Screening For Congenital Hypothyroidism Research Articles

Prevalence of Transient Hypothyroidism in Children Diagnosed with Congenital Hypothyroidism between 2000 and 2016.

Newborn screening (NBS) for congenital hypothyroidism (CH) was introduced in Switzerland in 1977, which allowed for the preclinical, biochemical diagnosis. The aim of this study was to evaluate the prevalence of transient CH (tCH) in the canton of Zurich. In this analytical cohort study, all newborns born in the canton of Zurich, between the 1st of January 2000 and the 30st of June 2016, with a TSH value above 15 mU/L (whole blood) were included. There were 115 cases out of 247,918 babies born during the study period. However, 23 cases had to be excluded due to missing data. The definite diagnosis was made after a thyroxine withdrawal at 2 years of age. The total prevalence of confirmed CH and the female to male ratio (f/m) were 1:2695 and 2.17:1; for permanent CH (pCH), 1:3443 and 2.8:1; and for tCH, 1:12,396 and 1:1, respectively. The TSH value was significantly higher in pCH compared to tCH, at 130.3 (62.9-171.9) and 36.4 (26.5-53.3) (median and interquartile range), respectively (p < 0.001). The prevalences found for congenital hypothyroidism and its transient form are comparable to previous studies. TSH concentration at birth was predictive for the further course of the disease. Low birth weight correlated with a tCH, whereas low gestational age did not. The dominance of the female sex in congenital hypothyroidism is supported by a gender ratio of 2.17:1.

Comparing the Characteristics of Neonates with FalsePositive Congenital Hypothyroidism Screening Results with Affected Neonates

Background: Congenital hypothyroidism is one of the most common preventable causes of mental retardation. The present study aimed to compare the characteristics of neonates with false-positive congenital hypothyroidism screening test results with affected neonates in Kerman. Methods: This cross-sectional study was conducted on neonates called to confirm congenital hypothyroidism from 2016 to 2017. The neonate characteristics (year and season of birth, sex, umbilical hernia, fontanelle conditions, constipation, jaundice, abnormalities, head circumference, height and weight at birth, gestational age, type of delivery, parental consanguinity, history of thyroid disease in the family, childbirth location, history of hospitalization, and place of residence) and maternal characteristics (age, number of deliveries, history of stillbirth, history of illness, and drug use during pregnancy) were extracted from their medical records. The collected data were analyzed with SPSS software (version 20) using the chi-square and independent samples t test. Results: From a total of 985 neonates who had a positive screening test, congenital hypothyroidism was confirmed in only 58 neonates(5.9%), and the other 927 neonates(94.1%) only had a positive screening test. The neonates’ and mothers’ characteristics were not significantly different in the two groups, except for constipation, which had a higher frequency in the neonates with a positive congenital hypothyroidism screening results than in the affected neonates (P=0.004). Conclusion: In this study, the characteristics of neonates who only had a positive hypothyroidism screening test result were not significantly different from those of the affected neonates. It is recommended that further studies be conducted over a longer period.

Guidelines for Newborn Screening of Congenital Hypothyroidism (2021 Revision).

Purpose of developing the guidelines: Newborn screening (NBS) for congenital hypothyroidism (CH) was started in 1979 in Japan, and early diagnosis and treatment improved the intelligence prognosis of CH patients. The incidence of CH was once about one in 5,000-8,000 births, but has been increased with diagnosis of subclinical CH. The disease requires continuous treatment and specialized medical facilities should conduct differential diagnosis and treatment in patients who are positive by NBS to avoid unnecessary treatment. The Guidelines for Mass Screening of Congenital Hypothyroidism (1998 version) were developed by the Mass Screening Committee of the Japanese Society for Pediatric Endocrinology in 1998. Subsequently, the guidelines were revised in 2014. Here, we have added minor revisions to the 2014 version to include the most recent findings. Target disease/conditions: Primary congenital hypothyroidism. Users of the Guidelines: Physician specialists in pediatric endocrinology, pediatric specialists, physicians referring pediatric practitioners, general physicians, laboratory technicians in charge of mass screening, and patients.

Etiological Profile, Targeted Levothyroxine Dosing and Impact of Partial Newborn Screening in Congenital Hypothyroidism-A Single Centre Experience.

