Characteristics of Patients with Classic Congenital Adrenal Hyperplasia Missed on the Newborn Screen

Newborn screening for congenital adrenal hyperplasia (CAH) has been in place in the USA for over 20 years. However, not all patients with classic CAH are diagnosed as neonates. Our aim was to characterize patients with classic CAH who were missed on the newborn screen (NBS) in Indiana and determine if discriminating features were present that might have led to earlier detection.

Medical records of children diagnosed with classic CAH due to 21-hydroxylase deficiency seen at Riley Hospital for Children in Indiana between January 2005 and December 2020 were reviewed. Patient characteristics, visit information, and laboratory results were collected. Statistical analysis was performed using SPSS version 28.

A total of 64 patients were identified of whom 12 (19%) were missed on the NBS. Mean age at diagnosis was 21.7 months (range: 2-74 months), 67% were girls and 66% had salt-wasting CAH. Eight (67%) presented with clinical evidence of hyperandrogenism, including clitoromegaly (n = 7), posterior labial fusion (n = 5), and pubic hair (n = 2). Screening was pursued due to a family history of CAH in the remaining 4. Genetic confirmation was present in 50%. There was no history of antenatal steroid exposure in any of the missed patients. No differences were seen with regard to sex, ethnicity, gestational age, birth weight, type of CAH, or serum 17-hydroxyprogesterone (17OHP) level at diagnosis in patients who were missed compared with those diagnosed on the NBS (14,948 ng/dL vs. 16,701 ng/dL, p = 0.74). However, the mean testosterone level at diagnosis was lower in patients who were missed compared with those who were diagnosed earlier (68 ± 60.28 ng/dL vs. 196.2 ± 206.0 ng/dL, p = 0.02). A positive family history of CAH was present in 42% of the missed patients. The timing of the NBS collection was not different between the two groups, p = 0.36.

Nearly one-fifth of our patients with classic CAH were missed on the NBS. No specific features were identified that distinguished these children from those who were detected at birth. It is critical to maintain a high index of suspicion for CAH in order to recognize these patients as early as possible so as to avoid adverse effects and potential life-threatening adrenal crises.