What is the name of the blood vessel carries blood away from the fetus to the placenta?

Overview of Fetal Circulation and Cardiac Adaptation at Birth

One must not assume that the fully developed fetal heart is analogous to the infant or child heart. This section discusses the difference between the fetal myocardium and the postnatal myocardium and unique fetal blood flow through naturally occurring shunts, blood flow to the placenta, and pulmonary blood flow.

The fetal myocardium has significant differences from the pediatric and adult myocardium. It is composed of a greater proportion of noncontractile elements (60% versus 30%), and fetal cardiomyocytes can divide, whereas adult cardiomyocytes can only hypertrophy. In addition, the removal of calcium from troponin C is slower in the fetus, resulting in slower muscle relaxation. The right ventricle handles more volume, its radius is greater, the radius-to-wall thickness is greater, and it hypertrophies to maintain appropriate wall tension. As a result, the wall thickness of the right ventricle is approximately equal to that of the left in fetal life.

These differences result in increased stiffness and impaired relaxation of the fetal heart as demonstrated in the Doppler pattern across the atrioventricular (AV) valves. In the fetus, passive ventricular filling is impaired, and active atrial filling is responsible for emptying the atria. As a result, the right ventricle is more sensitive to changes in preload and shows signs of dysfunction before the left ventricle. Increased preload, as seen in anemia, viral illness, and significant arterial to venous malformations (AVMs) results in fetal hydrops. There is a gradual change from the “fetal heart” to an “adult heart” that progresses throughout the neonatal period to adulthood. These changes can be easily demonstrated by echocardiography.

The fetus has a unique physiology consisting of various shunts to promote oxygenated blood to the brain and deoxygenated blood to the placenta. The foramen ovale is designed to allow higher oxygenated blood from the placental veins preferentially to the left atrium. The increased oxygenated blood from the placenta travels through the umbilical vein to the ductus venosus. The blood then travels to the inferior vena cava (IVC) and is directed across the foramen ovale by the Eustachian valve. Lower oxygenated blood flow from the fetal brain is preferentially directed from the superior vena cava (SVC) to the right ventricle and eventually across the ductus arteriosus to the placenta. The ductus arteriosus is responsible for carrying most of the cardiac output from the “pulmonary circulation” to the descending aorta and the placenta. The flow pattern is typically a predominant systolic peak with continuous low-velocity diastolic flow. Continuous diastolic flow toward the descending aorta is a result of low-resistance placental circulation. Elevated diastolic flow in the ductus arteriosus is a sign of ductal constriction or lower body arteriovenous malformations. The aortic isthmus has a distinctive wave form in the fetus. The aortic isthmus is located between the left subclavian artery and the insertion of the ductus arteriosus. It is unique in that it straddles two different output systems (the “systemic” output of the left ventricle and the “pulmonic” output of the right ventricle that is directed toward the placenta). Flow is normally toward the placenta in both systole and diastole at the level of the aortic isthmus. Decreased flow in the aortic isthmus from inappropriate shunting can result in isthmus hypoplasia and eventually coarctation of the aorta. Left ventricular outflow tract obstruction or significant left ventricular dysfunction results in reversal of flow toward the head in systole. Reversal of flow may also be seen in decreased upper body vascular resistance (AVMs or stressed fetus).

Fetal Circulation and Physiology

Fetal circulation is significantly different from that of a newborn (Fig. 37.4).15 Oxygen-rich blood from the placenta passes through the umbilical vein directly to the fetal liver, where the circulation splits and flows into both the ductus venosus (20%–30% of flow) and portal sinus circulation. It then passes into the inferior vena cava and enters the right atrium. The majority of this blood flows through the foramen ovale, into the left atrium, then the left ventricle, and empties into the aorta (a small portion travels through the pulmonary arteries to perfuse lung tissue). This shunted portion traveling through the foramen ovale has the highest oxygen levels and directly perfuses the brain (carotid arteries) and heart (coronary arteries). Fetal deoxygenated blood returning from the superior vena cava and lower extremities is directed toward the right ventricle and pulmonary trunk. The majority of this blood flow passes through the ductus arteriosus, into the descending aorta, and perfuses the lower extremities and hypogastric arteries. Deoxygenated fetal blood returns to the placenta via two umbilical arteries.

