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Background: The current neonatal screening program ("the heel prick") involves taking a few drops of blood from almost every newborn in the Netherlands to determine whether the child is suffering from one of three congenital disorders: phenylketonuria, congenital hypothyroid, or adrenogenital syndrome. This study investigated the preferences and views of parents and future parents with respect to information about, and consent to, neonatal screening and the possible expansion of the program. Methods: Seven focus group discussions took place with future parents, parents with a healthy child, and parents with children affected by disorders for which screening is possible, now or in the future (total of 36 participants). The discussions were audiotaped, transcribed, and analyzed for content. Results: Parents were not well informed about what the heel prick involves at present. Nevertheless, they see it as a routine procedure and do not think about the possibility of refusing it. If the heel-prick program were to be expanded, parents would like to be informed earlier, preferably during pregnancy. In addition, most parents preferred an opt-out consent approach. Conclusions: If the neonatal screening program is to be expanded, parents would prefer for information about the program be given during pregnancy. In addition, they preferred an opt-out consent approach, on condition that screening was for the purpose of preventing irreversible harm. Parental opinion was divided on this issue if the aim of screening were to be widened. © 2007, Blackwell Publishing, Inc.

The Dutch neonatal screening scheme for Congenital Hypothyroidism (CH) is primarily based on the determination of thyroxine (T4) in filter paper blood spots. In the lowest 5% of T4 values, thyroxine binding globulin (TBG) is measured in order to be able to correct for occasional low TBG levels. However, because the commercial TBG kit has been withdrawn from the market, alternative strategies are needed to be explored including the assessment of free T4.We evaluated the Neonatal Free Thyroxine (fT4) enzyme immunoassay (EIA) kit of Bio-Rad.FT4 as measured in a daily run of random samples correlated with T4. We also observed a correlation between fT4 and T4, and between fT4 and T4/TBG ratio in blood spots with low T4 concentrations. The correlation between fT4 and T4 in blood spots of proven CH-patients was highly significant. ROC curves were constructed for the fT4 assay and the T4/TBG ratio based on 27 CH patients and 215 controls with a complete set of data. The curves of both assays seemed to be rather similar.We conclude that the validity of the fT4 and the T4/TBG-approach seems to be the same. A study with a larger sample size giving the same or even more favorable results for the fT4-approach is necessary before we will change the present CH protocol. •The paper describes the evaluation of a free T4 enzyme immunoassay in blood spots.•The aim is to replace total T4 and TBG for a single fT4 measurement.•Despite a correlation between fT4 and T4 in CH-patients, no cut-off value can be established.•Determination of fT4 levels in blood spots was inferior to the present CH-protocol. © 2013 Elsevier B.V.

Objective: In newborn screening programs for congenital adrenal hyperplasia, 17-α-hydroxyprogesterone (17OHP) cutoff levels are based on birth weight (BW) or on gestational age (GA). We investigated which approach would result in the greatest specificity and sensitivity. Study design: For the determination of 17OHP, a neonatal 17OHP assay was used in filter paper blood of 9492 newborns. The relationships between 17OHP and BW and between 17OHP and GA were studied by regression analysis. Reference curves with a specificity of 99.95% were constructed with the method that summarizes the distribution by three smoothed curves representing the skewness (L curve), the median (M curve), and the coefficient of variation (S curve). Median cutoff levels for BW and for GA according to the 99.95% reference curves were calculated. Results: Regression analysis showed that GA is a better predictor of 17OHP than BW (R2 was 50.6 vs. 35.8%, respectively). At a specificity of 99.95%, the calculated median 17OHP cutoff level was lower for GA [12.6 μg/liter (38 nmol/liter)] than for BW [17.6 μg/liter (54 nmol/liter)], thus leading to a greater sensitivity. Conclusion: This study demonstrates that GA is a better predictor of 17OHP in newborns and will result in greater specificity than BW despite the fact that the determination of GA might be less reliable than BW. Copyright © 2005 by The Endocrine Society.

Background: Advances in genomics will open up opportunities in the fields of genetic testing, early diagnosis and disease treatment. While neonatal screening is the field of application par excellencefor these developments, the debate on its potential benefits and drawbacks is mainly theoretically driven and based on the opinions of professionals. Methods: We conducted a qualitative study of the perceptions, preferences and needs of parents (and parents to be) with respect to expansion of the neonatal screening programme. Seven focus group discussions were conducted. Using disease scenarios, 4 examples of conditions amenable to neonatal screening were discussed in depth. All focus group discussions were audio taped and content analysed. Results: Participants thought that the medical benefits of screening were very important for the child. Assuming the availability of effective early medical treatment, almost 100% would be willing to participate in a screening programme. If such treatment were absent, their potential willingness would be much lower. Conclusions: The divergence in attitudes and preferences we found in this study reflected the complexity inherent in any consideration of screening for additional conditions. To implement such options successfully and to direct applied research in genomics, it is important to develop a better understanding of the thinking of target groups, namely parents. Copyright © 2008 S. Karger AG.

Context: Patients with thyroidal congenital hypothyroidism (CH-T) born in The Netherlands in 1981-1982 showed persistent intellectual and motor deficits during childhood and adulthood, despite initiation of T4 supplementation at a median age of 28 d after birth. Objective: The present study examined whether advancement of treatment initiation to 20 d had resulted in improved cognitive and motor outcome. Design/Setting/Patients: In 82 Dutch CH-T patients, born in 1992 to 1993 and treated at a median age of 20 d (mean, 22 d; range, 2-73 d), cognitive and motor outcome was assessed (mean age, 10.5 yr; range, 9.6-11.4 yr). Severity of CH-T was classified according to pretreatment free T4 concentration. Main Outcome Measure: Cognitive and motor outcome of the 1992-1993 cohort in comparison to the 1981 to 1982 cohort was the main outcome measure. Results: Patients with severe CH-T had lower full-scale (93.7), verbal (94.9), and performance (93.9) IQ scores than the normative population (P < 0.05), whereas IQ scores of patients with moderate and mild CH-T were comparable to those of the normative population. In all three severity subgroups, significant motor problems were observed, most pronounced in the severe CH-T group. No correlations were found between starting day of treatment and IQ or motor outcome. Conclusions: Essentially, findings from the 1992-1993 cohort were similar to those of the 1981-1982 cohort. Apparently, advancing initiation of T4 supplementation from 28 to 20 d after birth did not result in improved cognitive or motor outcome in CH-T patients. Copyright © 2007 by The Endocrine Society.

Doel. Evaluatie van de Nederlandse screening op congenitale hypothyreoïdie (CHT). Opzet. Descriptief. Plaats. Landelijk. Methoden. Gegevens over de screening in de periode 1 januari 1981-31 december 1990 werden verkregen van de entadministraties, van laboratoria en van kinderartsen naar wie kinderen met afwijkende uitslagen verwezen werden. Resultaten. Van alle levendgeborenen werden 1.797.719 (99,5) kinderen gescreend op congenitale hypothyreoïdie (CHT). Er kwamen 10.165 kinderen (0,57 van alle gescreenden) voor verwijzing in aanmerking. Van de verwezen kinderen hadden 529 primaire CHT en 53 congenitaal thyreotropinedeficiëntiesyndroom (CTDS). De prevalentie van primaire CHT en CTDS was respectievelijk 1:3400 en 1:25.000. De sensitiviteit van het programma ten aanzien van primaire CHT was 99 en ten aanzien van CTDS 74. De specificiteit en de voorspellende waarde ten aanzien van alle vormen van CHT waren respectievelijk 99 en 6. Een van de doelen van het screeningsprogramma is bij alle patiënten de behandeling te beginnen voor de leeftijd van 22 dagen. Vóór screening was het cumulatieve percentage patiënten dat op de 21e dag reeds werd behandeld 6, na introductie van de screening was dat 54. Gescreende patiënten met een ernstige vorm van CHT werden in 72 van de gevallen behandeld voor dag 22. Conclusie. De screening levert een belangrijke bijdrage aan een vroegtijdige en effectieve opsporing van CHT-patiënten. Maatregelen om het aantal fout-positieve uitslagen te beperken zijn inmiddels genomen of zijn nog in onderzoek. Hoewel patiënten dankzij de screening veel eerder worden behandeld dan voor de screening, valt hier nog een aanzienlijke winst te boeken. Alleen door een gezamenlijke inspanning van de uitvoerders van de hielprik, de laboratoria, de entadministraties, huisartsen en kinderartsen kan dit bereikt worden. Chemicals/CAS: Thyrotropin, 9002-71-5.

