Pregnancy and Congenital Heart Disease Moderator: Roy M. Pitkin, M D ; Discussants: Joseph K. Perloff, M D ; Brian J. Koos, M D , DPhil; and Marie H. Beall, M D

Congenital heart disease as a complicating factor in pregnancy has assumed increasing clinical importance because improved techniques of surgical repair have resulted in a larger proportion of affected women living to the reproductive age. The most serious forms are those associated with pulmonary hypertension (such as the Eisenmenger syndrome), which carry a prohibitively high risk of maternal death. Complex forms of cyanotic heart disease, of which the commonest is the tetralogy of Fallot, are only slightly less dangerous. It has recently been recognized that children born to women with congenital heart disease are at increased risk of having cardiac defects; fetal echocardiography is therefore an important diagnostic test. Optimal care of the pregnant woman with congenital heart disease is best provided by a team consisting of internist-cardiologist, obstetrician-perinatologist, obstetric anesthesiologist, and ultrasonographer-echocardiographer. Annals of Internal Medicine. 1990;112:445-454.

Dr Roy M. Pitkin (Department of Obstetrics and Gynecology, U C L A School of Medicine, Los Angeles, California): Two trends, occurring simultaneously during the past 25 years, have led to the emergence of congenital heart disease as a significant portion of high-risk pregnancies. One is the remarkable improvement in methods of management, particularly surgical, of congenital cardiac defects, so that many affected persons who formerly would have died in infancy or childhood are now surviving to adulthood. The other is the dramatic decline in the incidence of rheumatic fever and its cardiac sequelae, particularly evident in industrialized societies, that has resulted in a diminishing frequency of rheumatic heart disease among women of reproductive age. As a result of these developments, a former ratio of three or four to one for rheumatic to congenital in series of patients with carAn edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles, California. William M. Pardridge, MD, Professor of Medicine, is Director of Conferences. Authors who wish to cite a section of the conference and specifically indicate its author can use this example as the form of the reference: Koos BJ. Clinical management of pregnant women with congenital heart disease, pp 448-451. In: Pitkin RM, moderator. Pregnancy and congenital heart disease. Ann Intern Med. 1990;112:445-454.

diac disease complicating pregnancy is now essentially reversed. Even though the prognosis of the pregnant woman with congenital heart disease is vastly improved over that of former times, it still presents a classic high-risk pregnancy involving both mother and infant. The principal danger for the woman is that of cardiac decompensation because of inability to meet the additional demands imposed by the physiologic changes of pregnancy and parturition; infection, hemorrhage, and thromboembolism are threats that compound the risk. The fetus faces the danger of having its supply of oxygen and other nutrients impaired by the mother's cardiovascular insufficiency. The newborn has the recently recognized risk of hereditary transmission of congenital cardiac malformation. The careful, thorough, and sophisticated care needed by the pregnant woman with congenital heart disease is best provided by a team consisting of a cardiologist (adult or pediatric) who appreciates the physiologic and psychologic aspects of pregnancy, an obstetrician familiar with cardiovascular function and disease, and (as the time of delivery approaches) an anesthesiologist who understands both cardiology and parturition. Optimally, this team should also include physicians experienced in cardiac diagnosis in the fetus and in the newborn. Cardiovascular Adjustments of Normal Pregnancy From the maternal point of view, gestation involves a set of remarkable physiologic adjustments, which in concert promote development of the fetus and placenta while also preserving maternal homeostasis. Many of these adjustments involve the cardiovascular system, directly or indirectly placing increased demands on the heart, arterial and venous circulations, and respiratory system. The healthy woman is able to meet these demands without difficulty but the one with a compromised cardiovascular condition may not. A thorough understanding of maternal physiology is thus essential for proper clinical management. Blood Volume Expansion of plasma volume, perhaps the most striking maternal alteration of pregnancy, begins within a few weeks of conception, continues during the second and early third trimester, and then slows and ceases during the last 6 to 8 weeks of gestation ( 1 ) . At its maximum, the augmentation averages 5 0 % over prepregnant normal values, although considerable indi-