Congenital hypothyroidism (CH) is the most common cause of preventable intellectual disability. Newborn screening (NBS) for CH has been in vogue in many parts of the world since 1970, but despite its well-known benefits, many developing countries including India have not been able to establish universal NBS for CH till date. The aim of this study was to review the clinical aspects of congenital hypothyroidism in a tertiary care university referral teaching hospital, focusing on aetiology of CH, predictors of permanence, optimal targeted dose strategies based on aetiology and the effect of newborn screening on the time to diagnosis. The electronic medical records of 233 children with CH referred to our centre between January 2009 and December 2019 were analysed. A partial NBS was established in the state in 2012. Dyshormonogenesis (57.5%) was the most common aetiology of CH. The incidence of transient CH in children with a gland in situ (GIS) was 35%. Levothyroxine (LT-4) dose of >2.75 μg/kg/day (sensitivity 76.5, specificity 72), >2.15 μg/kg/day (sensitivity 82.4, specificity 61.9) and >1.85 μg/kg/day (sensitivity 76.5, specificity 61.9) at years 1, 2 and 3, respectively, were predictors of permanent CH. An initial LT-4 dose ≥8 μg/kg was sufficient and very seldom led to undertreatment in children with dyshormonogenesis. On the contrary, even doses ≥13 mcg/kg/day led to frequent undertreatment in children with thyroid dysgenesis. After the introduction of newborn screening, the median age at diagnosis came down from 45 days (IQR 14-180 days) to ten days (IQR 3-12 days). Targeted dosing based on aetiology of CH may be more appropriate to optimise outcomes. The time to diagnosis of CH reduced significantly after the adoption of even a partial NBS program highlighting the urgent need for implementation of the same in resource poor settings.

Utility of basal and peak TSH values in TRH stimulation testing for predicting the long-term therapeutic prognosis of primary congenital hypothyroidism.

In Japan, most neonates undergo screening for congenital hypothyroidism (CH). A TRH stimulation test (TRH-T) may be performed after initial treatment as a useful method for reevaluating the patient's thyroid status. However, no studies have compared basal and peak TSH values in TRH-T in patients with long-term follow-up. This was a retrospective and observational study. The inclusion criteria were as follows: (1) CH diagnosis based on positive newborn screening, (2) follow-up > 15 yr, and (3) TRH-T after LT4 discontinuation. The participants were divided into a no-treatment group (No-T group) and a treatment group (T group). The No-T and T groups included 14 and nine patients, respectively. The age at TRH-T was 5.38 yr for the No-T group and 4.25 yr for the T group, with no significant difference. The basal and peak TSH levels were significantly lower in the No-T group. The areas under the Receiver operating characteristic curve for basal and peak TSH values were 0.984 and 0.905, respectively. When the basal TSH level was under 4.594 IU/mL, the No-T group had a sensitivity of 1.00 and a specificity of 0.93. Basal TSH levels alone may be sufficient for predicting the long-term therapeutic prognosis of patients with CH.

Neonatal Screening for Congenital Hypothyroidism through Dried Blood Spots: A Cross-sectional Study

Introduction: Congenital Hypothyroidism (CH) is defined as the partial or complete loss of thyroid gland function present at birth. During the first 2-3 years of life, thyroid hormone plays a crucial role in brain development. If a baby is born with a deficiency of thyroid hormone (CH) and is not diagnosed and treated appropriately, it can lead to intellectual disability and growth retardation in the affected child. Aim: To screen newborns for CH using Dried Blood Spot (DBS) sampling. Additionally, the study aimed to compare mean TSH values between two comparison groups based on gender, birth weight, gestational age, and type of delivery. Materials and Methods: This cross-sectional study was conducted at Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India, from November 2021 to October 2022. A total of 250 live-birth newborns delivered either by Spontaneous Vaginal Delivery (SVD) or Lower Segment Caesarean Section (LSCS) were included in the study after obtaining written informed consent from their parents. Blood samples were obtained on DBS cards through heel prick in all newborns. TSH levels were assessed using a neonatal TSH sandwich ELISA kit. The cut-off value of TSH to label as screen positive was set at &gt;20 mIU/L. A two-tailed Independent t-test was performed to compare mean TSH values between the two comparison groups based on gender, birth weight, gestational age, and type of delivery. Results: Out of the 250 babies, 137 (54.8%) were male and 113 (45.2%) were female. The gestational age ranged from a minimum of 29 weeks to a maximum of 41 weeks in both male and female babies. TSH levels in male babies ranged from 0.16 mIU/L to 10.27 mIU/L, with a mean value of 3.98±2.16 mIU/L. TSH levels were below 20 mIU/L in all 250 newborns, indicating negative screening results for CH in all the neonates. Conclusion: The results concluded that the serum levels of TSH obtained through heel prick were not statistically significant in both term and preterm newborns, as well as in Normal Birth Weight (NBW) and Low Birth Weight (LBW) newborns. Furthermore, there was no significant difference based on the type of delivery (SVD/LSCS) or the gender of the newborn (male or female).

