# The Pharmacoepigenomics of Recurrent Preterm Birth in Non-Hispanic Black Women

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $750,563

## Abstract

PROJECT SUMMARY
There is a critical gap in our understanding of mechanisms that underlie spontaneous preterm birth (SPTB) in
non-Hispanic (NH) black women. Preterm delivery (<37 weeks gestation) is the leading cause of mortality
among non-anomalous neonates; survivors are at increased risk for lifelong intellectual, physical, and social
disabilities compared with their term counterparts. NH black women are twice as likely as women of other
races to deliver preterm. 17-alpha hydroxyprogesterone caproate (17P) prevents recurrent SPTB in some
women, but is less effective for NH black compared with NH white women. The reasons for this variable
responsiveness are poorly understood, and represent a critical knowledge gap. The long-term goal of this
research is to identify NH black women at risk for 17P non-response, provide them with alternate therapies,
and thereby reduce the risk of recurrent SPTB. The objective here is to quantify the role of nitric oxide (NO)
pathways in the pathophysiology of recurrent SPTB among NH black women receiving 17P. Our central
hypothesis is that aberrations in the NO pathway predispose NH black women to 17P non-response for the
recurrent SPTB prevention. This hypothesis is based on our preliminary data and published literature showing
maternal genotype, maternal blood-derived and placental-derived proteomic profiles, and DNA methylation in
the NO pathway differ among women destined to be 17P non-responders. Furthermore, our studies show
strong race-disparity in NO pathway genes. The rationale for this work is that it will provide new insight and
increased understanding into the pathophysiology and biologic mechanisms of non-response to 17P for SPTB
prevention among NH black women, a group at disproportionately high risk of 17P treatment failure. The
central hypothesis will be tested by pursuing three Aims: (1) Determine which genes in the NO pathway are
differentially expressed in the mid-trimester among women destined to be 17P non-responders, (2) Establish
which NO pathway genes display differential CpG methylation in the mid-trimester in 17P non-responders, and
(3) Quantify conservation of gene expression and epigenetic markers between mother and offspring. These
aims will be assessed using longitudinal samples from 300 NH black women. This approach is innovative,
because this project will examine epigenetic and expression changes in maternal circulating blood and in fetal-
derived tissues in response to 17P, shedding light on acute changes that occur in response to 17P. The
proposed research is significant because as methylation and gene expression patterns are recognizable in the
second trimester, they may provide the basis for development of diagnostic tests to identify women at risk for
recurrent PTB despite 17P prophylaxis. This project is directly aligned with the mission of the NIMHD, and will
provide immediate and sustained clinical and public health impact to reduce disparities in PTB
outcomes in NH black wo...

## Key facts

- **NIH application ID:** 9899112
- **Project number:** 5R01MD011609-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** TRACY A. MANUCK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $750,563
- **Award type:** 5
- **Project period:** 2017-08-08 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899112

## Citation

> US National Institutes of Health, RePORTER application 9899112, The Pharmacoepigenomics of Recurrent Preterm Birth in Non-Hispanic Black Women (5R01MD011609-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9899112. Licensed CC0.

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