Two-thirds of fetal blood volume is within the placenta. During the second and third trimesters, the fetal blood volume is approximately 110 to 160 mL/kg, and after midgestation can be estimated from GA: Estimated fetal blood volume (mL) = 11.2 × GA − 209.4.30,31 Hemoglobin F (HbF) is the primary oxygen carrier in the developing fetus, with a gradual shift from HbF to adult Hb (HbA) production starting at 32 weeks' gestation.32 Hb levels in the fetus typically increase from 11 g/dL (17 weeks GA) to about 18 g/dL in a term newborn.33,34

The fetal heart rate is the primary determinant of fetal cardiac output, as the fetal myocardium is less compliant than adult myocardium, operating near the upper end of the Frank-Starling curve and less responsive to changes in preload.35 Normal fetal cardiac output is 425 to 550 mL/kg/min throughout gestation.

The fluid-filled lungs of the fetus may potentially impair ventricular filling, thus preventing an increase in cardiac output after an increase in preload.36 Fetal lung epithelium produces more than 100 mL/kg per day of fluid that facilitates pulmonary development. This pulmonary fluid leaves via the trachea and is either swallowed by the fetus or becomes part of the amniotic fluid.

The immature fetal liver is able to synthesize coagulation factors, the concentration of which increases with GA. These coagulation factors do not cross the placenta into maternal circulation, and are not as effective at clot formation compared with those factors found in adults. About 75% of umbilical venous blood initially passes through the fetal liver. Drugs in the umbilical blood thus undergo initial hepatic metabolism (first-pass metabolism) before these substances reach the fetal brain or heart. Although these fetal metabolic enzymes are less functional that those of adults, most drugs are still significantly metabolized. Additionally, drugs entering the fetal circulation enter the inferior vena cava via the ductus venosus. This blood is mixed with the venous blood returning from the lower extremities and pelvic viscera of the fetus, thus further diluting any concentrations of drugs passed through the placenta.

By 18 weeks' gestation, the fetus exhibits a neuroendocrine stress response to noxious stimuli.37 This response occurs at the level of the spinal cord and brainstem, as thalamocortical connections necessary for the perception of pain are not present until after 24 to 26 weeks' gestation.38,39 During fetal surgery, opioids are directly administered to the fetus to decrease the physiologic stress from the procedure.

Fetal and Neonatal Circulation

Some key features of fetal circulation that differ from that of the child are the presence of the ductus venosus, the ductus arteriosus, and a patent foramen ovale. During fetal development, blood oxygenated by the placenta flows to the fetus through the umbilical vein, bypasses the fetal liver through the ductus venosus, and returns to the fetal heart through the inferior vena cava. Blood returning from the inferior vena cava then enters the right atrium and is preferentially shunted to the left atrium through the patent foramen ovale (Fig. 170.1). Blood in the left atrium is then pumped from the left ventricle to the aorta. The oxygenated blood ejected through the ascending aorta is preferentially directed to the fetal coronary and cerebral circulations.

Deoxygenated blood returns from the superior vena cava to the right atrium and ventricle to be pumped into the pulmonary artery. Fetal pulmonary vascular resistance (PVR), however, is higher than fetal systemic vascular resistance (SVR); this forces deoxygenated blood to mostly bypass the fetal lungs (seeFig. 170.1). This poorly oxygenated blood enters the aorta through the patent ductus arteriosus and mixes with the well-oxygenated blood in the descending aorta. The mixed blood in the descending aorta then returns to the placenta for oxygenation through the two umbilical arteries.

Once the infant is delivered and the umbilical cord is cut, expansion and aeration of the lungs cause a decrease in PVR, which enhances pulmonary blood flow. Increased global oxygenation causes a physiologic closure of the umbilical arteries, umbilical vein, ductus venosus, and ductus arteriosus. Increasing pulmonary blood flow to the infant's left atrium promotes closure of the foramen ovale. Complete anatomic closure of the foramen ovale does not occur until about 3 months of age. Although the ductus arteriosus functionally closes at about 10 to 15 hours of life, complete anatomic closure does not occur until 2 to 3 weeks of life.

In the absence of any congenital cardiac defects, these transitional circulatory changes pose no physiologic problems to the infant. However, closure of the ductus arteriosus can cause life-threatening complications in neonates, with specific congenital cardiac defects, who are dependent on the patency of the ductus arteriosus for survival.