A case of syndromic congenital hypothyroidism with a 15.2 Mb interstitial deletion on 2q12.3q14.2 involving &lt;i&gt;PAX8&lt;/i&gt;

Paired box 8 (PAX8) mutations are an established genetic cause of congenital hypothyroidism (CH). The majority of these mutations are found in the protein-coding exons of the gene. The proband, a 3-yr-old girl, had tetralogy of Fallot and polydactyly soon after birth. She was diagnosed with CH in the newborn screening for CH. She had a high serum TSH level (239 mU/L) and low free T4 level (0.7 ng/dL). Ultrasonography revealed thyroid hypoplasia. We performed array comparative genomic hybridization because the patient exhibited a variety of symptoms across multiple organ systems. The analysis revealed a novel heterozygous deletion that spanned a 15.2 Mb region in 2q12.3q14.3 (GRCh37; chr2:109,568,260-124,779,449). There were 71 protein-coding genes in this region, including two genes (PAX8 and GLI2) associated with congenital endocrine disorders. The common clinical features of the two previously reported patients with a total PAX8 deletion and our case were CH, short stature and intellectual disability, but the severity of hypothyroidism and other clinical features were variable. In conclusion, we describe a syndromic CH patient with a novel 2q12.3q14.3 deletion involving PAX8. Patients with CH, whose unifying diagnosis is not obvious, could have a genomic deletion involving PAX8.

Frequency of Congenital Hypothyroidism in Newborn at Tertiary Care Hospital in Quetta

Objective: To determine the frequency of congenital hypothyroidism (CH) in newborn at tertiary care hospital in Quetta, Pakistan. Study design: Cross-sectional study. Place and Duration: The Department of Paediatrics, Unit-II, Bolan Medical College Hospital, Quetta, Pakistan from January 2022 to June 2022. Methodology: Neonates of both genders born with birth weight above 1500 grams having gestational age above 28 weeks, presenting between 3 to 5 days following birth were analyzed. At the time of enrollment, demographic characteristics of the neonates were noted and screening of CH was done. The CH was labeled as serum TSH ≥ 20mU/ml and T4 &lt; 9 pmol/l. Results: During the study period, a total of 383 neonates as per inclusion/exclusion criteria were analyzed. There were 239 (62.4%) boys and 144 (37.6%) girls. The mean age was 3.87+0.843 days. The mean TSH level was 12.807+5.11 mU/ml (ranging 7 to 50 mU/ml). We noted that CH was found in 10 neonates (2.6%). Practical Implications: The reported frequency of CH seems higher as compared to contemporary literature which raises the importance of CH screening programs at national level. Conclusion: The frequency of congenital hypothyroidism was 2.6% among newborns at a tertiary care hospital of Quetta, Pakistan. Keywords: Congenital hypothyroidism, newborn, thyroid-stimulating hormone.

Newborn Screening for Congenital Hypothyroidism and Congenital Adrenal Hyperplasia in Egypt

Newborn Screening for Congenital Hypothyroidism and Congenital Adrenal Hyperplasia in Egypt

Congenital Hypothyroidism: Screening and Management.

Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Newborn screening (NBS) for CH should be performed in all infants. Prompt diagnosis by NBS leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet practiced in all countries globally. Seventy percent of neonates worldwide do not undergo NBS. The recommended initial treatment of CH is levothyroxine, 10 to 15 mcg/kg daily. The goals of treatment are to maintain consistent euthyroidism with normal thyroid-stimulating hormone and with free thyroxine in the upper half of the age-specific reference range during the first 3 years of life. Controversy remains regarding the detection of thyroid dysfunction and optimal management of special populations, including preterm or low-birth-weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism. 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, accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Physicians 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 are present (such as large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid-stimulating hormone and free thyroxine is indicated, regardless of NBS results.

Cost-Effectiveness of Newborn Screening for Phenylketonuria and Congenital Hypothyroidism

To evaluate the long-term costs and health effects of the Swedish newborn screening program for classic phenylketonuria (PKU) alone and in combination with congenital hypothyroidism compared with no screening. A decision-analytic model was developed to estimate and compare the long-term (80years) costs and health effects of newborn screening for PKU and congenital hypothyroidism. Data were obtained from the literature and translated to Swedish conditions. A societal perspective was taken, including costs falling on health care providers, municipal care and services, as well as production loss due to morbidity. Screening 100 000 newborns for PKU resulted in 73 gained quality-adjusted life-years (QALYs) compared with no screening. When adding congenital hypothyroidism, the number of gained QALYs was 232 compared with PKU alone, adding up to a total of 305 QALYs gained. Corresponding cost estimates were $80.8, $70.3, and $10.05 million USD for no screening, PKU screening, and PKU plus congenital hypothyroidism screening, respectively, indicating that screening for PKU plus congenital hypothyroidism was more effective and less costly compared with the other strategies. The majority of cost savings with PKU plus congenital hypothyroidism screening was due to reductions in productivity losses and municipal care and services costs. The Swedish newborn screening program for PKU and congenital hypothyroidism saves substantial costs for society while generating additional QALYs, emphasizing the importance of public investments in early diagnosis and treatment.

Treatment of Congenital Hypothyroidism: Impact of Secular Changes in Levothyroxine Initial Dose on Early Growth

Introduction: Newborn screening of congenital hypothyroidism (CH) has enabled early treatment with levothyroxine (LT4), ensuring normal growth and development. The initial LT4 dose recommendation has increased over decades. We evaluated whether the increased LT4 dosing influenced thyroid-stimulating hormone (TSH) and thyroxine (fT4) concentrations, growth, or treatment-related symptoms. Methods: LT4 doses, TSH, fT4, anthropometrics, and treatment-related symptoms until age 2 years were evaluated in 172 Finnish CH patients born between 1980 and 2018. The patients were grouped according to birth decade: 1980s (n = 19, mean LT4 starting dose 6.8 μg/kg/day), 1990s (n = 50, 7.4 μg/kg/day), 2000s (n = 59, 9.7 μg/kg/day), and 2010s (n = 44, 10.8 μg/kg/day). Results: TSH concentrations were higher during the first 2 years of life in children born in the 1980s compared to children born later. TSH concentrations were often subnormal in children receiving higher LT4 doses (children born in the 2000s and 2010s). However, symptoms of overtreatment were uncommon. Linear or head growth showed no differences between the groups during the first 2 years of life. Although growth was within the normal spectrum, children in all groups were shorter than their target length at 2 years and their weight-for-length was above the mean through the first 2 years of life. Discussion: Current treatment practice with higher LT4 dose normalizes TSH rapidly without significant increase in side effects. However, irrespective of initial LT4 dose, children were shorter than expected at 2 years of age. Effects of different initial LT4 dose on cognitive development urges further investigation.

Thyroid Function in 509 Premature Newborns Below 31 Weeks of Gestational Age: Evaluation and Follow-up

