The placenta is the center of the chronic disease universe

Abstract

Over the past quarter century it has become clear that adult onset chronic diseases like heart disease and type 2 diabetes have their roots in early development. The report by David Barker and colleagues showing an inverse relationship between birthweight and mortality from ischemic heart disease was the first clear-cut demonstration of fetal programming. Because fetal growth depends upon the placental capacity to transport nutrients from maternal blood, it has been a suspected causative agent since the original Barker reports. Epidemiological studies have shown that placental size and shape have powerful associations with offspring disease. More recent studies have shown that maternal phenotypic characteristics, such as body mass index and height, interact with placental size and shape to predict disease with much more precision than does birthweight alone. For example, among people in the Helsinki Birth Cohort, who were born during 1924–1944, the risk for acquiring colorectal cancer increased as the placental surface became longer and more oval. Among people in whom the difference between the length and breadth of the surface exceeded 6 cm, the hazard ratio for the cancer was 2.3 (95% CI 1.2–4.7, p=0.003) compared with those in whom there was no difference. Among Finnish men, the hazard ratio for coronary heart disease was 1.07 (1.02–1.13, P =0.01) per 1% increase in the placental weight/birthweight ratio. Thus, it appears that the ratio of birthweight to placental weight, known as placental efficiency, predicts cardiovascular risk as well. Babies born with placentas at the extremes of efficiency are more vulnerable for adult onset chronic diseases. Recent evidence suggests that placental growth patterns are sex specific. Boys’ placentas are, in general, more efficient than those made by girls. Another recent discovery is that the size, shape and efficiencies of the placenta can change over years of time with very narrow confidence limits. This suggests that the growth of the placenta within a population of women is strongly affected by their nutritional environment. Even though it is known that an individual placenta can expand to improve its nutrient acquisition capacity in the first 2/3rd of gestation, the mechanisms by which placentas grow in response to a specific nutritional environment are not known. Discovering those mechanisms is the task of the current generation of scientists. While it may seem obvious that good nutrition is highly important for women who are pregnant because it supports optimal placentation and fetal development, more research is needed to determine the mechanisms by which maternal nutrition, placenta growth and fetal health are related.

Maternal vascular malperfusion of the placental bed associated with hypertensive disorders in the Boston Birth Cohort

“…Current research, arising from life course perspectives [7] and the fetal origins hypothesis [8], has extended the placenta’s impact to predict adult chronic diseases [9], and potentially transgenerational effects [10]. Key gaps in our knowledge, and the limited means of studying placental structure, function and development, have spurred initiatives to encourage use of innovative strategies and novel technologies to study the placenta, such as the Human Placental Project [11].…”

Roles of MicroRNA across Prenatal and Postnatal Periods

“…These biomolecules act both locally and systemically, exchanging information and regulating the physiological and metabolic processes required during intrauterine fetal life [3,4,5]. The intrauterine environment strongly influences growth and fetal development, in addition to the health status of both the mother and child long after birth [5,6,7,8]. …”

Research standardization tools: pregnancy measures in the PhenX Toolkit

“…The placenta provides significant insight into environmental exposures over the course of the gestation, and offers indispensable information about pregnancy outcome, as emphasized by the current NIH Human Placenta Project . 34-37 While considered an asset to the domain, the placental assessment protocol lacked the prerequisite that measures in the PhenX Toolkit must be characterized by an actual phenotype and was added to the Supplemental Information section of the Pregnancy domain as an additional resource for users.…”