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. 2025 Nov;48(11):2713-2720.
doi: 10.1007/s40618-025-02669-3. Epub 2025 Sep 15.

Newborn screening for congenital adrenal hyperplasia due to 21 hydroxylase deficiency: the Italian experience 2006-2019

Federico Baronio  1 , Enrica Abrigo  2 , Sara Azzolini  3 , Paolo Cavarzere  3 , Cristina Cereda  4 , Luisa De Sanctis  2 , Silvia Laura Carla Meroni  5 , Jessica Munarin  2 , Francesca Righetti  6 , Gianni Russo  5 , Francesca Teofoli  7 , Antonio Balsamo  8
Affiliations

Newborn screening for congenital adrenal hyperplasia due to 21 hydroxylase deficiency: the Italian experience 2006-2019

Federico Baronio et al. J Endocrinol Invest. 2025 Nov.

Abstract

Purpose: 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: 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.

Results: 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.

Conclusions: 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.

Keywords: 17-hydroxyprogesterone; 21 hydroxylase deficiency; Congenital adrenal hyperplasia; Newborn screening; Newborns; Salt wasting.

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Conflict of interest statement

Declarations. Competing interests: The authors have no competing interests to declare that are relevant to the content of this article. Ethics approval: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee Area Vasta Emilia Centro (AVEC) at the IRCSS AOU of Bologna (783/2020/Oss/AOUBo) on 17th September 2020. Consent to participate: The Ethics Committee of Area Vasta Emilia Centro at the IRCCS AOU of Bologna, according to the general authorization of the Italian Privacy Guarantor n. 9/2016, authorized, in the absence of informed consent, the processing and publication of the retrospectively obtained and anonymized data for this non-interventional study; however, informed consent was obtained from the patient’s parents/legal representatives when possible.

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