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

Audrie Lin,Christine P Stewart,Mahbubur Rahman,Jue Lin,Leanne Unicomb,Salma Akther,Syeda L Famida,Palash Mutsuddi,Shahjahan Ali,Ziaur Rahman ,Alan Hubbard ,Benjamin F Arnold ,Saheen Hossen ,Abul K Shoab ,Firdaus S Dhabhar ,Lia C H Fernald ,Jade Benjamin‐Chung ,Andrew Mertens ,John M Colford ,Stephen P Luby

doi:10.7554/elife.29365

Abstract

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. In a trial in rural Bangladesh, 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. 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). 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. Funded by The Bill and Melinda Gates Foundation. NCT01590095.

Highlights

Children in low-income countries often experience infectious diseases and nutritional deficiencies leading to impaired growth, poor development, and early mortality (Black et al, 2017; GBD 2015 Mortality and Causes of Death Collaborators, 2016; Victora et al, 2008)
We conducted a substudy within the trial to evaluate if the N + WSH intervention would slow telomere attrition among children in their first two years of life (Arnold et al, 2013)
We demonstrate an effect of an intervention on telomere length (TL) in infants and report the trajectories of infant TL in a low-income country

Summary

Introduction

Children in low-income countries often experience infectious diseases and nutritional deficiencies leading to impaired growth, poor development, and early mortality (Black et al, 2017; GBD 2015 Mortality and Causes of Death Collaborators, 2016; Victora et al, 2008). Shorter TL has been linked to several age-related conditions including diabetes, heart disease, and early mortality (Cawthon et al, 2003; Fitzpatrick et al, 2007; Salpea et al, 2010) It remains an open debate whether TL serves as a ‘molecular clock’ that gauges cumulative stress exposures over a lifespan or plays a role in the etiology of various diseases (Blackburn et al, 2015; Hamad et al, 2016; Zhan et al, 2015). Results: 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.

Methods

Results

Conclusion