Screening For Congenital Hypothyroidism Research Articles

Evaluation of the First Three Years of Treatment of Children with Congenital Hypothyroidism Identified through the Alberta Newborn Screening Program.

The effectiveness of newborn screening (NBS) for congenital hypothyroidism (CH) relies on timely screening, confirmation of diagnosis, and initiation and ongoing monitoring of treatment. The objective of this study was to ascertain the extent to which infants with CH have received timely and appropriate management within the first 3 years of life, following diagnosis through NBS in Alberta, Canada. Deidentified laboratory data were extracted between 1 April 2014 and 31 March 2019 from Alberta Health administrative databases for infants born in this time frame. Time to lab collection was anchored from date of birth. Timeliness was assessed as the frequency of monitoring of Thyroid Stimulating Hormone (TSH) and appropriateness as the frequency of children maintaining biochemical euthyroidism. Among 160 term infants, 95% had confirmation of diagnosis by 16 days of age. The cohort had a median of 2 (range 0-5) TSH measurements performed in the time interval from 0 to 1 month, 4 (0-12) from 1 to 6 months, 2 (0-10) from 6 to 12 months, and 7 (0-21) from 12 to 36 months. Approximately half were still biochemically hypothyroid (TSH > 7 mU/L) at 1 month of age. After becoming euthyroid, at least some period of hypo- (60%) or hyperthyroidism (TSH < 0.2 mU/L) (39%) was experienced. More work needs to be performed to discern factors contributing to prolonged periods of hypothyroidism or infrequent lab monitoring.

Newborn screening for congenital hypothyroidism and the time influence on the sampling

Newborn screening for congenital hypothyroidism and the time influence on the sampling

Neonatal Screening for Congenital Hypothyroidism: A Study Conducted in a Tertiary Care Hospital of Gujarat

Neonatal Screening for Congenital Hypothyroidism: A Study Conducted in a Tertiary Care Hospital of Gujarat

Screening T4 and TSH in Early Detection of Congenital Hypothyroidism in Newborns: What’s the Dilemma?

Untreated congenital hypothyroidism (CH) leads to intellectual disability. Newborn screening (NBS) for CH should be done on all infants. Prompt diagnosis by NBS leads to early and adequate treatment outcomes in very normal neurocognitive outcomes in adulthood. Newborn screening (NBS) for congenital hypothyroidism (CH) is one of the major achievements in preventive medicine. Most neonates born with CH have a normal appearance and no detectable physical signs. Blood spot thyroid stimulating hormone (TSH), thyroxine (T4), or both can be used for CH screening. The latter is more sensitive but not cost-effective, so screening by TSH or T4 is used in various programs worldwide. TSH screening is more specific in the diagnosis of CH. T4 screening is more sensitive in detecting newborns with rare hypothalamic-pituitary-hypothyroidism, but it’s less specific with a high frequency of false positives especially in low birth weight and premature infants. NBS alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis and accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Doctors need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism appear (such as large posterior fontanelles, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid hormone and free thyroxine is indicated, regardless of NBS results. So all these babies should be treated as having CH during the first 3 years of life, taking into account the risk of mental retardation. Re-evaluation after 3 years is required in such patients.

History of Neonatal Screening of Congenital Hypothyroidism in Portugal.

Congenital hypothyroidism (CH) leads to growth and development delays and is preventable with early treatment. Neonatal screening for CH was initiated in Portugal in 1981. This study examines the history of CH screening in the country. Data were obtained from annual reports and from the national database of neonatal screening laboratory. The CH screening strategy primarily relies on the thyroid-stimulating hormone (TSH), followed by total thyroxine measurement as the second tier for confirmation. The TSH cutoff started at 90 mIU/L, decreasing to the actual 10 mIU/L. The coverage of the screening program has increased rapidly; although voluntary, it reached about 90% in 6 years and became universal in 10 years. Guideline and cutoff updates led to the identification of over 200 additional cases, resulting in specific retesting protocols for preterm and very-low-birth-weight babies. The actual decision tree considers CH when TSH levels are above 40 mIU/L. Data from the CH screening also provide an indication of the iodine status of the population, which is presently indicative of iodine insufficiency. The Portuguese neonatal screening for CH is a history of success. It has rapidly and continuously adapted to changes in knowledge and has become a universal voluntary practice within a few years.