The objective of this study was to investigate whether universal neonatal hearing screening could be integrated in the youth health care program. The screening was performed by nurses of the well baby clinics. A three stage transient evoked otoacoustic emission screening was performed in three different screening settings in order to study the most effective set up regarding participation, refer rates, and costs. In one setting parents visited the well baby clinic, and in two settings babies were screened at home (either in combination with the screening for metabolic diseases or during an intake visit). Screening was performed on 3114 healthy newborns. The setting where universal neonatal hearing screening is integrated with the screening for metabolic diseases, proved to be most efficient and effective. The participation rate of 88.9% was highest in this setting and the overall refer rate (1.4%) was the lowest. The implementation of universal neonatal hearing screening by the well baby clinic nurses was judged to be possible. The results of this study formed the basis for nationwide implementation. © 2009 British Society of Audiology, International Society of Audiology, and Nordic Audiological Society.

Objective: To investigate whether false-positive outcomes on neonatal hearing screening cause long-lasting parental concerns. Methods: A general population of parents whose children had participated in the universal neonatal hearing screening (UNHS) programme were examined. Parents filled out a questionnaire 6 months after UNHS. Outcomes were compared for all parents whose child tested positive or inconclusive in at least one of three tests but afterwards proved not to have hearing impairment (cases, n = 154| and a random sample of parents whose child passed the first test (controls, n = 288). Parental anxiety as measured with the State-Trait Anxiety Inventory (STAI), attitude towards the child (child health rating and experienced problems) and sensitivity to hearing problems were measured. Results: Median STAI score was equal for cases and controls. Parental attitudes toward the child also did not differ. The difference in the proportion of parents who worried about their child's hearing was statistically significant between cases and controls (p = 0.001) and varied with the number of screens; 4% of controls were worried about the child's hearing, as compared to 10% of cases whose children were tested twice, and 15% of cases whose children were tested three times. Conclusions: False-positive UNHS test results do not cause long-term general parental anxiety. However, 6 months after screening, a considerable proportion of parents continued to experience hearing-specific worries regarding their child.

Congenital hypothyroidism (CH) may be of thyroidal (CHT) or central origin (CHC). Worldwide, most neonatal screening programs are TSH based and effectively detect CHT. Only a few screening programs measure total or free T4 and TSH simultaneously or stepwise, enabling detection of CHT as well as CHC. A frequently used argument against screening for CHC is its presumed mild hypothyroid character. In the recently published European Society for Paediatric Endocrinology (ESPE) CH consensus guidelines on screening, diagnosis and management, severity of CH is classified based on initial free T4 (FT4) concentrations. Objective: To assess disease severity of CHC compared to CHT in a Dutch cohort of CH patients. Methods: Pre-treatment FT4 concentrations were analyzed in all children with CH detected by the Dutch neonatal T4+TSH+T4-binding-globulin (TBG) screening between 1995 and 2011. Disease severity was classified using the FT4-based ESPE classification. Results: Between 1995 and 2011, 1288 children were diagnosed with CH. Data of 1200 (CHC: 143, CHT: 1057) were available for analysis. Based on FT4 concentrations 4 children with CHC (2.8%) had severe CH, 75 (52.4%) moderate and 64 (44.8%) mild. In the CHT group 280 children (26.5%) had severe CH, 341 (32.3%) moderate and 436 (41.2%) mild. Discussion:/Conclusion /Conclusion: Our results indicate that, based on initial FT4-values, severe CH was much more prevalent in CHT compared to CHC. However CHC itself should not be considered as only mild since more than half of CHC patients have moderate CH with initial FT4 below 10 pmol/l.

