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

Naomi Pode-Shakked, Ayala Blau, Ben Pode-Shakked, Dov Tiosano, Naomi Weintrob, Ori Eyal, Amnon Zung, Floris Levy-Khademi, Yardena Tenenbaum-Rakover, David Zangen, David Gillis, Orit Pinhas-Hamiel, Neta Loewenthal, Liat De Vries, Zohar Landau, Mariana Rachmiel, Abdulsalam Abu-Libdeh, Alon Eliakim, David Strich, Ilana KorenAlina German, Joseph Sack, Shlomo Almashanu

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)3172-3180
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume104
Issue number8
DOIs
StatePublished - 19 Jun 2019

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