# Assessing the relationship between environmental enteric dysfunction and poor growth via a newly developed 11-plex assay

> **NIH NIH R21** · BOSTON CHILDREN'S HOSPITAL · 2020 · $185,158

## Abstract

Project Summary:
 Undernutrition remains one of the greatest human development challenges of our time. In 2017, an
estimated 151 million children < 5 years of age (i.e., 22.2% of the global population) were stunted, increasing
their risk for morbidity and mortality in childhood, suboptimal cognitive development, poorer educational
outcomes, and lower economic productivity and earnings in adulthood. It has been increasingly appreciated
that growth failure can begin in utero and worsen during early infancy; recently, environmental enteric
dysfunction (EED) has been hypothesized as an important causal factor. EED is an acquired, subclinical
condition of the small intestine associated with chronic exposure to an unhygienic environment where enteric
pathogens persist. Histologic features include mucosal inflammation, villous blunting, altered barrier integrity,
and reduced intestinal absorptive capacity. Despite EED’s purported link to poor health and nutrition outcomes
in young children in low- and middle- income countries (LMICs), our knowledge of EED is relatively limited.
Research gaps include the role of infant EED on subsequent poor growth and development and the possible
role of maternal EED on adverse birth outcomes.
 The Trial of Vitamins-5 (ToV5) is an individually randomized, double-blind, placebo-controlled trial (R01
HD83113; ClinicalTrials.gov: NCT02305927) of maternal vitamin D3 (cholecalciferol) supplementation
conducted among 2,300 HIV-infected pregnant women in Dar es Salaam, Tanzania. Following enrollment into
the trial, mothers were followed-up at monthly clinic visits during pregnancy, at delivery, and then with their
child at monthly postpartum clinic visits. Using data and serum samples collected in the ToV5 study, the main
objectives of the current proposal are to assess 1) the relationship between infant EED and linear growth, i.e.,
length-for-age Z-score (LAZ) at 12 months of age; 2) the relationship between infant EED and development,
measured by the Caregiver-Reported Early Development Index (CREDI) at 12 months of age; and 3) the
relationship between maternal EED during pregnancy and birth outcomes, primarily infant birth weight and
duration of gestation. We also aim to 4) examine relationships between the EED, systemic inflammation, and
micronutrient biomarkers from a newly developed 11-plex multi-micronutrient and EED assessment tool
(MEEDAT); consisting of intestinal fatty acid–binding protein (I-FABP), soluble CD14 (sCD14), insulin-like
growth factor 1 (IGF-1), fibroblast growth factor 21 (FGF21), alpha-1-acid glycoprotein (AGP), C-reactive
protein (CRP), ferritin, soluble transferrin receptor (sTfR), retinol binding protein 4 (RBP4), thyroglobulin (Tg),
and Plasmodium falciparum exposure (HRP2); and anti-flagellin/anti-LPS Igs. Overall, this proposed research
will contribute to our understanding of the consequences of EED in LMICs, specifically related to poor growth
and adverse birth outcomes, using two innovative me...

## Key facts

- **NIH application ID:** 10021657
- **Project number:** 5R21DK123636-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** CHRISTOPHER P DUGGAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $185,158
- **Award type:** 5
- **Project period:** 2019-09-21 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10021657

## Citation

> US National Institutes of Health, RePORTER application 10021657, Assessing the relationship between environmental enteric dysfunction and poor growth via a newly developed 11-plex assay (5R21DK123636-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10021657. Licensed CC0.

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