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

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $694,149

## Abstract

Project Summary
Advanced maternal age (≥35 years; AMA) is 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 University School of
Medicine, as well as the complementary expertise of our multidisciplinary team, 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.
We will: 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-
14y) and young maternal age (YMA, 5-8y). 2) Test the hypothesis that NHP AMA placentas have evidence of
decreased microvascular perfusion using serial contrast-enhanced ultrasound imaging throughout pregnancy,
in addition to standard Doppler measurements of uterine/umbilical flow, assessment of fetal growth and
survival, and histologic evaluation of placental biopsies throughout pregnancy. 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 7- to 9-year-old adult vervets and cardiac magnetic resonance
imaging techniques to quantify the extracellular volume fraction, a non-invasive measure of myocardial fibrosis.
Additionally, we will use echocardiography to quantify diastolic function, measure circulating biomarkers of
cardiac strain and remodeling, and interrogate a possible mechanism for developmental programming by
measuring components of the renin-angiotensin-aldosterone system. 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 the pathophysiological changes that occur in both mothers and
offsprin...

## Key facts

- **NIH application ID:** 10805491
- **Project number:** 5R01HL164434-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Sarah N Cilvik
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $694,149
- **Award type:** 5
- **Project period:** 2023-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805491

## Citation

> US National Institutes of Health, RePORTER application 10805491, Developmental Origins of Cardiovascular Disease in Offspring from Non-Human Primate Pregnancies at Advanced Maternal Age (5R01HL164434-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10805491. Licensed CC0.

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