When bones deceive: Beyond skeletal dysplasia

Congenital hypothyroidism results from a partial or complete loss of thyroid function. It is the most common treatable cause of mental retardation. Thyroid hormone facilitates the growth and development of the skeleton through its direct effects on chondrocyte proliferation and differentiation and its permissive effects on the growth hormone. Due to the congenital hypothyroidism screening programs, congenital hypothyroidism is rare, and hence, other differential diagnoses are often considered in children presenting later in life with short stature and coarse facies such as storage disorders, genetic disorders, and skeletal dysplasia. This article aims to assess and discuss the value of radiology, especially plain radiography and ultrasonography in the diagnosis of congenital hypothyroidism and prevent long-term mental retardation and neurological dysfunction.

Experiences and Challenges with Congenital Hypothyroidism Newborn Screening in Indonesia: A National Cross-Sectional Survey.

The expansion of newborn screening (NBS) for congenital hypothyroidism (CH) is essential to reducing the number of preventable intellectual disabilities in children. Because of logistical issues, including geographic extremes, distinct cultures, and 4.8 million births annually, Indonesia has struggled to achieve universal NBS coverage. A national cross-sectional electronic survey was conducted to explore challenges in CH NBS. Responses from 423 healthcare professionals and program administrators across 30 provinces in Indonesia were collected. The major challenges reported were refusal from families (39.2%), newborns being discharged <24 h (38.3%), and limited availability of filter paper (35.9%). The respondents considered refusal from families to be due to fear, while others did not understand the necessity of CH NBS. The vast majority of respondents believed that parents do not have sufficient understanding regarding CH NBS (96.5%). Our study found that only 38.5% of respondents had received formal CH NBS training, with pediatric endocrinologists being the only profession in which all respondents had been trained. Concerted efforts are needed to improve the access to and availability of resources, increase the capacity for sample collection and analysis, empower healthcare professionals, and develop educational resources to promote understanding and acceptance of NBS amongst families.

Concurrent &lt;i&gt;THRB&lt;/i&gt; and &lt;i&gt;DUOX2&lt;/i&gt; variants in a patient detected via newborn screening for congenital hypothyroidism: a case of resistance to thyroid hormone

Concurrent &lt;i&gt;THRB&lt;/i&gt; and &lt;i&gt;DUOX2&lt;/i&gt; variants in a patient detected via newborn screening for congenital hypothyroidism: a case of resistance to thyroid hormone

Knowledge and perception on expanded newborn screening in Sri Lanka among pregnant women attending antenatal clinics in Teaching Hospital Mahamodara

Introduction: Unlike in developed countries, there is no established expanded newborn screening (eNBS) in resource-limited settings. In Sri Lanka, the Ministry of Health has adopted screening only for congenital hypothyroidism, critical congenital heart diseases and congenital deafness as a policy in all newborns. Hence, there is a requirement to assess the need for eNBS in Sri Lanka. This requires epidemiological studies of the inherited metabolic disorders (IMDs) before investment to ensure costeffectiveness of the programme and reflections on acceptance by beneficiaries.Objectives: To evaluate the pregnant women's knowledge, attitudes and willingness towards eNBS.Method: A descriptive cross-sectional study was conducted at the Mahamodara Maternity Hospital antenatal clinics, Galle, Southern Province, Sri Lanka. A convenient sample was obtained from the antenatal clinics. A pre-tested intervieweradministered questionnaire was used to assess basic socio-demographic details, knowledge and perception of eNBSResults: A total of 602 pregnant women took part in the study. The mean age was 29±5.7 years; 67% were in the 25-40-year age group; 37.2% were primigravida and 60% were in the third trimester. More than 50% of the study participants knew about the heel prick test done at birth. However, only 34.8% and 28% were aware of the screening for congenital hypothyroidism and congenital heart disease, respectively; 93.6% of mothers had not heard of the term IMD, and only seven were aware of the term eNBS. Nevertheless, more than 80% of participants were willing to screen their babies at birth for underlying IMDs, even if it is available on payment, as the current programme was free of charge to the family. Similarly, 96.2% were willing to screen their babies for incurable diseases.Conclusions: Though most women were aware of the heel prick test done at birth, only a suboptimal proportion of them was aware of the disease/s checked using the test. In addition, there was poor knowledge about the IMDs and eNBS. However, there were positive attitudes towards eNBS.

