A cluster-randomized trial of water, sanitation, handwashing and nutritional interventions on stress and epigenetic programming

Abstract: 

A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1–2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N + WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N + WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from −0.16 to −0.19 log ng/mg of creatinine, P < 0.01), elevated post-stressor cortisol (0.24 log µg/dl; P < 0.01), higher cortisol residualized gain scores (0.06 µg/dl; P = 0.023), and decreased methylation of the NGFI-A binding site (−0.04; P = 0.037). The N + WSH intervention enhanced adaptive responses of the physiological stress system in early childhood.

Author: 
Andrew Mertens
Audrie Lin
Md. Ziaur Rahman
Sophia T. Tan
Dora Il’yasova
Ivan Spasojevic
Shahjahan Ali
Christine P. Stewart
Lia C. H. Fernald
Lisa Kim
Liying Yan
Ann Meyer
Md. Rabiul Karim
Sunny Shahriar
Gabrielle Shuman
Benjamin F. Arnold
Syeda L. Famida
Salma Akther
Md. Saheen Hossen
Palash Mutsuddi
Abul K. Shoab
Idan Shalev
Mahbubur Rahman
Leanne Unicomb
Christopher D. Heaney
Patricia Kariger
John M. Colford Jr.
Stephen P. Luby
Douglas A. Granger
Publication date: 
April 26, 2024
Publication type: 
Journal Article