# Mechanisms of maternal brain changes with birth interventions

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $77,362

## Abstract

Great progress has been made over the past decade in reduction of infant morbidity and mortality in the
perinatal period. During this same time period, however, less work has been done to reduce maternal risk factors
for health and wellness complications associated with birth. The use of birth interventions, such as induction or
augmentation of labor with exogenous oxytocin or delivery via cesarean section, has risen steadily for nearly 30
years in the United States and these interventions have recently been linked to a higher risk for development of
postpartum depression (PPD). Both interventions involve altering the levels of the neuropeptide oxytocin and
functioning of the oxytocin receptor in new mothers, which has itself been linked to a higher risk for developing
PPD. This proposal aims to explore the consequences of these common birth interventions on altered oxytocin
system functioning, with specific hypotheses: (a) that epigenetic regulation of the oxytocin receptor gene, OXTR,
changes across gestation in the maternal brain and can be indexed by measures of DNA methylation and
hydroxymethylation, (b) that vaginal birth acts to reset epigenetic regulation of OXTR back to pre-pregnancy
states, (c) that birth with artificially higher levels of oxytocin (labor induction) creates an earlier epigenetic shift in
OXTR back to a pre-pregnancy state, with consequences for maternal care and depression, and conversely (d)
that births with artificially lower levels of oxytocin (cesarean sections) prevent the timely postnatal shift in OXTR
regulation back to a pre-pregnancy state, again leading to changes in maternal behavior and an increased risk
for PPD.
The R01 parent grant provides an epigenetic timeline for change in the maternal brain across gestation and into
the postnatal period and assesses the impact of common birth interventions to this timeline. We developed an
animal model (prairie vole) to study the maternal brain and have made great progress in completing sample
collection in years 1 and 2 of the grant, as we move into year 3 we are poised to begin molecular analysis. This
grant and the molecular work associated with it provides an excellent training opportunity for students interested
in translational science, and in particular an incredible opportunity to cross-train a future nurse scientist whose
interests lie in maternal mental health and mitigating its effects on offspring health. Ms. McDonald will obtain
skills in understanding, assessing and applying epigenetic markers to work in real world maternal care and
mental health. With this training she will be poised to begin a career in precision health by applying the work we
have trained her to do in an animal model to human samples. We are well positioned to incorporate the diversity
supplement work into the broader program of research, and it is highly feasible to complete the supplement
project within the timeframe of the parent grant.

## Key facts

- **NIH application ID:** 10406415
- **Project number:** 3R01HD098117-03S1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** CAROL SUE CARTER PORGES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $77,362
- **Award type:** 3
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406415

## Citation

> US National Institutes of Health, RePORTER application 10406415, Mechanisms of maternal brain changes with birth interventions (3R01HD098117-03S1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10406415. Licensed CC0.

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