The placenta is an organ that functions as the fetus’ extracorporeal life-support system. The placenta serves as the fetal lung (respiration), kidney (excretion), gastrointestinal tract (nutrition), and skin (heat exchange) and as a barrier against certain substances dangerous to the fetus. In addition, it is an endocrine organ that produces steroid (estrogen, progesterone) and protein (human chorionic gonadotropin, human placental lactogen) hormones. Very early in gestation, the blastocyst implants in the decidualized endometrium and the trophoblast cells invade the maternal circulation, creating a lake of maternal blood that bathes the trophoblast and developing embryo. As the gestation grows, a number of spiral arteries that supply blood to the endometrium are penetrated and provide the basic architecture as the placenta develops, with villi forming cotyledons arranged around these spiral arteries. The fetal chorionic villi develop many convolutions and float in the maternal blood supplied from the previously invaded spiral arteries. This maternal blood occupies an area referred to as the intervillous space, and it is between this space and the fetal capillary (contained within the chorionic villus) that maternal-fetal and fetal-maternal exchange occurs. The human placenta is thus referred to as a hemochorial type because the mother’s blood comes into direct contact with the fetal chorionic villus (1). Oxygen, carbon dioxide, nutrients, waste products, water, and heat are exchanged at this level and must cross two layers of fetal trophoblast, the fetal connective tissue within the villus, and the fetal capillary wall (Fig. 2.1).

The uterine blood flow is supplied principally from the uterine arteries, but anastomoses occur between these vessels, other branches of the hypogastric arteries, and ovarian arteries. Significantly, the spiral arteries must traverse the full thickness of the myometrium to reach the intervillous space. Anything that affects maternal cardiac output will, of course, affect the flow through the spiral arteries. Additionally, as the
uterus contracts, the intramyometrial pressure may exceed the intraarterial pressure, causing occlusion of these vessels and resulting in cessation of blood flow to the intervillous space (Fig. 2.2) (2).

Approximately 85% of the total uterine blood flow goes to supply the placental (intervillous) circulation and 15% supplies the extraplacental uterine musculature (3). The intervillous space blood supplies the vascular support to the placenta itself, and if the blood flow to any area is sufficiently compromised, an infarction of the placenta may occur (4,5).

For clinical purposes, the intervillous space circulation is probably maximal when the mother is at rest, in the lateral position. Although estrogen administration to the pregnant ewe will increase uterine blood flow, it is not certain that this results in increased intervillous blood flow (5,6). Therefore, although we know of nothing that will increase effective uterine blood flow above that found in the resting lateral position, there are many things that will decrease uterine blood flow.

The anatomy and physiology of the fetal circulation are very complex. For the purposes of this chapter, we focus on the umbilical circulation and factors that affect placental exchange (Fig. 2.4).

The umbilical vessels are contained within the umbilical cord and are protected with an abundance of a substance
called Wharton’s jelly. Normally, there are two umbilical arteries that arise from the terminal ends of the fetal hypogastric arteries and a single umbilical vein that returns blood to the fetus from the placenta, channeling it partly through the liver and partly to the inferior vena cava via the ductus venosus. This well-oxygenated blood enters the right atrium and follows a course directing it mainly to the cephalic circulation, while blood returning from the upper body via the superior vena cava is channeled principally through the ductus arteriosus to the lower body and the placenta. Approximately 30% of the fetal cardiac output goes to the placenta, which comprises a low-resistance vascular bed. The oxygen content of the umbilical venous blood closely approximates that of the uterine venous drainage, which suggests that the pattern of umbilical and uterine flows functionally follows a concurrent relationship, although the flow relationships are clearly much more complex and authorities in the field are not in total agreement concerning this fact (22).

One must ask how the fetus can exist at a maximum pO₂ below that of the uterine vein (about 35 mm Hg), whereas the adult would be unable to survive under similar circumstances. The fetus has a number of unique characteristics that allow it thrive with such a low pO₂.

