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Impact of advanced maternal age on macrovascular and microvascular function during pregnancy
Dissertation

Impact of advanced maternal age on macrovascular and microvascular function during pregnancy

Ruda Lee
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2026
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Lee_Dissertation_final1.01 MB
Embargoed Access, Embargo ends: 06/29/2027

Abstract

Pregnancy at advanced maternal age (AMA), typically defined as ≥35 years, has become increasingly common worldwide and is associated with an elevated risk of adverse pregnancy outcomes, including hypertensive disorders of pregnancy. A healthy pregnancy requires significant maternal cardiovascular adaptations, such as increased cardiac output and decreased peripheral vascular resistance, to ensure adequate blood flow to the fetus and placenta. These substantial hemodynamic adaptations may be partially mediated by enhanced macro- and microvascular endothelial function and reduced arterial stiffness. Insufficient maternal vascular changes during pregnancy are linked to the pathophysiology of pregnancy complications. Thus, alterations in maternal vascular function may contribute to the increased risk of adverse pregnancy outcomes in pregnant women of AMA. However, maternal vascular function across pregnancy in women of AMA is relatively unexplored. The purpose of this dissertation was to comprehensively examine the effect of maternal age on vascular function during pregnancy. We assessed conduit artery endothelial function (flow-mediated dilation, FMD) and aortic stiffness (carotid-femoral pulse wave velocity, cfPWV) across the first, second, and third trimesters (Study 1), and assessed microvascular endothelial function (cutaneous microvascular responses to local heating) during the second trimester (Study 2).Study 1 examined macrovascular function across pregnancy and postpartum in healthy pregnant women of AMA compared with younger pregnant women. A total of 57 younger pregnant women (27 ± 3 years; 21–30 years) and 22 pregnant women of AMA (36 ± 1 years; 35–39 years) were studied. Endothelial function, arterial stiffness, arterial remodeling, and autonomic function were assessed during each trimester and in the postpartum period. Women of AMA demonstrated greater central and peripheral arterial stiffness and increased arterial wall thickness across all trimesters compared with younger pregnant women, with elevated arterial stiffness persisting postpartum. Additionally, women of AMA exhibited lower autonomic function compared with younger pregnant women. However, blood pressure and conduit artery endothelial function did not differ between groups. Study 2 evaluated microvascular function in pregnant women of AMA compared with younger pregnant women. Cutaneous vasodilatory responses to local heating were assessed during the second trimester in 12 younger pregnant women (28 ± 2 years; 24–30 years) and 14 pregnant women of AMA (39 ± 3 years; 35–47 years). To further determine the effect of age independent of pregnancy, 11 younger never-pregnant women (26 ± 2 years; 23–30 years) and 8 never-pregnant women age-matched to our AMA group (38 ± 3 years; 35–42 years) were also studied. Pregnant women of AMA exhibited attenuated cutaneous vasodilatory responses compared with younger pregnant women. In contrast, there were no group differences in microvascular function between younger and AMA age-matched never-pregnant women. Collectively, these findings indicate that healthy pregnant women of AMA show altered vascular function during pregnancy, characterized by increased arterial stiffness and reduced cutaneous microvascular function, compared with younger pregnant women. Importantly, the absence of age-related differences in microvascular function among never-pregnant women suggests that these alterations emerge specifically during pregnancy. These data from the two studies provide new insight into maternal vascular function during pregnancy at AMA and may help explain the increased risk of pregnancy complications in women of AMA.
Pregnancy Advanced maternal age Arterial stiffness Endothelial function Maternal health Obstetrics and gynecology

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