Weight-adjusted neonatal 17OH-progesterone cutoff levels improve the efficiency of newborn screening for congenital adrenal hyperplasia ABSTRACTObjective: To evaluate weight-adjusted strategy for levels of neonatal-17OHP in order to improve newborn screening (NBS) efficiency. Subjects and methods: Blood samples collected between 2-7 days of age from 67,640 newborns were evaluated. When N17OHP levels were ≥ 20 ng/mL, and a second sample was requested. We retrospectively analyzed neonatal-17OHP levels measured by Auto DELFIA-B024-112 assay, grouped according to birth-weight: G1: < 1,500 g, G2: 1,501-2,000 g, G3: 2,000-2,500 g and G4: > 2,500 g. 17OHP cutoff values were determined for each group using the 97. Keywords 21-hydroxylase deficiency; congenital adrenal hyperplasia; newborn screening; neonatal 17OH-progesterone levels; preterm and full-term newborns RESUMO Objetivo: Avaliamos retrospectivamente os valores da 17OHP ajustados para o peso ao nascimento para melhorar a eficiência da triagem neonatal. Sujeitos e métodos: 67.640 recém--nascidos com amostras coletadas entre 2-7 dias de vida. Uma segunda amostra foi solicitada na presença de testes com valores da 17OHP ≥ 20 ng/mL. 17OHP dosada pelo método DELFIA-B024-112 e correlacionada com o peso ao nascimento: G1 < 1.500 g, G2 1.501-2.000 g, G3 2.000-2.500 g e G4 > 2.500 g.

Neonatal 17-hydroxyprogesterone levels adjusted to sample collection age and birthweight reduced the FPR, and the use of N17OHP values based upon the 99·8th percentile improved the NBS efficacy.

Background: Newborn screening for congenital adrenal hyperplasia (CAH-NBS) is not yet a worldwide consensus, in part due to inconclusive evidence regarding cost-effectiveness because the analysis requires an understanding of the short- and long-term costs of care associated with delayed diagnosis.Objective: The present study aimed to conduct a cost-effectiveness analysis (CEA) to compare the costs associated with CAH-NBS and clinical diagnosis.Methods: A decision model comparing the two strategies was tested by sensitivity analysis. The cost analysis perspective was the public health system. Unscreened patients' data were extracted from medical records of Hospital das Clinicas, Saõ Paulo, and screened data were extracted from the NBS Referral Center of São Paulo. The population comprised 195 classical patients with CAH, clinically diagnosed and confirmed by hormonal/CYP21A2 analysis, and 378,790 newborns screened during 2017. Adverse outcomes related to late diagnosis were measured in both cohorts, and the incremental cost-effectiveness ratio (ICER) was calculated. We hypothesized that CAH-NBS would be cost-effective.Results: Twenty-five screened infants were confirmed with CAH (incidence: 1:15,135). The mortality rate was estimated to be 11% in unscreened infants, and no deaths were reported in the screened cohort. Comparing the unscreened and screened cohorts, mean serum sodium levels were 121.2 mEq/L (118.3–124.1) and 131.8 mEq/L (129.3–134.5), mean ages at diagnosis were 38.8 and 17 days, and hospitalization occurred in 76% and 58% of the salt-wasting patients with the in the two cohorts, respectively. The NBS incremental cost was US$ 771,185.82 per death averted, which yielded an ICER of US$ 25,535.95 per discounted life-year saved.Conclusions: CAH-NBS is important in preventing CAH mortality/morbidity, can reduce costs associated with adverse outcomes, and appears cost-effective.

Introduction: Liquid chromatography followed by mass spectrometry (LC-MS/MS) is considered the gold standard method to measure steroids. Newborn screening for congenital adrenal hyperplasia (CAH) involves measurement of 17α-hydroxyprogesterone (17-OHP) in blood dried spots by immunoassay. Because this testing has high false-positive rates, serum samples to measure 17-OHP, androstenedione, 21-desoxicortisol and cortisol simultaneously by liquid chromatography-tandem mass spectrometry (LC-MS/MS) are used for confirmatory test in our laboratory. Objective: To report an interference in androstenedione levels measured by LC-MS/MS assay in serum samples from newborns. Patients and methods: The method for androstenedione measurements was based on protein precipitation followed by a semi-automated and multiplexed on-line solid phase extraction coupled reverse phase separation and detection of underivatized analyte by tandem mass spectrometry. Among 312 samples 82 presented unexpected androstenedione results considering that 17OHP levels were &lt;5 ng/mL. These samples presented a high variability among 4 replicates (CV ranged from 20 to 133%). These samples also showed an inadequate ion ratio resulting in pseudo-elevated androstenedione, indicating a coeluition of an isobaric interferent. In routine samples from other patients this problem was not observed. Results: Since this fact suggests a possible interference in LC-MS/MS measurements and modification in chromatographic method was unable to resolve from the interference, alternative method for sample preparation was developed. Liquid-liquid extraction with diethyl ether was performed and eliminated the interference and provided substantial decrease in androstenedione values (9.3+12.94 ng/mL vs 5.2+9.59 ng/mL after extraction) with ion ration normalization and CV less 10% between replicates. The identity of this compound is still unknown. Therefore, it will be necessary additional studies to clarify this artifact. Conclusions: Although the measurement of androstenedione by reverse phase chromatography without derivatization followed by tandem mass spectrometry is the simplest and commonest approach to determine androstenedione, it is susceptible to interferences causing falsely elevated androstenedione levels in newborns.

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