyroid stimulating hormone in screening, recall and after discontinuing treatment at 3 years of age was significantly lower in dyshormonogenetic CH patients than dysgenetic ones(P < 0.01).Conclusion:Seven years of our experiences in CH screening program indicated that the etiology of CH in Isfahan, with a higher rate of CH, with a predominance of thyroid dyshormonogenesis is different from most of the studies world-wide and similar to other reports from Iran. The findings of the current study provide us baseline information for determination of CH pathogenesis in this region.

The relation between serum and filter paper TSH level in neonates with congenital hypothyroidism

Background:the aim of this study was to determine the relation between serum and filter paper thyroid-stimulating hormone (TSH) levels in neonates with congenital hypothyroidism (CH). We also tried to determine an appropriate cutoff point of filter TSH for recalling screened neonates.Materials and Methods:in this descriptive-analytic study, records of 2283 neonates who had been recalled during CH screening program in Isfahan (Iran) were studied. The relation between serum and filter paper TSH levels in the studied neonates was assessed and the best cutoff point of filter TSH and its sensitivity and specificity for proper diagnosis of CH were determined.Results:among the studied neonates, 103 (4.5%) were diagnosed with CH. Using receiver operating characteristic (ROC) curve, the best cutoff point for diagnosing CH was 7.5 with a sensitivity of 74.8% and specificity of 71.3%. The rates of false positive and false negative diagnoses at this cutoff point were28.7% and 25.2%, respectively. There was a significant relationship between serum and filter paper TSH levels.Conclusion:the cutoff point for recall should be changed to 7.5 for appropriate screening outcome. On the other hand, considering the low cost of filter paper and importance of missing any case of CH, changing the cutoff point is not necessary. However, further studies in different parts of Iran are required to obtain more accurate results and consider all related factors.

Newborn screening program for congenital hypothyroidism in Montenegro

Objective – The aim of this study was to assess the prevalence of congenital hypothyroidism (CH) over the last 5 years and analyze and summarize the status of newborn screening in Montenegro. Materials and methods – This is a population-based retrospective study. Blood samples were collected from the heels of newborns 48 – 96 hours after birth and thyroid-stimulating hormone (TSH) was determined. The cut off value in our laboratory was 10 mIU/l in whole blood. Dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) was used for detection. Results – Over the period January 2008 – December 2012, a total of 40,758 newborns were screened and 17 cases were confirmed as CH - both transient and permanent. The program covered all live born infants (100%). Recall rate was 0.97 – 1.36%. Mean age of starting treatment was 21.4±6.4 days. Conclusion – During the period of analysis in our study, 17 cases of CH were detected. The overall prevalence of CH was 1 in 2397 live births. This is the first report on newborn screening for congenital hypothyroidism in Montenegro.

Risk factors of congenital hypothyroidism using propensity score: a matched case-control study.

The aim of this study was to investigate the relationship between congenital hypothyroidism and several variables using two different adjustment methods. This matched case-control study was conducted in Hamadan Province, the west of Iran, in 2012 enrolling neonates born between 2005 and 2011 and covered by screening program for congenital hypothyroidism. The neonates with TSH titer more than 10 mU/l or T4 titer less than 6.4 μg/dl were considered as cases. Each case was individually matched for birth place and year with four neonates with normal TSH and T4 titers as controls. The data were analyzed using two different approaches including propensity score and multiple conditional logistic regression model. Of 1313 enrolled neonates, 277 (159 girls) were cases and 1036 (531 girls) were controls. The most important prognostic factors which had significant effect on congenital hypothyroidism included twin, birth season, maturity, jaundice at birth, birth weight, age at pregnancy, maternal anemia and goiter, gestational age, delivery type, father's education and smoking status, and consanguinity. The associations reported by logistic regression were stronger that of than propensity score analysis in most items, although the differences were not statistically significant. We addressed the effect of numerous potential risk factors on congenital hypothyroiditis and the impact of these factors on the disease occurrence. However, future prospective studies are needed to test these findings and hypothesis and to investigate the true effect of these potential risk factors on congenital hypothyroiditis.

Establishment and Development of a National Newborn Screening Programme for Congenital Hypothyroidism in Turkey

Objective: To assess the Turkish National Newborn Screening Programme (NNSP) for congenital hypothyroidism (CH). Retrospective study based on the data from NNSP.Methods: Since December 2006, a nationwide screening programme for CH has been conducted in Turkey by the Turkish Directorate of Public Health (TDPH) in cooperation with several institutions. We evaluated the database between January 2008 and July 2010 of this programme. According to the methodology of the NNSP, between three and five days of age (or at discharge from the hospital, if this occurs earlier) blood specimens were routinely collected from neonates on filter paper, by puncturing the heel. The accepted thyroid-stimulating hormone cut-off level for recall was 20 mU/L initially and 15 mU/L subsequently. The incidence of possible CH by years was reported.Results: During the evaluation period, 3223765 newborns were tested. The mean annual incidence of possible CH showed a gradual increase over the years (1:888 in 2008, 1:592 in 2009, and 1:469 in 2010). Regional differences were noted. Although the mean age of blood sampling did not change by years, the mean age at notification for suspected CH decreased from 19.2 to 15.7 days from 2008 to 2010.Conclusions: We reported the first assessment of NNSP in Turkey. An improvement in performance measures for the CH screening programme has been noted. Knowledge on incidence of confirmed CH is not yet available in the database. Conflict of interest:None declared.