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than in systolic pressure, the pulse pressure tends to widen. Vital capacity is unaffected by gestation but its components undergo some rearrangements ( 5 ) . Tidal volume increases at the expense of expiratory reserve volume, and this relative hyperventilation results in lowering of both end-tidal and arterial carbon dioxide tensions. These adjustments have little effect on maternal or fetal oxygenation (because of the shapes of the blood oxygen dissociation curves for adult and fetal hemoglobin) but do facilitate removal of carbon dioxide from the fetus. The lung is somewhat more collapsed than usual at the end of expiration-a state the woman may interpret as dyspnea. Figure 1. Plasma and erythrocyte increase during pregnancy. From Pitkin (2); reproduced with permission of Clinical Obstetrics and Gynecology.

vidual variation occurs. The erythrocyte volume also expands, but to a lesser extent and with a different pattern. The relations between plasma and erythrocyte volumes and hematocrit over the course of pregnancy (2) are illustrated in Figure 1. Extravascular fluid also increases, particularly during late gestation, and both dependent and generalized edema are so common as to be considered normal. Lower-extremity edema probably reflects a combination of progesterone-induced venous relaxation and obstruction of the pelvic veins by the enlarging uterus. The mechanism of generalized edema is not so clear but endocrine factors (estrogen, progesterone, reninangiotensin, and perhaps atrial naturietic factor) are thought to be involved. The Heart and Hemodynamic Functions The enlarging uterus causes upward pressure on the diaphragm, displacing the heart laterally and altering physical and roentgenographic findings. Flow murmurs are extremely common-indeed nearly universal-and a rather soft, blowing systolic m u r m u r heard best along the left sternal border is typical. Diastolic murmurs, by contrast, strongly suggest cardiac disease. Resting cardiac output rises by 3 0 % to 4 0 % , with much of the increase occurring relatively early, so that the maximum is reached by the midpoint of gestation ( 3 ) . Cardiac output increases additionally during labor, approximately 5 0 % of which results from blood squeezed from the uterus with contractions and approximately 5 0 % of which reflects a response to pain. The increase in cardiac output involves both stroke volume and rate ( 4 ) . Stroke volume increases early in gestation by about 20 mL, then declines toward the nonpregnant level during the last trimester. The pulse rate rises by about 10 beats per minute over baseline at the end of the second trimester, then falls slightly. Arterial pressure during gestation represents a "mirror image" to pulse rate, falling more or less progressively to a nadir in the late second or early third trimester and then rising slightly toward term. Because the pattern is usually somewhat more marked in diastolic


Clinical Implications The far-reaching maternal adjustments of normal pregnancy are clinically relevant in two general ways. In the normal pregnant woman, they can cause symptoms and signs which would otherwise suggest disease -cardiomegaly, tachycardia, murmurs, edema, and dyspnea. In the woman with cardiac disease, the increased workload imposed by pregnancy impinging on a marginal cardiac reserve can lead to decompensation.

Congenital Heart Disease Complicating Pregnancy Dr. Joseph K. Perloff (Departments of Medicine and Pediatrics, U C L A School of Medicine): For the internist or internist-cardiologist, the most important category of patients with unoperated congenital heart disease consists of those with the common anomalies listed in Table 1. Types of Congenital Heart Disease Ostium secundum atrial septal defect is of special importance because the natural history spans the childbearing age and because most affected persons are women. Young women with uncomplicated ostium secundum atrial septal defects generally tolerate pregnancy with no tangible ill effects. After age 40, they experience an increased incidence of supraventricular arrhythmias that may potentiate right ventricular failure and peripheral edema and increase the risk of venous stasis and paradoxic embolization. Pulmonary hypertension is relatively uncommon in persons with Table 1. Common Acyanotic and Cyanotic Malformations with Expected Adult Survival in Descending Order of Prevalence among Women Acyanotic Atrial septal defect (secundum) Patent ductus arteriosus Pulmonic valve stenosis Coarctation of the aorta Aortic valve disease Cyanotic The Fallot tetralogy

