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. 2019 Aug 1;104(8):3172-3180.
doi: 10.1210/jc.2018-02468.

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

Naomi Pode-Shakked  1   2   3 , Ayala Blau  4   5 , Ben Pode-Shakked  2   3   6 , Dov Tiosano  7   8 , Naomi Weintrob  3   9 , Ori Eyal  3   9 , Amnon Zung  10   11 , Floris Levy-Khademi  11   12 , Yardena Tenenbaum-Rakover  8   13 , David Zangen  11   14 , David Gillis  11   14 , Orit Pinhas-Hamiel  3   15 , Neta Loewenthal  16   17 , Liat de Vries  3   18 , Zohar Landau  3   19 , Mariana Rachmiel  3   20 , Abdulsalam Abu-Libdeh  21 , Alon Eliakim  3   22 , David Strich  23   24 , Ilana Koren  25 , Alina German  26 , Joseph Sack  3 , Shlomo Almashanu  4
Affiliations

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

Naomi Pode-Shakked et al. J Clin Endocrinol Metab. .

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.

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