Structural compromises are one of the important underpinnings of the developmental origins of health and disease. Quantifying anatomic changes during development is difficult but improved technology for clinical imaging has brought new research opportunities for visualizing such alterations. During prenatal life, maternal malnutrition, toxic social stress and exposure to toxic chemicals change fetal organ structures in specific ways. High placental resistance suppresses cardiomyocyte endowment. New imaging techniques allow quantification of nephrons in cadaverous kidneys without tedious dissection. High fat diets can lead to fatty liver and fibrosis. Pancreatic islet numbers and function are compromised by poor maternal diets. Both social and nutritional stressors change wiring and cellular composition of the brain for life. Advances in optical imaging also offer exciting new technologies for viewing structure and function in cells stressed during development.

Increasing numbers of women who are pregnant have a body mass index exceeding >30 kg/m2, the definition of obesity. The obese condition is associated with a number of adverse outcomes among mothers and offspring. Offspring are at greater risk for adult onset diseases, including obesity compared to babies born to women in the normal BMI category. The risk of mortality in offspring caused by ischemic heart disease increases linearly by three-fold between a BMI of 25 to 30 kg/m2. Women with obesity are less likely to breastfeed than normal weight women. An important aspect of the obese condition is an altered range of weight around which the body regulates appetite. The medical management of women who suffer obesity can include attention to a number of factors including lifestyle modifications. Importantly, eating a healthy diet during pregnancy has been shown to improve perinatal outcomes in women across the BMI spectrum.

Introduction

David Barker and colleagues first trained the spotlight on the idea that the prenatal environment shapes the lifelong health of the heart. They reported that the standardised mortality for ischaemic heart disease within a large population of English men and women was much higher in babies born at the 5- pound (2.3 kg) end of the birthweight scale compared to babies at the 9-pound (4.0 kg) end (Barker et al., 1989). Birthweight affected the death rate in men and women similarly across the weight range, with a significant sudden upturn in the heaviest babies studied. The latter group of heavier newborn babies may have included babies that were macrosomic and born to diabetic mothers. In a separate study, Rich-Edwards and coworkers (1997) found a similar relationship among >100,000 participants in the American Nurses study. In that study, the numbers of individuals who had symptoms for coronary disease and stroke increased with decreasing recalled birthweight.

The implications of the epidemiological findings of Barker's group are enormous. Cardiovascular disease is the most devastating disease on earth and, as a category, kills more men and women than any other disease. In the USA alone, the costs to society for cardiovascular disease currently exceed $350 billion annually. Furthermore, the rates of death due to cardiovascular events around the world are on the increase (American Heart Association 2004, World Health Organization, 2003, 2004a). Over half of all cardiovascular deaths worldwide are of women (World Health Organization 2004b, 2004c).

Functional adaptations of fetal ventricles

Embryonic and fetal circulations

As cardiac myocytes differentiate, they take on the well-described characteristics of striated muscle that underlie the function of the newly formed heart (Faber, Green, & Thornburg, 1974; Keller, Hu, & Tinney 1994). Thus, as shown in previous chapters, the embryonic heart displays many functional features in common with the fully mature heart. The embryonic mammalian heart becomes a four-chambered muscular pump at the completion of the cardiac septation stage and remains so throughout the animal's life. However, from the time of septation, the right and left ventricles operate as parallel pumps in the embryo and fetus to accommodate use of the placenta as the organ for nutrient and gas exchange for the duration of prenatal life.

Because the fetus depends on the placenta for oxygen acquisition, a significant portion of the cardiac output must pass through the placenta for gas exchange. Freshly oxygenated blood must then be distributed to vital organs. The fetal lungs obviously cannot be used for oxygenation before birth, and accordingly, they receive only a small fraction of the cardiac output (Heymann, Creasy, & Rudolph, 1973). The intrauterine circulatory arrangement is similar to the adult circulation but has four unique shunts: (1) placenta, (2) ductus venosus, (3) foramen ovale, and (4) ductus arteriosus (Figure 16.1). Blood from the fetal body is delivered to the placenta via a pair of umbilical arteries. In most species (the guinea pig is an exception), the oxygenated umbilical vein blood enters the fetal inferior vena cava at the site of the liver by passing through the ductus venosus.