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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 [euro] 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 [euro], 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 [euro]. 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 [euro] 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. www.pediatrics.org/cgi/doi/10.1542/ peds.2005-2782 doi:10.1542/peds.2005-2782 Key Words cost-effectiveness, economic evaluation, neonatal, screening-newborn Abbreviations CF--cystic fibrosis IRT--immunoreactive trypsin DGGE--denaturing gradient gel electrophoresis, CYSTIC FIBROSIS (CF) is 1 of the most common autosomal recessively inherited disorders in white populations. It is a life-threatening multiorgan disease. The pancreas and the respiratory tract are affected [...]

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 ([T.sub.4])-based strategies to screen for CH. Design, Setting, and Participants. In the Netherlands, since January 1, 1995, a primary [T.sub.4] determination with supplemental thyroid-stimulating hormone (TSH) and [T.sub.4]-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 [T.sub.4] levels, TSH elevation, and/or low [T.sub.4]/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 [T.sub.4] levels ([less than or equal to] -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 [T.sub.4]/TBG ratio into a program using a primary [T.sub.4] with supplemental TSH approach generates an extra cost of $11 206 per additional case detected. The average costs to detect I 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 I case per 26 000 infants to 1 case per 29 000 infants). Conclusions. The [T.sub.4] 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. Pediatrics 2005;116:168-173; average cost, cost-effectiveness, congenital hypothyroidism, laboratory approach, marginal cost, screening, thyroid-stimulating hormone, thyroxine, thyroxine-binding globulin. ABBREVIATIONS. CH, congenital hypothyroidism; TSH, thyroid-stimulating hormone; TBG, thyroxine-binding globulin; [T.sub.4], thyroxine; CH-C, congenital hypothyroidism of central origin; CH-T, congenital hypothyroidism of thyroidal origin., Congenital hypothyroidism (CH) refers to a heterogeneous group of disorders that have in common a lack of thyroid hormone already present in the neonatal period. Because thyroid hormone is essential [...]

Objective. To evaluate whether congenital adrenal hyperplasia (CAH) patients can be detected by newborn screening before the occurrence of life-threatening salt wasting and whether the prevalence, specificity, and sensitivity are adequate enough for a routine screening procedure. Design. From 1998, a 2-year regional pilot screening for CAH was performed. In 1998, cutoff levels for 17OHP were primarily based on birth weight, and in 1999 on gestational age. In addition, nationwide, all newly diagnosed patients with CAH were reported to the Dutch Pediatric Surveillance Unit to compare screened CAH patients with CAH patients in the area without screening. Results. In 2 years, 176 684 newborns were screened and 15 CAH patients (7 males/8 females) were detected. Therapy was started at the median age of 7 days. In the area without screening, 223 307 infants were born and 19 CAH patients (10 males/9 females) were reported to the Dutch Pediatric Surveillance Unit. Therapy was started at the median age of 14 days. The mean (standard deviation) serum sodium concentration was 134.5 (3.4) mmol/L in the area of screening versus 124.5 (10.8) mmol/L in the area without screening. The overall prevalence was 1:11 764. In 1998 and 1999, the specificity was 99.76% and 99.97%, respectively. The positive predictive value was 4.5% and 16%, respectively. To date, no false-negative cases have been detected. Conclusion. Severe salt wasting can be prevented by neonatal screening. The prevalence, specificity, and sensitivity allowed addition of screening for CAH to the routinely performed national neonatal screening program. Pediatrics 2001;108:1320-1324; congenital adrenal hyperplasia, costs, neonatal screening, specificity, sensitivity, cutoff levels., ABBREVIATIONS. CAH, congenital adrenal hyperplasia; 17OHP, 17-hydroxyprogesterone; SW, salt-wasting; NSW, nonsalt-wasting; DPSU, Dutch Pediatric Surveillance Unit; PPV, positive predictive value. Congenital adrenal hyperplasia (CAH) is, in >90% of the patients, [...]

