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.

20 {YEARS} {OF} {NEONATAL} {SCREENING} {FOR} {CONGENITAL} {ADRENAL} {HYPERPLASIA} {IN} {NORTH}-{EASTERN} {ITALY}: {ROLE} {OF} {LC}-{MS}/{MS} {AS} A {SECOND} {TIER} {TEST}

Paolo Cavarzere
;
Marta Camilot;Rossella Gaudino;Franco Antoniazzi;Francesca Teofoli;Giorgio Piacentini
2022-01-01

Abstract

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.
Newborn screening, congenital adrenal hyperplasia, liquid chromatography-tandem mass spectrometry
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1071867
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