First, the fetal hemoglobin concentration is higher than that in the adult, allowing for a much greater oxygen carrying capacity. Second, the fetal cardiac output far exceeds that of the adult on a volume per unit body weight basis. Third, the fetal hemoglobin dissociation curve favors a higher saturation at a given pO₂ (Fig. 2.5). So, although the fetal pO₂ is lower, the fetus is able to compensate by having an increased oxygen content, due to the high hemoglobin concentration and the characteristic of the fetal hemoglobin dissociation curve. The more rapid circulation then increases the amount of oxygen that can be delivered to the fetal tissue per unit time (23).

Oxygen crosses the placenta by simple diffusion. If the relative flows on the two sides of the placenta are held constant, the differential pO₂ between the intervillous space and the fetal capillary determines the rate of maternal-fetal oxygen transfer. Thus, administration of high concentrations of oxygen to the mother may increase her pO₂ several hundred millimeters of mercury and the maternal-fetal oxygen gradient may be markedly increased by this maneuver (24). Moreover, if the fetal pO₂ is increased by only a few millimeters of mercury, the fetal blood oxygen content may increase
significantly because, in either the physiologic or hypoxic range, the fetal hemoglobin saturation curve is quite steep (Fig. 2.5) (25).

Clinically, however, even though maternal hyperoxia maybe of some help, most causes of fetal hypoxia are related to restriction of umbilical or intervillous space blood flow. Under conditions of diminished flow on either side of the placenta, changing the pO₂ gradient will not be of as much help as restoring the blood flow. It is still reasonable to administer oxygen to the mother (26) in such situations, but one must remember that restoration of flow is usually more important.

The FHR, under physiologic conditions, represents the final product of intrinsic and extrinsic rate-determining or rate-modifying factors. Technically, the FHR represents the reciprocal of the interval between two successive beats. Most data on FHR use an electrical marker (specifically the peak of the fetal electrocardiogram [ECG] R wave) to signify the time of the beat. Unless otherwise stated, we will refer to the rate calculated from intervals between fetal ECG R waves. FHR changes constitute the basis for electronic fetal monitoring, and for this reason, one must look carefully at the factors that determine or modify the rate.

Schifferli and Caldeyro-Barcia (30) discovered that the baseline heart rate decreases with gestational age. At 15 weeks’ gestation, the average baseline rate is approximately 160 beats per minute (BPM) (Fig. 2.6). Although premature fetuses may have a slightly increased rate over that found at term, within the limits of fetal viability (from 28 weeks to term), the average baseline FHR difference is only approximately 10 BPM. One must, therefore, be careful not to attribute a baseline tachycardia to prematurity when it may well be a sign of fetal compromise. Any baseline FHR above 160 BPM must be explained on some basis other than fetal prematurity.

Schifferli and Caldeyro-Barcia (30) further noted that if one administers atropine to a fetus, the resulting increase in heart rate is of greater magnitude as one approaches term, and that the postatropine heart rate is usually in the range of 160 BPM. Because atropine is a parasympathetic blocking agent, it would appear that the gradual decrease in FHR that
occurs with increasing gestational age can be explained as an increase in parasympathetic tone (Fig. 2.6).

Renou et al. (31) have shown that upon administering atropine directly to a human fetus during labor, three phenomena are observed. First, there is a modest increase in the baseline FHR, presumably due to blocking of the tonic parasympathetic effect described by Schifferli and Caldeyro-Barcia (30). Second, Renou et al. noted a loss of the variability of the FHR, suggesting that a continuous balance between the parasympathetic slowing effect and the sympathetic accelerating effect may have been disturbed. Third, they noted that a majority of patients demonstrated the appearance of FHR accelerations during uterine contraction. This suggests that, before release of parasympathetic tone by atropine, the accelerating forces were present but suppressed. Renou et al. then added a β-adrenergic blocking agent (propranolol) to these atropinized fetuses and noted abolition of the accelerations and a decrease in the baseline FHR (Fig. 2.7). It
would thus appear that the accelerating forces unmasked by atropine blockade were of β-sympathomimetic origin. With this information, it is then possible to think of the baseline FHR as a product of the modulated influences of the parasympathetic and sympathetic nervous systems. Furthermore, the baseline FHR variability probably represents an instantaneous product of these two forces that are constantly working in a push-pull relationship; the presence of good FHR variability probably requires the integrity of these two modulating forces.