Effects of water, sanitation, handwashing, and nutritional interventions on environmental enteric dysfunction in young children: A Cluster-randomized, Controlled Trial in Rural Bangladesh

Audrie Lin, Shahjahan Ali, Benjamin F. Arnold, Md Ziaur Rahman, Mohammad Alauddin, Jessica Grembi, Andrew N. Mertens, Syeda L. Famida, Salma Akther, Md Saheen Hossen, Palash Mutsuddi, Abul K. Shoab, Zahir Hussain, Mahbubur Rahman, Leanne Unicomb, Sania Ashraf, Abu Mohd Naser, Sarker M. Parvez, Ayse Ercumen, Jade Benjamin-ChungRashidul Haque, Tahmeed Ahmed, Md Iqbal Hossain, Nuzhat Choudhury, Kaniz Jannat, Sarah T. Alauddin, Sandra G. Minchala, Rabije Cekovic, Alan E. Hubbard, Christine P. Stewart, Kathryn G. Dewey, John M. Colford, Stephen P. Luby

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Background. We hypothesized that drinking water, sanitation, handwashing (WSH), and nutritional interventions would improve environmental enteric dysfunction (EED), a potential contributor to stunting. Methods. Within a subsample of a cluster-randomized, controlled trial in rural Bangladesh, we enrolled pregnant women in 4 arms: control, WSH, child nutrition counseling plus lipid-based nutrient supplements (N), and nutrition plus WSH (N+WSH). Among the birth cohort, we measured biomarkers of gut inflammation (myeloperoxidase, neopterin), permeability (alpha-1-antitrypsin, lactulose, mannitol), and repair (regenerating gene 1β) at median ages 3, 14, and 28 months. Analysis was intention-to-treat. Results. We assessed 1512 children. At age 3 months, compared to controls, neopterin was reduced by nutrition (-0.21 log nmol/L; 95% confidence interval [CI], -.37, -.05) and N+WSH (-0.20 log nmol/L; 95% CI, -.34, -.06) interventions; similar reductions were observed at 14 months. At 3 months, all interventions reduced lactulose and mannitol (-0.60 to -0.69 log mmol/L). At 28 months, myeloperoxidase was elevated in the WSH and nutrition arms (0.23-0.27 log ng/mL) and lactulose was higher in the WSH arm (0.30 log mmol/L; 95% CI, .07, .53). Conclusions. Reductions in permeability and inflammation at ages 3 and 14 months suggest that the interventions promoted healthy intestinal maturation; however, by 28 months, the WSH and nutrition arms showed elevated EED biomarkers. These results underscore the importance of developing a better understanding of EED pathophysiology and targeting interventions early in childhood, when they are likely to have the largest benefit to intestinal health. Clinical Trials Registration. NCT01590095.

Original languageEnglish (US)
Pages (from-to)738-747
Number of pages10
JournalClinical Infectious Diseases
Volume70
Issue number5
DOIs
StatePublished - Mar 1 2020

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

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