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

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

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, 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.

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. 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).

Conclusions: 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.

Funding: Funded by The Bill and Melinda Gates Foundation.

Clinical trial number: NCT01590095.

Keywords: child intervention; epidemiology; global health; human; low-income; nutrition; randomized controlled trial; telomere length; water, sanitation, hygiene.

Conflict of interest statement

No competing interests declared.

Co-founder of Telomere Diagnostics Inc., a telomere measurement company.

Figures

Figure 1.. Flowchart of participants’ progress through…
Figure 1.. Flowchart of participants’ progress through the phases of the trial.
Figure 2.. Kernel density plots summarize the…
Figure 2.. Kernel density plots summarize the distribution of the telomere lengths (T/S ratios) among enrolled children.
In each panel, a dashed orange line illustrates the distribution of T/S ratio among control children and a solid blue line illustrates the distribution of T/S ratio among N+WSH intervention children. Even if a child was not present at Year 1, they were included in the analysis if they provided a sample at Year 2.
Author response image 1.
Author response image 1.

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