Noninherited Risk Factors for CHD (Many Potentially Modifiable)

Genetic Factors Associated with CHD

New findings with molecular genetic studies indicate that the genetic contribution to the etiology of CHD has been underestimated. With the rapid changes in this field it is certain that our understanding will be evolving and the identifiable genetic etiologies of CHD will continue to expand.⁷⁰⁰ Review of current literature will always be necessary to have an accurate understanding of these factors.

Humans normally have 46 chromosomes (23 pairs). The first 22 pairs are autosomal (non-sex) chromosomes and the 23rd pair determines gender (XX = female, XY = male). Each chromosome has two arms held together by a centromere—a short arm (p) and a long arm (q). There are more than 35,000 pairs of genes on our chromosomes,¹⁹⁰ and each gene is composed of hundreds or thousands of base pairs. An abnormality in a single base pair can cause a malfunction. Changes in the deoxyribonucleic acid (DNA) sequence (a mutation) in a single gene changes the path of a protein, which is like changing one part of a recipe. (The results can range from asymptomatic to disastrous malformations.) Mutations may occur de novo (a new mutation that is not inherited from a parent) or may result from autosomal-dominant or -negative inheritance. Many gene mutations associated with cardiovascular malformations are now being identified.^190,277,700

Before advanced cytogenetic tests were available, chromosome abnormalities were found in approximately 8% to 13% of neonates with CHD,²⁶³ but with new testing the prevalence of chromosome aberrations is now estimated to be much higher.⁷⁰⁰ These abnormalities can be aneuploidies (abnormal number of chromosomes) such as trisomies (an extra chromosome), or tetrasomies. Other chromosome abnormalities are caused by deletions (a missing piece), duplications (extra genetic material on chromosome), or translocations (genetic material transferred from one chromosome to another).^190,277 Single gene defects have been thought to account for about 3% to 5% of those CHDs with a genetic etiology, but new findings indicate that this range substantially underestimated the problem. Any genetic defect can start an embryonic chain reaction, which can create mild to severe phenotypic expression of the abnormality.⁸⁰³

Inheritance of genetic abnormalities associated with CHD can occur in several ways. Deletions, duplications, and single gene defects can all be the result of a mutation (a sporadic change in DNA sequence triggering abnormalities) or Mendelian inheritance from parents with the same gene anomaly. If both parents must contribute the abnormality it is autosomal recessive—both parents carry the genetic difference, but the parents will only have the disorder if they, too, have two genes with the difference. If the anomaly is inherited when only a single parent is a carrier, the inheritance is autosomal dominant, and in this situation that parent also has the condition.

Cardiovascular malformations can occur as a part of a group or pattern of anomalies. A syndrome, a combination of multiple anomalies occurring together resulting from a single cause (the cause is often a genetic error but the cause may be unknown), is thought to cause about 5% of the CHD. More than 400 genetic syndromes list CHD as a possible manifestation.^651,803 Associations, a group of anomalies that occur in a recurrent pattern, may also involve CHDs. There may be no known genetic basis for an association. Inherited metabolic diseases have a variety of genetic etiologies and may include cardiovascular problems.

For more information on characteristics and etiologies of specific defects and conditions see Tables 8-1 and 8-2. There are hundreds of syndromes and conditions with multiple manifestations that involve cardiovascular malformations. Table 8-2 includes an abbreviated table, and a more comprehensive table with genetic associations is provided in Evolve Table 8-1 in the Chapter 8 Supplement on the Evolve Website.

Table 8-1 Cardiac Defects and Associated Genetics, Teratogens, and Exposures^{328,414,700,871,932}

