Screening for congenital hypothyroidism in Maltese newborns using cord blood

Routine screening for congenital hypothyroidism (CHT) has been introduced because clinical features of CHT may not be evident before the baby is a few weeks old and treatment at this stage may already be too late. Since a newborn testing programme employing liquid cord blood for other conditions had already been developed in the University of Malta and the Department of Health, we explored the possibility of implementing newborn thyroid testing using liquid cord blood. A similar programme had been implemented successfully in Finland and Philadelphia. Between September 1989 and August 1995 around 32,000 newborns were tested. This is nearly complete ascertainment. Preliminary testing was by radioimmunoassay for TSH. The sera of those with TSH levels more than 13mU/l were further tested for free T4. If the free T4 level was below 12 pmol/l, the babies were recalled for clinical evaluation and repeat testing. Other babies were recalled for technical reasons, giving a total recall rate of 3.88%. CHT was identified in seven newborns and treatment started within 3 weeks of delivery. One baby was reported normal on screening but was suspected to have CHT on clinical grounds at 3 weeks of age, confirmed biochemically. The incidence of CHT in Malta is therefore 1 in 4500.peer-reviewe

Trends in Scottish newborn screening programme for congenital hypothyroidism 1980-2014: strategies for reducing age at notification after initial and repeat sampling

Objectives: To determine ages at first capillary sampling and notification and age at notification after second sampling in Scottish newborns referred with elevated thyroid-stimulating hormone (TSH). Subjects and methods: Referrals between 1980 and 2014 inclusive were grouped into seven 5-year blocks and analysed according to agreed standards. Results: Of 2 116 132 newborn infants screened, 919 were referred with capillary TSH elevation ≥8 mU/L of whom 624 had definite (606) or probable (18) congenital hypothyroidism. Median age at first sampling fell from 7 to 5 days between 1980 and 2014 (standard 4–7 days), with 22, 8 and 3 infants sampled >7 days during 2000–2004, 2005–2009 and 2010–2014. Median age at notification was consistently ≤14 days, range falling during 2000–2004, 2005–2009 and 2010–2014 from 6 to 78, 7–52 and 7–32 days with 12 (14.6%), 6 (5.6%) and 5 (4.3%) infants notified >14 days. However 18/123 (14.6%) of infants undergoing second sampling from 2000 onwards breached the ≤26-day standard for notification. By 2010–2014, the 91 infants with confirmed congenital hypothyroidism had shown favourable median age at first sample (5 days) with start of treatment (10.5 days) approaching age at notification. Conclusion: Most standards for newborn thyroid screening are being met by the Scottish programme, but there is a need to reduce age range at notification, particularly following second sampling. Strategies to improve screening performance include carrying out initial capillary sampling as close to 96 hours as possible; introducing 6-day laboratory reporting and use of electronic transmission for communicating repeat requests

Neonatal screening for congenital hypothyroidism in Pakistan

Congenital hypothyroidism is a preventable cause of mental retardation. Since clinical signs of congenital hypothyroidism do not generally become obvious before three months of age, screening programmes have been introduced in North America and Europe, which consist of T4 or TSH screening on newborn infants on the third day of life. The screening for congenital hypothyroidism was initiated in Pakistan by the Aga Khan University Hospital (AKUH) in March 1987. By April 1988, 5000 neonates were screened and five cases of congenital hypothyroidism were diagnosed. The study revealed the incidence of hypothyroidism to be one case per 1000 newborns which is about 4 times more than that in the Wes

Intellectual and motor development of young adults with congenital hypothyroidism diagnosed by neonatal screening

Contains fulltext : 35756.pdf (publisher's version ) (Open Access)CONTEXT: Long-term follow-up data on cognitive and motor functioning in adult patients with congenital hypothyroidism, diagnosed by neonatal screening, are scarce. Hence, it is still unclear whether the frequently reported cognitive and motor deficits observed during childhood persist in adulthood. OBJECTIVE: The objective of this study was to examine cognitive and motor functioning in young adults with congenital hypothyroidism, born in the first 2 yr after the introduction of the Dutch neonatal screening program. DESIGN/SETTING/PATIENTS: Seventy patients were tested (mean age, 21.5 yr); 49 of them were previously tested at 9.5 yr. The median age at the start of treatment was 28 d (range, 4-293 d). Congenital hypothyroidism was classified as severe, moderate, or mild, according to pretreatment T(4) concentrations. MAIN OUTCOME MEASUREMENT: The main outcome measurement was the influence of the severity of congenital hypothyroidism and age at which T(4) supplementation was started on cognitive and motor outcome. RESULTS: Patients, particularly those with severe congenital hypothyroidism, had significantly higher (i.e. worse) motor scores (total score, 7.8; ball skills, 2.0; balance, 4.1) compared with controls (total score, 3.2; ball skills, 0.7; balance, 1.1), and lower full-scale (95.8), verbal (96.4), and performance (95.6) intelligence quotient (IQ) scores than the normal population. No significant change in IQ from childhood to adulthood was found, and for the majority of patients, motor score classification remained the same. The severity of congenital hypothyroidism, but not the starting day of treatment, was correlated with IQ and motor scores. CONCLUSIONS: It is concluded that the severity of congenital hypothyroidism, but not the timing of treatment initiation, is an important factor determining long-term cognitive and motor outcome. Clearly, detrimental effects on developmental outcome in patients with congenital hypothyroidism persist over time

