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

Audrie Lin (), Andrew N. Mertens, 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, Alan E. Hubbard, 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, Stephen P. Luby and Douglas A. Granger
Additional contact information
Audrie Lin: University of California, Santa Cruz
Andrew N. Mertens: University of California, Berkeley
Md. Ziaur Rahman: International Centre for Diarrhoeal Disease Research, Bangladesh
Sophia T. Tan: Stanford University
Dora Il’yasova: Duke University
Ivan Spasojevic: Duke University
Shahjahan Ali: International Centre for Diarrhoeal Disease Research, Bangladesh
Christine P. Stewart: University of California Davis
Lia C. H. Fernald: University of California, Berkeley
Lisa Kim: University of California, Berkeley
Liying Yan: EpigenDx Inc.
Ann Meyer: EpigenDx Inc.
Md. Rabiul Karim: International Centre for Diarrhoeal Disease Research, Bangladesh
Sunny Shahriar: International Centre for Diarrhoeal Disease Research, Bangladesh
Gabrielle Shuman: University of California, Berkeley
Benjamin F. Arnold: University of California
Alan E. Hubbard: University of California, Berkeley
Syeda L. Famida: International Centre for Diarrhoeal Disease Research, Bangladesh
Salma Akther: International Centre for Diarrhoeal Disease Research, Bangladesh
Md. Saheen Hossen: International Centre for Diarrhoeal Disease Research, Bangladesh
Palash Mutsuddi: International Centre for Diarrhoeal Disease Research, Bangladesh
Abul K. Shoab: International Centre for Diarrhoeal Disease Research, Bangladesh
Idan Shalev: Pennsylvania State University
Mahbubur Rahman: International Centre for Diarrhoeal Disease Research, Bangladesh
Leanne Unicomb: International Centre for Diarrhoeal Disease Research, Bangladesh
Christopher D. Heaney: Johns Hopkins University
Patricia Kariger: University of California, Berkeley
John M. Colford: University of California, Berkeley
Stephen P. Luby: Stanford University
Douglas A. Granger: University of California, Irvine

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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

Date: 2024
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DOI: 10.1038/s41467-024-47896-z

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