Objectives. There is little agreement as to the optimal cutoff point for thyrotropin testing in primary thyroxine screening programs for congenital hypothyroidism. Most programs in the United States use a cutoff point of 10% of the lowest thyroxine values, whereas in the Netherlands a cutoff point of 20% is used. Therefore, the results of the Dutch program may provide valuable information about the optimal cutoff point. Methods. The frequency distribution of screening thyroxine values was studied in all cases of permanent primary congenital hypothyroidism (n = 481) detected in 1 601 603 screened children born during the period from January 1, 1981, to December 31, 1989, in the Netherlands. Results. Programs using a 10% cutoff point would have missed 1.5% of cases. Above the 10% cutoff point, the marginal costs increase quite rapidly because of the escalating numbers of thyrotropin measurements necessary to detect one case of permanent primary congenital hypothyroidism: 20 000 in the range of 11% to 15 % and 40 000 in the range of 16% to 20%. Conclusions. Based on these findings, a cutoff point of at least 10% is recommended. (Am J Public Health 1993;83:868-871), Measuring thyrotropin levels in children whose thyroxine measurement is among the lowest 10% may be a cost-effective method of screening for congenital hypothyroidism. Congenital hypothyroidism is a thyroid deficiency present at birth which is associated with growth disorders and mental retardation. Thyroxine, a thyroid hormone which affects the rate of cell metabolism, is measured routinely in newborn infants. If the level of thyroxine is low, a second test is performed to measure levels of thyrotropin, another hormone involved in thyroid activity. A study in the Netherlands sought to determine what percentage of infants with low levels of thyroxine should have further testing. They studied thyroxine levels of 481 children diagnosed with congenital hypothyroidism from 1981 through 1989. If the cutoff had been the lowest 5%, approximately 3.5% of cases would have been missed. At a 10% cutoff, only 1.5% of cases would have been missed. A cutoff level higher than 10% increased testing costs dramatically. Up to 40,000 tests would have to be performed to detect one case at a 20% cutoff.

Context: Early treatment of primary congenital hypothyroidism (CH) prevents irreversible brain damage. Contrary to primary CH, outcome studies on central CH are scarce. Most patients with central CH have multiple pituitary hormone deficiencies (MPHD); these patients are also at risk for neonatal hypoglycemia.Objective: To assess cognitive and motor outcome in patients with early-treated central CH detected by the Dutch neonatal screening.Methods: In this cross-sectional study, primary outcome full-scale intelligence quotient (FSIQ) was measured in patients with MPHD and patients with isolated central CH born between January 1, 1995, and January 1, 2015, with siblings as controls. Secondary outcomes were intelligence test subscales and motor function. Linear mixed models were used to compare both patient groups and siblings, followed by post hoc tests in case of significant differences.Results: Eighty-seven patients (52 MPHD; 35 isolated central CH) and 52 siblings were included. Estimated marginal means for FSIQ were 90.7 (95% CI 86.4-95.0) in patients with MPHD and 98.2 (95% CI 93.0-103.5) in patients with isolated central CH. While patients with MPHD scored lower FSIQs than siblings (mean difference -7.9 points, 95% CI -13.4 to -2.5; P = .002), patients with isolated central CH did not. Processing speed was lower in both patient groups than in siblings (mean differences -10.5 and -10.3 points). Motor difficulties occurred significantly more often in patients (33%) versus siblings (5%; P = .004).Conclusion: In early-treated central CH, FSIQ is comparable with siblings in patients with isolated central CH, while patients with MPHD have a significantly lower FSIQ. This may be explained by disease-specific consequences of MPHD, such as neonatal hypoglycemia and more severe hypothyroidism. [ABSTRACT FROM AUTHOR]

