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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.
A regulated stress response is essential for healthy child growth and development. Here, the authors show that a nutrition, water, sanitation, and hygiene intervention enhanced adaptive responses of the physiological stress system in early childhood.
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1 University of California, Santa Cruz, Department of Microbiology and Environmental Toxicology, Santa Cruz, USA (GRID:grid.205975.c) (ISNI:0000 0001 0740 6917)
2 University of California, Berkeley, School of Public Health, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878)
3 International Centre for Diarrhoeal Disease Research, Bangladesh, Infectious Diseases Division, Dhaka, Bangladesh (GRID:grid.414142.6) (ISNI:0000 0004 0600 7174)
4 Stanford University, Division of Infectious Diseases and Geographic Medicine, Stanford, USA (GRID:grid.168010.e) (ISNI:0000 0004 1936 8956)
5 Duke University, Department of Medicine, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961)
6 Duke University, Department of Medicine, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961); Duke Cancer Institute, PK/PD Core Laboratory, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 0383 086X)
7 University of California Davis, Institute for Global Nutrition, Davis, USA (GRID:grid.27860.3b) (ISNI:0000 0004 1936 9684)
8 EpigenDx Inc., Hopkinton, USA (GRID:grid.47840.3f)
9 University of California, Francis I. Proctor Foundation, San Francisco, USA (GRID:grid.468726.9) (ISNI:0000 0004 0486 2046)
10 Pennsylvania State University, Department of Biobehavioral Health, University Park, USA (GRID:grid.29857.31) (ISNI:0000 0001 2097 4281)
11 Johns Hopkins University, Department of Environmental Health and Engineering, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311)
12 University of California, Irvine, Institute for Interdisciplinary Salivary Bioscience Research, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243); Johns Hopkins University School of Medicine, Department of Pediatrics, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311)