Progress of newborn screening in China.

Newborn screening (NBS) plays a significant role in reducing the risk of birth defects. NBS in China began in the early 1980s. Under the protection of laws and regulations and the leadership of the national health administration, approved screening centers in public hospitals took the responsibility for publicity, screening, diagnosis, treatment, follow-up and management of birth defects. As of 2022, 31 provinces (autonomous regions and municipalities directly under the central government) have carried out NBS for phenylketonuria, congenital hypothyroidism, and hearing loss, 23 provinces have carried out screening for glucose-6-phosphate dehydrogenase (with a screening rate of 89.24%), and 24 provinces have carried out screening for congenital adrenal cortical hyperplasia (91.45% screening rate). Over the past four decades, screening techniques have evolved from bacterial inhibition, fluorescence analysis, and tandem mass spectrometry for the detection of biochemical markers to genetic testing, which has greatly contributed to the expansion of the types of diseases screened for. The combined use of metabolomics and genomics is currently being explored. Effective management and rigorous quality control of NBS are prerequisites for improving the quality and ensuring the accuracy of screening. The Quality Management System for Newborn Screening System Network (QMS-NBS), established by the National Center for Clinical Laboratories, covers all screening centers and related blood collection agencies. The operation of the QMS-NBS allows the quality and performance of screening to be transparent and measurable, ensuring the quality and efficiency of screening. This article provides an overview of the history of NBS, especially the evolution of policies for the NBS in China, the construction of screening institutions, the number of newborns screened, the incidence rates of screened diseases, the changes in screening technology, the expansion of new diseases screened for, and the quality control of NBS. Overall, the progress in NBS in China has not only benefited from the development and standardization at the technological level, but also benefited from the construction of policies, regulations and ethics.

Newborn screening for congenital hypothyroidism, congenital adrenal hyperplasia and glucose-6-phosphate dehydrogenase deficiency in Bihar: A pressing priority in today's time.

Newborn screening (NBS) aims towards early detection of congenital disorders or prevention of intellectual and physical defects and life-threatening illness. Three disorders namely congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH) and glucose-6-phosphate dehydrogenase deficiency (G-6-PDD) were selected for a preliminary study for NBS. The study aimed to establish NBS in the Indian scenario that could lay a framework for future such initiatives. A screening programme was conducted at a tertiary care hospital for 1 year. All the neonates born at All India Institute of Medical Sciences (AIIMS), Patna, were screened for their blood levels of glucose-6-phosphate dehydrogenase (G-6-PD), 17-hydroxyprogesterone (17-OHP) and thyroid-stimulating hormone (TSH). Heel-prick blood samples were collected within 48-72 h of birth, and the level of these parameters was accessed by enzyme immunoassay (EIA). A total of 492 neonates were born from January 2020 to December 2020, of which 369 newborns were screened for CAH, CH and G-6-PDD. Of 369 neonates, one case (male) had an increased level of TSH, six cases (all males) had an increased level of 17-OHP and no case was found with G-6-PDD. Preliminary data on the prevalence of various genetic disorders revealed that CAH is the most prevalent disorder followed by CH in the population of Bihar. More efforts need to be undertaken to create awareness and to make screening a successful programme in India. A cost-effective nationwide screening programme is highly recommended for the detection of such cases at the earliest to avoid their future complication.