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ostium secundum atrial septal defect and, if present, occurs relatively late in life. Patent ductus arteriosus is becoming of less practical importance as a complication of pregnancy because surgical closure usually is done in childhood. An asymptomatic young woman with a small- or moderate-sized ductus and normal pulmonary arterial pressure can expect an uncomplicated pregnancy. With a large left-to-right shunt, the gestational fall in systemic vascular resistance serves to decrease ductal flow, but this effect may not compensate for the added hemodynamic burden of pregnancy. At highest risk is the patient with a nonrestrictive patent ductus arteriosus, suprasystemic pulmonary vascular resistance, and a reversed shunt; because the gestational decline in systemic vascular resistance augments the right-to-left shunt through the ductus, uterine arterial oxygen saturation is further reduced. The natural history of pulmonic valve stenosis lends itself to survival to adulthood even when there is significant obstruction to right ventricular outflow. Mildto-moderate pulmonic stenosis poses little or no threat to the mother, and occasionally even severe pulmonic stenosis is well tolerated despite the additional volume load of pregnancy imposed on an already pressureloaded right ventricle. Coarctation of the aorta carries a high risk because pregnancy increases the risk for aortic rupture or dissection. Additionally, cerebral hemorrhage may result from rupture of an aneurysm of the circle of Willis. The incidence of superimposed pre-eclampsia is lower in pregnant women with coarctation hypertension than with other forms of hypertension. Congenital aortic valve disease predominates in men, but an isolated functionally normal bicuspid aortic valve is likely to go unrecognized in young women because the clinical index of suspicion is low. Owing to the high susceptibility to infective endocarditis, the anomaly may first appear after delivery as fever or as acute aortic regurgitation. Chronic aortic regurgitation is generally well tolerated during pregnancy provided left ventricular function is normal at the outset. The gestational fall in systemic vascular resistance and the increase in cardiac rate (shorter diastole) decrease regurgitant flow. Asymptomatic women entering pregnancy with mild-to-moderate congenital aortic stenosis do well, but those with severe obstruction to left ventricular outflow have limited circulatory reserve; labor seems particularly hazardous in women with aortic stenosis ( 6 ) . The Fallot tetralogy is the commonest cyanotic malformation that permits survival to adulthood, and the sex distribution is nearly equal. Absence of symptoms before conception does not assure a smooth course. The gestational decrease in systemic vascular resistance coupled with the augmented cardiac output and increased venous return to the obstructed right ventricle result in an increase in right-to-left shunt and in a fall in systemic arterial oxygen saturation. Cyanosis deepens and the hematocrit rises. Labile hemodynamics during labor, delivery, and the puerperium compound the risk.

Certain congenital defects, such as ventricular septal defect, that are common in infants and children are seldom seen in adults. The occasional adult woman with a small-to-moderate-sized ventricular septal defect confronts pregnancy with a risk related to the magnitude of the left-to-right shunt and the adaptation of the left ventricle to volume overload. Large, nonrestrictive defects that permit survival into adulthood generally develop a progressive rise in pulmonary vascular resistance in childhood with reversed shunt. With the Eisenmenger complex, the mother can die during pregnancy, labor, delivery, or the puerperium; the total estimated risk is 30% to 70%. The fall in systemic vascular resistance during gestation increases the right-to-left shunt and reduces the systemic arterial oxygen saturation. Bearing down during labor elevates systemic resistance and may suddenly depress cardiac output and provoke fatal syncope ( 7 ) . The fixed pulmonary vascular resistance prevents rapid adaptation to the sudden fluctuations in systemic resistance, cardiac output, and blood volume that accompany labor, delivery, and the puerperium. Another uncommon but important disorder that permits adult survival is congenital complete heart block. Approximately 50% of these patients are women, and most reach childbearing age. Asymptomatic women with congenital complete heart block generally tolerate pregnancy uneventfully, provided that the duration of the QRS complexes is not prolonged. The recent availability of dual-chamber physiologic pacing systems offers the potential for improving cardiac output during pregnancy in women with heart block. In the Ebstein anomaly, whether acyanotic or cyanotic, the functionally inadequate right ventricle, already volume-loaded by tricuspid regurgitation, copes poorly with the gestational increase in cardiac output. Paroxysmal atrial arrhythmias are potential hazards, and when Wolff-Parkinson-White bypass tracts permit rapid ventricular rates, the consequences can be catastrophic. Cyanosis in the Ebstein anomaly results from a reversed shunt at atrial level. It may first become evident during pregnancy because of a rise in right ventricular filling pressure.