Aim: To determine the prevalence and independent relationship between hearing loss and risk factors in a representative neonatal intensive care unit (NICU) population. Methods: Automated auditory brainstem response (AABR) hearing screening has been introduced since 1998 in the Dutch NICUs. After a second AABR failure, diagnostic ABR was used to establish diagnosis of hearing loss. Newborns who died before the age of 3 months were excluded. In the present study only the NICU infants who were born with a gestational age <30 weeks and/or a birth weight <1000 g between October 1, 1998 and January 1, 2002 were included. Risk factors included in the study were familial hearing loss, in utero infections, craniofacial anomalies, birth weight <1500g, hyperbilirubinemia, ototoxic medications, cerebral complications, severe birth asphyxia, assisted ventilation ≥5 days and syndromes. Results: A nationwide cohort of 2186 newborns were included. Mean gestational age was 28.5 weeks (SD 1.6) and mean birth weight was 1039 g (SD 256). Prevalence of uni- or bilateral hearing loss was 3.2% (71/2186; 95% CI 2.6-4.1). Multivariate analysis revealed that the only independent risk factors for hearing loss were severe birth asphyxia (OR 1.7; 95% CI 1.0-2.7) and assisted ventilation ≥5 days (OR 3.6; 95% CI 2.1-6.0). Conclusion: The prevalence of hearing loss in a representative NICU population was 3.2%. Independent risk factors for hearing loss were severe birth asphyxia and assisted ventilation ≥5 days. © 2007 The Author(s).

Doel Evalueren van de uitkomsten van het eerste jaar na invoering van de uitbreiding van de landelijke hielprikscreening met sikkelcelziekte (SCZ). Opzet Prospectieve landelijke registratie van kinderen met vermoedelijk SCZ of een andere vorm van ernstige hemoglobinopathie. Methode De bloedspots werden geanalyseerd met een hemoglobinescheidingsmethode op basis van ‘high-performance liquid chromatography’ (HPLC). Kinderen met een afwijkende hielprikuitslag dienden te worden verwezen naar een kinderhematoloog in één van de 8 academische ziekenhuizen. Bevestiging van de diagnose gebeurde met een tweede HPLC-test, een DNA-test en een onderzoek naar hemoglobinopathie bij de ouders. De uiteindelijke diagnose werd vergeleken met de vermoedelijke diagnose uit de screening. Resultaten In het eerste jaar hadden 64 kinderen een afwijkende hielprikuitslag die wees op een hemoglobinopathie (prevalentie: 0,35‰). De vermoedelijke diagnose was bij 41 kinderen ‘SCZ’, bij 18 ‘α-thalassemie’, bij 4 ‘β-thalassemie’ en bij 1 een overige vorm van hemoglobinopathie (HbEE). De vermoedelijke diagnose kon bij alle kinderen bevestigd worden. Conclusie Het eerste jaar van de neonatale screening op SCZ was succesvol, aangezien het aantal kinderen bij wie een diagnose werd gesteld, overeenkwam met de verwachtingen. De positief voorspellende waarde van de hielprikuitslag voor SCZ was daarmee 100%. Het is nog te vroeg om een uitspraak te doen over eventuele foutnegatieve testresultaten.

Background: The clinical severity of phenylalanine hydroxylase deficiency is usually defined by either pre-treatment phenylalanine (Phe) concentration or Phe tolerance at 5 years of age. So far, little is known about the course of Phe tolerance or the ability of both pre-treatment Phe and Phe tolerance at early age to predict Phe tolerance at later age. Aim: This study was conducted to investigate the course of the individual Phe tolerance and to assess the predictive value of both the pre-treatment Phe concentration and Phe tolerance at 1 and 6 months and 1, 2, 3 and 5 years for Phe tolerance at 10 years of age. Method: Data on blood Phe concentration, prescribed Phe intake and weight of 213 early and continuously treated Dutch PKU patients up to 10 years of age were collected. Data acquired under good metabolic control were used in the study. Tolerance was expressed in mg/day and mg/kg per day. Results: Data at 1 and 6 months and at 1, 2, 3 and 5 years of 61, 58, 59, 57, 56 and 59 patients were included for comparison with the Phe tolerance at 10 years. Phe tolerances (mg/kg per day) at 2, 3 and 5 years showed a clear correlation with the tolerance at 10 years of age (r = 0.608, r = 0.725 and r = 0.661). Results for tolerance expressed as mg/day were comparable. Pre-treatment Phe concentrations did not correlate significantly with the tolerance. Conclusion: Pre-treatment Phe is unreliable but Phe tolerance is a reliable predictor of the tolerance at 10 years of age, starting at 2 years of age. © Springer Science+Business Media B.V. 2009. Chemicals / CAS: phenylalanine, 3617-44-5, 63-91-2; Phenylalanine, 63-91-2; Phenylalanine Hydroxylase, 1.14.16.1

