Newborn screening (NBS) for inborn errors of metabolism is one of the most advanced tools for secondary prevention in medicine, as it allows early diagnosis and prompt treatment initiation. The expanded newborn screening was introduced in Italy between 2016 and 2017 (Law 167/2016; DM 13 October 2016; DPCM 12-1-2017). A total of 1,586,578 infants born in Italy were screened between January 2017 and December 2020. For this survey, we collected data from 15 Italian screening laboratories, focusing on the metabolic disorders identified by tandem mass spectrometry (MS/MS) based analysis between January 2019 and December 2020. Aminoacidemias were the most common inborn errors in Italy, and an equal percentage was observed in detecting organic acidemias and mitochondrial fatty acids beta-oxidation defects. Second-tier tests are widely used in most laboratories to reduce false positives. For example, second-tier tests for methylmalonic acid and homocysteine considerably improved the screening of CblC without increasing unnecessary recalls. Finally, the newborn screening allowed us to identify conditions that are mainly secondary to a maternal deficiency. We describe the goals reached since the introduction of the screening in Italy by exchanging knowledge and experiences among the laboratories.

Background: Hepatoblastoma screening in the Beckwith–Wiedemann spectrum (BWSp) is currently based on measuring a specific serum marker alpha-fetoprotein (αFP) every three months until the fourth birthday. Frequent blood draws can be a burden for patients and their families. Methods: We have developed a less invasive alternative testing method based on measuring αFPs from dried blood spots (DBS). The method was validated with 259 simultaneous plasma and DBS αFP measurements in 171 children (132 controls and 39 patients with BWSp). Results: The DBS and plasma measurements overlapped across the wide range of αFP concentrations independent of patient age (p < 0.0001), demonstrating the utility of this method for longitudinal monitoring. Occasional differences between measurements by the two techniques fell within standard laboratory error and would not alter clinical management. Conclusions: This novel method shows consistent overlap with the traditional blood draws, thereby demonstrating its utility for hepatoblastoma screening in this setting and alleviating the burden of frequent blood draws. This also may help increase patient compliance and reduce costs of health care screening. The DBS-based method for the measurement of cancer biomarkers may also be applied to several other chronic diseases with increased risks of αFP-producing liver tumors.

Haemoglobinopathies are an increasing health concern in Europe due to changing population demographics. In Italy, however, newborn screening (NBS) for haemoglobinopathies is not yet included in the national mandatory screening panel. The primary aim of this study was to estimate the prevalence of haemoglobinopathies in a population-based neonatal cohort from the Piedmont region; a secondary exploratory objective was to characterise neonatal HbA₀ distribution and its association with molecular findings in selected samples. We conducted a retrospective, multicentre study of 2002 anonymised dried blood spot samples collected from term newborns 48–72 h after birth. Haemoglobin fractions were analysed by high-performance liquid chromatography (HPLC). HbA₀ distribution was characterised in newborns without structural haemoglobin variants using descriptive statistics. Molecular analysis was performed in an intentionally selected subset of samples with HbA₀ < 12%. HPLC identified 29 structural haemoglobin variants (22 HbS and 7 other variants), corresponding to a prevalence of 1.4%. After exclusion of these cases, HbA₀ distribution was analysed in 1973 newborns. Mean HbA₀ was 16.1% (SD 5.3), median HbA₀ was 15.5% (Q1–Q3: 12.3–19.1), and the distribution showed moderate positive skewness. Overall, 448/1973 newborns (22.7%) had HbA₀ < 12%. Among 12 selected newborns with HbA₀ < 12% who underwent molecular testing, detectable β-globin gene mutations were identified in five. DNA extracted from stored dried blood spots was suitable for molecular analysis. Structural haemoglobin variants were identified in a non-negligible proportion of newborns in this Northern Italian cohort. HPLC provided effective first-line identification of the variants observed, whereas neonatal HbA₀ showed substantial variability and an asymmetric distribution, supporting cautious interpretation of fixed absolute thresholds for suspected β-thalassaemia carrier status. Larger, systematically genotyped cohorts are required to assess the diagnostic performance of candidate HbA₀ thresholds.

Background/Objectives: Non-classical congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency represents the mildest form of congenital adrenal hyperplasia and is frequently diagnosed only after the onset of clinical signs in childhood. Newborn screening programs for CAH are primarily designed to detect classical forms and show limited sensitivity for NCCAH. The clinical significance of neonatal 17-hydroxyprogesterone (17-OHP) values below recall thresholds remains incompletely defined. Methods: We retrospectively analyzed clinical, auxological, hormonal, and genetic data from pediatric patients diagnosed with NCCAH between 2018 and 2023 at a tertiary referral center. Neonatal screening 17-OHP concentrations, basal and ACTH-stimulated 17-OHP levels at diagnosis, bone age advancement, pubertal status, and hydrocortisone treatment were evaluated. Correlations between hormonal parameters, age at onset, and treatment dose were assessed. Results: Thirty-five patients (30 females) were included, with a mean age at clinical onset of 7.52 ± 0.36 years for females and 6.25 ± 0.29 years for males. Premature pubarche was the most frequent presenting sign (94.3%), and central precocious puberty was diagnosed in 31.4% of cases. The mean neonatal screening 17-OHP level was 4.53 ± 0.7 ng/mL; only two patients exceeded the screening recall cut-off. At diagnosis, mean basal and ACTH-stimulated 17-OHP levels were 15.1 ± 3.35 and 55.2 ± 11.3 ng/mL, respectively. Age at clinical onset was inversely correlated with both basal and stimulated 17-OHP levels, while hydrocortisone dose correlated positively with biochemical severity. Bone age advancement was observed in all patients. Conclusions: Most children with NCCAH display mildly elevated neonatal 17-OHP values that do not trigger screening recall. Higher biochemical severity is associated with earlier clinical presentation and higher glucocorticoid requirements. Neonatal 17-OHP concentrations, even when below cut-off values, may represent an early indicator of disease severity and warrant further investigation.