Pilot Neonatal Screening Program for Central Congenital Hypothyroidism: Evidence of Significant Detection

Background/Aim: Congenital hypothyroidism (CH) is a heterogeneous entity. Neonatal screening programs based on thyrotropin (TSH) determination allow primary CH diagnosis but miss central CH (CCH). CCH causes morbidity, alerts to other pituitary deficiencies, and is more prevalent than previously thought. We aimed at developing a pilot neonatal screening program for CCH detection. Patients and Methods: A prospective 2-year pilot neonatal screening study based on simultaneous dried blood specimen TSH and thyroxine (T4) measurements was implemented in term newborns aged 2–7 days. Those with T4 ≤4.5 µg/dL (–2.3 SDS) and TSH <10 mIU/L were recalled (suspicious of CCH) and underwent clinical and biochemical assessment performed by expert pediatric endocrinologists. Results: A total of 67,719 newborns were screened. Primary CH was confirmed in 24 (1: 2,821). Forty-four newborns with potential CCH were recalled (recall rate 0.07%) at a mean age of 12.6 ± 4.8 days. In this group, permanent CCH was confirmed in 3 (1: 22,573), starting L-T4 treatment at a mean age of 12.3 ± 6.6 days; 14 boys showed T4-binding globulin deficiency (1: 4,837); 24 had transient hypothyroxinemia (21 non-thyroidal illness and 3 healthy); and 3 died before the confirmation stage. According to initial free T4 measurements, CCH patients had moderate hypothyroidism. Conclusions: Adding T4 to TSH measurements enabled the identification of CCH as a prevalent condition and contributed to improving the care of newborns with congenital hypopituitarism and recognizing other thyroidal disorders.

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A Newborn Falsely Suspected of Congenital Hypothyroidism due to Mutated Thyroxine-Binding Globulin with Low Binding Affinity

Hormone Research in Paediatrics ◽

10.1159/000516691 ◽

2021 ◽

pp. 1-5

Author(s):

Rutger C.C. Hengeveld ◽

Monique Albersen ◽

Michael A.H. Hadders ◽

Ilse Hellinga ◽

Hennie Bikker ◽

...

Keyword(s):

Congenital Hypothyroidism ◽

Neonatal Screening ◽

Screening Program ◽

Sequencing Analysis ◽

Free T4 ◽

Gene Encoding ◽

Central Hypothyroidism ◽

Thyroxine Binding Globulin ◽

Screening Programs ◽

Dna Sequencing Analysis

Introduction: Neonatal screening programs for congenital hypothyroidism (CH) have been implemented worldwide to facilitate early diagnosis and treatment. The Dutch neonatal CH screening is primarily based on the measurement of thyroxine (T4). When T4 is low, an additional thyroxine-binding globulin (TBG) measurement is performed to reduce the number of false-positive screening results due to harmless TBG deficiency. Here, we present a case of a rare functional TBG deficiency leading to a false suspicion of CH. Case Presentation: Neonatal screening in this patient revealed a decreased T4, normal TSH, and normal TBG concentration, suggesting central CH. However, free T4 was normal. DNA sequencing analysis revealed a novel, hemizygous mutation (c.139G>A) in SERPINA7, the gene encoding TBG, resulting in the substitution of the conserved amino acid alanine to threonine at position 27. Crystal structure analyses showed that this substitution has a detrimental effect on binding of T4 to TBG. Conclusions: The novel SERPINA7 variant in this patient led to a false suspicion of central hypothyroidism in the Dutch T4-based neonatal screening program. It is important to recognize patients with such TBG defects to prevent unnecessary additional testing and treatment.

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Clinical Effectiveness and Cost-Effectiveness of the Use of the Thyroxine/Thyroxine-Binding Globulin Ratio to Detect Congenital Hypothyroidism of Thyroidal and Central Origin in a Neonatal Screening Program

PEDIATRICS ◽

10.1542/peds.2004-2162 ◽

2005 ◽

Vol 116 (1) ◽

pp. 168-173 ◽

Cited By ~ 53

Author(s):

C. I. Lanting

Keyword(s):

Cost Effectiveness ◽

Congenital Hypothyroidism ◽

Neonatal Screening ◽

Screening Program ◽

Clinical Effectiveness ◽

Thyroxine Binding Globulin ◽

Central Origin ◽

Neonatal Screening Program

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Congenital Hypothyroidism in the Southern Bangladesh

TAJ Journal of Teachers Association ◽

10.3329/taj.v21i1.3212 ◽

1970 ◽

Vol 21 (1) ◽

pp. 18-22 ◽

Cited By ~ 1

Author(s):

C Habibur Rasul ◽

S Nahar Lucky ◽

S Rahman Miah ◽

F Moslem

Keyword(s):