Fetal Effects Maternal congenital heart disease threatens fetal growth, development, and viability by reducing the availability of oxygen in cyanotic conditions or by reducing uterine blood flow in patients with heart failure. In addition to immediate intrauterine hazards, the fetus is at independent risk for congenital cardiac malformations. Infants born to cyanotic mothers are often small for their gestational age or are preterm. Maternal cyanosis is a major hazard to fetal viability. The high rate of spontaneous abortion in cyanotic women roughly parallels the mother's hematocrit, but even relatively mild cyanosis increases the risk for fetal wastage. Cardiac surgery can eliminate cyanosis and improve maternal functional class.

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Pregnancy after Cardiac Surgery Because certain congenital cardiac malformations appreciably reduce sexual and ovarian function, successful cardiac surgery often improves fertility. Women who were physiologically ill equipped to bear children or who previously would probably not have reached childbearing age are now presenting for obstetric and cardiologic care after surgery. The prime objective of surgery is to increase the safety and success of pregnancy and the subsequent health of mother and child. Cardiac surgery should therefore be anticipatory. With few exceptions, surgery is not curative, leaving in its wake residua and sequelae of varying degrees of importance. The risk of pregnancy to the mother is then determined chiefly by the presence, type, and degree of these postoperative cardiac and vascular residua and sequelae. Successful closure of an ostium secundum atrial septal defect in children or young adults eliminates the risk for parodoxic embolization. There are usually few significant postoperative residua or sequelae, but occasionally atrial flutter develops years after a successful repair. Nevertheless, an asymptomatic woman of childbearing age who has had closure of her ostium secundum atrial septal defect in childhood or young adulthood will generally have minimal maternal risk during pregnancy. Surgical closure of a small patent ductus arteriosus in a child with normal pulmonary artery pressure is one of the few categoric cures of congenital heart disease, and such patients are considered normal. However, after operative closure of a large, nonrestrictive patent ductus arteriosus, pulmonary vascular resistance may decline but fail to return to normal. If surgical repair or balloon dilatation of congenital pulmonic valve stenosis leaves little or no postinterventional gradient, the mother can anticipate a normal pregnancy except for the risk of infective endocarditis. Mild-to-moderate postoperative low-pressure pulmonary regurgitation is not an important sequela. Surgical repair of coarctation of the aorta, especially (although not necessarily) in early childhood, reduces the gestational risk for aortic rupture or dissection. The likelihood of infective endocarditis at the site of repair is diminished if not eliminated (depending chiefly on the surgical technique), but the risk for infection on a coexisting bicuspid aortic valve is unaffected. Whether successful repair decreases the hazard of rupture of an aneurysm of the circle of Willis is open to question, but the incidence of death from postoperative intracranial hemorrhage is reassuringly low (8). When congenital aortic valve stenosis with a gradient of 50 mm Hg or more occurs in a young woman, surgical relief or balloon dilatation can improve the response to pregnancy, except for the risk for infective endocarditis ( 9 ) . If a woman with free aortic regurgitation and normal left ventricular function wishes to become pregnant, it may be better if she conceives before the aortic valve is replaced. If an aortic prosthesis is needed in a woman of childbearing age, a tissue


