Combined Gestational Age- And Birth Weight-Adjusted Cutoffs For Newborn Screening Of Congenital Adrenal Hyperplasia

Context: Congenital adrenal hyperplasia (CAH) was among the first genetic disorders included in newborn screening (NBS) programs worldwide, based on 17 alpha-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.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.