Birth Weight ◽

Congenital Hypothyroidism ◽

Neonatal Screening ◽

Screening Program ◽

National Level ◽

Retarded Child ◽

Thyroid Function Test ◽

Cord Blood Sample ◽

College Hospital ◽

Neonatal Screening Program

Congenital hypothyroidism is the commonest preventable cause of mental retardation. It is more prevalent in endemic goiter regions like Bangladesh. But magnitude of the problem has not been studied at national level. This study was done to detect the frequency of congenital hypothyroidism in southem part of Bangladesh & to develop neonatal screening program. All the living newborns delivered between Oct 01 to June 05 Khulna Medical College Hospital were included in the study, After taking the relevant information from mother, cord blood sample were collected from the newborn within 120 hours of birth and kept in freezer. At the end of collection of each two months, the lot was sent to the laboratory of Institute of Nuclear Medicine, Dhaka for radioimmunoassay of TSH. Potential cases with TSH above 10 MIU were recalled for thyroid function test for confirmation of diagnosis. Fifteen hundred samples were collected in total during 45 months of study. One forty seven unsatisfactory samples were discarded; thereby 1353 samples were eventually assayed for TSH. Among the study population 88.2% hailed from Khulna district and the rest of the cases came from neighboring districts. Male to female baby ratio was 1.2:1. Regarding the birth weight 33.4% babies were low birth weight. TSH above 10 was found in 35 babies among whom one baby was hypothyroid and the other member of the twin was also hypothyroid although the TSH level was below 10. None of newborn had TSH level above 20. Thus frequency of congenital hypothyroidism was 1.5 per thousand living newborn. Congenital hypothyroidism in southern part of the country is quite high in relation to global incidence. Although this is not the national picture but the high figure is alarming. Therefore neonatal screening program should be implemented as soon as possible to reduce the number of mentally retarded child. doi: 10.3329/taj.v21i1.3212 TAJ 2008; 21(1): 18-22

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Descriptive Epidemiology of Missed Cases of Phenylketonuria and Congenital Hypothyroidism

PEDIATRICS ◽

10.1542/peds.78.4.553 ◽

1986 ◽

Vol 78 (4) ◽

pp. 553-558

Author(s):

Candy Holtzman ◽

William E. Slazyk ◽

José F. Cordero ◽

W. Harry Hannon

Keyword(s):

Congenital Hypothyroidism ◽

Neonatal Screening ◽

Telephone Survey ◽

Screening Program ◽

Descriptive Epidemiology ◽

Screening Programs ◽

Specimen Collection ◽

True Number ◽

Laboratory Procedures

We conducted a structured telephone survey of state public health laboratory directors of neonatal screening programs to determine the extent of the problem of missed cases of phenylketonuria (PKU) and congenital hypothyroidism. A total of 76 missed cases were reported—43 PKU and 33 congenital hypothyroidism. We looked at the following characteristics of the missed cases: the stage at which the miss occurred, which included specimen collection, laboratory procedures, or follow-up; the size of the program; the type of screening program; the age of the infant at the time of screening; and any legal action that resulted from the miss. The 76 missed cases probably represent an underascertainment of the true number, yet we believe that our data provide an overview of some of the problems associated with mass neonatal screening. There was one missed case of PKU for every 70 cases detected, and one missed case of congenital hypothyroidism for every 120 cases detected; in other words, two congenital hypothyroidism cases were missed for every 1 million infants screened. Regarding the stage of screening in which the miss occurred, 14% occurred during specimen collection, 45% during the laboratory procedures stage, 16% during follow-up, 11% were the result of biologic variation, and in 14% the stage could not be identified. We conclude that neonatal screening programs have been highly successful but that there may be additional safeguards to be developed, tested, and implemented when practical.

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Clinical Effectiveness and Cost-effectiveness of the Use of the Thyroxine/Thyroxine-Binding Globulin Ratio to Detect Congenital Hypothyroidism of Thyroidal and Central Origin in a Neonatal Screening Program

Yearbook of Neonatal and Perinatal Medicine ◽

10.1016/s8756-5005(08)70340-8 ◽

2006 ◽

Vol 2006 ◽

pp. 257-258

Author(s):

P.M. Gerrits

Keyword(s):

Cost Effectiveness ◽

Congenital Hypothyroidism ◽

Neonatal Screening ◽

Screening Program ◽

Clinical Effectiveness ◽

Thyroxine Binding Globulin ◽

Central Origin ◽

Neonatal Screening Program

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Current status of the congenital hypothyroidism neonatal screening program in Adana Province, Turkey

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0433 ◽

2018 ◽

Vol 31 (6) ◽

pp. 619-624 ◽

Cited By ~ 2

Author(s):

Yılmaz Kor ◽

Deniz Kor

Keyword(s):