valve offers considerable advantage over the prosthetic type (10). There is justifiable optimism regarding pregnancy after successful intracardiac repair of the Fallot tetralogy, especially in women with little or no postoperative outflow gradient and no more than mild postoperative low-pressure pulmonary regurgitation. The electro-physiologic sequelae of repair cannot be ignored, however, whether the sequelae take the form of bifascicular block or, more importantly, of right ventricular electrical instability ( 1 1 ) . Surgical relief of cyanosis increases the probability of successful conception and materially improves stability of the pregnancy and growth and development of the fetus. If a moderately restrictive or nonrestrictive ventricular septal defect is closed sufficiently early in its natural course so that the development of postoperative pulmonary vascular disease is precluded, a relatively normal pregnancy can be anticipated. Significant postoperative electrophysiologic sequelae are exceptional (11). Surgical repair of Ebstein anomaly of the tricuspid valve preferably takes the form of reconstruction rather than valve replacement. A large, mobile, anterior tricuspid leaflet permits reconstruction into a relatively competent unicuspid valve, and surgical dissociation between right atrium and right ventricle eliminates active or potential bypass tracts. Clinical Management of Pregnant Women with Congenital Heart Disease Dr. Brian J. Koos (Department of Obstetrics and Gynecology, U C L A School of Medicine): A good outcome for the mother with congenital heart disease can usually be expected (12, 13), although the actual risk depends on the type of malformation and the functional impairment of the mother. For example, most women with acyanotic heart disease do well during pregnancy and have maternal mortality rates near those for normal patients; however, cyanotic heart disease is associated with greater maternal and fetal risk ( 1 4 ) . Generally, women with class I or II (New York Heart Association classification) cardiac disease have a reasonably good prognosis, whereas those with class III or IV disability are at high risk and need more intensive care. Despite optimal treatment, certain congenital heart conditions are associated with a high maternal mortality ( > 1 0 % ) , and pregnancy should be avoided (Table 2 ) . If such a patient conceives, therapeutic abortion should be seriously considered because the risk of termination is substantially less than that of completing the pregnancy. This is particularly true for conditions with pulmonary hypertension in which the maternal mortality risk for each pregnancy is about 3 0 % ( 1 5 ) . Other high-risk conditions include aortic coarctation complicated by cardiac failure, previous vascular accident or refractory hypertension, atrial septal defect associated with ventricular failure or serious arrhythmia, and patent ductus arteriosus with congestive heart failure (16).

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Table 2. Contraindications to Pregnancy Primary pulmonary hypertension The Eisenmenger syndrome The Fallot tetralogy Aortic coarctation, complicated Atrial septal defect, complicated Patent ductus arteriosus, complicated Preconceptional Aspects When possible, heart defects should be surgically corrected before pregnancy to increase the cyanotic patient's arterial oxygen tension and hemodynamic reserve. As a consequence, pregnancy will be better tolerated (16, 17), and is more likely to result in a normal infant. For example, palliation or correction of cyanotic heart disease reduces the risk for fetal wastage, premature delivery, and intrauterine growth retardation (12, 17). Such surgery during pregnancy is generally not advised, but if absolutely necessary, it can be done after 16 weeks' gestation. For symptomatic patients in early pregnancy, consideration should be given to elective abortion, with surgical repair done afterward (16). Because infections pose a danger, the risk should be minimized in patients with congenital heart disease. Before pregnancy, they should be immunized against polio, measles, tetanus, rubella, influenza, and pneumococci. The urine should be cultured, and asymptomatic bacteriuria should be treated. Contact with young children or other groups at high risk for infection should be discouraged. Antepartum Care Because normal blood volume is necessary for hemodynamic stability, patients should be encouraged to drink fluids; diuretics should be used cautiously if at all. Pressure-gradient elastic hose worn while walking will help maintain venous return and positions that impede venous return should be avoided. Because excessive heat produces peripheral vasodilation and promotes venous pooling, hot baths or showers should be discouraged. An increase in cardiac output normally occurs after eating, and this can be minimized by temperate intake. The patient is generally encouraged to exercise as she did before pregnancy. However, she may have to curtail her physical activity if the fetus fails to grow normally or if she develops increasing fatigue, shortness of breath, or palpitations. All patients with pulmonary hypertension or cyanotic heart disease should restrict their activity. The frequency with which pregnant women with congenital heart disease should be seen by a physician varies. In general, asymptomatic women should be examined every two to three weeks. Symptomatic women should be seen more often. The physician should be notified immediately if any signs suggesting cardiovascular decompensation develop. Management should also be individualized according to the type of congenital heart disease. For example, thrombocytopenia can occur in patients with pri-

