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Inflammation in pediatric Crohn’s may decrease levels of hormones important in statural growth

AUSTIN, Texas — The higher frequency of statural growth impairment in male children with Crohn’s disease appears to be due to less standardized height gain with skeletal maturation, rather than advanced bone age progression, according to preliminary data from the Growth Study presented at Crohn’s & Colitis Congress.

“Statural growth impairment in children is both a marker – and a complication – of poorly controlled Crohn’s disease,” Neera Gupta, MD, MAS, director of research of the Pediatric Inflammatory Bowel Disease Center at Weill Cornell Medicine, told Healio Gastroenterology and Liver Disease. “Growth is a dynamic marker of health status in children. In Crohn’s disease, as well as in some other chronic inflammatory conditions, growth impairment occurs more commonly in males than females for unknown reasons.”

Gupta and colleagues are currently enrolling patients into the Growth Study – a prospective, multicenter longitudinal study – to examine sex differences in statural growth impairment in school-aged children with CD with growth potential based on bone age.

Females are included in the study if they have a bone age of 4 years, 2 months to 12 years and males are included if they have a bone age of 5 years to 14 years.

Currently, 118 patients (65% male) are enrolled and have been assessed in this analysis.

The researchers additionally analyzed the concentration of selected cytokines in serum in 54 patients (56% male), using a V-Plex kit (Meso Scale Discovery).

The mean height Z score difference was -0.4 ± 1 (standard deviation (SD)) [range: -3.9-2) in males and -1.1 ± 1.1 (SD) [range: -3.9-0.9) in females. The absolute value of the mean height Z score difference was significantly lower in males (P = 0.021).

Gupta and colleagues showed a negative association between hormones important in growth and TNF-α, IL-4, IL-6, IL-10 and IL-12 in males, while they showed the negative association between IL-13 and hormones important in growth in females.

“This is important because our early data suggest that different molecular pathways lead to growth impairment in males vs. females. In the years to come, our approach to treatment may be sex-specific,” Gupta said in an interview. “Meaning, our approach to treatment may be different in males than females. Since growth is a dynamic marker of disease activity, if we can understand why this sex difference in risk for growth impairment exists, and thus improve our overall understanding of the underlying mechanisms of growth impairment, we should then be able to treat children more optimally.”

However, Gupta reiterated that these findings are preliminary, and more research is needed.

“We are continuing to follow the children for 2 years,” she said. “We’re going to analyze cytokines in more patients as more specimens become available in our study and as we increase our numbers, we will be able to do a multivariate analysis where we adjust for other variables.” – by Ryan McDonald

Editor’s note: This article has been updated with clarifications from the study author.

Reference:

Gupta N, et al. Poster 122. Presented at: Crohn’s & Colitis Congress. Jan. 23-25, 2020; Austin, Texas.

Disclosures: Gupta reports no relevant financial disclosures.

AUSTIN, Texas — The higher frequency of statural growth impairment in male children with Crohn’s disease appears to be due to less standardized height gain with skeletal maturation, rather than advanced bone age progression, according to preliminary data from the Growth Study presented at Crohn’s & Colitis Congress.

“Statural growth impairment in children is both a marker – and a complication – of poorly controlled Crohn’s disease,” Neera Gupta, MD, MAS, director of research of the Pediatric Inflammatory Bowel Disease Center at Weill Cornell Medicine, told Healio Gastroenterology and Liver Disease. “Growth is a dynamic marker of health status in children. In Crohn’s disease, as well as in some other chronic inflammatory conditions, growth impairment occurs more commonly in males than females for unknown reasons.”

Gupta and colleagues are currently enrolling patients into the Growth Study – a prospective, multicenter longitudinal study – to examine sex differences in statural growth impairment in school-aged children with CD with growth potential based on bone age.

Females are included in the study if they have a bone age of 4 years, 2 months to 12 years and males are included if they have a bone age of 5 years to 14 years.

Currently, 118 patients (65% male) are enrolled and have been assessed in this analysis.

The researchers additionally analyzed the concentration of selected cytokines in serum in 54 patients (56% male), using a V-Plex kit (Meso Scale Discovery).

The mean height Z score difference was -0.4 ± 1 (standard deviation (SD)) [range: -3.9-2) in males and -1.1 ± 1.1 (SD) [range: -3.9-0.9) in females. The absolute value of the mean height Z score difference was significantly lower in males (P = 0.021).

Gupta and colleagues showed a negative association between hormones important in growth and TNF-α, IL-4, IL-6, IL-10 and IL-12 in males, while they showed the negative association between IL-13 and hormones important in growth in females.

“This is important because our early data suggest that different molecular pathways lead to growth impairment in males vs. females. In the years to come, our approach to treatment may be sex-specific,” Gupta said in an interview. “Meaning, our approach to treatment may be different in males than females. Since growth is a dynamic marker of disease activity, if we can understand why this sex difference in risk for growth impairment exists, and thus improve our overall understanding of the underlying mechanisms of growth impairment, we should then be able to treat children more optimally.”

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However, Gupta reiterated that these findings are preliminary, and more research is needed.

“We are continuing to follow the children for 2 years,” she said. “We’re going to analyze cytokines in more patients as more specimens become available in our study and as we increase our numbers, we will be able to do a multivariate analysis where we adjust for other variables.” – by Ryan McDonald

Editor’s note: This article has been updated with clarifications from the study author.

Reference:

Gupta N, et al. Poster 122. Presented at: Crohn’s & Colitis Congress. Jan. 23-25, 2020; Austin, Texas.

Disclosures: Gupta reports no relevant financial disclosures.

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