Results of neonatal screening for congenital hypothyroidism and hyperphenylalaninemia in Zhejiang province from 1999 to 2022.

To analyze the results of neonatal screening for congenital hypothyroidism (CH) and hyperphenylalaninemia (HPA) in Zhejiang province from 1999 to 2022. A total of 11 922 318 newborns were screened from September 1999 and December 2022 in Zhejiang province. The blood thyroid stimulating hormone (TSH) levels were measured by a fluorescence method and blood phenylalanine (Phe) levels were measured by fluorescence method or tandem mass spectrometry. TSH≥9 μIU/mL was considered positive for CH, while Phe>120 μmol/L and/or Phe/Tyr ratio>2.0 were considered positive for HPA. The positive newborns in screening were recalled, and the gene variations were detected by high-throughput sequencing and MassARRAY tests. The overall neonatal screening rate during 1999-2022 was 89.41% (11 922 318/13 333 929) and the screening rate was increased from 6.46% in 1999 to 100.0% in 2022. A total of 8924 cases of CH were diagnosed among screened newborns with an incidence rate of 1/1336. A total of 563 cases of HPA were diagnosed, including 508 cases of classic phenylketonuria (cPKU) and 55 cases of tetrahydrobiopterin deficiency (BH4D), with an incidence rate of 1/21 176. Ninety-seven out of 8924 cases of CH underwent genetic analysis. Gene mutations were detected in 9 CH related genes, the highest frequency mutations were found in DUOX2 gene (69.0%) with c.3329G>A (p.R1110Q) (18.2%) and c.1588A>T (p.K530X) (17.3%) as the hotspot mutations. There were 81 PAH gene variants detected in a total of 250 cases of cPKU, and c728G>A (p.R243Q) (24.4%), c.721C>T (p.R241C) (15.0%) were the hotspot mutations. Meanwhile 7 novel variants in PAH gene were detected: c.107C>A (p.S36*), c.137G>T (p.G46V), c.148A>G(p.K50E), c.285C>T (p.I95I), c.843-10delTTCC, exon4-7del and c.1066-2A>G. There were 12 PTS gene variants detected in 36 cases of BH4D, and c.259C>T (p.P87S) (31.9%) was the hotspot mutation. The incident of CH has increased from 1999 to 2022 in Zhejiang province, and it is higher than that of national and global levels; while the incidence of HPA is similar to the national average. DUOX2 gene variation is the most common in CH patients; c.728G>A (p.R243Q) is the hotspot mutation in cPKU patients, while c.259C>T (p.P87S) is the hotspot mutation in BH4D patients.

Skrining Hipotiroid Kongenital (SHK) Pada Ibu Hamil di Puskesmas Tajurhalang Kabupaten Bogor

According to WHO, in several developed countries such as America, Japan, Australia and Europe, since 197-, neonatal screening programs for hypothyroidism have been implemented so as to reduce the occurrence of mental retardation in children (Apriliani et al., 2021). Symptoms of hypothyroidism in newborns are usually not very obvious and congenital hypothyroidism can cause severe mental retardation unless therapy is received early, so a congenital hypothyroid (HK) screening examination is very important to do(Apriliani et al., 2021). Congenital Hypothyroidism Screening is effective 48-72 hours after birth(Ida Bagus Eka Utama Wija, 2020). Based on the pre and post test scores from 30 participants, it was found that there was an increase in the good category in knowledge with an average score of 1.7 to 3.00, meaning that the counseling was successfully implemented.There needs to be awareness of pregnant women, where the task of building awareness is held by health workers, so it is hoped that health agencies which are already required to run the SHK program will be more aggressive and package their invitations to pregnant women well.

Optimizing the Dutch newborn screening for congenital hypothyroidism by incorporating amino acids and acylcarnitines in a machine learning-based model.