mary pulmonary hypertension or the Eisenmenger syndrome. Therefore, platelet counts are advisable in these patients, particularly before delivery when a platelet transfusion may be needed. Arterial blood gases may be periodically necessary in cyanotic patients to evaluate the extent of right-toleft shunt. Oxygen therapy in such patients is unlikely to benefit the mother (18). However, at least in normal women, fetal oxygen tensions can be raised 3 to 4 torr by maternal inhalation of 100% oxygen (19, 20). Oxygen therapy may thus be a consideration for cyanotic patients with a growth-retarded fetus, although the benefits of such therapy for the fetus are uncertain. Erythrocytosis and the associated increase in blood viscosity adversely affect cardiovascular function and may increase the risk for venous thrombosis. Phlebotomy is generally reserved for those with symptomatic hyperviscosity and should be done with a simultaneous intravenous infusion of an equal volume of isotonic saline to maintain vascular volume (18). Functional class III patients should be hospitalized for congestive heart failure or for conditions that predispose to this complication, such as severe anemia, arrhythmias, or infection (21). Patients with primary pulmonary hypertension or the Eisenmenger syndrome should be hospitalized by the twentieth week of pregnancy for optimal medical management. Functional class IV patients often need hospitalization throughout pregnancy. Intrapartum Management Pregnant women with congenital heart disease should anticipate a vaginal delivery, with cesarean section used only for obstetric indications. A cesarean may be appropriate when the blood pressure fluctuations associated with labor are contraindicated and cannot be controlled, such as with aortic coarctation or tetralogy of Fallot complicated by a previous vascular accident. Women with functional class I or II disability should be permitted to go into labor spontaneously and to labor in lateral position. Continuous monitoring of the maternal electrocardiogram permits early identification of significant arrhythmias. Pregnant women with primary pulmonary hypertension, the Eisenmenger syndrome, aortic coarctation, and functional class III or IV disease are at high risk for complications during labor, delivery, and the early puerperium. A pulmonary artery catheter may be helpful in monitoring these patients; reference values for hemodynamic measurements (16) are given in Table 3. The patient with congenital heart disease is better managed by treating her according to changes in measurements rather than to absolute values. Pulmonary wedge pressures should be kept on the high side (16 to 18 mm Hg) in women with pulmonary hypertension to provide some reserve against maternal hemorrhage (22). Elective induction of labor may be used for timing purposes in patients needing invasive monitoring. Some authorities advocate administering oxygen (4 to 6 L/min) to patients with cyanotic heart disease but

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Table 3. Normal Hemodynamic

Values in Late




Heart rate, beats/min Stroke volume, mL Cardiac index, L/min • m2 Pulmonary artery Mean pressure, mm Hg O2 saturation, % Pulmonary capillary wedge Mean pressure, mm Hg O2 saturation, %

70 to 105 70 to 100 3.5 to 5.0 < 16 60 to 70 < 13 > 98

* Lateral recumbency, modified from Metcalfe et al. (16).

this point is controversial. A large-bore catheter should be placed in a peripheral vein for infusion of blood or plasma expanders if needed. Another venous catheter should be inserted for administration of vasoactive agents. Care must be taken not to inject bubbles into the venous lines to avoid paradoxic air embolization. A systemic arterial catheter is convenient for continuous monitoring of arterial pressure and can be used to collect blood for arterial blood gas analysis. Although the risk for bacterial endocarditis is low with vaginal delivery (23), antibiotic prophylaxis is normally given for virtually all patients with congenital heart disease. Conventional treatment includes the administration of ampicillin, 2 g, and gentamycin, 1.5 mg/kg body weight, intramuscularly or intravenously at the start of active labor. These antibiotics are given at 8-hour intervals until the patient has received one dose at least 8 hours postpartum (24). Vancomycin can be substituted for ampicillin in patients allergic to penicillin. Antibiotic prophylaxis is not recommended for women with an isolated secundum atrial septal defect or with such a defect repaired without a patch more than 6 months before delivery (25). Pain management in women with corrected lesions or with class I or II disability should be the same as for normal patients during labor. However, those with greater functional impairment benefit from the hemodynamic stability provided by conduction anesthesia (26). Lumbar epidural anesthesia controls pain effectively during labor and delivery, but care must be given to avoid hypotension resulting from the concomitant loss of sympathetic tone, particularly in cases of the Eisenmenger syndrome or cyanotic heart disease, Table 4.

