Abstract
Disclosure: B.P. Hoffman-Kipp: None. H. Wang: None. S. Dettweiler: None. A. Mockler: None. M.E. Geffner: Neurocrine Biosciences, Spruce Biosciences, Eton Pharmaceuticals, UpToDate, Adrenas Therapeutics. M.S. Kim: Neurocrine Biosciences, Spruce Biosciences, Eton Pharmaceuticals, UpToDate, Adrenas Therapeutics.
Introduction: Classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most common primary adrenal insufficiency in children, involving androgen excess due to impaired steroidogenesis. Older children, adolescents, and adults with CAH exhibit up to double the prevalence of obesity compared to controls, with an earlier adiposity rebound (1.5-3 years) than normative populations reported in the U.K., Japan, and the U.S. However, more needs to be understood about the early onset of obesity in younger children with classical CAH. We aimed to examine disease-specific growth trajectories from early childhood (0-6 years) in a large cohort of children with classical CAH in the U.S. Methods: Early childhood growth data were studied in 95 children (55.8% female) with classical CAH due to 21-hydroxylase deficiency (86.3% salt-wasting form). Measurements from 1060 patient visits of children between birth to 6 years in the Endocrinology clinic at Children’s Hospital Los Angeles (1998-2024) were analyzed. Cohort-wide growth trajectories were visualized using generalized additive models and compared to reference population growth data (WHO < 2 years, CDC 2-6 years). The LMS modeling approach for non-normally distributed data was applied to estimate percentiles and z-scores for weight, weight-for-length (WFL, < 2 years), and BMI (2-6 years), and to generate total and sex-specific growth curves in early childhood. We categorized patients between 2-6 years of age for weight based on BMI percentile. Results: In infants with CAH, the median WFL began to surpass the 50th percentile for the reference population in the second month of life (6 weeks). The median WFL z-score in infants with CAH increased rapidly until 5 months of age, when it remained more stable until 2 years of age. This upward drift from the reference median became more pronounced with age in children with CAH, who exhibited a median BMI z-score of +1 at 4-5 years, reaching a BMI z-score of +1.4 (overweight) by 6 years. These trajectory patterns appeared to be driven by males with CAH compared to females. In children with CAH between 2-6 years of age, the percentage of children who were overweight ranged from 22-27% depending on the year of life. The percentage living with obesity increased with each year of life: 2-3 years, 14.1%; 3-4 years, 18.5%; 4-5 years, 21.2%; and 5-6 years, 30.0%. By 5 years, these children exhibited 2.3 times the prevalence of obesity seen in typical 2-5 year old children in the U.S. (NHANES). Conclusions: Infants with classical CAH exhibit different patterns of growth from month two of life, compared to reference populations, with a steadily increasing prevalence of obesity through their toddler and preschool years.
Presentation: Monday, July 14, 2025