Congenital hypothyroidism (CH) is an inborn thyroid hormone (TH) deficiency mostly caused by thyroidal (primary CH) or hypothalamic/pituitary (central CH) disturbances. Most CH newborn screening (NBS) programs are thyroid-stimulating-hormone (TSH) based, thereby only detecting primary CH. The Dutch NBS is based on measuring total thyroxine (T4) from dried blood spots, aiming to detect primary and central CH at the cost of more false-positive referrals (FPRs) (positive predictive value (PPV) of 21% in 2007-2017). An artificial PPV of 26% was yielded when using a machine learning-based model on the adjusted dataset described based on the Dutch CH NBS. Recently, amino acids (AAs) and acylcarnitines (ACs) have been shown to be associated with TH concentration. We therefore aimed to investigate whether AAs and ACs measured during NBS can contribute to better performance of the CH screening in the Netherlands by using a revised machine learning-based model. Dutch NBS data between 2007 and 2017 (CH screening results, AAs and ACs) from 1079 FPRs, 515 newborns with primary (431) and central CH (84) and data from 1842 healthy controls were used. A random forest model including these data was developed. The random forest model with an artificial sensitivity of 100% yielded a PPV of 48% and AUROC of 0.99. Besides T4 and TSH, tyrosine, and succinylacetone were the main parameters contributing to the model's performance. The PPV improved significantly (26-48%) by adding several AAs and ACs to our machine learning-based model, suggesting that adding these parameters benefits the current algorithm.

Screening and Management of Congenital Hypothyroidism — Guidelines by American Academy of Pediatrics, 2023

Screening and Management of Congenital Hypothyroidism — Guidelines by American Academy of Pediatrics, 2023

Congenital hypothyroidism screening by umbilical cord blood thyroid stimulating hormone: a cross sectional study

Background: Congenital hypothyroidism is one of the most important and common preventable cause of intellectual disability. The objective of the study is to determine the proportion of congenital hypothyroidism among newborn babies delivered at ESIC-MC and PGIMSR Hospital, Bangalore. Methods: Present study was a cross sectional study conducted in the Department of Paediatrics, ESICMC and PGIMSR over a period of 18 months from march 2021 to august 2022. All babies wherein the cord blood TSH was found to be over 20 mIU/l will be intimated within 24 hrs of the test. The babies were advised to give fresh samples TSH on day 3. Results: In the present study, of the 1900 deliveries, cord blood was available for 1669 newborns. Of the 1669 newborns, 3.1% (N=51) newborns had cord blood TSH more than 20 mIU/l and remaining 96.9%(n=1618) had cord blood TSH levels of less than 20 mIU/l. Out of 51 newborn who were screened positive for congenital hypothyroidism were subjected to futher testing by serum TSH on day 3. Serum TSH on day 3 levels was high (&gt;20 mIU/l) 11.7% (N=6) neonates and serum TSH (&lt;20 mIU/l) 88.2% (N=46) neonates. In this study, the proportion of congenital hypothyroidism was 0.4% (N=6) which was 1 in 278 babies delivered. Conclusions: The present study adds emphasis on the need for continuing screening for congenital hypothyroidisn, one of the preventable cause for intellectual disability. In developing countries, incidence is very high, the need for screening programs is the need of the hour.

Does prenatal exposure to multiple airborne and tap-water pollutants increase neonatal thyroid-stimulating hormone concentrations? Data from the Picardy region, France

ObjectiveSystematic screening for congenital hypothyroidism by heel-stick sampling has revealed unexpected heterogeneity in the geographic distribution of newborn thyroid-stimulating hormone concentrations in Picardy, France. We explored a possible relationship with environmental pollutants. MethodsZip code geolocation data from mothers of newborns without congenital hypothyroidism born in 2021 were linked to ecological data for a set of airborne (particulate matter with a diameter of 2.5 μm or less [PM2.5] or 10 μm or less [PM10]) and tap-water (nitrate and perchlorate ions and atrazine) pollutants. Statistical associations between mean exposure levels during the third trimester of pregnancy and Thyroid-stimulating hormone (TSH) concentrations in 6249 newborns (51 % male) were investigated using linear regression models. ResultsMedian neonatal TSH concentration (interquartile range, IQR) was 1.7 (1–2.8) mIU/L. An increase of one IQR in prenatal exposure to perchlorate ions (3.6 μg/L), nitrate ions (19.2 mg/L), PM2.5 (3.7 μg/m3) and PM10 (3.4 μg/m3), were associated with increases in TSH concentrations of 2.30 % (95 % CI: 0.95–3.66), 5.84 % (95 % CI: 2.81–8.87), 13.44 % (95 % CI: 9.65–17.28) and 6.26 % (95 % CI: 3.01–9.56), respectively. ConclusionsPrenatal exposure to perchlorate and nitrate ions in tap water and to airborne PM over the third trimester of pregnancy was significantly associated with increased neonatal TSH concentrations.

