Newborn screening for congenital adrenal hyperplasia due to 21 hydroxylase deficiency: the Italian experience...

Early identification of classic 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia (21OH-CAH) through newborn screening (NBS) is vital to prevent morbidity from salt-wasting crises. The aim of the study is to assess the efficacy of 21OH-CAH NBS from 2006 to 2019 in the five Regions of Italy where 21OH-CAH NBS is performed.

Methods included dried blood spot (DBS) tests for 17OH-progesterone (17OHP) within the first 48-72 h, with variable protocols. Dried blood spots have been screened with a time-resolved fluoroimmunoassay for 17OHP determination (DELFIA) as first tier test in all the Italian Regions. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was implemented in the Veneto region starting October 2017 as second-tier test.

Among 2,933,074 screened newborns, 161 (86 males, 75 females) had classic 21OH-CAH, with a cumulative incidence of 1 in 17,699. Salt-wasting CAH was the most prevalent form (71.9%). Mean age at blood sampling for true positives was 9 ± 18 days, with 28% suspected before NBS results. In Regions with a second-tier test, the recall rate (RR) was 0.17, and positive predictive value (PPV) was 4.3. No patients had adrenal crisis and 23% of cases were symptomatic before the NBS results were reported.

The study confirms the efficacy of NBS in early detection of classic 21OH-CAH, emphasizing the need for timely reporting and second-tier testing to improve outcomes.