Published online May 14, 2018. doi: 10.3748/wjg.v24.i18.2036
Peer-review started: February 3, 2018
First decision: February 20, 2018
Revised: April 12, 2018
Accepted: April 26, 2018
Article in press: April 26, 2018
Published online: May 14, 2018
Similar to impaired statural growth (height velocity), a dynamic marker of disease status, body composition deficits may reflect poorly controlled disease despite the absence of overt clinical intestinal symptoms. Delayed bone age (BA) is common in pediatric Crohn’s disease (CD). Determination of BA allows clinically meaningful interpretation of growth in the context of skeletal maturity in pediatric CD. The impact of accounting for BA in the interpretation of body composition is unclear. Accurate interpretation of body composition is important since it reflects nutritional and disease status. Not only is nutritional status an important determinant of pubertal development and growth velocity, it is a prognostic factor for disease course. The association between medications and serum inflammatory and hormonal biomarkers with anthropometric measurements is not well delineated in pediatric CD, particularly after adjusting for maturational status (BA).
Nutritional status is an important factor to consider when making therapeutic decisions given its association with poor outcomes. Yet, the impact of treatments on anthropometric measurements is poorly defined and has not received sufficient attention.
Our aims were to determine the distribution of anthropometric parameters based on CA (CA z-scores) and BA (BA z-scores) and characterize the associations between medications and serum biomarkers with anthropometric parameter z-scores in pediatric CD.
CD patients [< chronological age (CA) 21 years] were prospectively enrolled in a cross-sectional study. Descriptive statistics were generated for participants’ demographic characteristics and key variables of interest. Paired t-tests were used to compare anthropometric parameter z-scores calculated based on CA (CA z-scores) and BA (BA z-scores) for interpretation of anthropometric parameters. Linear regression was utilized to examine associations between medications and serum biomarkers with anthropometric parameter z-scores calculated based on CA (n = 82) and BA (n = 49). We reported regression coefficients as well as their corresponding p-values and 95% confidence intervals.
Mean CA at the time of the study visit was 15.3 ± 3.5 (standard deviation; range = 4.8-20.7) years. Mean triceps skinfold, subscapular skinfold and mid-arm circumference (MAC) BA z-scores were higher than corresponding CA z-scores. Medications were positively associated with subscapular skinfold (adalimumab and methotrexate) and BMI (adalimumab) CA z-scores. Azathioprine/6-mercaptopurine were negatively associated with MAC, subscapular skinfold, weight and BMI CA z-scores . ESR, CRP, and WBC count were negatively associated, while albumin and IGF-1 BA z-scores were positively associated with specific AP z-scores. Mean height CA z-scores were higher in females, not males, treated with infliximab. Hemoglobin was positively associated, while platelets, ESR and CRP were negatively associated with height CA z-scores in males, not females.
Our findings reinforce the importance of accounting for BA when interpreting anthropometric parameters in pediatric CD. The main findings of our study raise intriguing questions. Thiopurines were negatively associated with specific anthropometric parameters. Do thiopurines have a negative effect on nutritional status/disease status? Alternatively, is the efficacy of thiopurines suboptimal? Infliximab was positively associated with standardized height in females only. Is there a sex difference in response to infliximab from the standpoint of statural growth? Specific serum biomarkers were associated with standardized height in males only, supporting the hypothesis that inflammation has a more detrimental effect on statural growth in males. Our results suggest a mechanistic relationship between medications, inflammation and anthropometric status/disease status, as well as a difference by sex. The studies presented herein contribute to a better understanding of the relationship between medications and serum inflammatory and hormonal biomarkers with anthropometric parameters in pediatric CD. Prospective longitudinal study is required as a next step to further investigate these intriguing findings and would allow further risk stratification which will improve patient counseling, guide expectations, and facilitate an individualized treatment approach.
These findings serve as a foundation on which to build future studies with the goal of identifying patients at highest risk for poor outcomes, enhancing treatment algorithms, and ultimately developing individual treatment approaches based on risk stratification. The present study may provide a basis for mechanistic studies in many pediatric chronic inflammatory conditions.