# Preconception Maternal Nutrition, Offspring DNA Methylation, and InfantGrowth in Low Resource Settings

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2024 · $498,046

## Abstract

PROJECT ABSTRACT
 Growth stunting is a global health problem that impacts ~149 million children under 5 years of age living
primarily in low-and-middle income-countries, particularly low-income countries. Mothers and infants are
particularly vulnerable to the impacts of malnutrition, including inadequacy of micronutrients which contributes to
stunted growth resulting in life-long morbidity and mortality, lower education achievement, and loss of human
capital. The goal of this proposal is to determine if a preconception maternal nutrition supplement can alter
targeted and epigenome-wide DNA methylation (DNAme) in infants born in regions prone to high rates of growth
stunting. DNAme is an epigenetic mechanism that regulates gene transcription, and thus, phenotypical
differences and risk for noncommunicable diseases. Specifically, we will test if maternal consumption of a small
quantity lipid-based nutrient supplement (sqLNS) prior to conception alters infant DNAme at birth and beyond,
and if these epigenetic changes are associated with growth during the first two years of life. We will examine
DNAme of specific genomic regions called human metastable epialleles (MEs); MEs are systemic epigenetic
marks that can be detected at birth and known to be altered by maternal nutritional status at conception in
low resource settings. In addition, several epigenetic clocks (Horvath, PhenoAge, Hannum) have been
developed that estimate: 1) chronological age with ≥ 96% accuracy; 2) phenotypic age; and 3) epigenetic age
acceleration (EAA). Estimates of epigenetic age provide indications of life and health span. Obesity,
cardiovascular disease, cancers, and type 2 diabetes mellitus have been shown to be strongly associated with
increased EAA, potentially reducing life and health span. However, there are a paucity of studies addressing
MEs and EAA in the context of growth stunting, low resource settings, and in response to a preconception
maternal nutritional intervention. This proposal leverages a completed randomized controlled trial
(NCT01883193, Women First, WF) in mother-infant dyads from the Democratic Republic of the Congo (DRC),
Guatemala, India, and Pakistan. The WF RCT was comprised of three treatment arms: Arm 1 = women
consumed sqLNS ≥ 3 months prior to conception until delivery; Arm 2 = women consumed the same sqLNS
commencing at 12 weeks gestion until delivery; and Arm 3 = no sqLNS was consumed. We propose the following
aims to advance our understanding of maternal nutrition and offspring health and growth via DNAme changes:
Aim 1: Test if timing of sqLNS alters DNAme of specific genomic regions called human metastable epialleles
(MEs) at birth (placenta N = 463) and 3 months postnatally (buccal N = 391) using EPIC 850K arrays.
Aim 2: Determine maternal and infant factors that impact infant epigenetic and gestational age acceleration
(GAA, placenta N =463).
Aim 3: Targeted DNAme profiles (MEs & EAA) and epigenome-wide DNAme will be predictive of neona...

## Key facts

- **NIH application ID:** 11011211
- **Project number:** 7R01HD110585-02
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Sarah Jean Borengasser
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $498,046
- **Award type:** 7
- **Project period:** 2024-01-15 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11011211

## Citation

> US National Institutes of Health, RePORTER application 11011211, Preconception Maternal Nutrition, Offspring DNA Methylation, and InfantGrowth in Low Resource Settings (7R01HD110585-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11011211. Licensed CC0.

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