ADD, Attention deficit disorder; AS, aortic stenosis; ASD, atrial septal defect; AV, atrioventricular; AVC, atrioventricular canal; AVSD, atrioventricular septal defect; BAV, bicuspid aortic valve; CA, coronary artery; CHD, congenital heart defect; CNS, central nervous system; CoA, coarctation of aorta; CV, cardiovascular; DCM, dilated cardiomyopathy; DORV, double-outlet right ventricle; GI, gastrointestinal; GU, genitourinary; HCM, hypertrophic cardiomyopathy; HLHS, hypoplastic left heart syndrome; IAA, interrupted aortic arch; IVC, inferior vena cava; LSVC, persistent left superior vena cava; LV, left ventricular; LVOTO, left ventricular outflow tract obstruction; MV, mitral valve; NSAIDs, nonsteroidal antiinflammatory drugs; PA, pulmonary artery; PAPVR, partial anomalous pulmonary venous return; PAtresia, pulmonary atresia; PDA, patent ductus arteriosus; PKU, phenylketonuria; PPS, peripheral pulmonary stenosis; PS, pulmonary stenosis; RVOTO, right ventricular outflow tract obstruction; SVC, superior vena cava; SVT, supraventricular tachycardia; TAPVR, total anomalous pulmonary venous return; TEF, tracheoesophageal fistula; TGA, transposition of great arteries; TOF, tetralogy of Fallot; VSD, ventricular septal defect.

See Table 8-2 for more information on specific genes, syndromes, and conditions.

Genetic Testing, Counseling, and Nursing Implications

Genetic testing can reveal important genetic patterns that are critical for identifying other important organ system involvement; gaining prognostic information; learning important reproductive risks for the family; and considering the appropriate testing of other family members.⁷⁰⁰ Genetic testing can be performed on blood lymphocytes, cord blood, skin, amniotic fluid, chorionic villi, and bone marrow. Current genetic tests available to be used in assessing CHD include:

As more etiologic genes are identified, progress can be made in determining mechanisms and interactions that cause various phenotypes. That may lead to the development of targeted therapies for patients and fetuses.⁸⁷¹

Genetic counseling is warranted when there is one major or two minor birth defects and may be employed to attempt to determine exact causes of anomalies in individual situations. Testing must be accurately ordered to direct the proper studies to obtain complete results. Simply ordering a karyotype will not achieve the targeted exploration that can be achieved with FISH or A-CGH studies. Information gathered enables practitioners to counsel the family on problems associated with a condition, allowing them to be proactive in their child’s care. Discussions with the family should be informative but not directive so that parents may make their own decisions.^190,651

At the very least, preconceptual and prenatal counseling of all women of child-bearing age is important to encourage the use of multivitamins and folic acid supplements, avoiding contact with people with flu or other febrile illnesses, and avoiding exposure to organic solvents during pregnancy. Targeted counseling should be done with women who have specific risk factors to discuss any medications that must be considered with pregnancy. Prenatal testing is also available for some conditions, and early diagnoses can affect care management, morbidity, mortality, and family well-being.

Another feature of genetic counseling is providing recurrence risks. With the exception of possibly teratogen exposures, parents can be counseled that their actions did not cause the condition. For chromosomal deletions, duplications, translocations, and gene anomalies, parental testing may be recommended to determine recurrence risks. In cases of gene anomalies, commercial testing is available for some mutations. Testing capabilities continue to expand so follow-up genetic consultation may be warranted to realize the advantages of new technologies.

Recurrence risks for chromosomal trisomies are low if there are no other birth defects in the family and maternal age is not advanced. For a parent with an autosomal dominant genetic anomaly, there is a 50% risk of recurrence. In parents who have an autosomal negative genetic anomaly (without the evidence of the problem), both parents must have the anomaly to cause the resulting disorder. In these cases the recurrence risk for the couple is 25%. In X-linked recessive anomalies, the risk is 50% for a male to be affected and 50% for a female to be a carrier. In cases of unknown etiology (possibly multifactorial inheritance), if no other child in the family is affected the recurrence risk is presumed to be 3% to 5%, but this changes if a subsequent sibling is affected.^190,651

Information about genetic conditions is widely available via websites and targeted support groups and associations (e.g., Online Mendelian Inheritance in Man, www.ncbi.nlm.nih.gov/Omim/). Web-based databases and support groups that provide valuable information are provided in the Chapter 8 Supplement on the Evolve Website.

