Elsevier

Placenta

Volume 31, Supplement, March 2010, Pages S54-S59
Placenta

Review: The Placenta is a Programming Agent for Cardiovascular Disease

https://doi.org/10.1016/j.placenta.2010.01.002Get rights and content

Abstract

Cardiovascular disease remains the number one killer in western nations in spite of declines in death rates following improvements in clinical care. It has been 20 years since David Barker and colleagues showed that slow rates of prenatal growth predict mortality from ischemic heart disease. Thus, fetal undergrowth and its associated cardiovascular diseases must be due, in part, to placental inadequacies. This conclusion is supported by a number of studies linking placental characteristics with various adult diseases. A “U” shaped relationship between placental-to-fetal weight ratio and heart disease provides powerful evidence that placental growth-regulating processes initiate vulnerabilities for later heart disease in offspring. Recent evidence from Finland indicates that placental morphological characteristics predict risks for coronary artery disease, heart failure, hypertension and several cancers. The level of risk imparted by placental shape is sex dependent. Further, maternal diet and body composition strongly influence placental growth, levels of inflammation, nutrient transport capacity and oxidative stress, with subsequent effects on offspring health. Several animal models have demonstrated the placental roots of vulnerability for heart disease. These include findings that abnormal endothelial development in the placenta is associated with undergrown myocardial walls in the embryo, and that placental insufficiency leads to depressed maturation and proliferation of working cardiomyocytes in the fetal heart. Together these models suggest that the ultimate fitness of the heart is determined by hemodynamic, growth factor, and oxygen/nutrient cues before birth, all of which are influenced, if not regulated by the placenta.

Introduction

Across the globe, far more people die of cardiovascular disease than any other disease in spite of the decline in cardiovascular related deaths since the early 1970s. Nevertheless, the annual cost of cardiovascular disease continues to increase in the US and is expected to reach the half trillion dollar mark next year. This continual rise in cost is due in part to the increase in the numbers of people with myocardial damage who now progress to heart failure. Heart failure is the fastest growing reason for hospitalization in the US, and the most expensive. An additional dark cloud sits on the horizon. An increasing number of children and adolescents are gaining excessive body weight and crossing the health threshold into the realm of chronic disease. This portends a further increase in health care costs in the coming decades as increasing numbers of middle aged adults with type 2 diabetes and coronary heart disease require medical attention [1]. Medical scientists are wondering how this epidemic of metabolic disease evolved and how it might be stopped. There is reason to believe that a better understanding of early human development might shed light on the problem.

Section snippets

Programming of cardiovascular disease

Twenty years ago David Barker and colleagues showed that mortality due to ischemic heart disease increased with decreasing birthweights over the 5 to 9 pound (2.3–4.1 kg) range; in addition, they found that babies at the largest end of the birthweight scale, above 9.5 pounds (4.3 kg), also had high rates of mortality [2]. Thus it appears that babies at both ends of the birthweight spectrum are at high risk for cardiovascular disease in adulthood. Over the intervening 20 years, a number of human

The placenta and cardiovascular disease: data from the Helsinki Birth Cohorts

The Helsinki Birth Cohorts have been especially helpful in uncovering the relationships between placental size and shape, and cardiovascular diseases in later life. Two primary Helsinki Birth Cohorts have been studied: men and women born between 1924 and 1933, and a younger cohort born between 1934 and 1944. Data from these cohorts are highly valuable because they contain information regarding birth size, placental size, childhood growth and health records. The team of Johann Eriksson, Eero

Fetal cardiac development is vulnerable to placental vascular development

The heart must grow in capacity throughout gestation to provide sufficient blood flow for growing fetal organs. Thus, the fractional cardiac output that supplies the placenta remains constant, at least over the last half of gestation [11]. Increases in placental flow impedance, as found in placental insufficiency, lead to adjustments in growth by the embryonic and fetal heart. This is understandable because the heart must eject against the instantaneous resistance of the placental bed, the