Neonatal screening for primary and central congenital hypothyroidism: is it time to go Dutch?

Thyroid hormone (TH) is indispensable for brain development in utero and during the first two to three years of life, and the negative effects of TH deficiency on brain development are irreversible. Detection of TH deficiency early in life by neonatal screening allows early treatment, thereby preventing brain damage. Inborn shortage of TH, also named congenital hypothyroidism (CH), can be the result of defective thyroid gland development or TH synthesis (primary or thyroidal CH (CH-T)). Primary CH is characterized by low blood TH and elevated thyroid-stimulating hormone (TSH) concentrations. Less frequently, CH is due to insufficient stimulation of the thyroid gland because of disturbed hypothalamic or pituitary function (central CH). Central CH is characterised by low TH concentrations while TSH is normal, low or slightly elevated. Most newborn screening (NBS) programs for CH are primarily TSH-based thereby do not detect central CH. Only a few NBS programs worldwide aim to detect both forms of CH by different strategies. In the Netherlands, we have a unique T4-TSH-thyroxine-binding globulin (TBG) NBS algorithm for CH which enables detection of primary and central CH. Although the necessity of central CH detection by NBS is still under debate, it has been shown that most central CH patients have moderate-to-severe hypothyroidism instead of mild, and that early detection of central CH by NBS problably improves its clinical outcome and clinical care for central CH patients with multiple pituitary hormone deficiency. We are therefore convinced that detection of central CH by NBS is of utmost importance.

An observational study on the prevalence of congenital hypothyroidism and factors affecting TSH levels in premature babies at tertiary care rural centre

Background: Premature babies, particularly those with very low birth weight (VLBW), are at a higher risk of developing congenital hypothyroidism. The inadequate development of the hypothalamic-pituitary axis in preterm infants contributes to the higher prevalence of this condition in this population. However, the optimal screening and treatment protocols for congenital hypothyroidism in preterm newborns remain unclear. Methods: This was a hospital-based observational study conducted over a period of 18 months. The study included 150 preterm babies born at the Sri Adichunchanagiri hospital and research centre. Non-probability sampling was used to select the study subjects. Data on demographic and clinical factors were collected from mothers and newborns. Blood samples were collected at day 3 of life to estimate thyroid-stimulating hormone levels. Correlations between TSH levels and various parameters were analyzed using statistical methods. Results: The study found that the prevalence of congenital hypothyroidism in preterm newborns was 2%. The mean TSH level at day 3 was 7.56 mIU/L, and 9.3% of cases had TSH levels above 20 mIU/l. Significant associations were found between high TSH levels and primiparity, vaginal delivery, and maternal gestational diabetes mellitus. There was an inverse correlation between TSH levels and gestational age, birth weight, and Apgar scores at 1 and 5 minutes. Conclusions: The study revealed a prevalence of congenital hypothyroidism of 2% in preterm newborns. Risk factors such as primiparity, vaginal delivery, and maternal GDM were associated with high TSH levels. These findings highlight the importance of screening and early detection of congenital hypothyroidism in premature babies to improve outcomes.

A Detailed Analysis of the Various Perinatal Factors Influencing Neonatal TSH: Results from a 6 Months Congenital Hypothyroidism Screening Program.

A Detailed Analysis of the Various Perinatal Factors Influencing Neonatal TSH: Results from a 6 Months Congenital Hypothyroidism Screening Program.