Screening for Congenital Hypothyroidism: Comparison of Borderline Screening Cut-Off Points and the Effect on the Number of Children Treated with Levothyroxine

Background: The newborn screening programme for congenital hypothyroidism (CH) has led to the prevention of severe developmental delay associated with this condition. In the UK, thyroid-stimulating hormone (TSH) screening cut-off points have changed over time, in some instances prompted by changing methodological platforms. The use of borderline cut-off points varies throughout the country. Objective: To use discordance in cut-off points to assess the performance of the UK Newborn Screening Programme Centre (UKNSPC) definitions. Methods: Between January 2006 and December 2007, 223,658 newborn infants were screened by the Great Ormond Street Hospital (GOSH) for CH. All children with positive results and those with blood-spot TSH concentrations >6 mU/l on repeat screening were referred to GOSH. We compared the numbers of children detected and treated for CH using the GOSH cut-off points (>6 mU/l) and those of the national screening programme (>10 mU/l). Children were defined as transient CH if levothyroxine treatment had been discontinued by 3 years. Results: Of the children screened between January 2006 and December 2007, 167 out of 223,658 fulfilled the GOSH screening criteria; 136 of these required levothyroxine treatment, but 29 (21%) of the children treated would not have been detected by the current UKNSPC guidelines. Transient CH was found in 17/47 (36%) of the treated children detected with a cut-off point >6 mU/l. Raising the cut-off point to >10 mU/l reduced the number of children treated for transient CH to 4/18 (22%). Conclusion: A significant number of children with true and transient CH are missed with a screening cut-off point of >10 mU/l. Our data suggests that a cut-off point of 6 mU/l is appropriate.

Risk factors for congenital hypothyroidism in Egypt: results of a population case-control study (2003–2010)

BACKGROUND AND OBJECTIVESAlthough the prevention of the neuropsychological consequences of congenital hypothyroidism (CH) through the use of replacement therapy represents an important public health success, knowledge about the modifiable risk factors could reduce the number of infants affected by this disease. This study was carried out to identify risk factors for CH at Fayoum Governorate, Egypt.DESIGN AND SETTINGSThis was a population-based case-control study, which started in 2003 and was carried out for 8 years through Fayoum center of the Egyptian Ministry of Health and Population screening program for CH.METHODSThis study was a population-based case-control study carried out by using national project for CH. One control was enrolled for each new CH infant; 320 cases and 320 controls were enrolled in 8 years. Maternal and neonatal influences were investigated.RESULTSA statistically significant association of CH was observed with birth defects, female gender, gestational age >40 weeks, and gestational diabetes. An increased risk for CH was detected in twins by a multivariate analysis.CONCLUSIONOur results suggest a multifactorial origin of CH in which genetic (high frequency of additional malformations) and environmental factors (especially maternal diabetes) play a role in the development of the disease.

Congenital Hypothyroidism due to Defects of Thyroid Development and Mild Increase of TSH at Screening: Data From the Italian National Registry of Infants With Congenital Hypothyroidism

Over the years lower TSH cutoffs have been adopted in some screening programs for congenital hypothyroidism (CH) worldwide. This has resulted in a progressive increase in detecting additional mild forms of the disease, essentially with normally located and shaped thyroid. However, the question of whether such additional mild CH cases can benefit from detection by newborn screening and early thyroid hormone treatment is still open. The aim of this study was to estimate the frequency of cases with mild increase of TSH at screening in the Italian population of babies with permanent CH and to characterize these babies in terms of diagnosis classification and neonatal features. Data recorded in the Italian National Registry of infants with CH were analyzed. Between 2000 and 2006, 17 of the 25 Italian screening centers adopted a TSH cutoff at screening of <15.0 μU/mL. It was found that 21.6% of babies with permanent CH had TSH at screening of 15.0 μU/mL or less, whereas this percentage was 54% in infants with transient hypothyroidism. Among the babies with permanent CH and mild increase of TSH at screening (≤15 μU/mL), 19.6% had thyroid dysgenesis with serum TSH levels at confirmation of the diagnosis ranging from 9.9 to 708 μU/mL. These babies would have been missed at screening if the cutoff had been higher. Lowering TSH cutoff in our country has enabled us to detect additional cases of permanent CH, a number of which had defects of thyroid development and severe hypothyroidism at confirmation of the diagnosis.

The Italian screening program for primary congenital hypothyroidism: actions to improve screening, diagnosis, follow-up, and surveillance.

The Italian screening program for primary congenital hypothyroidism (CH) is an integrated system including neonatal screening, diagnosis, treatment, follow-up, and nationwide surveillance of the disease. The aim of the Italian screening program for CH is to identify not only babies with severe permanent CH (core target), but also babies with mild persistent and transient forms of CH who could have a benefit from an early replacement therapy (secondary target). In the last years, despite the important results obtained in terms of standardization of screening and follow-up procedures, it has become clear the need of optimizing the program in order to harmonize the screening strategy and the screening procedures among Regions, and to improve the diagnostic and therapeutic approach in all affected infants. On the basis of available guidelines, the experience of the Italian screening and clinical reference centers, and the knowledge derived from the nation-wide surveillance activity performed by the Italian National Registry of Infants with CH, the Italian Society for Pediatric Endocrinology and Diabetology together with the Italian Society for the Study of Metabolic Diseases and Neonatal Screening and the Italian National Institute of Health promoted actions aimed at improving diagnosis, treatment, follow-up and surveillance of CH in our country. In this paper the most important actions to improve the Italian screening program for CH are described.