TY - JOUR

T1 - Neonatal Screening for Congenital Adrenal Hyperplasia in Denmark

T2 - 10 Years of Experience

AU - Lind-Holst, Marie

AU - Bækvad-Hansen, Marie

AU - Berglund, Agnethe

AU - Cohen, Arieh S.

AU - Melgaard, Lars

AU - Skogstrand, Kristin

AU - Duno, Morten

AU - Main, Katharina M.

AU - Hougaard, David Michael

AU - Gravholt, Claus Højbjerg

AU - Hansen, Dorte

N1 - Publisher Copyright: © 2022 S. Karger AG, Basel. Copyright: All rights reserved.

PY - 2022

Y1 - 2022

N2 - Introduction: Early detection of salt-wasting congenital adrenal hyperplasia (SW-CAH) is important to reduce CAH-related morbidity. However, neonatal screening has shown to have a low positive predictive value (PPV), especially among preterm newborns. Here, the Danish CAH screening is evaluated by comparing incidence and morbidity of SW-CAH 10 years before and after introduction of screening. Furthermore, sensitivity, specificity, and PPV are determined. Methods: All newborns in Denmark born during 1999-2018 and diagnosed with SW-CAH were identified in the Danish National Patient Registry and/or at the Department of Clinical Genetics, Rigshospitalet. Newborns with a positive neonatal CAH screening were identified at Statens Serum Institut. Correct diagnosis was evaluated by medical record review. Results: A total of 65 newborns with SW-CAH were identified. The incidence of SW-CAH was 5:100,000 both before and after introduction of screening. Performance of sensitivity and specificity of the screening were 97% and 100%, respectively, and the PPV was 55% for the given period. Stratified according to gestational age, the PPV was 33% and 61% for pre -and fullterm newborns, respectively. Though not significant, the proportion of newborns presenting with SW-crisis decreased after introduction of screening from 29% versus 10% (p = 0.07). Discussion and Conclusion: Neonatal screening for SW-CAH has not led to an increase in the incidence of newborns diagnosed with SW-CAH. The screening algorithm has effectively identified newborns with SW-CAH. After 2009, there was a tendency toward a lower proportion of newborns with SW-crisis at diagnosis. Finally, the study emphasizes the benefits of using second-tier screening as well as repeated screening of premature newborns.

AB - Introduction: Early detection of salt-wasting congenital adrenal hyperplasia (SW-CAH) is important to reduce CAH-related morbidity. However, neonatal screening has shown to have a low positive predictive value (PPV), especially among preterm newborns. Here, the Danish CAH screening is evaluated by comparing incidence and morbidity of SW-CAH 10 years before and after introduction of screening. Furthermore, sensitivity, specificity, and PPV are determined. Methods: All newborns in Denmark born during 1999-2018 and diagnosed with SW-CAH were identified in the Danish National Patient Registry and/or at the Department of Clinical Genetics, Rigshospitalet. Newborns with a positive neonatal CAH screening were identified at Statens Serum Institut. Correct diagnosis was evaluated by medical record review. Results: A total of 65 newborns with SW-CAH were identified. The incidence of SW-CAH was 5:100,000 both before and after introduction of screening. Performance of sensitivity and specificity of the screening were 97% and 100%, respectively, and the PPV was 55% for the given period. Stratified according to gestational age, the PPV was 33% and 61% for pre -and fullterm newborns, respectively. Though not significant, the proportion of newborns presenting with SW-crisis decreased after introduction of screening from 29% versus 10% (p = 0.07). Discussion and Conclusion: Neonatal screening for SW-CAH has not led to an increase in the incidence of newborns diagnosed with SW-CAH. The screening algorithm has effectively identified newborns with SW-CAH. After 2009, there was a tendency toward a lower proportion of newborns with SW-crisis at diagnosis. Finally, the study emphasizes the benefits of using second-tier screening as well as repeated screening of premature newborns.

KW - 17-Hydroxyprogesterone

KW - 21-Hydroxylase deficiency

KW - Congenital adrenal hyperplasia screening

KW - Genetic diseases

KW - Liquid chromatography with tandem mass spectrometry

KW - Newborn screening

KW - Screening for congenital adrenal hyperplasia

U2 - 10.1159/000522230

DO - 10.1159/000522230

M3 - Journal article

C2 - 35114680

AN - SCOPUS:85130003824

VL - 95

SP - 35

EP - 42

JO - Hormone Research in Paediatrics

JF - Hormone Research in Paediatrics

SN - 1663-2818

IS - 1

ER -