Background. The objective of this study was to determine the importance of parental factors possibly related to dietary control in early and continuously treated patients with phenylketonuria (PKU). Methods. A questionnaire was disseminated among parents of 238 patients with PKU born after the nationwide introduction of newborn screening for PKU (1 September 1974) until 31 December 1995. The questionnaire was based on a behavioural model measuring people's attitudes, subjective norms, and self-efficacy. Dietary control was defined on the basis of mean phenyl-alanine (Phe) concentration of the PKU patients measured between 1 January 1994 and 31 December 1996. Results. Response rate was 71%. Attitudes: children of parents who believed that their child adheres well to the diet, even if his or her Phe concentrations are sometimes too high, had lower Phe concentrations than children of parents who disagree with this statement (adjusted difference -103 μmol/L, p < 0.001). Subjective norm: Phe concentrations were higher when parents answered that their relatives did not approve when their child deviates from the diet (p = 0.004). Self-efficacy: children of parents who reported difficulties in having their child eat the synthetic protein substitute three times a day had higher Phe concentrations than those of parents who did not have such difficulties (adjusted difference 156 μmol/L, p = 0.007). Conclusion. More attention should be given to parents having their child eat the synthetic protein substitute at least three times a day and to teaching parents to keep strictly to the diet without being too rigid. These factors were strongly associated to dietary control and may be amenable to change. © SSIEM and Springer 2005. Chemicals / CAS: phenylalanine, 3617-44-5, 63-91-2; protein, 67254-75-5; Phenylalanine, 63-91-2

OBJECTIVES. The purpose of this work was to assess the costs of 4 neonatal screening strategies for cystic fibrosis in relation to health effects. In each strategy, the first test was the measurement of serum concentration of immunoreactive trypsin. The second step consisted of either a second immunoreactive trypsin test (strategy 1) or a multiple mutation analysis (strategy 2). In strategies 3 and 4, a third step was added to strategy 2: a second immunoreactive trypsin test (strategy 3) or an extended mutation analysis of the cystic fibrosis gene, that is, a denaturing gradient gel electrophoresis analysis (strategy 4). METHODS. We conducted an economic-modeling exercise in the Netherlands based on published data and expert opinions. Subjects were a hypothetical cohort of 200 000 neonates, the approximate number of children born annually in the Netherlands, and we assessed the costs and number of life-years gained as a result of neonatal screening for cystic fibrosis. The costs and effects of changes in reproductive decisions because of neonatal screening were also assessed. RESULTS. Immunoreactive trypsin + immunoreactive trypsin had the most favorable cost-effectiveness ratio of €24 800 per life-year gained. Immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis achieved more health effects than immunoreactive trypsin + DNA + immunoreactive trypsin at lower cost. The incremental costs per life-year gained of the immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis strategy compared with the immunoreactive trypsin + immunoreactive trypsin strategy were €130 700, whereas the incremental costs of the immunoreactive trypsin + DNA strategy compared with the immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis strategy were €2 154 300. When changes in reproductive decisions as a result of neonatal screening are also taken into account, neonatal screening for cystic fibrosis may lead to financial savings of approximately €1.8 million annually, depending on the screening strategy used. CONCLUSIONS. Cystic fibrosis screening for neonates is a good economic option, and positive health effects can also be expected. Immunoreactive trypsin + immunoreactive trypsin and immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis are the most cost-effective strategies. Copyright © 2006 by the American Academy of Pediatrics. Chemicals / CAS: DNA, 9007-49-2; trypsin, 9002-07-7; Trypsin, EC 3.4.21.4

Aim: As part of a future national neonatal hearing screening programme in the Netherlands, automated auditory brainstem response (AABR) hearing screening was implemented in seven neonatal intensive care units (NICUs). The objective was to evaluate key outcomes of this programme: participation rate, first stage success rate, pass/referral rates, rescreening compliance, diagnostic referral rates, age of first diagnostic evaluation and prevalence of congenital hearing loss (CHL). Methods: This prospective cohort study collected data on 2513 survivors. NICU graduates with one or more risk factors according to the Joint Committee on Infant Hearing were included in a two-stage AABR hearing screening programme. Conventional ABR was used to establish a diagnosis of CHL. Results: A total of 2513 newborns enrolled in the programme with a median gestational age of 31.6 (range 24-43) wk and a median birthweight of 1450 (range 510-4820) g. In 25 (1%) cases parents refused screening. Four out of 2513 newborns were initially lost; 2484 newborns have been tested initially. A final 98% participation rate (2465/2513) was obtained for the whole programme. After a median postmenstrual age at the first test of 33.7 (range 27-54) wk, a pass rate of 2284/2484 (92%) resulted at the first stage. The rescreening compliance after the first test was 92% (184/200). A referral rate for diagnostic ABR of 3.1% (77/2484) resulted. Of the 77 referrals 14 (18.2%) had normal screening thresholds, 15 (19.5%) had unilateral CHL and 48 (62.3%) had bilateral CHL. The prevalence of unilateral CHL was 0.6% (15/2484) and of bilateral CHL 1.9% (48/2484). Conclusion: A financially supported two-stage AABR hearing screening programme can be successfully incorporated in NICU centres and detects a high prevalence of CHL in NICU graduates. Neonatal hearing screening should be part of standard clinical practice in all NICU infants.