A new mutation in the promoter region of the PAX8 gene causes true congenital hypothyroidism with thyroid hypoplasia in a girl with Down's syndrome

<b>Background:</b> Thyroid dysfunction is common in newborn infants with Down's syndrome (DS), but defects causing classic thyroid dysgenesis (TD) with permanent congenital hypothyroidism (CH) have not been described.<p></p> <b>Objective:</b> We studied a girl with DS and CH who had a mutation in the promoter sequence of the PAX8 gene.<p></p> <b>Results:</b> A female infant was found to have trisomy 21 and CH, with a venous thyrotropin (TSH) of >150 mU/L and a free thyroxine (fT4) of 15.1 pmol/L (day 12). Thyroid peroxidase antibodies and thyroglobulin antibodies were elevated. Scintigraphy showed normal uptake, but ultrasound identified a small gland with heterogenous echotexture and cystic changes. Sequence analysis of the PAX8 gene revealed a new heterozygous maternally inherited mutation (−3C>T) close to the transcription initiation site. Electromobility shift assay studies of the wild type and the mutant PAX8 sequence incubated with nuclear extracts from PCCL3 cells exhibited that the sequence at position −3 is not involved in specific protein binding. However, the mutant PAX8 promoter showed a significantly reduced transcriptional activation of a luciferase reporter gene in vitro tested in HEK, PCCL3, as well as in HeLa cells, indicating that this mutation is very likely to lead to reduced PAX8 expression.<p></p> <b>Conclusions:</b> The persistent CH in this patient with DS is likely to be attributable to the diminished PAX8 expression due to a new heterozygous mutation in the PAX8 promoter sequence. Our case shows that true CH may occur in DS, as in the general population. Furthermore, it is possible that the trisomy 21 itself may have resulted in a more severe phenotypic expression of the PAX8 mutation in the child than the mother

Epidemiology of neonatal congenital hypothyroidism during 2011-2017

Introduction: Neonatal hypothyroidism is a condition of treatable thyroid deficiency that can lead to severe retardation if not diagnosed on time or inappropriately treated. The present study is an epidemiologic study of neonatal congenital hypothyroidism in Lordegan during 2012-2018. Materials and Methods: This descriptive-analytical study was performed to evaluate the epidemiological characteristics of congenital hypothyroidism. The data were entered into SPSS version 20 software and analyzed by statistical tests, Chi square, ANOVA, T-Test, Pearson Correlation and Spearman Correlation at 0.05 Level. Results: The analysis of 7-years data showed that from the screening of 39332 newborns, 335 were identified as definitive patients, 159 males, 176 females, 275 rural (82.1%) and 169 neonates with a history of family marriage (50.4%). There was a significant relationship between neonatal birth weight and congenital hypothyroidism (P = 0.000). There was a significant relationship between type of delivery and hypothyroidism (P = 0.000). In the treated children, there was a direct relationship between the age of onset of treatment and their TSH level, which was statistically significant (P = 0.013). Conclusion: Due to the high prevalence of congenital hypothyroidism in Lordegan, it is necessary to study further the factors affecting the incidence of congenital hypothyroidism as well as educate pregnant women and timely screening for this disease. keywords: Congenital Hypothyroidism, Epidemiology, Neonata

Neonatal Sludge: A finding of congenital hypothyroidism

Congenital hypothyroidism is one of the most urgent diseases of the neonate. When diagnosed and treated at an early stage, its most important complication, mental retardation, is preventable. The signs of congenital hypothyroidism are nonspecific in neonates. Only 5% of the cases have characteristic clinical findings. One of the most important and earliest signs is prolonged jaundice during the neonatal period. We report herein a case of congenital hypothyroidism, who presented with icterus accompanied with sludge formation into the gallbladder, which disappeared after treatment with L-thyroxine

