P122 SEX DIFFERENCES IN STATURAL GROWTH IMPAIRMENT IN PEDIATRIC CROHN’S DISEASE: EARLY FINDINGS FROM THE GROWTH STUDY
Authors: Gupta Neera , Lustig Robert , Andrews Howard , Sylvester Francisco , Keljo David , Patel Ashish , Guthery Stephen , Gokhale Ranjana , Goyal Alka , Rosh Joel , Leu Cheng-Shiun 
Published: January 2020

Abstract

Background
Statural growth impairment is both a marker and complication of poorly controlled Crohn’s disease (CD), and occurs more commonly in males than females. The specific molecular mechanisms responsible for this sex difference in growth impairment in CD remain poorly characterized.

Methods
We are conducting a prospective multicenter longitudinal study (Growth Study) examining sex differences in statural growth impairment in school-age children with CD with growth potential based on bone age (BA) [females (BA 4 yrs, 2 mos to 12 years, 0 months) and males (BA 5 years, 0 months to 14 yrs, 0 mos)]. We have enrolled 118 (65% male) patients. Variable Z scores calculated based on BA are denoted as Variable BA-Z scores; those calculated based on chronological age (CA) are denoted as Variable CA-Z scores. Height Z score difference was calculated as Height CA-Z score minus Height BA-Z score. We analyzed the concentration of selected cytokines in serum in 54 patients (56% male), using a V-Plex kit (Meso Scale Discovery, Rockville, MD). Serum hormone levels were analyzed at Esoterix Endocrinology (Calabasas Hills, CA). We used t-test and Chi-squared test to examine the sex difference for continuous variables and categorical variables respectively. We assessed the association between cytokines and hormones via linear regression.

Results
The mean height Z score difference was -0.4 ± 1.0 (SD) [range: -3.9 to 2.0] in males and -1.1 ± 1.1 [-3.9 to 0.9] in females (Figure). The absolute value of the mean height Z score difference was significantly lower in males (P= 0.021). The mean BA Z score was (0.0 ± .04 [-0.7 to 0.9]) in males and (0.0 ± 0.2 [-0.4 to 0.5]) in females (P= 0.952). Race/ethnicity [76% White], Tanner stage [63% pre/early puberty; 37% mid/late puberty], mean disease duration [2.3 ± 1.9 (SD) (range: 0.1 to 8.3) years], medication use [65% infliximab; 39% methotrexate; 13% azathioprine/6-mercaptopurine; 9% adalimumab], and mean disease activity indices (indicated remission) did not differ by sex (P= NS for all). TNF-α, IL-4, IL-6, IL-10, and IL-12 were significantly negatively associated with hormones important in growth in males, while IL-13 was significantly negatively associated with hormones important in growth in females (Table).

Conclusions
Statural growth remains compromised in males compared with females in a novel contemporary cohort of children with CD. Our early data suggest that the higher frequency of growth impairment in males appears to be due to less standardized height gain with skeletal maturation, rather than advanced BA progression. BA does not appear to be significantly delayed in this cohort. Furthermore, our preliminary data suggest that systemic inflammation exerts a greater negative impact on hormone levels important in growth in males, and that different molecular pathways lead to growth impairment in males versus females. We are further investigating these preliminary findings in the ongoing prospective multicenter longitudinal Growth Study.