The nursing implications of genetics involvement in congenital heart defects are significant. Nurses who are familiar with the patterns of anomalies can have a heightened index of suspicion when a single malformation is noted and findings can be unmasked. Nursing knowledge can be enhanced by familiarity with the most current scientific statements from the American Heart Association Congenital Heart Defects Committee, Council on Cardiovascular Disease in the Young on both the genetic basis and the noninherited risk factors for congenital heart disease.^414,700

Nurses are in a unique position to gather information from families and communicate those findings. Facts about previous pregnancies, parents’ siblings, childhood deaths, other birth defects, exposures, and much more can be revealing. Nurses are also in a unique position to support families through these challenging situations. Nurses must be prepared to provide families with appropriate resources and encourage referrals.

This quote from Joey’s Journey: Our Life with Lissencephaly, at http://lfurlotte.tripod.com expresses how parents may feel when they begin a journey with a child affected by anomalies and the support others can provide: “Life will never be the same again. However, with a little different perspective, life does go on and happiness does return.”⁴¹⁵

Formation of the Heart Tube: Day 22

The cardiovascular system is the first system to function in the embryo. The critical period of cardiovascular growth begins at 15 to 18 days of gestation and is initiated by a period of rapid cell proliferation. During this period, the developing heart is most susceptible to teratogens (factors that can be harmful). Early development of the cardiovascular system is necessary because of the increasing need for nutritional and oxygen requirements by the rapidly growing embryo and for elimination of carbon dioxide and waste products. Moore et al.,⁶²⁷ Ransom and Srivastava,⁷²³ and Sander et al.,⁷⁶⁴ describe heart development as involving five primary steps:

The primordial heart and vascular system appear in the middle of the third week. The cardiovascular system is primarily derived from embryonic mesoderm and neural crest cells. The precardiac stem cells (mesoderm) migrate to form the cardiac crescents that fuse to form the single heart tube at 22 days (Fig. 8-1).^{627,723,764,902}

Fig. 8-1 Cardiac embryologic development—coiling of the heart tube. At approximately the 21st to 22nd day of fetal life, the two lateral endothelial heart tubes fuse to form a single endocardial tube. A, Between the 22nd and 28th days of life, the heart tube thickens. B, and C, the tube then coils to the right. D, By approximately the 28th day of fetal life, the tube is completely coiled, and major chambers can be identified. At this time, blood is flowing through the heart, and septation of the heart and great vessels can occur.

(Illustration by Marilou Kundemueller.)

At this time (22 days), circulation begins with ebb-and-flow blood flow from the venous to arterial poles. Premyocardial cells and neural crest cells continue to migrate into the region of the heart tube. The regulation of the mesoderm is partially controlled by retinoids, isoforms of vitamin A, that bind to specific nuclear receptors and regulate gene transcription and by extracellular matrix proteins, such as fibronectin, that direct cellular migration. The teratogenic effects caused by interaction of retinoid-like drugs on cell receptors are seen clinically (see Noninherited Risk Factors).⁷⁹

Formation of the Heart Loop: Day 22 to 28

Before and during the looping process, sections of the single heart tube begin to develop specialized cells that will ultimately become the chambers of the mature heart. A cascade of genes is expressed in the anterior (ventricular) and the posterior (atrial) portions of the tube. These genes regulate the cellular processes that transform the heart tube into a four-chambered heart. This transformation occurs through a balance of cell growth, cell differentiation, and cell death (apoptosis). Disruptions in these genetic mechanisms and specific cellular signaling processes result in cardiac malformations seen in congenital heart disease. Problems include defects in cardiac looping, septation, and chamber formation.⁷⁶⁴

The endocardial heart tube begins to expand and elongate and develops areas of dilation: the bulbus cordis (including the truncus arteriosus, conus arteriosus, and conus cordis), ventricle, atrium, and sinus venosus. This expansion and elongation results in coiling of the heart tube anteriorly and to the right (this is referred to as “dextral,” or “D-looping”), with creation of a bulboventricular loop (see Fig. 8-1, B and C).

Because the venous and arterial poles of the heart tube are fixed during this time of coiling, torsion occurs within the anterior portion of the loop, the truncus arteriosus. This torsion will later contribute to the formation of a spiral septum within the truncus. By the 26th day of gestation, a truncus arteriosus is visible in the center of the anterior portion of the heart, and a common atrium and ventricle are recognizable (see Fig. 8-1, D). By day 28 the looping process is complete.

