# The Impact of Maternal Obesity and Poor Antenatal Nutrition on Offspring RDoC Dimensions and Risk for Neurodevelopmental Disorders

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $760,473

## Abstract

PROJECT SUMMARY
The goal of this proposal, is to discover prenatal determinants of post-natal behavioral precursors, emerging in the first 36
months after birth, of neurodevelopmental and psychiatric disorders. Epidemiological studies have demonstrated an
association between developmental exposure to maternal obesity, gestational diabetes, and hypertension and increased
incidence of neurodevelopmental disorders; however, the mechanisms for this association remain largely unknown. Our
own work, using non-human primate models, demonstrates causal effects on offspring temperament, operating via
changes in inflammation and neurotransmitter synthesis and relate behaviorally to negative valence, supporting the
timeliness of a more focused, prospective human study to isolate potential mechanisms. From the RDoC perspective, we
therefore prioritize the negative valence domain, which our conceptual framework also places as central to developmental
risk in very early life. We also secondarily consider key modulating domains, including positive valence, social processes,
and cognitive systems. Working from a liability x experience model, and considering emerging concepts of developmental
programming, we highlight two powerful but insufficiently understood environmental inputs in early development:
maternal obesity and poor antenatal nutrition. We hypothesize that maternal obesity and poor nutrition alter the in-utero
milieu that offspring are exposed to during fetal development resulting in increased exposure to inflammatory factors.
Those, in turn, alter brain development (not directly evaluated here) and ultimately behavior (which we study carefully).
The overarching hypothesis is that increased exposure to inflammatory factors during fetal development predicts
alterations in infant negative valence, shaping a cascade of behavioral development that increases the outcomes related to
ADHD, irritability, and behavioral risk for psychiatric disorder. To address this hypothesis, a powerful yet novel
combination of a well-established infant/toddler behavioral characterization is coupled with detailed measurements of the
nutritional, metabolic, inflammatory, and hormonal profile of the in-utero environment. We also examine selected
postnatal moderators and other relevant RDoC-dimensions, in line with our model. Aim 1 evaluates the extent to which in
humans' developmental exposure to maternal obesity and/or poor maternal nutrition predicts offspring infant and toddler
behavior, in particular negative affectivity. Aim 2 examines changes in the in-utero environment induced by maternal
obesity and poor nutrition and tests the hypothesis that increased exposure to inflammation during development underlies
the behavioral changes in the offspring. Aim 3 examines the hypothesis that the programming of offspring behavior via
maternal obesity-induced inflammation is moderated by the nutrients and hormones that offspring are exposed to during
fetal development. Results will...

## Key facts

- **NIH application ID:** 10176597
- **Project number:** 5R01MH117177-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** JOEL T NIGG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $760,473
- **Award type:** 5
- **Project period:** 2018-08-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176597

## Citation

> US National Institutes of Health, RePORTER application 10176597, The Impact of Maternal Obesity and Poor Antenatal Nutrition on Offspring RDoC Dimensions and Risk for Neurodevelopmental Disorders (5R01MH117177-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176597. Licensed CC0.

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