Fetal Circulation

The fetal circulation is characterized by low systemic vascular resistance (SVR) with high systemic blood flow and high pulmonary vascular resistance with low pulmonary blood flow. Given the low oxygen tension of the fetus, the fetal circulation allows for preferential flow of the most oxygenated blood to the heart and brain, two of the three “vital organs.”1 With the placenta rather than the lungs being the organ of gas exchange, most of the right ventricular output is diverted through the patent ductus arteriosus (PDA) to the systemic circulation. In fact, the pulmonary blood flow constitutes only approximately 7% to 8% of the combined cardiac output in fetal lambs.2 However, Doppler and magnetic resonance imaging studies have shown that the proportion of combined cardiac output that supplies the lungs is significantly higher in the human fetus (11% to 25%), with some studies reporting an increase in this proportion with advancing gestational age to a peak approximately 30 weeks’ gestation.3–6 In fetal life, both ventricles contribute to the systemic blood flow, and the circulation therefore depends on the persistence of shunts via the foramen ovale and PDA between the systemic and pulmonary circuits, with the two circulations functioning in “parallel.” The right ventricle is the dominant pumping chamber, and its contribution to the combined cardiac output is approximately 60%. The combined cardiac output is in the range of 400 to 450 mL/kg/min in the fetus, which is much higher than the systemic flow after birth (approximately 200 mL/kg/min). Approximately, one-third of the combined cardiac output (150 mL/kg/min) perfuses the placenta via the umbilical vessels. However, placental blood flow decreases to 21% of the combined cardiac output near term.7 The umbilical vein carries the oxygenated blood from the placenta through the portal veins and the ductus venosus to the inferior vena cava (IVC) and eventually to the heart. Approximately 50% of oxygenated blood in the umbilical vein is shunted through the ductus venosus and IVC to the right atrium, where the oxygenated blood is preferentially directed to the left atrium through the patent foramen ovale. This percentage decreases as gestation advances. One of the unique characteristics of the fetal circulation is that arterial oxygen saturation (SaO2) is different between the upper and lower body. Having the most oxygenated blood in the left atrium ensures supply of adequate oxygen to the heart and brain. Furthermore, in response to hypoxemia, most of the blood flow in the umbilical vein bypasses the portal circulation via the ductus venosus and again delivers the most oxygenated blood to the heart and brain.

Regulation of Fetal Circulation

Fetal cardiovascular function continuously adapts to varying metabolic and environmental conditions through regulation by the neurologic and endocrine systems. The predominant form of neuroregulation occurs in response to baroreceptor and chemoreceptor afferent input to the autonomic nervous system and through modulation of myocardial adrenergic receptor activity. Thus, the autonomic nervous system functions to reversibly redirect blood flow and oxygen delivery as required.

Arterial baroreceptor function has been demonstrated in several different fetal animal models. The predominant baroreceptors are located within the vessel walls of the aortic arch and at the bifurcation of the common carotid arteries. These receptors project signals to the vasomotor center in the medulla, from which autonomic responses emanate. The baroreceptors are functional early in fetal development and undergo continuous adaptation to the increases in blood pressure observed over time.84 A sudden increase in fetal mean arterial pressure—as occurs with partial or complete occlusion of the umbilical arteries—results in cholinergic stimulation and subsequent fetal bradycardia.

Peripheral chemoreceptors are present within the vessel walls of the aortic arch and at the bifurcation of the common carotid arteries. In some animal species, peripheral chemoreceptors are transiently present in the adrenal gland but disappear after birth.85 The fetal aortic chemoreceptors are responsive even to small changes in arterial oxygenation,86,87 which contrasts to the less active fetal carotid chemoreceptors. Dawes et al.88 concluded that the carotid chemoreceptors are important for postnatal respiratory control, whereas the aortic chemoreceptors are more involved in the control of cardiovascular responses and the regulation of oxygen delivery. Central chemoreceptors, located in the medullar oblongata, appear to play little if any role in fetal circulatory responses.

The neural control of the fetal circulation is far more dependent on chemoreceptor-mediated responses than neural control of the adult circulation.89 Acute fetal hypotension often stimulates a reflex response, which can include both bradycardia and vasoconstriction. Vasoconstriction is dependent on increases in both sympathetic autonomic activity and the rate of secretion of several vasoactive hormones, including arginine, vasopressin, renin, angiotensin, and aldosterone. Fetal bradycardia is most likely caused by activation of peripheral chemoreceptors.89

Foetal Circulation

The foetal circulation differs radically from the postnatal circulation (Fig. 12.1). Blood from the right heart is deflected away from the lungs, partly through the foramen ovale and partly through the ductus arteriosus. Less than 10% of the output of the right ventricle reaches the lungs, the remainder passing to the systemic circulation and the placenta. Right atrial pressure exceeds left atrial pressure and this maintains the patency of the foramen ovale. Finally, because the vascular resistance of the pulmonary circulation exceeds that of the systemic circulation before birth, pressure in the right ventricle exceeds that in the left ventricle and these factors control the direction of flow through the ductus arteriosus.

