Cutoff levels for newborn screening of 21-OH deficiency in a Brazilian metropolitan area.

Abstract

Objective: To evaluate the accuracy of neonatal 17-hydroxyprogesterone (N17OHP) levels adjusted for birth weight (BW) and time of the sample collection (TC) and propose optimized cutoff values to improve the effectiveness of newborn screening tests for congenital adrenal hyperplasia (CAHNBS) programs, utilizing a comprehensive dataset encompassing all newborn screening tests for 21-hydroxylase deficiency (21OHD) conducted over a decade in a Brazilian metropolitan region.

Methods: A cross-sectional study analyzed all CAHNBS tests from newborns aged 2 to 7 days in the Federal District, Brazil, from January 2012 to September 2022. The accuracy of cutoff values based on the 99.5th percentile (99.5P) for BW and TC was compared to the CAHNBS program of São Paulo and a threshold of ≥20 mg/dL. New cutoff values were proposed to enhance screening effectiveness.

Results: Among the 340,291 newborns screened, CAH-21OHD was confirmed in 11 cases. The N17OHP cutoff in this sample reduced false positives for neonates ≤ 2500 g but increased them for those > 2500 g The proposed cutoff values based on 99.5P from the sample for neonates ≤ 2500 g, combined with a fixed cutoff ≥ 20 mg/dL for those > 2500 g, showed superior specificity (99.83 %, 95 % CI: 99.81-99.84 %), LR+ (579.16, 95 % CI: 524.23-627.87), PPV (1.84, 95 %CI: 1.70-1.99), and accuracy (99.83 %, 95 %CI: 99.81-99.84 %) than prior criteria.

Conclusion: The proposed 17OHP cutoff strategy effectively reduced false positives, improving specificity, LR+, PPV, and accuracy Thus, it optimized CAHNBS programs while minimizing unnecessary costs and parental distress.