The embryonic heart begins to contract by day 26 to 28, with cycles that are similar to those in mature hearts.⁷² In this “in-series circulation,” blood flows from the morphologically right atrium to the morphologically left atrium, left ventricle, right ventricle and then the truncus arteriosus.⁹⁰²

As the common atrium and ventricle divide into the chambers of the right and left heart, individual chambers are identified by their structure and appearance, or morphology. Structures should be identified by morphology rather than location because the location of the ventricles and great vessels may be abnormal when congenital heart disease is present.

When the ventricles rotate or loop normally to the right, a D-bulboventricular loop has occurred. The anatomic (i.e., morphologic) right ventricle is anterior (and to the right), and the anatomic (i.e., morphologic) left ventricle is posterior (and to the left). Later, normal division of the great vessels will result in location of the aorta posterior and to the right of the pulmonary artery. When the great vessels are in normal position and relationship, they are labeled “d-related great vessels” because the aorta is located to the right (dextral) of the pulmonary artery.

Malrotation during the formation of the ventricular loop may cause various cardiac malpositions (such as dextrocardia) and malformations. As noted, the normal direction for the ventricular loop is to the right, or D-looping. If the ventricles loop to the left instead, L-looping has occurred, so the morphologic left ventricle is located to the right, and the morphologic right ventricle is on the left (Fig. 8-2).

Fig. 8-2 Cardiac loop formation, The primordial heart tube during the fourth week. A, Normal looping (bending) to the right. B, Abnormal looping (bending) to the left.

(From Moore KL, Persaud TVN, Torchia MG: The cardiovascular system. The developing human: clinically oriented embryology, ed 8. Philadelphia, 2008, Saunders Elsevier.)

L-looping of the ventricles frequently is associated with transposed great vessels; this combination commonly is referred to as “corrected transposition of the great arteries.” It is a type of “transposition,” because the aorta lies to the left of the pulmonary artery. The great vessels are transposed: the ascending aorta is anterior and arises from an anatomic (morphologic or structural) right ventricle, sweeping to the left, and the pulmonary artery is posterior and arises from the anatomic (or morphologic or structural) left ventricle. The term “corrected” is appropriate because the hemodynamic pathways are not altered; systemic venous return ultimately enters the pulmonary circulation, and pulmonary venous return enters the systemic circulation. The systemic venous return enters the right atrium, flows through a mitral valve into a morphologic left ventricle, and is then ejected into a posterior pulmonary artery. The pulmonary venous return flows into the left atrium, exits through a tricuspid valve into a structural right ventricle and is then ejected into an anterior aorta. Although the heart is not normal, the child will be asymptomatic unless a complicating heart lesion is present.

Complete congenital heart block, ventricular septal defect, tricuspid valve anomalies, and cardiac malpositions are common among children with l-transposition. It is important to remember that the mitral valve is located with the morphologic left ventricle in corrected transposition, and that these structures receive systemic venous return; the tricuspid valve is associated with the morphologic right ventricle, receiving pulmonary venous return. Therefore if tricuspid atresia is present, obstruction to pulmonary venous return occurs (because the tricuspid valve is located abnormally on the left side). Ebstein’s malformation, an abnormality of the tricuspid valve, produces signs associated with mitral insufficiency (e.g., pulmonary edema). The use of the phrase “ventricular inversion with transposed great vessels” probably would be less confusing than “corrected transposition.”