The umbilical veins drain via the ductus venosus into the inferior vena cava, which contains better oxygenated blood than the superior vena cava. The anatomy of the atria and the foramen ovale is such that the better oxygenated blood from the inferior vena cava passes preferentially into the left atrium and then to the left ventricle and so to the brain. (This is not shown in Fig. 12.1). Overall gas tensions in the foetus are of the order of 6.4 kPa (48 mm Hg) for Pco2 and 4 kPa (30 mm Hg) for Po2. The fact that the foetus remains apnoeic for much of the time in utero with these blood-gas levels is probably in part attributable to central hypoxic ventilatory depression (page 65).

Fetal Circulation and Placental Villous Angiogenesis

The fetal circulation enters the placenta via the umbilical vessels. Inside the placenta, fetal vessels branch successively into units within the cotyledons and then into capillary loops within the chorionic villi.10 From post-conception day 32 until the end of the first trimester, the endothelial tube segments formed by vasculogenesis in the placental villi are transformed into primitive capillary networks by the balanced interaction of two parallel mechanisms; (a) elongation of pre-existing tubes by non-branching angiogenesis, and (b) ramification of these tubes by lateral sprouting (sprouting angiogenesis). A third process, termed intussusceptive microvascular growth, rarely contributes. In the third month of pregnancy, some of the centrally located endothelial tubes of immature intermediate villi achieve large diameters of 100 µm and more. Within a few weeks, they establish thin media- and adventitia-like structures by concentric fibrosis in the surrounding stroma and by differentiation of precursor pericytes and smooth muscle cells expressing α- and γ-smooth muscle actins in addition to vimentin and desmin. This is followed quickly by the expression of smooth muscle myosin.8,20 These vessels are forerunners of the villous arteries and veins and are developmentally regulated through the platelet-derived growth factor (PDGF) pathway.21

After post-conception week 24 and continuing through term, patterns of villous vascular growth switch from the prevailing branching angiogenesis to a prevalence of non-branching angiogenesis. Analysis of proliferation markers at this stage reveals a relative reduction of trophoblast proliferation and an increase in endothelial proliferation along the entire length of these villous structures, resulting in non-sprouting angiogenesis by proliferative elongation. The final length of these peripheral capillary loops exceeds 4000 µm and they grow at a rate which exceeds that of the villi themselves, resulting in coiling of the capillaries.22,23 The looping capillaries bulge towards, and obtrude into, the trophoblastic surface and thereby contribute to formation of the terminal villi. Each of the latter is supplied by one or two capillary coils and is covered by an extremely thin (<2 µm) layer of trophoblasts that contributes to the so-called vasculosyncytial membranes. These are the principal sites of diffusional exchange of gases between mother and fetus. Normally, the capillary loops of 5–10 such terminal villi are connected to each other in series by the slender, elongated capillaries of the central mature intermediate villus.

The fetal vessels (chorionic vessels) from the individual cotyledons of the placenta unite at the placental surface to form the umbilical vessels that then traverse the umbilical cord. The umbilical cord consists of one vein and two arteries. The connective tissue surrounding these vessels in the umbilical cord is referred to as Wharton’s jelly. Most umbilical cords are twisted at birth, probably related to fetal activity in utero. The umbilical vein carries oxygenated blood from the placenta to the fetus and the umbilical arteries carry deoxygenated blood back to the placenta.

Physiology of Nitric Oxide in the Pulmonary Circulation

The fetal circulation is characterized by high PVR. Pulmonary blood flow accounts for less than 10% of combined ventricular output in the late-gestation ovine fetus.27 Mechanisms responsible for maintaining high fetal PVR and causing sustained pulmonary vasodilation at birth are incompletely understood; however, studies in fetal and transitional pulmonary vasoregulation have led to increased understanding of the normal physiologic control of PVR. Fetal and neonatal pulmonary vascular tone is modulated through a balance between vasoconstrictor and vasodilator stimuli, including mechanical factors (e.g., lung volume) and endogenous mediators.

