Newborn screening for congenital adrenal hyperplasia: a 3 years study embedded in 25 years of regional experience in Italy.

PURPOSE: Newborn screening for congenital adrenal hyperplasia (CAH) using 17-hydroxyprogesterone (17-OHP) is hampered by high false-positive rates, especially in preterm and low birth weight infants. Second-tier strategies aim to improve specificity, but population-based data are limited. The aim was to evaluate CAH screening approach using birth weight-adjusted cut-offs and repeated sampling in a large regional cohort. METHODS: We analyzed data from 90,092 infants screened in Piedmont, Italy (2019-2022). 17-OHP was measured in dried blood spots, with birth weight-adjusted thresholds and repeated sampling when indicated. 17-OHP distributions were examined by birth weight and gestational age, and outcomes assessed via recall rate and confirmed diagnoses. RESULTS: Of 90.092 infants, 746 were recalled (0.82%), and 119 referred for specialist evaluation. Eight infants were diagnosed with classic salt-wasting CAH and one with non-classical CAH (incidence 1:11.261). 17-OHP concentrations inversely correlated with birth weight, capturing most biological variability. Repeated sampling significantly reduced false positives across all birth weight categories. Gestational age stratification offered no clear advantage over birth weight-based thresholds. CONCLUSIONS: Birth weight-based CAH screening effectively lowers false positives while identifying classic CAH. Refining percentile-informed cut-offs, particularly in higher birth weight infants, could further enhance efficiency without compromising safety.