The First-year Outcomes of the Nationwide Neonatal CAH Screening in Türkiye: High Rate of False Positives for 21-hydroxylase Deficiency and a Higher Detection Rate of Non-classical Cases
Articles > Article · 2025
Authors: Tulay Guran, Elif Yuruker, Ahmet Anik, Muge Atar, Emine Camtosun, Elif Eviz, Mehmet Isakoca, Eda Mengen, Busra Gurpinar Tosun, Ihsan Turan, Aylin Kilinc Ugurlu, Edip Unal, Dogus Vuralli, Gulay Can Yilmaz, Yuksel Hakan Aydogmus, Şükran DARCAN
Journal of Clinical Research in Pediatric Endocrinology, International, WoS, 2025, vol 17, pp 488-493
DOI: 10.4274/jcrpe.galenos.2025.2024-9-11
Summary
Objective: Neonatal screening for congenital adrenal hyperplasia (CAH) was implemented nationwide in Türkiye in 2022. The performance of this screening program in its first year was assessed. Methods: This retrospective, descriptive study included neonates born in Türkiye between January 1 and December 31, 2022, with gestational age ≥32 weeks and birth weight ≥1500 grams. The screening protocol used a two-tier approach. In the first step, 17α-hydroxyprogesterone (17-OHP) levels were measured using fluoroimmunoassay (FIA) in dried blood spots (DBS) collected at 3-5 days of life. Infants with positive results underwent second-tier testing using liquid chromatography-tandem mass spectrometry to measure 17-OHP, 21-deoxycortisol (21-DF), cortisol (F), and 11-deoxycortisol (S) in DBS. Those with a steroid ratio (21-DF+17-OHP)/F ≥1 were referred to pediatric endocrinology clinics for diagnostic evaluation. Results: Of 1,096,069 neonates screened (including 149,652 refugees), second-tier tests were performed on 70,455 (6.88%) infants, and 3,429 (0.27%) were referred to clinics, resulting in 91 confirmed cases of classical 21-hydroxylase deficiency (21-OHD) CAH (77; salt-wasting, 14; simple virilizing). Twenty-two patients were diagnosed with non-classical 21-OHD CAH. The frequency of classical 21-OHD was 1 in 12,044. The first-tier FIA-17-OHP values were below 17.5 ng/mL in 99.8% of healthy neonates with ≥36 weeks gestation or ≥2500 grams and below 50 ng/mL in those with 32-36 weeks or 1500-2500 grams. Conclusion: Neonatal CAH screening facilitates early diagnosis of 21-OHD and improved patient care. Using refined cut-offs may reduce referrals six-fold and eliminate second-tier testing for 95% of infants. Ongoing evaluation can enhance the efficiency and cost-effectiveness of the screening protocol.