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

TL;DR

This study proposes optimized cutoff levels for newborn screening of 21-OH deficiency in Brazil, improving accuracy and reducing false positives.

Contribution

The study introduces new cutoff values for 17-hydroxyprogesterone based on birth weight and sample timing to enhance screening effectiveness.

Findings

The new cutoff values improved specificity, LR+, PPV, and accuracy compared to prior criteria.

False positives were reduced for neonates ≤2500 g, though increased for those >2500 g.

The optimized strategy minimizes unnecessary costs and parental distress in CAH screening.

Abstract

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 (CAH—NBS) programs, utilizing a comprehensive dataset encompassing all newborn screening tests for 21-hydroxylase deficiency (21OHD) conducted over a decade in a Brazilian metropolitan region.

A cross-sectional study analyzed all CAH—NBS 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 CAH—NBS program of São Paulo and a threshold of ≥20 mg/dL. New cutoff values were proposed to enhance screening effectiveness.

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.

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