Clinical characteristics and follow-up burden of false-positive newborn CAH screening results: a single-center experience

Newborn screening for congenital adrenal hyperplasia (CAH) prevents life-threatening salt-wasting crises, however, generates substantial false positives, particularly in preterm infants, due to physiological 17-hydroxyprogesterone (17-OHP) elevations. Türkiye recently expanded CAH screening nationally, yet real-world referral burden, clinical determinants of high number of false-positive referrals, and associated costs remain incompletely characterized. We aimed to describe clinical determinants of false-positive CAH screening results and quantify downstream follow-up and costs among infants referred for elevated dried blood spot 17-OHP. We retrospectively reviewed 106 infants referred to a tertiary pediatric endocrinology clinic between January 1, 2022 and July 20, 2023 for elevated NBS 17-OHP. Demographic and perinatal characteristics, hospitalization status, 17-OHP values, diagnostic outcomes, follow-up intensity, and direct healthcare costs until CAH exclusion/confirmation were collected. Non-parametric comparisons used Mann-Whitney U test; categorical variables used Fisher’s exact test ( p < 0.05). CAH was confirmed in 4/106 infants (3.8%), resulting in a PPV of 3.8%, while 102/106 (96.2%) represented false-positive referrals. Preterm birth was common (58.5%) and was associated with significantly higher 17-OHP compared with term infants ( p < 0.001). A history of hospitalization was frequent (63.2%) among referred infants. The median cost per infant until CAH exclusion was 280.5 TL (~ 11.2 USD; range 60–5000 TL [~ 2.4–200 USD]). In contrast, expenditures exceeded 15,000 TL (~ 600 USD) in one infant evaluated during severe clinical decompensation. Overall, 12.7% required > 5 outpatient visits before CAH was definitively excluded; all infants with confirmed CAH required > 5 visits. In conclusion, false-positive CAH referrals in our cohort were frequently observed in premature infants and those with a history of neonatal illness and hospitalization. These data align with international experience showing that gestational age is a major driver of false-positive CAH screens. Gestational age-adjusted first-tier 17-OHP cut-offs and standardized repeat/second-tier testing pathways may reduce unnecessary referrals and healthcare utilization while preserving timely identification of clinically significant CAH. Multicenter linkage of screening and clinical outcomes is needed to define safe population-specific thresholds in Türkiye.