Formation of Cardiovascular Septation: Day 26 to 49

Cardiac septation occurs after the looping process is complete. During the septation process, septae are formed that ultimately close the ostium primum, the central atrioventricular canal, and the interventricular foramen. At the end of this period, the in-series circulation becomes two parallel circulations.⁹⁰²

Atrial Septation: Day 30 to 35

Septation of the atria begins around day 30. Two septae develop and are modified to form a flapped orifice, the foramen ovale as illustrated in Fig. 8-3. The first septum to form is the septum primum, which grows from the anterior, superior portion of the atrium and extends toward the center of the heart. The development of the septum primum leaves a gap, the ostium primum, in the inferior portion of the atrial wall; this gap normally is closed by the fusion of the endocardial cushions. As the ostium primum is closing, perforations produced by apoptosis begin to form in the central portion of the septum primum. These perforations coalesce to create the ostium secundum (see Fig. 8-3, C and D).⁶²⁷

Fig. 8-3 Atrial and ventricular septation. (A-E) Drawings of the developing heart showing partitioning of the atrioventricular canal, primordial atrium and ventricle. A, Sketch showing the plane of the sections. B, Frontal section of the heart during the fourth week (approximately 28 days) showing the early appearance of the septum primum, interventricular septum, and dorsal endocardial cushion. C, Similar section of the heart (approximately 32 days) showing perforations in the dorsal part of the septum primum. D, Section of the heart (approximately 35 days) showing the foramen secundum. E, At approximately 8 weeks, showing the heart after it is partitioned into four chambers. The arrow indicates the flow of well-oxygenated blood from the right to the left atrium. F, Sonogram of a second trimester fetus showing the four chambers of the heart. Note the septum secundum (arrow) and the descending aorta.

(Courtesy of Dr. G. J. Reid, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Manitoba, Women’s Hospital, Winnipeg, Manitoba, Canada.) (From Moore KL, Persaud TVN, Torchia MG: The cardiovascular system. The developing human: clinically oriented embryology, ed 8. Philadelphia, 2008, Saunders Elsevier.)

The septum secundum is the second septum to form within the atria. It is a thick crescent-shaped muscular fold that grows immediately adjacent to the septum primum. As it grows, it overlaps the foramen secundum in the septum primum. The atrial partition is incomplete, forming an oval foramen (in Latin, the foramen ovale).⁶²⁷

The portion of the septum primum that is attached to the cranial portion of the atrium gradually disappears. The remaining portion of the primum septum that is attached to the fused endocardial cushions forms the flap of tissue called the valve of the oval foramen.⁶²⁷

Before birth the foramen ovale allows the oxygenated blood from the placenta entering the right atrium via the inferior vena cava to flow to the left atrium and to the fetal brain. (See section, Fetal Circulation that follows.) The flap of the oval foramen normally prevents flow in the opposite direction.⁶²⁷

Atrial septal defects occur when the primum septum or the secundum septum or both do not completely form. Atrial septal defects include an ostium primum, secundum atrial septal defect, or common atrium. An ostium primum atrial septal defect is located near the atrioventricular valves. This defect will not close spontaneously. An ostium secundum atrial septal defect is thought to result from excessive apoptosis of the septum primum, so that a large defect is present in the area of the foramen ovale. Some secundum defects decrease in size and some undergo spontaneous closure.⁷²³

Septation of the Truncus Arteriosus: Day 26 to 42

Active proliferation of the mesenchymal cells in the walls of the bulbus cordis form the conotruncal or bulbar ridges. Similar ridges form in the truncus arteriosus (Fig. 8-4).

Fig. 8-4 Division of truncus arteriosus into pulmonary artery and aorta. Partitioning of the bulbus cordis and truncus arteriosus. A, Ventral aspect of heart at 5 weeks. The broken lines and arrows indicate the levels of the sections shown in B. B, Transverse sections of the truncus arteriosus and bulbus cordis, illustrating the truncal and bulbar ridges. C, The ventral wall of the heart and truncus arteriosus has been removed to demonstrate these ridges. D, Ventral aspect of heart after partitioning of the truncus arteriosus. The broken lines and arrows indicate the levels of the sections shown in E. E, Sections through the newly formed aorta (A) and pulmonary trunk (PT), showing the aorticopulmonary septum. F, 6 Weeks. The ventral wall of the heart and pulmonary trunk has been removed to show the aorticopulmonary septum. G, Diagram illustrating the spiral form of the aorticopulmonary septum. H, Drawing showing the great arteries (ascending aorta and pulmonary trunk) twisting around each other as they leave the heart.

(From Moore KL, Persaud TVN, Torchia MG: The cardiovascular system. The developing human: clinically oriented embryology, ed 8. Philadelphia, 2008, Saunders Elsevier.)