Preterm and low birth weight (LBW) neonates may present with thyroid dysfunction during a critical period for neurodevelopment. These alterations can be missed on routine congenital hypothyroidism (CH) screening which only measures thyroid stimulating hormone (TSH). The objective of this study was to evaluate a protocol for thyroid function screening (TFS) six years after national implementation. Serum TSH and free thyroxine (fT4) were measured during the second week of life in neonates below 31 weeks. Patients with abnormal TFS (fT4 <0.8 ng/dL and/or TSH >5 mU/L) were followed up with repeated tests until normal levels were reported. Patients who were still on levothyroxine (LT4) at three years of age were re-evaluated. Five-hundred and nine neonates were included. Thyroid dysfunction was detected in 170 neonates (33%); CH n=20 (3.9%) including typical CH n=1; delayed TSH elevation CH n=19; hypothyroxinemia of prematurity (HOP) n=15 (2.9%); and transient hyperthyrotropinemia n=135 (26.5%). Twenty-one neonates (4.1%) were treated (20 for CH and 1 for HOP). At 3-year follow-up only three patients were diagnosed with permanent CH and still need treatment. LBW infants tended to have TSH levels higher than those with adequate weight. This protocol was able to detect thyroid dysfunction in preterm neonates who were not identified by the current program based on TSH determination in whole-blood. This thyroid dysfunction seems to resolve spontaneously in a few months in the great majority of neonates, but in some cases LT4 could be needed. There is a critical need for specific guidelines regarding the follow-up and re-evaluation of transient CH in preterm neonates.

ODP385 False Negative in the Screening for Congenital Hypothyroidism in Twin Newborns

Abstract Background In the neonatal screening for congenital hypothyroidism, false negative cases can be recorded, as evidenced in some twin newborns of the same sex, presumably due to fetal blood exchange. Clinical Case Neonate obtained by caesarean section indicated for twin pregnancy. The newborn and his twin, both male, presented normal TSH values (&amp;lt;10 mlU/L) in the neonatal screening for congenital hypothyroidism; but in the second screening, routinely performed in newborns obtained from twin or multiple pregnancies, in the second week of life, a TSH level of 27 mlU/L was evidenced in the newborn; the free T4 value was analyzed and was found to be low. With the diagnosis of congenital hypothyroidism, therapy with levothyroxine was started. Conclusion It is important to carry out a second neonatal screening for congenital hypothyroidism in cases of multiple pregnancy, especially twins of the same sex, in the second week of life, to avoid possible false negatives TSH values. Presentation: No date and time listed

ODP378 Biliary Sludge in a Neonate with Congenital Hypothyroidism

Abstract Background Most cases of congenital hypothyroidism are asymptomatic. When signs are evident, they are nonspecific. Characteristic clinical findings, including prolonged jaundice are seen in less than 5% of affected neonates. Clinical Case Female newborn, full term, appropriate weight for gestational age, five days old, Kramer zone 3 jaundice. The laboratory ruled out hemolysis, blood group incompatibility and TORCH infections. Hepatobiliary ultrasound showed biliary sludge. The screening for congenital hypothyroidism reported a TSH value of 38 mlU/L; the free T4 value was analyzed and was low. With the diagnosis of congenital hypothyroidism, levothyroxine therapy was started. The biliary sludge disappeared two weeks after initiation of hormone therapy. Conclusion It is important to exclude other causes of biliary sludge formation, such as sepsis, parenteral nutrition, hemolytic disease, metabolic diseases, some drugs and pyloric stenosis. Congenital hypothyroidism may be associated with biliary sludge formation; thyroid hormones have an inhibitory effect on the contractility of the sphincter of Oddi. Presentation: No date and time listed

The incidence of congenital hypothyroidism in neonates born in Chaharmahal and Bakhtiari province from 2015 to 2021; A cross-sectional study

Introduction: Congenital hypothyroidism (CH) is one of the most common endocrine and metabolic disorders and a common preventable cause of mental retardation across the world. This disorder can be prevented if diagnosed and treated before the age of four weeks. Objectives: This study was performed to investigate the incidence rate of CH in infants in Chaharmahal and Bakhtiari province. Patients and Methods: The data of this study were obtained by the CH screening program from 2015 to 2021 in the health deputy of Chaharmahal and Bakhtiari province. Results: A total of 651 patients were diagnosed with CH, which showed an incidence rate of 5.06 per 1000 births (1 per 198 live births) in the province. The highest incidence of the disease was obtained in 2016 and the lowest incidence in 2021. Lordegan city had the highest incidence rate (8.1 per 1000 live births) and Kiar had the lowest one (1.67 per 1000 live births) during the study period. Moreover, the highest and lowest incidence rates in terms of season were observed in winter and summer, respectively. Conclusion: It can be concluded that Chaharmahal and Bakhtiari province, especially Lordegan, is one of the regions with high prevalence of CH in Iran, therefore the incidence rate is not only higher than the national average but also higher than the global average. Hence, the potential causes of this observation deserve further investigation.