Cognitive Outcomes for Congenital Hypothyroid and Healthy Children: A Comparative Study

How to Cite This Article: Ordooei M, MottaghiPisheh H, Fallah R, Rabiee A. Cognitive Outcomes for Congenital Hypothyroid andHealthy Children: A Comparative Study. Iran J Child Neurol. 2014 Autumn;8(4): 28-32.AbstractObjectiveEarly diagnosis and treatment of congenital hypothyroidism (CH) and the prevention of developmental retardation is the main goal of public health national screening programs. This study compares the cognitive ability of children with CH diagnosed by neonatal screening with a healthy control group (2007) in Yazd, Iran.Materials & MethodsIn a case-controlled study, the intelligent quotient (IQ) of 40 five-year-old children with early treated CH and good compliance were evaluated by the Wechsler preschool and primary scale of intelligent test and compared to 40 healthy age and gender matched children as controls.Results22 boys (55%) and 18 girls (45%) in both groups were evaluated. In children with CH, 19 (47.5%) and 21 (52.5%) persons had transient and permanent hypothyroidism, respectively.Range of TSH and T4 level at the onset of diagnosis were 11.41–81 mu/l and 1.50–14.20 μg/dl, respectively.The intelligence levels of all children with CH were within the average or normal range and IQs ranged from 91–108.Children with CH had lower full-scale IQs (107.25 ± 2. 9 versus 110.50 ± 2.66, p=0.001), verbal IQ (106.95 ± 3.5 versus 109.90 ± 3.44, P-value=0.001) and performance IQ (106.3 ± 3.68 versus 108.87 ± 3.70) than the control group.However, no statistically significant differences were observed for mean IQ scores in permanent and transient CH.ConclusionChildren with CH who had early treatment and good compliance had normal cognitive abilities, but may have a decreased IQ relative to the healthy control group.ReferencesLeFranchi S. Hypothyroidism. Kliegman RM, Stanton BF, Schor NF, St. Geme JW, Behrman RE. Nelson Textbook of Pediatrics. Philadelphia, Saunders 2011; 19th edition, Pp: 1895-1900.Nouri-Shadkam M, Jafarizadeh M, Mirzaei M, Motlagh M.E, Eslami Z, Afkhami-Ardekani M, et al. Prevalence of congenital hypothyroidism and transient increased levels of TSH in Yazd province. J Shahid Sadoughi Univ Med Sci 2008; 16:15-20. [Article in Persian]Hashemipour M, Hovsepian S, Kelishadi R, Iranpour R, Hadian R, Haghighi S, et al. Permanent and transient congenital hypothyroidism in Isfahan-Iran. J Med Screen 2009; 16:11-6.Dalili S, Rezvany SM, Dadashi A, Medghalchi A, Mohammadi H, Dalili H, et al. Congenital hypothyroidism: a review of the risk factors. Acta Med Iran 2012; 50:735-9.Zeinalzadeh AH, Talebi M. Neonatal screening for congenital hypothyroidism in East Azerbaijan, Iran: the first report. J Med Screen 2012; 19:123-6.Karamizadeh Z, Saneifard H, Amirhakimi G, Karamifar H, Alavi M. Evaluation of congenital hypothyroidism in Fars province, Iran. Iran J Pediatr 2012; 22:107-12.Bargagna S, Canepa G, Costagli C, Dinetti D, Marcheschi M, Millepiedi S, et al. Neuropsychological follow-up in early-treated congenital hypothyroidism: a problemoriented approach. Thyroid 2000; 10:243-9.van der Sluijs Veer L, Kempers MJ, Maurice-Stam H, Last BF, Vulsma T, Grootenhuis MA. Health- related quality of life and self-worth in 10-year old children with congenital hypothyroidism diagnosed by neonatal screening. Child Adolesc Psychiatry Ment Health 2012; 6:32.Soliman AT, Azzam S, Elawwa A, Saleem W. Linear growth and neurodevelopmental outcome of children with congenital hypothyroidism detected by neonatal screening: A controlled study. Indian J Endocrinol Metab 2012; 16:565-8.Bongers-Schokking JJ. Influence of timing and dose of thyroid hormone replacement on mental, psychomotor, and behavioral development in children with congenital hypothyroidism. J Pediatr 2005; 147:768-74.Wechsler, D. The Wechsler Preschool and Primary Scale of Intelligence - Manual. New York: psychological Corporation, 1967.Romero JB, Palacios GC, Gómez N, Silva A, Fabela JH. Intelligence quotient related with congenital hypothyroidism etiology. Rev Med Inst Mex Seguro Soc 2011; 49:179-83. [Article in Spanish]Kik E, Noczyńska A. Evaluation of mental development of children with congenital hypothyroidism detected in screening test--personal observations. Pediatr Endocrinol Diabetes Metab 2010; 16:100-8. [Article in Polish]Arenz S, Nennstiel-Ratzel U, Wildner M, Dörr HG, Intellectual outcome, motor skills and BMI of children with congenital hypothyroidism: a population-based study. Acta Paediatr 2008; 97:447-50.Alvarez González MA, Carvajal Martínez F, Pérez Gesén C, Olivares Torres A, Fernández Yero JL, Robaina Alvarez R, et al. Prognosis of cognition in congenital hypothyroidism following early treatment. Double effect hypothesis. Rev Neurol 2004, 16-31; 38:513-7. [Article in Spanish]Boileau P, Bain P, Rives S, Toublanc JE. Earlier onset of treatment or increment in LT4 dose in screened congenital hypothyroidism: which as the more important factor for IQ at 7 years? Horm Res 2004; 61:228-33.Salerno M, Militerni R, Bravaccio C, Micillo M, Capalbo D, Di MS, Tenore A. Effect of different starting doses of levothyroxine on growth and intellectual outcome at four years of age in congenital hypothyroidism. Thyroid 2002; 12:45-52.Dimitropoulos A, Molinari L, Etter K, Torresani T, Lang- Muritano M, Jenni OG, Largo RH, Latal B. Children with congenital hypothyroidism: long-term intellectual outcome after early high-dose treatment. Pediatr Res 2009; 65:242-8.Joseph R. Neuro-developmental deficits in early-treated congenital hypothyroidism. Ann Acad Med Singapore 2008; 37(12 Suppl):42-3.Kempers MJ, van der Sluijs Veer L, Nijhuis-van der Sanden MW, Kooistra L, Wiedijk BM, Faber I, et al.Intellectual and motor development of young adults with congenital hypothyroidism diagnosed by neonatal screening. J Clin Endocrinol Metab2006; 91:418-24.Rovet JF. Children with congenital hypothyroidism and their siblings: do they really differ? Pediatrics 2005;115:e52-7.Kempers MJ, van der Sluijs Veer L, Nijhuis-van der Sanden RW, Lanting CI, Kooistra L, Wiedijk BM, et al. Neonatal screening for congenital hypothyroidism in the Netherlands: cognitive and motor outcome at 10 years of age. J Clin Endocrinol Metab2007; 92:919-24.Azizi F, Afkhami M, Sarshar A, Nafarabadi M. Effects of transient neonatal hyperthyrotropinemia on intellectual quotient and psychomotor performance. Int J Vitam Nutr Res 2001; 71:70-3.Salerno M, Militerni R, Di Maio S, Bravaccio C, Gasparini N, Tenore A. 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Discontinuation of thyroid hormone treatment among children in the United States with congenital hypothyroidism: findings from health insurance claims data

