Advanced Maternal Age Worsens Postpartum Vascular Function.

Jude S. Morton,Alison S. Care,Christy-Lynn Cooke,Sandra T. Davidge,Raven Kirschenman

doi:10.3389/fphys.2017.00465

Abstract

The age at which women experience their first pregnancy has increased throughout the decades. Pregnancy has an important influence on maternal short- and long-term cardiovascular outcomes. Pregnancy at an advanced maternal age increases maternal risk of gestational diabetes, preeclampsia, placenta previa and caesarian delivery; complications which predict worsened cardiovascular health in later years. Aging also independently increases the risk of cardiovascular disease; therefore, combined risk in women of advanced maternal age may lead to detrimental cardiovascular outcomes later in life. We hypothesized that pregnancy at an advanced maternal age would lead to postpartum vascular dysfunction. We used a reproductively aged rat model to investigate vascular function in never pregnant (virgin), previously pregnant (postpartum) and previously mated but never delivered (nulliparous) rats at approximately 13.5 months of age (3 months postpartum or equivalent). Nulliparous rats, in which pregnancy was spontaneously lost, demonstrated significantly reduced aortic relaxation responses (methylcholine [MCh] Emax: 54.2 ± 12.6%) vs. virgin and postpartum rats (MCh Emax: 84.8 ± 3.5% and 84.7 ± 3.2% respectively); suggesting pregnancy loss causes a worsened vascular pathology. Oxidized LDL reduced relaxation to MCh in aorta from virgin and postpartum, but not nulliparous rats, with an increased contribution of the LOX-1 receptor in the postpartum group. Further, in mesenteric arteries from postpartum rats, endothelium-derived hyperpolarization (EDH)-mediated vasodilation was reduced and a constrictive prostaglandin effect was apparent. In conclusion, aged postpartum rats exhibited vascular dysfunction, while rats which had pregnancy loss demonstrated a distinct vascular pathology. These data demonstrate mechanisms which may lead to worsened outcomes at an advanced maternal age; including early pregnancy loss and later life cardiovascular dysfunction.

Highlights

Pregnancy has been considered as a “window” to future cardiovascular health, influencing both short- and long-term cardiovascular outcomes for both the mother and the child (Jacobs et al, 2012; Cain et al, 2016)
Analysis of the delta area under curve (AUC) demonstrated that there was a significant reduction in nitric oxide (NO)-mediated vasodilation in the nulliparous compared to the postpartum group ( AUC: nulliparous 91.4 ± 32.4 vs. postpartum 205.5 ± 19.7; p = 0.017)
The primary undertaking of the current study was to investigate the postpartum vascular phenotype in rats which became pregnant at an advanced maternal age, compared to those who were aged but not pregnant, to determine potential mechanisms of increased cardiovascular risk in later life

Summary

Introduction

Pregnancy has been considered as a “window” to future cardiovascular health, influencing both short- and long-term cardiovascular outcomes for both the mother and the child (Jacobs et al, 2012; Cain et al, 2016). Pregnancy is considered to be cardioprotective when compared to nulligravidity (Clapp Iii and Capeless Md, 1997; Jacobs et al, 2012). The age at which women first become pregnant has gradually increased throughout the decades. This change has been driven by many factors such as relationship status, finances and education (Proudfoot et al, 2009). In Western societies such as the US, the number of women who gave birth to their first child when they were over the age of 35 increased from 5.8% in 1994 (1996) to 9.1% in 2014 (Martin et al, 2009). In Canada first births to women over 35 accounted for 11.2% of all births in 2009 (2012)

Methods

Results

Conclusion