Background Little is known about costs and effects of vision screening strategies to detect amblyopia. Aim of this study was to compare costs and effects of conventional (optotype) vision screening, photoscreening or a combination in children aged 3–6 years. Methods Population-based, cross-sectional study in preventive child health care in The Hague. Children aged 3 years (3y), 3 years and 9 months (3y9m) or 5–6 years (5/6y) received the conventional chart vision screening and a test with a photoscreener (Plusoptix S12C). Costs were based on test duration and additional costs for devices and diagnostic work-up. Results Two thousand, one hundred and forty-four children were included. The estimated costs per child screened were €17.44, €20.37 and €6.90 for conventional vision screening at 3y, 3y9m and 5/6y, respectively. For photoscreening, these estimates were €6.61, €7.52 and €9.40 and for photoscreening followed by vision screening if the result was unclear (combination) €9.32 (3y) and €9.33 (3y9m). The number of children detected with amblyopia by age were 9, 14 and 5 (conventional screening), 6, 13 and 3 (photoscreening) and 10 (3y) and 15 (3y9m) (combination), respectively. The estimated costs per child diagnosed with amblyopia were €1500, €1050 and €860 for conventional vision screening, €860, €420 and €1940 for photoscreening and €730 (3y) and €450 (3y9m) for the combination. Conclusions Combining photoscreening with vision screening seems promising to detect amblyopia in children aged 3y/3y9m, whereas conventional screening seems preferable at 5/6y. As the number of study children with amblyopia is small, further research on the effects of these screening alternatives in detecting children with amblyopia is recommended. [ABSTRACT FROM AUTHOR]

Abstract Background It is generally assumed that most patients with celiac disease (CD) have a slowed growth in terms of length (or height) and weight. However, the effectiveness of slowed growth as a tool for identifying children with CD is unknown. Our aim is to study the diagnostic efficiency of several growth criteria used to detect CD children. Methods A case-control simulation study was carried out. Longitudinal length and weight measurements from birth to 2.5 years of age were used from three groups of CD patients (n = 134) (one group diagnosed by screening, two groups with clinical manifestations), and a reference group obtained from the Social Medical Survey of Children Attending Child Health Clinics (SMOCC) cohort (n = 2,151) in The Netherlands. The main outcome measures were sensitivity, specificity and positive predictive value (PPV) for each criterion. Results Body mass index (BMI) performed best for the groups with clinical manifestations. Thirty percent of the CD children with clinical manifestations and two percent of the reference children had a BMI Standard Deviation Score (SDS) less than -1.5 and a decrease in BMI SDS of at least -2.5 (PPV = 0.85%). The growth criteria did not discriminate between the screened CD group and the reference group. Conclusion For the CD children with clinical manifestations, the most sensitive growth parameter is a decrease in BMI SDS. BMI is a better predictor than weight, and much better than length or height. Toddlers with CD detected by screening grow normally at this stage of the disease.

Abstract Background To promote early diagnosis and treatment of short stature, consensus meetings were held in the mid nineteen nineties in the Netherlands and the UK. This resulted in guidelines for referral. In this study we evaluate the referral pattern of short stature in primary health care using these guidelines, comparing it with cut-off values mentioned by the WHO. Methods Three sets of referral rules were tested on the growth data of a random sample (n = 400) of all children born between 01-01-1985 and 31-12-1988, attending school doctors between 1998 and 2000 in Leiden and Alphen aan den Rijn (the Netherlands): the screening criteria mentioned in the Dutch Consensus Guideline (DCG), those of the UK Consensus Guideline (UKCG) and the cut-off values mentioned in the WHO Global Database on Child growth and Malnutrition. Results Application of the DCG would lead to the referral of too many children (almost 80%). The largest part of the referrals is due to the deflection of height, followed by distance to target height and takes primarily place during the first 3 years. The deflection away from the parental height would also lead to too many referrals. In contrast, the UKCG only leads to 0.3% referrals and the WHO-criteria to approximately 10%. Conclusion The current Dutch consensus guideline leads to too many referrals, mainly due to the deflection of length during the first 3 years of life. The UKCG leads to far less referrals, but may be relatively insensitive to detect clinically relevant growth disorders like Turner syndrome. New guidelines for growth monitoring are needed, which combine a low percentage of false positive results with a good sensitivity.