The mesenchymal cells in these ridges are primarily from neural crest cells. As cell proliferation occurs, the truncal and bulbar ridges create a 180-degree spiraling. This spiraling may be enhanced by the streaming of blood from the ventricles, as illustrated, or may result from passive untwisting as the pulmonary artery passes from the anterior pulmonary valve to the posterior pulmonary bifurcation.⁹⁰²

The spiraling of the conotruncal septum aligns the future pulmonary artery to the anterior and rightward right ventricle, where it joins with the outflow tract (infundibulum) created by incorporation of the bulbus cordis into the right ventricle. The future aorta communicates with the posterior and leftward left ventricle at the aortic vestibule created by incorporation of the bulbus cordis below the aortic valve.⁶²⁷ Differences in cell growth create a separation between the tricuspid and pulmonary valve. Disappearance of this segment below the aortic valve provides fibrous continuity between the mitral and aortic valve.⁷⁹

Defects in the conotruncal and aortic arch development do not close spontaneously. Congenital heart defects that result from defective conotruncal development include: truncus arteriosus, tetralogy of Fallot, pulmonary atresia, double-outlet right ventricle, interrupted aortic arch, and aortopulmonary window. These defects are often associated with genetic deletions of chromosome 22q11 (see section, Genetic Factors Associated with CHD).^627,723 Failure of appropriate conal reabsorption of the subaortic conus is thought to produce improper truncal rotation and result in d-transposition of the great vessels.

Classification of Complex Cardiac Malpositions and Malformations

Complex cardiac malformations and malpositions can be described according to a labeling system proposed by Van Praagh.⁹⁰² This classification included 10 cardiac segments, but three were used most often. The positions of the viscera, the ventricular loop, and the great arteries are all labeled separately, using three letters within curved brackets, such as {A, B, C}.

The cardiac chambers and organ segments are identified by morphology (i.e., structure and appearance); the segments then can be referred to as concordant (consistent in position), or discordant (inconsistent in position). Although this segmental description of congenital heart defects is not used for the most common forms of defects, it is used in the classification of cardiac malpositions (e.g., dextrocardia or dextroversion) and complex transpositions. A variation of the Van Praagh segmental classification has been published recently³⁴³ using six segments (systemic and pulmonary veins, atrial situs, atrioventricular connection, ventricles and infundibulum, ventricle to artery connection, and great arteries and the ductus arteriosus). The following section identifies the three most commonly used segments for identification.

Development of the Aortic Arch: Day 28 to 49

Two large arteries form at the distal end of the truncus arteriosus during the fourth and fifth weeks of fetal development. Although these original arteries ultimately disappear, they give rise to six pairs of arteries, the six aortic arches. By the end of the fourth week the first two pairs and the fifth pair of aortic arches have disappeared, and the sixth pair of arches now is joined to the pulmonary trunk and contributes to the development of the ductus arteriosus. Ultimately the third aortic arch will form the common carotid artery, the external carotid artery, and part of the internal carotid artery. The fourth aortic arch forms part of the final aortic arch and the proximal portion of the right subclavian artery. The sixth aortic arch provides the proximal segment of both pulmonary arteries and the ductus arteriosus, and a branch develops with the lung buds to provide pulmonary blood flow (see Evolve Fig. 8-1 in the Chapter 8 Supplement on the Evolve Website). Abnormalities in formation of the aortic arches can result in an interrupted aortic arch, aortic atresia, patent ductus arteriosus, vascular rings (including double aortic arches), and aberrant origin of the right subclavian artery.