Severe neonatal hyperbilirubinemia secondary to combined RhC hemolytic disease, congenital hypothyroidism and large adrenal hematoma: a case report

BackgroundABO blood group incompatibility, neonatal sepsis, G-6-PD deficiency, thyroid dysfunction, and hereditary spherocytosis are all probable causes of neonatal hyperbilirubinemia. However, the etiology of some hyperbilirubinemia is extremely complicated, which may be caused by multiple factors, resulting in severe jaundice. We report a case of severe jaundice due to three causes, showing the significance for the investigation of the etiology of neonatal hyperbilirubinemia.Case presentationAt 96 h of life, a full-term and vaginal delivery male infant with yellowish discoloration of body was transferred to our hospital. When he entered neonatal intensive care unit on the fourth day after birth, he developed jaundice and the transcutaneous bilirubin was 28 mg/dl. Total bilirubin was 540.2 μmol/L, while the indirect bilirubin was 516.7 μmol/L. Both parents and the baby’s blood types were O Rh(D +), and direct coomb’s test was negative. But mother’s indirect coomb’s test was positive. Investigating for minor blood group revealed that the father’s blood type of Rh was CCDee, the mather’s was ccDEE, and CcDEe for the baby. After intensive phototherapy and double volume exchange transfusion, the total bilirubin remained at 303 μmol/L. At day 10, the bilirubin level was 303.5 μmol/L, intensive phototherapy was continued, and intravenous immunoglobulin was used again. The test for thyroid hormones at day 10, the TSH was 13.334mIU/L. And the screening for congenital hypothyroidism showed the TSH was 33mIU/L. Because of the palpable abdominal mass, ultrasound and MRI was done, showed a huge mass in the right adrenal gland. Brainstem auditory evoked potential was performed at day 7, which indicated hearing impairment (65db for left ear and 70db for the right). Euthyrox and intermittent phototherapy were given as following treatment. The jaundice did not subside until the 12th day.ConclusionEven if their parents' ABO blood group and Rh (d) are consistent, a Coomb test is required for newborns with hyperbilirubinemia since they may have minor blood group incompatibilities. When bilirubin rises rapidly or the clinical treatment effect is inadequate, additional causes should be aggressively screened. Adrenal ultrasound should be performed on newborns with palpable abdominal mass, anemia and jaundice to determine whether there is adrenal hemorrhage.

ESTABLISHING A NATIONWIDE NEWBORN SCREENING PROGRAM FOR CONGENITAL HYPOTHYROIDISM: A SYSTEMATIC REVIEW

Objective: The congenital hypothyroidism (CH) is a treatable hormonal disease that if left untreated in neonates, results in irreversible mental retardation. Newborn screening for CH and thyroid hormone replacement therapy started within two weeks of age can control cognitive development. This study aimed to estimate CH incidence in Pakistani population. Material and Methods: Electronic databases and the bibliography of articles were searched, and a systematic review of publications reporting the incidence of CH in Pakistan was carried out. The studies fulfilling the following criteria were analyzed: retrospective and prospective studies, adult population; pediatric population; Thyroid Stimulating Hormone (TSH); Dried Blood Spot (DBS); serum testing quantitative; English language. Results: We identified nine studies that narrated the incidence of CH in our country. According to this systematic review, the maximum estimated incidence of CH was 1:1600 reported for Pakistani population. Compared to the incidence of CH from other parts of the world (1:2000-1:4000), incidence from Pakistan is high. Conclusion: According to these findings, this high incidence highlights the need for a National Newborn Screening (NBS) program for CH. We have proposed a strategy for establishing a nationwide NBS program for CH. Key Words: Newborn screening, Congenital hypothyroidism, Pakistan, Thyroid-stimulating hormone, Mental retardation

Fifty years of newborn screening for congenital hypothyroidism: current status in Australasia and the case for harmonisation