Placental insufficiency

Most of our understanding of the biological mechanisms that underpin placental insufficiency has come from animal models. The functional surface area of the sheep placenta can be reduced by various means including umbilical arterial embolization with microspheres or by carunclectomy. The first method produces placental insufficiency by infusion of 50 μm mucopolysaccharide microspheres into the umbilico-placental circulation; embolization causes umbilical blood flow to decrease as placental

The placenta is the link between maternal nutrition, fetal growth and cardiovascular disease risk

Human and animal studies have consistently shown that maternal diet during pregnancy has a profound impact on fetal growth and future risk of chronic disease. Children born to poorly nourished (including high protein and fat intake) mothers have a significantly higher incidence of coronary heart disease and hypertension in adulthood [27], [28]. As mentioned above, recent studies from the Helsinki Birth Cohort demonstrate that placental size and shape, conditioned by maternal height, are also

Future directions

Despite several decades of materno-feto-placental studies, many fundamental questions remain unanswered. We know that as the interface between mother and fetus, the placenta is critical for normal fetal growth and development but the mechanisms underlying the placental origins of adult cardiovascular disease in offspring remain unclear. A thorough investigation of maternal influences on placental development (both at the time of implantation and throughout pregnancy) in addition to the specific

Conflict of interest statement

All authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific work.

Acknowledgements

This research at Oregon Health and Science University was supported by the National Institute of Child Health and Human Development Program Project Grant (P01HD34430), Fellowships by the American Heart Association (Louey and O'Tierney) and the M. Lowell Edwards Endowment (Thornburg).

References (52)

  • K. Bibbins-Domingo et al.

    Adolescent overweight and future adult coronary heart disease

    N Engl J Med

    (2007)
  • K.R. Risnes et al.

    Placental weight relative to birth weight and long-term cardiovascular mortality: findings from a cohort of 31,307 men and women

    Am J Epidemiol

    (2009)
  • T. Forsen et al.

    Growth in utero and during childhood among women who develop coronary heart disease: longitudinal study

    BMJ

    (1999)
  • T. Forsen et al.

    Mother's weight in pregnancy and coronary heart disease in a cohort of finnish men: follow up study

    BMJ

    (1997)
  • A.V. Chobanian

    Shattuck Lecture. The hypertension paradox – more uncontrolled disease despite improved therapy

    N Engl J Med

    (2009)
  • D.J. Barker et al.

    The surface area of the placenta and hypertension in the offspring in later life

    Int J Dev Biol

    (2009)
  • E. Kajantie et al.

    Pre-eclampsia is associated with increased risk of stroke in the adult offspring: the Helsinki birth cohort study

    Stroke

    (2009)
  • E. Kajantie et al.

    In preeclampsia, the placenta grows slowly along its minor axis

    Int J Dev Biol

    (2009)
  • M.G. Sutton et al.

    Relationship between placental blood flow and combined ventricular output with gestational age in normal human fetus

    Cardiovasc Res

    (1991)
  • T. Kiserud et al.

    Fetal cardiac output, distribution to the placenta and impact of placental compromise

    Ultrasound Obstet Gynecol

    (2006)
  • C.A. Shaut et al.

    HOXA13 is essential for placental vascular patterning and labyrinth endothelial specification

    PLoS Genet

    (2008)
  • J.S. Robinson et al.

    Studies on experimental growth retardation in sheep. The effect of removal of a endometrial caruncles on fetal size and metabolism

    J Dev Physiol

    (1979)
  • G. Pardi et al.

    Diagnostic value of blood sampling in fetuses with growth retardation

    N Engl J Med

    (1993)
  • A. Barbera et al.

    Right ventricular systolic pressure load alters myocyte maturation in fetal sheep

    Am J Physiol Regul Integr Comp Physiol

    (2000)
  • S. Louey et al.

    Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes

    J Physiol

    (2007)
  • J.L. Morrison et al.

    Restriction of placental function alters heart development in the sheep fetus

    Am J Physiol Regul Integr Comp Physiol

    (2007)
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