<p>Abstract</p> <p>Background</p> <p>Thyroid hormone treatment in children with congenital hypothyroidism can prevent intellectual disability. Guidelines recommend that children diagnosed with congenital hypothyroidism through newborn screening remain on treatment to at least 3 years of age, after which a trial off therapy can determine which children have transient hypothyroidism. The purpose of this study was to describe the rate at which children with congenital hypothyroidism in the United States discontinue thyroid hormone treatment in early childhood.</p> <p>Methods</p> <p>Retrospective analysis of the 2002-2006 MarketScan^®Commercial Claims and Encounters research databases and the 2001-2005 MarketScan Multi-State Medicaid databases. Children were classified as having congenital hypothyroidism based on billing codes and having filled a prescription for thyroid hormone treatment. Kaplan-Meier curve analysis was used to determine discontinuation rates.</p> <p>Results</p> <p>There were a total of 412 Medicaid-enrolled children and 292 privately-insured children with presumed congenital hypothyroidism included in this study. The overall birth prevalence of congenital hypothyroidism across both datasets was about 1 per 2,300. By 36 months, the percentage who had discontinued thyroid replacement treatment was 38% (95% Confidence Interval: 32%-44%). Medicaid-enrolled children had a more rapid decline in the first 24 months of treatment compared to those with private insurance (<it>P </it>= 0.02).</p> <p>Conclusions</p> <p>More than one-third of children treated for congenital hypothyroidism discontinued treatment within 36 months, which is inconsistent with current guidelines. It is not known how many of these children required continued treatment or experience adverse effects from discontinuation. These findings emphasize the critical need for follow-up systems to monitor the outcome of newborn screening.</p