# Developmental Origins of Cardiovascular Disease in Offspring from Non-human Primate Pregnancies at Advanced Maternal Age

> **NIH NIH R56** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2022 · $708,146

## Abstract

Project Summary
Advanced maternal age (≥35 years; AMA) represents a steadily increasing public health concern as a non-
modifiable risk factor for adverse pregnancy outcomes such as pre-eclampsia, stillbirth, and fetal growth
restriction. These outcomes indicate an unfavorable intrauterine environment, which can also predispose
offspring to long-term health risks such as cardiovascular disease. The effects of maternal age on the
intrauterine environment and developmental programming have only been investigated in a handful of studies,
which have shown a slight positive correlation between offspring blood pressure and maternal age in humans,
with evidence of diastolic dysfunction and poor response to ischemia in adult male rodents. Non-human
primates (NHP), such as the vervet, represent a critical preclinical model of pregnancy that closely mirrors
human reproductive anatomy/physiology and fetal development, while allowing for better control over
confounders, such as diet and environment. Using the NIH-supported Vervet Research Colony (VRC) at Wake
Forest School of Medicine, we are uniquely poised to longitudinally assess the effects of maternal age on NHP
pregnancy physiology and chronic cardiovascular disease in offspring, through a combination of imaging and
repeated sampling of blood and placental tissue. Our specific aims are: 1) Test the hypothesis that NHP AMA
pregnancies demonstrate poor maternal cardiovascular adaptation to pregnancy in the form of cardiac diastolic
dysfunction using serial echocardiography, blood pressure measurement, and maternal blood biomarker
analysis throughout pregnancy in vervets at AMA (11-14 years old; N=16) and young maternal age (YMA; 5-8
years old; N=16). 2) Test the hypothesis that NHP AMA placentas have evidence of decreased microvascular
perfusion using serial contrast-enhanced ultrasound (CEUS) imaging throughout pregnancy. In addition, we
will acquire standard Doppler measurements of uterine/umbilical flow, follow fetal growth by ultrasound,
perform placental biopsies to follow villus histology throughout pregnancy, and quantify fetal mortality. 3) Test
the hypothesis that adult offspring from NHP AMA pregnancies show evidence of diastolic dysfunction and
increased myocardial fibrosis compared to YMA offspring using current 8- to 10-year-old adult vervets and
advanced cardiac magnetic resonance imaging (cMRI) techniques to quantify the extracellular volume fraction,
a non-invasive measure of myocardial fibrosis (AMA males N=4-6, YMA males N=4-6, AMA females N=6-8,
YMA females N=6-8). Additionally, we will use echocardiography to quantify diastolic function and measure
blood biomarkers of cardiac strain and remodeling. These studies will be among the first to investigate how
AMA affects placental function and developmental programming of cardiovascular disease in a clinically
relevant NHP model. Understanding of the pathophysiological changes that occur in both mothers and
offspring from AMA pregnancies i...

## Key facts

- **NIH application ID:** 10687414
- **Project number:** 1R56HL164434-01
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Sarah N Cilvik
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $708,146
- **Award type:** 1
- **Project period:** 2022-09-16 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10687414

## Citation

> US National Institutes of Health, RePORTER application 10687414, Developmental Origins of Cardiovascular Disease in Offspring from Non-human Primate Pregnancies at Advanced Maternal Age (1R56HL164434-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10687414. Licensed CC0.

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