1. Epidemiology and Global Health
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Effects of water, sanitation, handwashing, and nutritional interventions on telomere length among children in a cluster-randomized controlled trial in rural Bangladesh

  1. Audrie Lin  Is a corresponding author
  2. Benjamin F Arnold
  3. Andrew N Mertens
  4. Jue Lin
  5. Jade Benjamin-Chung
  6. Shahjahan Ali
  7. Alan E Hubbard
  8. Christine P Stewart
  9. Abul K Shoab
  10. Md Ziaur Rahman
  11. Md Saheen Hossen
  12. Palash Mutsuddi
  13. Syeda L Famida
  14. Salma Akther
  15. Mahbubur Rahman
  16. Leanne Unicomb
  17. Firdaus S Dhabhar
  18. Lia C H Fernald
  19. John M Colford
  20. Stephen P Luby
  1. University of California, Berkeley, United States
  2. University of California, San Francisco, United States
  3. International Centre for Diarrhoeal Disease Research, Bangladesh, Bangladesh
  4. University of California, Davis, United States
  5. University of Miami, United States
  6. Stanford University, United States
Research Article
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Cite as: eLife 2017;6:e29365 doi: 10.7554/eLife.29365

Abstract

Background: Shorter childhood telomere length (TL) and more rapid TL attrition are widely regarded as manifestations of stress. However, the potential effects of health interventions on child TL are unknown. We hypothesized that a water, sanitation, handwashing (WSH), and nutritional intervention would slow TL attrition during the first two years of life. Methods: In a trial in rural Bangladesh (ClinicalTrials.gov, NCT01590095), we randomized geographical clusters of pregnant women into individual water treatment, sanitation, handwashing, nutrition, combined WSH, combined nutrition plus WSH (N+WSH), or control arms. We conducted a substudy enrolling children from the control arm and the N+WSH intervention arm. Participants and outcome assessors were not masked; analyses were masked. Relative TL was measured at 1 and 2 years after intervention, and the change in relative TL was reported. Analysis was intention-to-treat. Findings: Between May 2012 and July 2013, in the overall trial, we randomized 720 geographical clusters of 5551 pregnant women to a control or an intervention arm. In this substudy, after 1 year of intervention, we assessed a total of 662 children (341 intervention and 321 control) and 713 children after 2 years of intervention (383 intervention and 330 control). Children in the intervention arm had significantly shorter relative TL compared with controls after 1 year of intervention (difference -163 base pairs (bp), P=0.001). Between years 1 and 2, TL increased in the intervention arm (+76 bp) and decreased in the controls (-23 bp) (P=0.050). After 2 years, there was no difference between the arms (P=0.305). Interpretation: Our unexpected finding of increased telomere attrition during the first year of life in the intervention group suggests that rapid telomere attrition during this critical period could reflect the improved growth in the intervention group, rather than accumulated stress.

Article and author information

Author details

  1. Audrie Lin

    School of Public Health, University of California, Berkeley, Berkeley, United States
    For correspondence
    audrielin@berkeley.edu
    Competing interests
    No competing interests declared.
    ORCID icon 0000-0002-3877-3469
  2. Benjamin F Arnold

    School of Public Health, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
    ORCID icon 0000-0001-6105-7295
  3. Andrew N Mertens

    School of Public Health, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  4. Jue Lin

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    Jue Lin, is a co-founder of Telomere Diagnostics Inc., a telomere measurement company..
  5. Jade Benjamin-Chung

    School of Public Health, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  6. Shahjahan Ali

    Infectious Disease Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
    Competing interests
    No competing interests declared.
  7. Alan E Hubbard

    School of Public Health, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  8. Christine P Stewart

    Department of Nutrition, University of California, Davis, Davis, United States
    Competing interests
    No competing interests declared.
  9. Abul K Shoab

    Infectious Disease Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
    Competing interests
    No competing interests declared.
  10. Md Ziaur Rahman

    Infectious Disease Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
    Competing interests
    No competing interests declared.
  11. Md Saheen Hossen

    Infectious Disease Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
    Competing interests
    No competing interests declared.
  12. Palash Mutsuddi

    Infectious Disease Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
    Competing interests
    No competing interests declared.
  13. Syeda L Famida

    Infectious Disease Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
    Competing interests
    No competing interests declared.
  14. Salma Akther

    Infectious Disease Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
    Competing interests
    No competing interests declared.
  15. Mahbubur Rahman

    Infectious Disease Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
    Competing interests
    No competing interests declared.
  16. Leanne Unicomb

    Infectious Disease Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
    Competing interests
    No competing interests declared.
  17. Firdaus S Dhabhar

    Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, United States
    Competing interests
    No competing interests declared.
  18. Lia C H Fernald

    School of Public Health, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  19. John M Colford

    School of Public Health, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  20. Stephen P Luby

    Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.

Funding

Bill and Melinda Gates Foundation (Global Development grant OPPGD759)

  • John M Colford

The funder approved the study design, but was not involved in data collection, analysis, interpretation or any decisions related to publication. The corresponding author had full access to all study data and final responsibility for the decision to submit for publication.

Ethics

Human subjects: Primary caregivers of all children provided written informed consent. The study protocols were approved by human subjects committees at icddr,b (PR-11063 and PR-14108), the University of California, Berkeley (2011-09-3652 and 2014-07-6561) and Stanford University (25863 and 35583).

Reviewing Editor

  1. Eduardo Franco, Reviewing Editor, McGill University, Canada

Publication history

  1. Received: June 7, 2017
  2. Accepted: October 3, 2017
  3. Accepted Manuscript published: October 5, 2017 (version 1)
  4. Version of Record published: November 7, 2017 (version 2)

Copyright

© 2017, Lin et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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