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. 2025 Nov:171:71-81.
doi: 10.1016/j.placenta.2025.09.014. Epub 2025 Sep 22.

Cardiovascular health in early pregnancy and circulating placental biomarkers

Andrea C Kozai  1 , Bethany Barone Gibbs  2 , Samuel Parry  3 , Sadiya S Khan  4 , William Grobman  5 , Lisa D Levine  3 , Rebecca McNeil  6 , David M Haas  7 , Jessica L Pippen  8 , Robert M Silver  9 , Judith H Chung  10 , Janet M Catov  11
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Free article

Cardiovascular health in early pregnancy and circulating placental biomarkers

Andrea C Kozai et al. Placenta. 2025 Nov.
Free article

Abstract

Background: Maternal cardiovascular and placental health are related to pregnancy outcomes, yet how cardiovascular health (CVH) in early pregnancy affects placentation is not well characterized. Our objective was to estimate associations between CVH and concentrations of placental proteins. We hypothesized that more favorable CVH metrics would be associated with more favorable circulating concentrations of pregnancy-associated plasma protein A (PAPP-A), vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble FMS-like tyrosine kinase 1 (sFlt-1), and soluble endoglin (sEng) in the 1st and 2nd trimesters.

Methods: Participants from the nuMoM2b prospective cohort with valid biomarker measures were included (n = 2188). Maternal CVH was defined using the American Heart Association's Life's Essential 8 composite score, averaging six components measured in the 1st trimester: body mass index (BMI), blood pressure, physical activity, diet, sleep duration, and smoking. Individual component scores were also evaluated. Linear regression associated scores with 1st and 2nd trimester circulating placental biomarkers.

Results and conclusions: Higher (more favorable) composite CVH scores were associated with higher PAPP-A (favorable) in both trimesters. In contrast, higher CVH scores were associated with lower VEGF, higher sFlt-1, and higher sEng in the 1st trimester (adverse). Healthier BMI scores demonstrated similar associations as those found with composite CVH. Greater physical activity was associated with more favorable 1st trimester profiles (higher VEGF and lower sFlt-1), but lower 2nd trimester PAPP-A. Composite CVH, potentially driven by BMI and physical activity components, may be an important factor relating to circulating concentrations of placental biomarkers in the first half of pregnancy.

Keywords: Angiogenic balance; Health behaviors; Life's essential 8; Maternal fetal health; Placental growth and development; nuMoM2b.

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Conflict of interest statement

Declaration of competing interest The authors have no interests to declare relating to this work.

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