Prenatal Exposures

Exposure Rubella retinoic acid

valproic acid hydantoin lithium ethanol


with Congenital Heart

in which systemic hypotension increases the degree of shunt and arterial oxygen saturation. Narcotics injected into the epidural space provide analgesia during labor without affecting muscle tone or sympathetic outflow. This form of analgesia does not reduce venous return and is preferred for patients whose cardiac function is particularly sensitive to changes in preload or afterload. Because epidural narcotics do not provide perineal anesthesia, a pudendal block is usually necessary for delivery. When the cervix is fully dilated, the normal parturient is encouraged to push. The Valsalva maneuver in patients with heart disease is undesirable, however, because it reduces cardiac output; consequently, it is better to have the fetus pass through the pelvis under the force of uterine contractions alone. When it is safe to do so, forceps are used to facilitate delivery. After expulsion of the placenta, bleeding should be minimized by uterine massage and intravenous administration of oxytocin. A rapid intravenous injection of oxytocin should not be given because this can cause significant hypotension (27). Blood loss at delivery should be monitored carefully, especially in women with pulmonary hypertension or cyanotic heart disease in whom systemic arterial hypotension increases the extent of right-to-left shunt. Because of the possibility of hemorrhage, blood should be available for transfusion. Intravenous volume replacement should be given promptly according to changes in pulmonary wedge pressures. The Puerperium Postpartum patients are particularly prone to thromboembolism; the risk for this complication can be minimized by early, assisted walking and by the use of elastic support stockings. The latter also help maintain venous return in patients with pulmonary hypertension or tetralogy of Fallot. Patients with pulmonary hypertension are at particular risk during the postpartum period, and sudden death can occur a week or more after delivery (15). The exact cause of this high mortality is not known, but it may be related to microthrombi in pulmonary vessels. As a result, some have advocated prophylactic anticoagulation for these women during pregnancy and the postpartum period (15), but this management is controversial. Disease*

Typical Cardiac Lesion Septal defects, patent ductus, pulmonic stenosis Conotruncal malformations (the tetralogy of Fallot, transposition of the great vessels) Coarctation of the aorta ventricular septal defect, ventricular septal defect heart Pulmonary or aortic stenosis, coarctation, patent ductus The Ebstein anomaly Atrial and ventricular septal defects

* Adapted from Jones (29) and Shepard (30).


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Noncardiac Malformations. Mental deficiency, deafness, cataracts, corneal opacity, chorioretinitis Hydrocephalus, microcephaly, microtia, craniofacial anomalies Mengomyelocele, craniofacial anomalies Mild mental deficiency, craniofacial and limb anomalies Mental deficiency, microcephaly, various craniofacial and skeletal anomalies

Table 5. Some Genetic Disorders Associated Disorder The Holt-Oram syndrome The Kartagener syndrome The multiple lentigines syndrome

with Congenital Heart


Disease* Noncardiac Malformations

Typical Cardiac Lesion

Autosomal Autosomal recessive

Atrial septal defect Septation defects

Upper-limb defects of varying severity Situs inversus, bronchiectasis

Autosomal dominant

Pulmonic stenosis

Multiple lentigines, minor craniofacial anomalies, deafness

Autosomal recessive

Not stated

Autosomal dominant

Ventricular septal defect, rightsided aortic arch, the tetralogy of Fallot, aberrant left subclavian artery

Absent radius, thumbs present, thrombocytopenia worse in infancy Mild mental impairment, small stature, cleft palate, hearing loss, minor craniofacial anomalies

The thrombocytopeniaabsent radius syndrome The Shprintzen syndrome

* Adapted from Jones (29).