The pharmacologic activity of nitrovasodilators derives from the release of NO, which was recognized as a potent vascular smooth muscle relaxant as early as 1979.28 In 1987 investigators from two separate laboratories reported that the endothelium-derived relaxing factor was NO or an NO-containing substance.29,30 NO modulates basal pulmonary vascular tone in the late-gestation fetus; pharmacologic NO blockade inhibits endothelium-dependent pulmonary vasodilation and attenuates the rise in pulmonary blood flow at delivery, implicating endogenous NO formation in postnatal adaptation after birth.31 Increased fetal oxygen tension augments endogenous NO release,32,33 and the increases in pulmonary blood flow in response to rhythmic distension of the lung and high inspired oxygen concentrations are mediated in part by endogenous NO release.34 However, in these studies the pulmonary circulation was structurally normal. Studies using a model of PPHN in which marked structural pulmonary vascular changes are induced by prolonged fetal ductus arteriosus compression demonstrated that the structurally abnormal pulmonary circulation also was functionally abnormal.35,36 Despite the progressive loss of endothelium-dependent (acetylcholine) vasodilation with prolonged ductus compression in this model, the response to endothelium-independent (atrial natriuretic peptide, NO) vasodilation was intact.

Exogenous (inhaled) NO causes potent, sustained, selective pulmonary vasodilation in the late-gestation ovine fetus.11 Based on the chronic ambient levels considered to be safe for adults by regulatory agencies in the United States,37 studies were performed in near-term lambs using iNO at doses of 5, 10, and 20 ppm. iNO caused a dose-dependent increase in pulmonary blood flow in mechanically ventilated newborn lambs.11 iNO at 20 ppm did not decrease coronary arterial or cerebral blood flow in this model.

Roberts et al.38 studied the effects of iNO on pulmonary hemodynamics in mechanically ventilated newborn lambs. iNO reversed hypoxic pulmonary vasoconstriction, and maximum vasodilation occurred at doses greater than 80 ppm. They also found that the vasodilation caused by iNO during hypoxia was not attenuated by respiratory acidosis in this model. Berger et al.39 investigated the effects of iNO on pulmonary vasodilation during group B streptococcal sepsis in piglets. iNO at 150 ppm for 30 minutes caused marked pulmonary vasodilation but was associated with physiologically significant increases in methemoglobin concentrations. Corroborating studies in other animal models support the observations that iNO is a selective pulmonary vasodilator at low doses (less than 20 ppm).40-42

Changes in the Circulation at Birth

During fetal circulation, the PVR is high and only 10%–20% of the cardiac output goes through the pulmonary vasculature. The low resistance, high volume of the placenta enhances shunting of the blood away from the lungs through the foramen ovale or the ductus arteriosus. Pulmonary blood flow and PVR changes throughout the pregnancy in a U-shaped curve. The PVR is high at 20 weeks GA, with 13% cardiac output going to lungs, then PVR drops around 30 weeks gestation to increase blood flow to lungs to 25%–30% of cardiac output, before an increase in PVR near term causes a drop in pulmonary blood flow to around 20%.195 The combination of increased arterial oxygen content, removal of the low resistance of the placenta, and removal of placental derived prostaglandins lead to rapid transitions from fetal to newborn circulations. Removal of the placenta decreases venous return to the right atrium, decreases right atrial (RA) pressure, and increases systemic vascular resistance (SVR) leading to increased left atrial pressure, which leads to closure of the foramen ovale. The flow through the ductus arteriosus decreases such that it passively closes within 3–7 days after birth. In normal newborns, PVR falls rapidly in the first minutes after birth, with recruitment of FRC and then more gradually over the next days. Aeration of the lungs, through stimulation of stretch receptors, vasodilates the pulmonary vascular bed and increases the pulmonary blood flow.196,197 Opening of the alveoli also leads to decrease perivascular fluid and improved gas exchange (see clearance of airway fluid). In utero the PVR remains high due to low levels of pulmonary vasodilators (oxygen, prostacyclin [PGI2] and NO), and high levels of vasoconstrictors (endothelin-1 [ET-1]).198 PGI2 is produced by the vascular endothelial cells, pulmonary stretch increases its release, and causes relaxation of smooth muscle surrounding the arterioles. Blockade of prostaglandins in utero does not affect resting PVR, whereas exogenous PGI2 causes vasodilation after birth.199 NO is also produced by the vascular endothelial cells through the cleavage of L-arginine by NO synthase. NO diffuses into the smooth muscles cells to stimulate vessel relaxation through production of guanosine monophosphate. Because oxygen tension helps to regulate NO production, fetal NO levels are low in the relative hypoxic environment. Endogenous NO production responds to the increased PaO2 associated with initiation of ventilation at birth. PGI2 activity may be modulated by NO because NO synthase inhibitors decrease the effectiveness of exogenous PGI2. Along with increasing vasodilators, endogenous vasoconstrictors (thromboxane and ET-1) decrease at birth to allow relaxation of the vasculature. In newborns with significant hypoxia or sepsis, levels of ET-1 and thromboxane A2, along with leukotrienes, are increased and can cause severe pulmonary hypertension. Prostaglandin E2, which helps to maintain ductal patency in utero, is produced by the placenta and PGE2 metabolism within the lungs is enhanced by ventilation, thus decreasing levels of PGE2 help to facilitate ductal closure. Although there is some variation, most infants complete this cardiovascular transition by 8 hours of age and the ductus arteriosus typically closes by 24 hours of age. Pulmonary vascular pressure decreases to 50% of systemic vascular pressure by 24 hours of life, and adult levels of PVR are typically reached by 6 weeks of age.198

