Challenges in Assessing the Cost-Effectiveness of Newborn Screening: The Example of Congenital Adrenal Hyperplasia

Grosse, Scott D.; Vliet, Guy Van

doi:10.3390/ijns6040082

Cited by 14 publications

(9 citation statements)

References 102 publications

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“…Earlier studies reported CAH screening would be either unlikely to be cost-effective or cost-effective only if a single test is performed [19,38]. While recent studies in Canada, Brazil and Sweden concluded that NBS screening for CAH enables to reduce morbidity and mortality [39,40] as well as costs associated with adverse outcomes, transportation, and hospitalization length [41]. The long-term health benefits of NBS for CAH are unknown and should be addressed in future studies.…”

Section: Discussionmentioning

confidence: 99%

Impact of Newborn Screening on Clinical Presentation of Congenital Adrenal Hyperplasia

et al. 2021

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Background and Objectives: The main reason for Newborn screening (NBS) for congenital adrenal hyperplasia (CAH) is to prevent adrenal insufficiency that can lead to life-threatening conditions. On the other hand, screening programs are not always sensitive and effective enough to detect the disease. We aimed to evaluate impact of the national NBS on the clinical presentation of patients with CAH in Lithuania. Materials and Methods: A retrospective study was performed on data of 88 patients with CAH from 1989 to 2020. Patients with confirmed CAH were divided into two groups: (1) 75 patients diagnosed before NBS: 52 cases with salt-wasting (SW), 21 with simple virilising (SV) and two with non-classical (NC) form; (2) 13 patients diagnosed with NBS: 12 cases with SW and 1 case with SV form. For the evaluation of NBS effectiveness, data of only male infants with salt-wasting CAH were analysed (n = 36, 25 unscreened and nine screened). Data on gestational age, birth weight, weight, symptoms, and laboratory tests (serum potassium and sodium levels) on the day of diagnosis, were analysed. Results: A total of 158,486 neonates were screened for CAH from 2015 to 2020 in Lithuania and CAH was confirmed in 13 patients (12 SW, one–SV form), no false negative cases were found. The sensitivity and specificity of NBS program for classical CAH forms were 100%; however, positive predictive value was only 4%. There were no significant differences between unscreened and screened male infant groups in terms of age at diagnosis, serum potassium, and serum sodium levels. Significant differences were found in weight at diagnosis between the groups (−1.67 ± 1.12 SDS versus 0.046 ± 1.01 SDS of unscreened and screened patients respectively, p = 0.001). Conclusions: The sensitivity and specificity of NBS for CAH program were 100%, but positive predictive value—only 4%. Weight loss was significantly lower and the weight SDS at diagnosis was significantly higher in the group of screened patients.

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Section: Discussionmentioning

confidence: 99%

Impact of Newborn Screening on Clinical Presentation of Congenital Adrenal Hyperplasia

et al. 2021

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“…We tried to adjust the cut-off threshold in relation to GA [14], but a significant reduction in recall rate, especially between preterm newborns, was only achieved in 2017, when we routinely implemented the LC-MS/MS second-tier test in the workflow. Furthermore, scientific literature has acknowledged the importance of LC-MS/MS in improving the specificity of CAH newborn screening [4, 17-19, 21, 37] and in reducing both the overall economic costs, since it makes confirmatory tests less frequently needed [38], and the emotional burden bore by families when a newborn is recalled for further diagnostic ascertainments. In addition, two-tier testing strategy has the advantage of reducing the duration of follow-up in newborns with positive CAH screening [25].…”

Section: Discussionmentioning

confidence: 99%

Twenty Years of Neonatal Screening for Congenital Adrenal Hyperplasia in North-Eastern Italy: Role of Liquid Chromatography-Tandem Mass Spectrometry as a Second-Tier Test

