학술논문
Combined Gestational Age- and Birth Weight-Adjusted Cutoffs for Newborn Screening of Congenital Adrenal Hyperplasia
CLINICAL RESEARCH ARTICLE
CLINICAL RESEARCH ARTICLE
Document Type
Academic Journal
Author
Pode-Shakked, Naomi; Blau, Ayala; Pode-Shakked, Ben; Tiosano, Dov; Weintrob, Naomi; Eyal, Ori; Zung, Amnon; Levy-Khaddemi, Floris; Tenenbaum-Rakover, Yardena; Zangen, David; Gillis, David; Pinhas-Hamiel, Orit; Loewenthal, Neta; Vries, Liat de; Landau, Zohar; Rachmiel, Mariana; Abu-Libdeh, Abdulsalam; Eliakim, Alon; Strich, David; Koren, Ilana; German, Alina; Sack, Joseph; Almashanu, Shlomo
Source
Journal of Clinical Endocrinology & Metabolism. August 2019, Vol. 104 Issue 8, p3172, 9 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by deficiencies of steroidogenic enzymes leading to inborn errors of cortisol biosynthesis. More than 90% of cases are [...]
ORCiD numbers: 0000-0001-9179-6355 (N. Pode-Shakked); 0000-0001-6017-9629 (B. Pode-Shakked). 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 birth-weight (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. (J Clin Endocrinol Metab 104: 3172-3180, 2019)
ORCiD numbers: 0000-0001-9179-6355 (N. Pode-Shakked); 0000-0001-6017-9629 (B. Pode-Shakked). 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 birth-weight (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. (J Clin Endocrinol Metab 104: 3172-3180, 2019)