Observational Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2018; 24(18): 2036-2046
Published online May 14, 2018. doi: 10.3748/wjg.v24.i18.2036
Thiopurines are negatively associated with anthropometric parameters in pediatric Crohn’s disease
Neera Gupta, Robert H Lustig, Cewin Chao, Eric Vittinghoff, Howard Andrews, Cheng-Shiun Leu
Neera Gupta, Division of Gastroenterology and Nutrition, Department of Pediatrics, Weill Cornell Medicine, New York, NY 10021, United States
Robert H Lustig, Division of Endocrinology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94158, United States
Cewin Chao, Department of Nutrition and Food Services, University of California, San Francisco, San Francisco, CA 94143, United States
Eric Vittinghoff, Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, United States
Howard Andrews, Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, United States
Cheng-Shiun Leu, Department of Biostatistics, Columbia University Medical Center, New York, NY 10032, United States
Author contributions: Gupta N initial concept, secured funding; Gupta N, Lustig RH, Vittinghoff E and Leu CS study design; Gupta N data collection; Lustig RH bone age interpretation; Chao C anthropometric measurements; Gupta N and Leu CS data management; Gupta N, Vittinghoff E and Leu CS statistical analyses; Gupta N, Lustig RH, Chao C, Vittinghoff E, Andrews H and Leu CS data interpretation; Gupta N initial manuscript preparation; Gupta N, Lustig RH, Chao C, Vittinghoff E, Andrews H and Leu CS manuscript editing and revising; Gupta N finalized submission.
Supported by National Institutes of Health, No. DK077734 (NG); Children’s Digestive Health and Nutrition Foundation (now known as North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Foundation)/Crohn’s and Colitis Foundation of America (now known as Crohn’s and Colitis Foundation) Award for New Investigators, No. CDHNF-06-002 (NG); Crohn’s and Colitis Foundation of America (now known as Crohn’s and Colitis Foundation) Career Development Award, No. Award ID 1743 (NG); University of California San Francisco Department of Pediatrics Pediatric Clinical Research Center Clinical Research Pilot Funding Award (NG), and National Institutes of Health/National Center for Research Resources University of California San Francisco-Clinical and Translational Science Institute, No. UL1 RR024131.
Institutional review board statement: We obtained Institutional Review Board Approval for the study protocol.
Conflict-of-interest statement: Robert H Lustig wrote two trade books on metabolic health, but not related to the issues of this paper. The other authors have no conflicts of interest relevant to this article to disclose.
STROBE statement: The guidelines of the STROBE Statement have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Neera Gupta, MD, MAS, Associate Professor, Division of Gastroenterology and Nutrition, Department of Pediatrics, Weill Cornell Medicine, 505 East 70th Street, Helmsley Tower, 3rd Floor, New York, NY 10021, United States. neg9020@med.cornell.edu
Telephone: +1-646-9623869 Fax: +1-646-9620246
Received: February 3, 2018
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
Processing time: 97 Days and 11.5 Hours
Abstract
AIM

To determine the distribution of anthropometric parameter (AP)-z-scores and characterize associations between medications/serum biomarkers and AP-z-scores in pediatric Crohn’s disease (CD).

METHODS

CD patients [< chronological age (CA) 21 years] were 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 AP-z-scores calculated based on CA (CA z-scores) and bone age (BA) (BA z-scores) for interpretation of AP’s. Linear regression was utilized to examine associations between medications and serum biomarkers with AP-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.

RESULTS

Mean CA at the time of the study visit was 15.3 ± 3.5 (SD; range = 4.8-20.7) years. Mean triceps skinfold (P = 0.039), subscapular skinfold (P = 0.002) and mid-arm circumference (MAC) (P = 0.001) BA z-scores were higher than corresponding CA z-scores. Medications were positively associated with subscapular skinfold [adalimumab (P = 0.018) and methotrexate (P = 0.027)] and BMI CA z-scores [adalimumab (P = 0.029)]. Azathioprine/6-mercaptopurine were negatively associated with MAC (P = 0.045), subscapular skinfold (P = 0.014), weight (P = 0.002) and BMI (P = 0.013) 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 (P < 0.05). Mean height CA z-scores were higher in females, not males, treated with infliximab (P = 0.038). Hemoglobin (P = 0.018) was positively associated, while platelets (P = 0.005), ESR (P = 0.003) and CRP (P = 0.039) were negatively associated with height CA z-scores in males, not females.

CONCLUSION

Our results suggest poor efficacy of thiopurines and a possible sex difference in statural growth response to infliximab in pediatric CD. Prospective longitudinal studies are required.

Keywords: Inflammatory bowel disease; Azathioprine/6-mercaptopurine; Biologics; Nutrition

Core tip: Azathioprine/6-mercaptopurine were negatively associated with specific anthropometric parameters, suggesting a possible negative effect vs poor efficacy of thiopurines in pediatric Crohn’s disease (CD). Infliximab was positively associated with standardized height in females only, suggesting a possible sex difference in response to infliximab from the standpoint of statural growth in pediatric CD. Specific serum biomarkers were associated with standardized height in males only, supporting that inflammation has a more detrimental effect on statural growth in males with pediatric CD.