178 - Cardiovascular Risk in Nonhuman Primate Offspring from Pregnancies at Advanced Maternal Age

Monday, May 1, 2023

9:30 AM – 11:30 AM ET

Poster Number: 178
Publication Number: 178.403

Sarah N. Cilvik, Wake Forest School of Medicine of Wake Forest Baptist Medical Center, Lewisville, NC, United States; Carmen Kiper, Wake Forest Baptist Health - Brenner Children's Hospital, Winston Salem, NC, United States; Andrew M.. South, Wake Forest School of Medicine of Wake Forest Baptist Medical Center, Winston Salem, NC, United States; Kylie Kavanagh, Wake Forest University School of Medicine, Winston Salem, NC, United States; Giselle C. Melendez, Wake Forest School of Medicine of Wake Forest Baptist Medical Center, Winston Salem, NC, United States

Presenting Author(s)

Sarah N. Cilvik, MD, PhD (she/her/hers)

Assistant Professor, Pediatrics-Neonatology
Wake Forest University School of Medicine - Atrium Health Wake Forest Baptist
Lewisville, North Carolina, United States

Background: Advanced maternal age (≥35 years; AMA) is a risk factor for adverse pregnancy outcomes such as pre-eclampsia, stillbirth, and fetal growth restriction. These outcomes indicate an unfavorable intrauterine environment, which can predispose offspring to long-term health risks such as cardiovascular disease. Studies have shown a positive correlation between offspring blood pressure and maternal age in humans, in addition to evidence of diastolic dysfunction and poor response to ischemia in adult male rodents from AMA pregnancies.

Objective: Test the hypothesis that young adult offspring from nonhuman primate (NHP) AMA pregnancies have evidence of early cardiovascular disease, as measured by circulating biomarkers and cardiac imaging.

Design/Methods:

We sedated 7- to 9-year-old (yo; human equivalent ~25-32yo) NHP (vervet) offspring from prior young maternal age (YMA, 5-8yo; n=2 males, n=1 female) or advanced maternal age (AMA, 12-15yo; n=2 males, n=3 females) pregnancies. We measured circulating biomarkers of cardiovascular and renal dysfunction, including NTproBNP, PICP, cystatin C, and components of renin-angiotensin-aldosterone system signaling. We performed cardiac magnetic resonance (CMR) imaging to evaluate cardiovascular function and extracellular volume fraction (ECVF), which provides an estimate of myocardial fibrosis. We have only analyzed data from male offspring at the time of this submission; female data and statistical analyses will be available at time of presentation. Findings are reported as mean ± SEM.

Results:

In male offspring from AMA pregnancies, there was a consistent trend toward higher concentrations of all biomarkers measured: plasma renin activity, 4.51 ± 0.48 ng/mL/h (AMA males) vs. 0.76 ± 0.66 ng/mL/h (YMA males); serum aldosterone 16.96 ± 4.56 ng/dL (AMA males) vs. 4.86 ± 2.75 ng/dL (YMA males); plasma NTproBNP 874.0 ± 66.7 pg/mL (AMA males) vs. 798.9 ± 6.0 pg/mL (YMA males); plasma PICP 193.2 ± 2.6 ng/mL (AMA males) vs. 175.7 ± 7.7 ng/mL (YMA males); plasma cystatin C 0.579 ± 0.048 mg/L (AMA males) vs. 0.536 ± 0.030 mg/L (YMA males). In contrast, CMR analysis did not show cardiovascular dysfunction or adverse remodeling.

Conclusion(s):

Our preliminary data demonstrate a biomarker profile consistent with increased cardiovascular risk in male offspring from AMA pregnancies without evidence of cardiovascular dysfunction under sedated and non-stress conditions. Additional planned studies will increase sample size, compare sex-dependent differences, follow biomarkers and function over time, and assess cardiac response to stress.