Growth Study highlights statural growth impairment among pediatric patients with Crohn’s disease

As a parent, seeing your child grow is an indicator that they are healthy. When IBD is diagnosed in childhood, one of the ways it impacts kids is in their growth. Some children with Crohn’s disease don’t grow at a normal rate and in some, their final adult height is less than expected because of their Crohn’s disease.

Dr. Neera Gupta, pediatric gastroenterologist and physician-scientist at Weill Cornell Medicine and NewYork-Presbyterian Komansky Children’s Hospital, and her team have been studying growth in pediatric patients with IBD. Dr. Gupta (principal investigator) received funding in 2014 from the National Institutes of Health to lead a study examining the sex-specific effects of Crohn’s disease on the growth of pediatric patients (Growth Study).

Dr. Gupta and her fellow researchers recently published new findings from the Growth Study in Inflammatory Bowel Diseases, and we asked her some questions about what patients with IBD should know about the study results:

What is the Growth Study?

Dr. Gupta: The Growth Study is a prospective, multicenter longitudinal cohort study examining sex differences in statural growth impairment in pediatric patients with Crohn’s disease. Statural growth impairment is more common in males than females with Crohn’s disease.

Why is research on growth impairment in pediatric Crohn’s disease important?

Dr. Gupta: Growth is a dynamic marker of health status in children. Growth is a dynamic marker of disease activity in children with Crohn’s disease. Statural growth impairment is both a marker of and complication of poorly controlled Crohn’s disease and occurs in up to 80% of patients, three times more commonly in males. If a child with Crohn’s disease is not growing well, it is important to consider the possibility of ongoing intestinal inflammation, even the in the absence of other [disease] symptoms, such as diarrhea or abdominal pain. 

Our research suggests a possible sex difference in statural growth response to specific therapies, raising the possibility of sex-specific molecular pathways leading to growth impairment. Understanding [the causes of] sex differences in growth impairment may help us to develop new targeted medical treatment strategies to improve growth and to identify and optimize treatment for high-risk patients. Importantly, understanding the underlying mechanisms of sex differences in growth impairment will allow us to lay the foundation for the development of a sex-specific treatment approach in pediatric Crohn’s disease, which currently does not exist.

Who participated in this study?

Dr. Gupta: We enrolled females with Crohn’s disease who were between five and 14 years old and males who were between six and 16 years old. During their screening visit, eligibility for bone age (the degree of maturation of a child’s bones) was determined. If bone age was obtained, female patients with bone age greater than four years and two months and less than 12 years, and male patients with bone age greater than five years and less than 14 years were eligible to participate.

What were the study’s main findings?

Dr. Gupta: The results that we presented in this manuscript suggest that females grow better than males with bone age progression. We identified several sex-specific clinical variables associated with statural growth: 

• Initial classification of disease as Crohn’s disease
• Perianal disease behavior at diagnosis
• Specific symptoms/extraintestinal manifestations at presentation
• Specific medication use:
  • azathioprine/6-merpcaptopurine
  • probiotics 
  • infliximab
  • biologics
  • methotrexate
  • vitamin D

Each of the identified variables was either significantly associated with growth in one sex and not the other sex or was more strongly associated with growth in one sex than in the other sex.

What is the significance of these findings?

Dr. Gupta: Our findings suggest that sex-specific molecular pathways lead to statural growth impairment in Crohn’s disease and suggest a need for a sex-specific treatment approach in pediatric Crohn’s disease, which is not currently part of the pediatric Crohn’s disease management algorithm.

Can you explain some of the different clinical variables that were associated with statural growth in male versus female patients?

Dr. Gupta: An initial classification of Crohn’s disease or perianal disease at diagnosis were associated with better growth in female patients. Arthralgia (joint pain) at IBD symptom onset, azathioprine/6-merpcaptopurine use, or probiotic use were associated with worse growth in female patients. Patient-reported poor growth at symptom onset, infliximab, biologics, methotrexate, or vitamin D use were associated with better growth in male patients. Initial classification as Crohn’s disease or anorexia or mouth sores at symptom onset were associated with worse growth in male patients.

What are some avenues for future research on growth impairment in Crohn’s disease? Do you have any plans to do similar research in ulcerative colitis patients?

Dr. Gupta: It is important to continue to improve our understanding of the biological mechanisms that lead to statural growth impairment by sex. Improved understanding will set the stage for identifying and developing sex-specific management approaches that enable normal growth and development in both male and female patients. Findings from the Growth Study will enable us to identify factors for each sex that predict which patients are at highest risk for statural growth impairment refractory to standard therapeutic approaches. Our findings will direct future studies focused on improving statural growth impairment in patients with high risk. Furthermore, we aim to define the optimal timing of and specific treatments for both male and female pediatric patients based on their individual risk for statural growth impairment. Sex will likely be an important future determinant of treatment decisions, which will represent a major advancement in clinical decision making for pediatric Crohn’s disease.

Yes, I think it’s important to study growth and nutrition in pediatric patients with ulcerative colitis as well.

Click here to learn more about the ways IBD impacts pediatric patients.