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BackgroundStatural growth impairment is more common in males with Crohn's disease (CD). We assessed sex differences in height Z score differences and bone age (BA) Z scores and characterized age of menarche in a novel contemporary cohort of pediatric CD patients undergoing screening for enrollment in the multicenter longitudinal Growth Study.MethodsCrohn's disease patients (females with chronological age [CA] 5 years and older and younger than 14 years; males with CA 6 years and older and younger than 16 years) participated in a screening visit for the Growth Study. Height BA-Z scores are height Z scores calculated based on BA. Height CA-Z scores are height Z scores calculated based on CA. The height Z score difference equals height CA-Z score minus height BA-Z score.ResultsOne hundred seventy-one patients (60% male) qualified for this analysis. Mean CA was 12.2 years. Mean height CA-Z score was -0.4, and mean height BA-Z score was 0.4 in females. Mean height CA-Z score was -0.1, and mean height BA-Z score was 0.2 in males. The absolute value of the mean height Z score difference was significantly greater in females (0.8) than males (0.3; P = 0.005). The mean BA-Z score in females (-1.0) was significantly lower than in males (-0.2; P = 0.002). The median CA at menarche was 13.6 (95% CI, 12.6-14.6) years.ConclusionsOur screening visit data suggest that standardized height gain is lower in males with skeletal maturation and delayed puberty is common in females in CD. We are investigating these findings in the ongoing Growth Study.

BackgroundStatural growth impairment is more common in males with Crohn's disease (CD). We assessed sex differences in height Z score differences and bone age (BA) Z scores and characterized age of menarche in a novel contemporary cohort of pediatric CD patients undergoing screening for enrollment in the multicenter longitudinal Growth Study.MethodsCrohn's disease patients (females with chronological age [CA] 5 years and older and younger than 14 years; males with CA 6 years and older and younger than 16 years) participated in a screening visit for the Growth Study. Height BA-Z scores are height Z scores calculated based on BA. Height CA-Z scores are height Z scores calculated based on CA. The height Z score difference equals height CA-Z score minus height BA-Z score.ResultsOne hundred seventy-one patients (60% male) qualified for this analysis. Mean CA was 12.2 years. Mean height CA-Z score was -0.4, and mean height BA-Z score was 0.4 in females. Mean height CA-Z score was -0.1, and mean height BA-Z score was 0.2 in males. The absolute value of the mean height Z score difference was significantly greater in females (0.8) than males (0.3; P = 0.005). The mean BA-Z score in females (-1.0) was significantly lower than in males (-0.2; P = 0.002). The median CA at menarche was 13.6 (95% CI, 12.6-14.6) years.ConclusionsOur screening visit data suggest that standardized height gain is lower in males with skeletal maturation and delayed puberty is common in females in CD. We are investigating these findings in the ongoing Growth Study.

Ileal strictures are the major indication for resective surgery in Crohn's disease (CD). We aimed to define ileal gene programs present at diagnosis linked with future stricturing behavior during five year follow-up, and to identify potential small molecules to reverse these gene signatures. Antimicrobial serologies and pre-treatment ileal gene expression were assessed in a representative subset of 249 CD patients within the RISK multicenter pediatric CD inception cohort study, including 113 that are unique to this report. These data were used to define genes associated with stricturing behavior and for model testing to predict stricturing behavior. A bioinformatics approach to define small molecules which may reverse the stricturing gene signature was applied. 19 of the 249 patients developed isolated B2 stricturing behavior during follow-up, while 218 remained B1 inflammatory. Using deeper RNA sequencing than in our prior report, we have now defined an inflammatory gene signature including an oncostatin M co-expression signature, tightly associated with extra-cellular matrix (ECM) gene expression in those who developed stricturing complications. We further computationally prioritize small molecules targeting macrophage and fibroblast activation and angiogenesis which may reverse the stricturing gene signature. A model containing ASCA and CBir1 serologies and a refined eight ECM gene set was significantly associated with stricturing development by year five after diagnosis (AUC (95th CI) = 0.82 (0.7-0.94)). An ileal gene program for macrophage and fibroblast activation is linked to stricturing complications in treatment naïve pediatric CD, and may inform novel small molecule therapeutic approaches.