Congenital Hypothyroidism ◽

Neonatal Screening ◽

Screening Program ◽

Thyroid Stimulating Hormone ◽

Initial Evaluation ◽

Current Status ◽

The Mean ◽

Neonatal Screening Program ◽

Heel Prick

Abstract Background: Congenital hypothyroidism (CH) is a common cause of mental retardation; it has a worldwide incidence ranging from 1:3000 to 1:4500 live births. Predictably, an increase in the reported incidence of primary CH occurs when the cut-off levels of thyroid-stimulating hormone are lowered. We aimed to evaluate the results of a congenital hypothyroidism screening program and current status in this study. Methods: Analysis results of 1300 infants who were referred to the endocrinology polyclinic because of suspected CH within the scope of the Ministry of Health National Neonatal Screening Program were retrospectively evaluated. Results: The diagnosis of CH and initiation of treatment were both done in 223 (18.5%) and 10 (0.8%) infants as a result of the initial evaluation and follow-up, respectively. The mean capillary and venous thyroid-stimulating hormone (TSH) levels of 223 patients were 40.78 (5.5–100) μIU/mL and 67.26 (10.7–100) μIU/mL, respectively. These patients’ mean heel prick time was 8.65 (0–30, median: 7) days. The mean age of the 223 infants whose treatment was initiated as a result of the initial evaluation was 19.87 (4–51, median: 20) days, and the mean age of the infants whose treatment was started at follow-up was 43.71 (29–65) days. The duration between heel prick time and venous TSH time was 11.10 (2–28, median: 11) days and was longer than planned (3–5 days). Conclusions: Although the duration for the diagnosis and initiation of CH treatment were markedly reduced with the implementation of the screening program in Turkey compared to those before the implementation of the screening program, we have not yet achieved the ideal time (≤14 days).

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High Prevalence of Congenital Hypothyroidism in the Greek Cypriot Population: Results of the Neonatal Screening Program 1990- 2000

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem.2005.18.5.453 ◽

2005 ◽

Vol 18 (5) ◽

Cited By ~ 11

Author(s):

N. Skordis ◽

M. Toumba ◽

S.C. Savva ◽

E. Erakleous ◽

M. Topouzi ◽

...

Keyword(s):

Congenital Hypothyroidism ◽

Neonatal Screening ◽

Screening Program ◽

Greek Cypriot ◽

High Prevalence ◽

Neonatal Screening Program

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Influence of topical iodine-containing antiseptics used during delivery on recall rate of congenital hypothyroidism screening program

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2016-0164 ◽

2017 ◽

Vol 30 (9) ◽

Cited By ~ 1

Author(s):

Majid Valizadeh ◽

Farzaneh Moezzi ◽

Zohreh Khavassi ◽

Mohammad Movahedinia ◽

Seideh Mazloomzadeh ◽

...

Keyword(s):

Phase I ◽

Congenital Hypothyroidism ◽

Phase Ii ◽

Screening Program ◽

Recall Rate ◽

Local Hospital ◽

Screening Programs ◽

Blood Specimens ◽

Heel Prick ◽

Tsh Levels

AbstractBackground:The proportion of newborns recalled during neonatal screening programs for congenital hypothyroidism (CH) varies substantially by country and may be higher in settings where povodine iodine (PVP-I) is used during delivery. We assessed this hypothesis by substituting PVP-I for chlorhexidine (CHL) and evaluated the reduction in the recall rate of the Irainian newborn screening program.Methods:This study investigated 2282 neonates of mothers admitted to a local hospital for delivery between December 2012 and October 2013. We measured thyorid stimulating hormone (TSH) levels in heel-prick blood specimens of infants, aged between 3 and 5 days, born to mothers who received PVP-I (phase I) and those who received CHL after withdrawal of PVP-I from obstetric procedures (phase II). Then we compared the median TSH levels and the recall rate based on a TSH level ≥5 mU/L.Results:Of 2282 cases, 1094 infants were born to mothers exposed to PVP-I during phase I (PVP-I group) and 1188 ones were born to mothers exposed to chlorhexidine in phase II (CHL group); 6.56% of the PVP-I group and 1.91% of the CHL group were recalled later during screening (p<0.001). The median TSH level was significantly higher in the PVP-I group compared to the CHL group (1.35 vs. 1.00, p<0.001).Conclusions:Replacement of iodine-containing antiseptics by iodine-free ones, during delivery resulted in a significant reduction in the recall rate of the Iranian screening program for CH.

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

Advances in Endocrinology ◽

10.1155/2015/387684 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6

Author(s):

Sze Lyn Jeanne Wong ◽

Muhammad Yazid Jalaludin ◽

Azriyanti Anuar Zaini ◽

Nurshadia Samingan ◽

Fatimah Harun

Keyword(s):

Cord Blood ◽

Congenital Hypothyroidism ◽

Screening Program ◽

Recall Rate ◽

Medical Centre ◽

Asian Countries ◽

Predictive Values ◽

Screening Programs ◽

Premature Babies ◽

Blood Screening

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.

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