Development of the Ventricular Myocardium, Conduction System, and Coronary Circulation

After the neural crest cells enter the endocardial cushions, they migrate to the myocardium. The myocardium then develops into a working myocardium and the cardiac conduction system. Originally the atrium acts as the pacemaker of the heart. The sinoatrial node develops during the fifth week. Additional cells from the right atrial wall join with cells from the atrioventricular region to form the atrioventricular node and His bundle located just above the endocardial cushions. Bundle branches are found throughout the ventricular myocardium.⁶²⁷

Additional cells develop from a small, transient organ, the proepicardium, on the dorsal thoracic wall. The proepicardial cells contain mesothelial cells that migrate to the heart and form the epicardium that lines the heart. These cells migrate further and differentiate to form the coronary vasculature and cardiac fibroblasts.⁷⁶⁴

In prenatal life myocardial cells undergo significant changes to increase in number (hyperplasia) and size (hypertrophy). The myocardial cells also change shape from round to cylindrical, become more regular in the orientation of the myofibrils (the contractile element), and have increasing proportions of myofibrils. Developmental changes are also seen in the sarcolemma (plasma membrane) and sarcoplasmic reticulum. Both control the ion channels and transmembrane receptors that regulate cardiac function, depolarization, and repolarization. Maturation of these cells and functions continues into the neonatal period.⁷⁹

Fetal Circulation

Fetal circulation differs anatomically and physiologically from postnatal circulation in several important ways. In the fetus, oxygenation of the blood occurs in the placenta, which is a relatively inefficient oxygenator. The fetus is hypoxemic, with an aortic arterial oxygen tension of approximately 20 to 30   mm Hg; the saturation of fetal hemoglobin is higher at this oxygen tension than is normal hemoglobin, so oxygen saturation is approximately 60% to 70%. The fact that the oxygen tension is normally much lower in the fetus than postnatally may account for the ability of the neonate to tolerate cyanotic heart disease.²⁷⁸ Despite this arterial hypoxemia, the fetus does not have tissue hypoxia because fetal cardiac output is higher than at any other time in life, averaging approximately 400 to 500   mL/kg per minute. Approximately 20% of the normal fetal oxygen consumption of 8   mL/kg per minute is required to develop new tissue.²⁷⁸ Fetal cardiac output is constant (at approximately 400 to 500   mL/kg per minute) at a heart rate greater than 120 to 180/min. Changes in preload result in very little change in cardiac output, and changes in afterload are not well tolerated.²⁷⁸

Fetal circulation is designed to deliver the best-oxygenated and nutrient rich blood from the placenta to the fetal brain and heart (Fig. 8-5). This blood enters the fetus through the umbilical vein. The blood flow splits in the liver with almost half going through the hepatic veins and portal system of the liver and the rest through the ductus venosus, where it joins the inferior vena cava near its junction with the right atrium. In the right atrium the blood from the inferior vena cava (with a PO₂ of 32 to 35   mm Hg and an oxygen saturation of 70%—the highest fetal PO₂) is divided into two streams. About 40% of this blood passes through the foramen ovale into the left atrium, where it joins the small amount of blood from pulmonary venous return. It then passes through the mitral valve to the left ventricle and then to the ascending aorta where it supplies the coronary, carotid, and subclavian arteries. The preferential streaming of this blood results in an ascending aortic arterial oxygen tension (PaO₂) of 26 to 28   mm Hg and an oxygen saturation of 65%.^278,686 Ten percent of the blood flow from the left ventricle passes through the aortic arch into the descending aorta, where it joins 90% of the blood leaving the right ventricle. The fetal right ventricle pumps more than two thirds of the combined ventricular output, so the right ventricle is relatively muscular.

Fig. 8-5 Fetal circulation. Fetal blood is oxygenated in the placenta (which is a less efficient oxygenator than the lungs). The oxygenated blood enters the fetus through the umbilical vein and enters the ductus venosus, bypassing the hepatic circulation and flowing into the inferior vena cava. When this blood reaches the right atrium, it is diverted by the crista dividens toward the atrial septum, and flows through the foramen ovale into the left atrium. The blood then passes through the left ventricle and ascending aorta to perfuse the head and upper extremities. This pathway allows the best-oxygenated blood from the placenta to perfuse the fetal brain. Venous blood from the head and upper extremities returns to the fetal heart through the superior vena cava, enters the right atrium and ventricle, and flows into the pulmonary artery. Because pulmonary vascular resistance is high, this blood is diverted through the ductus arteriosus into the descending aorta. Ultimately, much of this blood will return to the placenta through the umbilical arteries.

(Illustration by Marilou Kundemueller.)

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