Combined Gestational Age- and Birth Weight-Adjusted Cutoffs for Newborn Screening of Congenital Adrenal Hyperplasia

Abstract

Context Congenital adrenal hyperplasia (CAH) was among the first genetic disorders included in newborn screening (NBS) programs worldwide, based on 17α-hydroxyprogesterone (17-OHP) levels in dried blood spots. However, the success of NBS for CAH is hampered by high false positive (FP) rates, especially in preterm and low-birthweight infants. Objective To establish a set of cutoff values adjusting for both gestational age (GA) and birthweight (BW), with the aim of reducing FP rates. Design This cross-sectional, population-based study summarizes 10 years of experience of the Israeli NBS program for diagnosis of CAH. Multitiered 17-OHP cutoff values were stratified according to both BW and GA. Participants A total of 1,378,132 newborns born between 2008 and 2017 were included in the NBS program. Results Eighty-eight newborns were ultimately diagnosed with CAH; in 84 of these, CAH was detected upon NBS. The combined parameters-adjusted approach significantly reduced the recall FP rate (0.03%) and increased the positive predictive value (PPV) (16.5%). Sensitivity among those referred for immediate attention increased significantly (94%). There were four false negative cases (sensitivity, 95.4%), all ultimately diagnosed as simple-virilizing. Sensitivity and specificity were 95.4% and 99.9%, respectively, and the percentage of true-positive cases from all newborns referred for evaluation following a positive NBS result was 96%. Conclusions The use of cutoff values adjusted for both GA and BW significantly reduced FP rates (0.03%) and increased overall PPV (16.5%). Based on our 10 years of experience, we recommend the implementation of this two parameter-adjusted approach for NBS of classic CAH in NBS programs worldwide.