et al. 2022

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Background: Newborn screening for congenital adrenal hyperplasia (CAH) based on 17-OHP concentration in dried blood spots has been taking place in North Eastern Italy since 2001. Since 2017, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been introduced, for the first time in Italy, as a second tier test. Aims: Our study aims to evaluate, on the one hand, the effectiveness of the newborn screening for CAH after 20 years of testing and, on the other, the impact that the introduction of the second tier test had on the diagnostic accuracy of the screening program. Method and Materials: Since 2001 dried blood spots taken from newborns have been screened with a time-resolved fluoroimmunoassay for 17-OHP determination. Over the years, the cut-off levels of 17-OHP were adjusted according to gestational age (GA). Since 2017, a second tier test in LC/MSMS was introduced for samples displaying fluoroimmunoassay 17-OHP exceeding the cut-off. Results: 862.521 newborns have been screened over a period of twenty years. The total incidence of 21-hydroxylase deficiency (21-OHD) was 1:25.368, moreover a case of 11-β-hydroxylase deficiency was identified. All these diagnosis were genetically confirmed. Sensitivity and specificity of the screening program were 97% and 99.4%, respectively. The use of LC-MS/MS as second tier test significantly reduced the recall rate and increased the positive predictive value. Conclusions: Screening for CAH is useful in the neonatal diagnosis of classic form of 21-OHD, allowing a precocious treatment of affected children. The introduction of a LC-MS/MS second tier reduced the recall rate, avoiding unnecessary blood withdraws and medical evaluations and preventing stress to families. Furthermore, it helped identify rarer forms of CAH.

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“…Elevated levels of 17OHP may be associated with 3βHSD2 deficiency due to peripheral conversion by the 3βHSD type I enzyme. High 17OHP levels are false positives for 21OH deficiency in neonatal screening programs according to some of the mentioned studies [ 5 , 60 , 101 , 102 , 103 , 104 ]. Certain countries introduced screening protocols based on 17OHP immunoassays (dried blood spot) which are less useful in non-severe cases and non-classical forms of 21OH deficiency and non-21OH types [ 24 , 103 , 105 ].…”

Section: Discussionmentioning

confidence: 99%

Approach of Heterogeneous Spectrum Involving 3beta-Hydroxysteroid Dehydrogenase 2 Deficiency

et al. 2022

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We aim to review data on 3beta-hydroxysteroid dehydrogenase type II (3βHSD2) deficiency. We identified 30 studies within the last decade on PubMed: 1 longitudinal study (N = 14), 2 cross-sectional studies, 1 retrospective study (N = 16), and 26 case reports (total: 98 individuals). Regarding geographic area: Algeria (N = 14), Turkey (N = 31), China (2 case reports), Morocco (2 sisters), Anatolia (6 cases), and Italy (N = 1). Patients’ age varied from first days of life to puberty; the oldest was of 34 y. Majority forms displayed were salt-wasting (SW); some associated disorders of sexual development (DSD) were attendant also—mostly 46,XY males and mild virilisation in some 46,XX females. SW pushed forward an early diagnosis due to severity of SW crisis. The clinical spectrum goes to: premature puberty (80%); 9 with testicular adrenal rest tumours (TARTs); one female with ovarian adrenal rest tumours (OARTs), and some cases with adrenal hyperplasia; cardio-metabolic complications, including iatrogenic Cushing’ syndrome. More incidental (unusual) associations include: 1 subject with Barter syndrome, 1 Addison’s disease, 2 subjects of Klinefelter syndrome (47,XXY/46,XX, respective 47,XXY). Neonatal screening for 21OHD was the scenario of detection in some cases; 17OHP might be elevated due to peripheral production (pitfall for misdiagnosis of 21OHD). An ACTH stimulation test was used in 2 studies. Liquid chromatography tandem–mass spectrometry unequivocally sustains the diagnostic by expressing high baseline 17OH-pregnenolone to cortisol ratio as well as 11-oxyandrogen levels. HSD3B2 gene sequencing was provided in 26 articles; around 20 mutations were described as “novel pathogenic mutation” (frameshift, missense or nonsense); many subjects had a consanguineous background. The current COVID-19 pandemic showed that CAH-associated chronic adrenal insufficiency is at higher risk. Non-adherence to hormonal replacement contributed to TARTs growth, thus making them surgery candidates. To our knowledge, this is the largest study on published cases strictly concerning 3βHSD2 deficiency according to our methodology. Adequate case management underlines the recent shift from evidence-based medicine to individualized (patient-oriented) medicine, this approach being particularly applicable in this exceptional and challenging disorder.

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Challenges in Assessing the Cost-Effectiveness of Newborn Screening: The Example of Congenital Adrenal Hyperplasia

Cited by 14 publications

References 102 publications

Impact of Newborn Screening on Clinical Presentation of Congenital Adrenal Hyperplasia

Impact of Newborn Screening on Clinical Presentation of Congenital Adrenal Hyperplasia

Twenty Years of Neonatal Screening for Congenital Adrenal Hyperplasia in North-Eastern Italy: Role of Liquid Chromatography-Tandem Mass Spectrometry as a Second-Tier Test

Approach of Heterogeneous Spectrum Involving 3beta-Hydroxysteroid Dehydrogenase 2 Deficiency

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