Childhood growth prior to screen-detected celiac disease: prospective follow-up of an at-risk birth cohort

Abstract

Objectives

To determine the association between childhood growth prior to the development of celiac disease (CD) and CD autoimmunity (CDA) identified by periodic serological screening.

Study design

The Diabetes Autoimmunity Study in the Young cohort includes 1979 genetically at-risk children from Denver, Colorado, with annual growth measurements from age nine months until ten years. Between 1993 and February 2019, 120 children developed CDA defined by persistent positive tissue transglutaminase autoantibodies (TGA); among these, 71 met our criteria for CD based on histopathological findings or high TGA levels. Age- and sex-specific z-scores of weight, body mass index (BMI), and height prior to seroconversion were derived using US reference charts as standards. Joint modeling of serial growth measurements was used to estimate adjusted hazard ratios (aHRs) accounting for celiac-associated human leukocyte antigens, early-life feeding practices, and socio-demographics.

Results

In the first 10 years of life, there were no significant associations between the child’s current weight, BMI and height and the risk of screening-detected CDA or CD, neither was the weight nor BMI velocity associated with CDA or CD as identified by screening (all aHRs approximated 1). Increased height velocity was associated with later CD, but not CDA, development (aHR per 0.01-z score/year, 1.28; 95% confidence interval [CI] 1.18–1.38 and 1.03; 0.97–1.09, respectively).

Conclusions

In the first 10 years of life, from prospectively collected serial growth measurements, we found no evidence of impaired childhood growth before CD and CDA development as identified through early and periodic screening.

Keywords:

• Height
• weight
• body mass index
• anthropometric measures

Acknowledgements

Thanks to Dr. German Tapia, the Norwegian Institute of Public Health, for the construction of the forest plot to visualize our data.

Author contributions

Dr. Stahl conceptualized and designed the study, analyzed and interpreted the data, and drafted the initial manuscript.

Fran Dong was responsible for the methodology and data curation, performed the statistical analysis for the joint model, and revised the manuscript for important intellectual content.

Dr. Lamb assisted with methodology and revised the manuscript for important intellectual content.

Kathleen Waugh and Iman Taki were responsible for data curation and critically revised the manuscript for important intellectual content.

Dr. Størdal and Dr. Stene assisted with study design and methodology, provided supervision, and critically reviewed the manuscript for important intellectual content.

Dr. Rewers and Dr. Norris provided study supervision, funding acquisition, and critically revised the manuscript for important intellectual content.

Dr. Liu helped conceptualize and design the study, provided study oversight, and critically revised the manuscript for important intellectual content.

Dr. Mårild was involved in study concept and design, study supervision, analyzed and interpreted the data, and critically revised the manuscript for important intellectual content.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

M.J.R and J.M.N. were supported by the National Institutes of Health [grants R01-DK-032493, R01-DK-104351 and R01 DK050979]. K.M. was supported by grants from the Swedish state under the agreement between the Swedish government and the country councils, the ALF-agreement. M.G.S. was supported by the NIH training T32 DK067009 grant and supported by NIH/NCATS Colorado CTSI Grant Number UL1 TR002535. Contents are the authors’ sole responsibility and do not necessarily represent official NIH views.