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Randomized Controlled Trial
. 2024 Apr 26;15(1):3572.
doi: 10.1038/s41467-024-47896-z.

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

Audrie Lin  1 , Andrew N Mertens  2 , Md Ziaur Rahman  3 , Sophia T Tan  4 , Dora Il'yasova  5 , Ivan Spasojevic  5   6 , Shahjahan Ali  3 , Christine P Stewart  7 , Lia C H Fernald  2 , Lisa Kim  2 , Liying Yan  8 , Ann Meyer  8 , Md Rabiul Karim  3 , Sunny Shahriar  3 , Gabrielle Shuman  2 , Benjamin F Arnold  9 , Alan E Hubbard  2 , Syeda L Famida  3 , Salma Akther  3 , Md Saheen Hossen  3 , Palash Mutsuddi  3 , Abul K Shoab  3 , Idan Shalev  10 , Mahbubur Rahman  3 , Leanne Unicomb  3 , Christopher D Heaney  11 , Patricia Kariger  2 , John M Colford Jr  2 , Stephen P Luby #  4 , Douglas A Granger #  12   13
Affiliations
Randomized Controlled Trial

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

Audrie Lin et al. Nat Commun. .

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.

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Conflict of interest statement

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. In the interest of full disclosure, Douglas Granger is the founder and chief scientific and strategy advisor at Salimetrics LLC and SalivaBio LLC and these relationships are managed by the policies of the committees on conflict of interest at the Johns Hopkins University School of Medicine and the University of California at Irvine. Liying Yan is the president of EpigenDx, Inc. Ann Meyer is the Associate Director of Operations at EpigenDx, Inc. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Participant enrollment for the WASH Benefits stress response and DNA methylation study population.
Source data are provided as a Source Data file.
See this image and copyright information in PMC

References

    1. Slopen N, McLaughlin KA, Shonkoff JP. Interventions to improve cortisol regulation in children: a systematic review. Pediatrics. 2014;133:312–326. doi: 10.1542/peds.2013-1632. - DOI - PMC - PubMed
    1. Victora CG, et al. Maternal and child undernutrition: consequences for adult health and human capital. Lancet. 2008;371:340–357. doi: 10.1016/S0140-6736(07)61692-4. - DOI - PMC - PubMed
    1. Johnson SB, Riley AW, Granger DA, Riis J. The science of early life toxic stress for pediatric practice and advocacy. Pediatrics. 2013;131:319–327. doi: 10.1542/peds.2012-0469. - DOI - PMC - PubMed
    1. Nater UM, Rohleder N. Salivary alpha-amylase as a non-invasive biomarker for the sympathetic nervous system: current state of research. Psychoneuroendocrinology. 2009;34:486–496. doi: 10.1016/j.psyneuen.2009.01.014. - DOI - PubMed
    1. Granger DA, Kivlighan KT, el-Sheikh M, Gordis EB, Stroud LR. Salivary alpha-amylase in biobehavioral research: recent developments and applications. Ann. NY. Acad. Sci. 2007;1098:122–144. doi: 10.1196/annals.1384.008. - DOI - PubMed

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