# Maternal metabolic and molecular changes induced by preconception weight loss and their effects on birth outcomes

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $598,970

## Abstract

Abstract
Maternal obesity during pregnancy increases the risk of hypertension, gestational diabetes and abnormalities in
fetal growth with higher infant birth weight and BMI in both early and late childhood. Extensive literature provides
evidence for epigenetic programming of the developing fetus in response to the maternal metabolic milieu, but
there is minimal direct evidence that changes in the fetal environment can alter the epigenome. The proposed
study will test the hypothesis that significant weight loss prior to conception will improve the intrauterine metabolic
environment as reflected in the maternal metabolome and inflammation-related proteome and result in changes
in methylation patterns in cord blood leukocytes. To test this hypothesis, three Specific Aims are proposed. Aim
1, will examine the metabolic intrauterine environment in 300 obese women (BMI>30 kg/m2 ≤ 45 kg/m2) who
will be randomized to either Very Low Energy Diet (VLED) targeting a >15% body weight loss or Standard of
Care (SOC) interventions. Along with 120 lean women (LEAN) serving as comparators, VLED and SOC women
will undergo extensive prepregnancy clinical and physiological phenotyping and blood collections. Obese women
will undergo additional phenotyping after weight loss and all women will have additional testing at each trimester.
We expect 87 offspring in each group. Fetal growth will be assessed by ultrasound and offspring birth weight
(Ponderal index), adiposity (Pea Pod Air Displacement Plethysmography). In Aim 2, plasma metabolomics and
(hybrid targeted/untargeted and lipidomics) and inflammatory markers will be used to assess intervention
associated changes in VLED and SOC women and compared to VLED women. To assess the intrauterine
environment, metabolomic profiles and inflammatory proteome will be measured in the first trimester and at term
in all mothers and in fetal cord blood. Multivariate computational models will assess the association of maternal
and neonate metabolome and inflammatory markers to fetal growth and newborn weight and adiposity. In Aim
3, DNA methylation patterns and RNA-seq will be obtained from fetal cord blood lymphocytes of all offspring.
Differences in methylation patterns between VLED, SOC and LEAN will be assessed and changes in mRNA
levels will be determined to assess the effect of methylation on gene expression. Multivariate analysis of
methylation patterns will be related to the metabolome and to fetal growth and birth outcomes. Using sparse
multivariate factor analysis regression model (smFARM) and other statistical approaches, we will determine how
the maternal metabolome and proteome is associated with cord blood DNA methylation and investigate whether
fetal growth or birth weight and other outcomes are mediated by specific metabolites. The results of these studies
will provide the first prospective assessment of the benefit of preconception weight loss on the intrauterine
environment and molecular changes in the newborn a...

## Key facts

- **NIH application ID:** 10116866
- **Project number:** 1R01DK124862-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** CHARLES F BURANT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $598,970
- **Award type:** 1
- **Project period:** 2020-09-22 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116866

## Citation

> US National Institutes of Health, RePORTER application 10116866, Maternal metabolic and molecular changes induced by preconception weight loss and their effects on birth outcomes (1R01DK124862-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10116866. Licensed CC0.

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