Objective - To compare the cost effectiveness of various strategies for neonatal hearing screening by estimating the cost per hearing impaired child detected. Design - Cost analyses with a simulation model, including a multivariate sensitivity analysis. Comparisons of the cost per child detected were made for: screening method (automated auditory brainstem response or otoacoustic emissions); number of stages in the screening process (two or three); target disorder (bilateral hearing loss or both unilateral and bilateral loss); location (at home or at a child health clinic). Setting - The Netherlands Target population - All newborn infants not admitted to neonatal intensive care units. Main outcome measure - Costs per child detected with a hearing loss of 40 dB or more in the better ear. Results - Costs of a three stage screening process in child health clinics are €39.0 (95% confidence interval 20.0 to 57.0) per child detected with automated auditory brainstem response compared with €25.0 (14.4 to 35.6) per child detected with otoacoustic emissions. A three stage screening process not only reduces the referral rates, but is also likely to cost less than a two stage process because of the lower cost of diagnostic facilities. The extra cost (over and above a screening programme detecting bilateral losses) of detecting one child with unilateral hearing loss is €1500-4000. With the currently available information, no preference can be expressed for a screening location. Conclusions - Three stage screening with otoacoustic emissions is recommended. Whether screening at home is more cost effective than screening at a child health clinic needs further study.

Context. Since the introduction of screening for congenital hypothyroidism (CH) in 1974, the optimal laboratory strategy has been the subject of debate. Objective. To assess the clinical effectiveness and cost-effectiveness of various types of thyroxine (T4)-based strategies to screen for CH. Design, Setting, and Participants. In the Netherlands, since January 1, 1995, a primary T4 determination with supplemental thyroid-stimulating hormone (TSH) and T4-binding globulin (TBG) measurements has been used. Results were calculated from cumulative findings for 1 181 079 children screened between January 1, 1995, and December 31, 2000. Main Outcome Measures. Rates of detection of patients with CH of thyroidal origin (CH-T) or CH of central origin (CH-C), false-positive rates, laboratory costs, and costs of initial diagnostic evaluations. Results. All known infants (n = 393) with CH-T and 92% (n = 66) of infants with CH-C were detected on the basis of low T4 levels, TSH elevation, and/or low T4/TBG ratios. If the decision to refer had been based solely on TSH elevation, then 94% of patients with CH-T and none of the patients with CH-C would have been detected. If low T4 levels (≤-3.0 SD) and TSH elevation had been used as the criteria for referral, then the rates of detection would have been 96% for CH-T and 31% for CH-C. The false-positive rates for the 3 approaches were 0.5, 3.3, and 4.7 cases per case detected, respectively. The introduction of the T4/TBG ratio into a program using a primary T4 with supplemental TSH approach generates an extra cost of $11 206 per additional case detected. The average costs to detect 1 patient are comparable for the 3 approaches. In addition, our data revealed a substantially greater prevalence of CH-C than reported previously (1 case per 16 404 children, compared with earlier estimates of 1 case per 26 000 infants to 1 case per 29 000 infants). Conclusions. The T4 plus TSH plus TBG approach is a recommendable strategy for neonatal CH screening. It offers outstanding detection of patients with CH-C, in addition to those with CH-T, with acceptable costs. Copyright © 2005 by the American Academy of Pediatrics. Chemicals / CAS: thyrotropin, 9002-71-5; thyroxine, 7488-70-2; Thyrotropin, 9002-71-5; Thyroxine, 7488-70-2; Thyroxine-Binding Proteins