Background: In North-Eastern Italy, a newborn screening for congenital adrenal hyperlpasia (CAH) has been taking place since 2001 to diagnose the classical form of 21-hydroxylase deficiency (21-OHD). Thanks to the screening program based on 17-OHP levels in dried blood spots, early diagnosis of CAH is possible, allowing appropriate precocious treatment and reducing mortality rates. Unfortunately, a high false positive rate, especially in preterm, low-birth-weight and critically ill newborns, is described.
Aims: The aims of our study are to summarize the results of the newborn screening for CAH held in the last eighteen years in North-Eastern Italy and to evaluate the diagnostic utility of simultaneous determination of 17-OHP, cortisol, 11-deoxycortisol, delta 4-androstenedione and 21-deoxycortisol by liquid chromatograpy-tandem mass spectrometry (LC-MS/MS) as second tiers performed on the same blood spot.
Materials and Methods: Since 2001 dried blood spots from newborns have been screened with a time-resolved fluoroimmunoassay method (DELFIA) for 17-OHP determination. Over the years, the cutoff levels of 17OHP were adjusted according to gestational age. Since 2017, samples resulted above the cutoff have been immediately analyzed by LC-MS/MS in order to differentiate affected patients from false positive newborns.
Results: Since 2001, 786.302 newborns have been screened, with 34 diagnosis of classic form of 21-OHD and a total incidence of 1:23126. To date, we have no information about false negative cases (sensitivity of 100%). Over the years, adjustments of cutoff values for 17-OHP based on gestational age and, in particular, the use of LC-MS/MS, as a second-tier test for positive CAH screening significantly reduced the recall rate (RR). RR varied by a maximum value of 1.06 in 2009 to 0.85 in 2016 before LC-MS/MS, and reached the value of 0.45 in 2017 and of 0.17 in 2018 after the introduction of LC-MS/MS.
Conclusions: The screening for CAH proved to be useful in the neonatal diagnosis of classic form of 21-OHD, allowing a precocious and appropriate treatment, significantly reducing mortality as well. Moreover, the use of LC-MS/MS as a second tier test resulted in a useful tool to improve the positive predictive value of the screening program. LC-MS/MS is not suitable to replace the conventional method, but it is extremely useful as a second-tier test in particular in preterm, low-birth-weight and critically ill neonates, preventing unnecessary blood draws, medical evaluations and stress to families.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology