Sex-Specific Pathways Lead to Statural Growth Impairment in Children with Crohn's Disease

Objectives To examine the underlying mechanisms that lead growth impairment to occur more commonly in males than females with Crohn's disease (CD). Study design Children and adolescents with CD were enrolled in a prospective multicenter longitudinal cohort study. Height Z-score difference was computed as height Z- score based on chronological age (height chronological age-Z-score) minus height Z-score based on bone age (height bone age-Z-score) using longitudinal data. Specific serum cytokines were measured, hormone Z-scores were calculated based on bone age (bone age-Z), and their longitudinal associations were examined. Results There were 122 children with CD (63% male) who completed 594 visits. The mean +/- SD chronological age was 11.70 +/- 1.79 years. The mean +/- SD height chronological age-Z-score was +/- 0.03 +/- 0.99 in males and +/- 0.49 +/- 0.87 in females. The mean +/- SD height bone age-Z-score was 0.23 +/- 0.93 in males and 0.37 +/- 0.96 in females. The magnitude of the mean height Z-score difference was greater in females (+/- 0.87 +/- 0.94) than males (+/- 0.27 +/- 0.90; P =.005), indicating growth was better in females than males. The following negative associations were identified: in females, interleukin (IL)-8 (P <.001) and IL-12p70 (P =.035) with gonadotropin-bone age-Zscores; IL-8 (P =.010), IL-12p70 (P =.020), and interferon-g (P =.004) with sex hormone-bone age-Z-scores, and IL-8 (P =.044) and interferon-g (P <.001) with insulin-like growth factor 1-bone age-Z-scores; in males, IL-1 beta (P =.019) and IL-6 (P =.025) with insulin-like growth factor 1-bone age-Z-scores. Conclusions Our data suggest that sex-specific molecular pathways lead to growth impairment in children with CD (primarily growth hormone/insulin-like growth factor-1 axis in males and primarily hypothalamicpituitary-gonadal axis in females). Mapping these sex-specific molecular pathways may help in the development of sex-specific treatment approaches targeting the underlying inflammation characteristic of CD.