Fetal Circulation in Congenital Heart Disease: Effects on Cerebral Blood Flow

The fetal circulation is unique in a number of respects that can impact cerebral blood flow and development. In the normal fetus, cerebral blood flow is supplied by highly oxygenated blood from the ductus venosus preferentially streaming across the foramen ovale to the left atrium and ventricle (Fig. 57.1). In contrast, in fetuses with transposition of the great arteries (TGA), the aorta and pulmonary artery are transposed and thus the higher oxygenated blood reaches the pulmonary vasculature as opposed to the cerebral vasculature. Similarly, in hypoplastic left heart syndrome (HLHS), inadequate left heart structures lead to reversal of blood flow in the foramen ovale with mixing of oxygenated and deoxygenated blood in the right ventricle and, in cases of aortic atresia, retrograde flow in the ascending aorta. The effects of these abnormal flow patterns on brain development are uncertain but may involve different mechanisms, despite the fact that both decrease the oxygen content of the blood delivered to the brain. Other mechanisms may be responsible such as inadequate substrate delivery (glucose) because of decreased perfusion pressure and flow to the brain (Rudolph, 2016). In d-transposition of the great arteries (dextroposition [d]-TGA), the pulsatility and perfusion pressure of the cerebral circulation are normal. However, in HLHS, the hypoplastic isthmus and aortic arch may function as resistors, potentially decreasing the pulsatility and perfusion pressure to the cerebral circulation. In contrast, in d-TGA, decreased pulsatility and perfusion to the brain can result from preferential blood flow to the pulmonary vasculature because of a lower pulmonary vascular resistance than usual.

Cerebral Doppler ultrasound can assess fetal cerebral vascular resistance in the middle cerebral artery (MCA) and provide insight into fetal cerebral blood flow patterns. By calculating the MCA pulsatility index (PI, a measure of vascular resistance in the circulatory bed downstream from the point of Doppler sampling), studies have identified a pattern of “brain-sparing” in fetuses with intrauterine growth restriction and placental insufficiency as a mechanism of autoregulation of fetal cerebral blood flow (Wladimiroff et al., 1987; Mari and Deter, 1992). In normal pregnancies, the cerebral/umbilical PI ratio is more than 1.0, whereas in many growth-restricted fetuses the ratio is less than 1.0 and predicts adverse perinatal and neurologic outcomes (Rizzo et al., 1989; Gramellini et al., 1992). This autoregulatory mechanism is thus paradoxically a harbinger for poor outcome in the setting of fetal growth restriction.

There have been several studies examining in utero blood flow patterns in human fetuses with CHD. These have demonstrated lower MCA PI in fetuses who have lesions with the most intracardiac mixing, such as HLHS (Fig. 57.2). In fact, fetuses with HLHS have been shown to have the lowest cerebral/umbilical PI ratio among different types of CHD (Donofrio et al., 2003; Kaltman et al., 2005). This is likely secondary to the lower oxygen content of blood delivered to the brain as well as abnormalities in cerebral perfusion with a hypoplastic aortic isthmus.

Cerebral blood flow characteristics have been shown to predict ND outcomes in fetuses with CHD. In a retrospective multicenter study of infants with HLHS, a lower MCA PI in utero predicted a better ND outcome at 14 months of age as assessed by the Bayley Scales of Infant Development (BSID) II (Williams et al., 2013). These findings suggest that the autoregulatory response of cerebral vasodilation in the setting of HLHS may be sufficient and adaptive to a state of chronic hypoxemia, which is in contrast to what is seen in the context of fetal growth restriction. Further large prospective studies are needed to understand the predictive utility of cerebral blood flow patterns in fetuses with CHD.