Since its implementation 50 years ago in Quebec, Canada, newborn screening for congenital hypothyroidism has become one of the most successful public health measures worldwide. Screening programmes across Australia and New Zealand are characterised by significant commonalities in screening algorithms, and a high degree of regional cooperation in harmonisation efforts. We aimed to conduct a comprehensive survey of current performance and practices related to the total testing process for congenital hypothyroidism screening and provide recommendations for harmonisation priorities within our region. A survey was conducted involving the six newborn screening laboratories which provide complete geographic coverage across Australasia. Approximately 360,000 newborns are screened annually. Survey questions incorporated pre-analytical, analytical, and post-analytical aspects of the screening programmes and an extensive 5-year (2016-2020) retrospective analysis of individual programme performance data. Responses from individual screening programmes were collated. The uptake of newborn screening was over 98% for the six major jurisdictions. All programmes have adopted a single-tier thyroid stimulating hormone (TSH) strategy using the Perkin Elmer GSP instrument. Significant similarities exist between programmes for recommended age of collection and recollection protocols for low birthweight newborns. The process for the determination of TSH cutoffs varies between programmes. TSH lower cut-offs for borderline-positive and positive notifications between 12-15 and 12-25mIU/L blood, respectively. Recall rates vary between 0.08 and 0.20%. The case definition forcongenital hypothyroidism generally includes biochemical and radiological parameters in addition to the commencement of thyroxine. All programmes reported collecting biochemical and clinical data on infants with positive screening tests, and positive predictive values vary between 23.6 and 77.3%. Variation in reported incidence (1:1,300-2,000) cannot be entirely explained by cutoff or recall rate (although one programme reporting fewer cases includes only permanent disease). Despite similarities between newborn screening algorithms for congenital hypothyroidism across Australia and New Zealand, differences in reported programme performance provide the basis for further harmonisation. Surveillance of a large population offers the potential for the ongoing development of evidence-based screening guidelines.

Neonatal thyrotropin - indicatior of monitoring of iodine deficiency severity. What's level is considered a «cutoff point»?

The issues of monitoring the effectiveness of iodine deficiency prevention programs are an important component in the process of iodine elimination. Neonatal thyrotropin (TSH) has been used as a criterion for the severity of iodine deficiency since 1994, however, the question of the "cut-off point" of the neonatal TSH level has been widely discussed in the recent literature. Evaluate the criterion for neonatal hyperthyroidism above 5 mIU/l from the perspective of monitoring iodine deficiency and establish a «cut-off point» on the model of healthy pregnant women with adequate iodine status. A prospective study was conducted in a population of pregnant women in the city of Tyumen, with the formation of observation groups according to the level of iodine excretion in the urine - the main group (with adequate iodine status throughout the entire gestation period) and the comparison group (women with iodine levels less than 150 μg/l). The results of neonatal screening for congenital hypothyroidism in children of women participating in the study were evaluated. The frequency of neonatal TSH above 5mIU/l was assessed in the observation groups. ROC-analysis was performed and a «cut-off point» of the level of neonatal TSH was established as an indicator of iodine deficiency. The median urinary iodine concentration in the population of pregnant women in Tyumen was 159.05 μg/l, the incidence of goiter was 0.38%, the incidence of neonatal hyperthyroidism above 5 mIU/l was 2.88%, which characterizes adequate iodine intake in the pregnant population women. The frequency of neonatal TSH above 5 mIU/l in newborns from women from the main group was 1.47%, and in the comparison group - 9.3% (p = 0.076). ROC analysis revealed a threshold value of neonatal TSH of 2.77 mIU/l at the cut-off point, which corresponded to the highest value of the Youden index. Urinary iodine concentrations greater than 150 μg/l were predicted for nTSH values below this value. Analysis of databases of neonatal screening for congenital hypothyroidism makes it possible to effectively, quickly and at minimal cost annually assess the iodine status in the population. The established «cut-off point» of neonatal TSH in the model of healthy pregnant women with adequate iodine intake in our work is 2.77 mIU/l, the absence of statistically significant differences in the incidence of neonatal hyperthyroidism above 5 mIU/l from women with different iodine status during pregnancy indicate the need to revise the existing threshold of 5 mIU/l and may be an incentive to conduct large-scale studies in regions with different iodine supply.