Breast feeding should be discouraged in patients with significant cardiac disability to reduce cardiovascular demand and to minimize the risk for mastitis. Due to the possibility of hypotension (28), bromocriptine should not be used to suppress lactation in patients in whom this complication would cause hemodynamic instability or increase the right-to-left shunt. In these women, breast engorgement can be managed with ice packs, breast binding, and analgesics. Appropriate methods of birth control for women with congenital heart disease depend on the type of lesion and associated risk factors. Because oral contraceptives predispose to thromboembolism, they should not be used by women with pulmonary hypertension or by women with coarctation of the aorta complicated by vascular accidents. Cyanosis, left ventricular outflow obstruction, arrhythmias, and myocardial decompensation are other contraindications to birth control pills. Oral contraceptives can be taken, however, by patients with uncomplicated atrial septal defects, ventricular septal defects, and patent ductus arteriosus. Because intrauterine devices increase the risk for pelvic infection and bacteremia, their use is discouraged in women with congenital heart lesions predisposing to bacterial endocarditis. Barrier methods of contraception are less effective than the pill or intrauterine device. The combination of a spermicidal agent and the conscientious use of either a condom or diaphragm, however, can provide an effective and safe form of contraception. Genetic Implications of Congenital Heart Disease Dr. Marie H. Beall (Department of Obstetrics and Gynecology, U C L A School of Medicine): The fetal risks related to maternal heart disease can be divided into risk for recurrence of the cardiac defect in the fetus, risk for various maternal drugs and exposures necessary for care of the cardiac defect, and fetal risk for the altered maternal physiology in congenital heart disease. Genetics of Congenital Heart Disease Most patients with congenital heart disease have no recognizable genetic syndrome and the recurrence risk

is determined empirically. In the case of a patient who has not been examined previously by a geneticist, the cardiologist should consider referring the patient for a formal evaluation. The counselor should examine the pedigree of the family and as much pregnancy history as possible. The pedigree may show a familial pattern of inheritance that would then guide counseling. The pregnancy history may show an exposure related to congenital heart disease (29, 30) (Table 4 ) . These patients with congenital heart disease would be expected to have the same recurrence risk as the general population. Other patients may have noncardiac anomalies suggestive or diagnostic of specific syndromes known to be inherited in a specific manner (29) (Table 5). Diagnosis of such a syndrome may be crucial in guiding prenatal diagnostic efforts as well as in predicting recurrence risk. Patients without a specific recognizable syndrome probably represent a heterogeneous group. Because we lack the ability to distinguish between high- and lowrisk patients, empiric risk figures associated with the mother's anatomic lesion are used to predict the risk for congenital heart disease in the fetus ( 3 1 , 32) (Table 6 ) . Many physicians have found that the risk for congenital heart disease in the fetus is higher with an affected mother than in the case of other first-degree relatives. The reason for this disparity is unknown, although several possible explanations (31, 32) have been reported. It has been argued that the study by Table 6. Recurrence Heart Diseases*

Risk fc>r Various

Maternal Cardiac Lesion

Materna /


Total Number Risk of of Mothers Recurrence Affected in Fetus

Aortic stenosis Ventricular septal defect Pulmonic stenosis Atrial septal defect Coarctation Patent ductus arteriosus The tetralogy of Fallot



95 36 347 248 783 146 828 196

17.9 13 9 9.5 6.5 4.6 4.1 4.1 2.6

* Adapted from Nora and Nora (31,32).

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Figure 2. "Four-Chamber View" of the fetal heart. Spine to right, transverse image. RA = right atrium; LA = left atrium; PVn = pulmonary vein; RV = right ventricle; LV = left ventricle; FO = foramen ovale. From Reed and colleagues (34); reproduced with permission from Alan R. Liss, Inc.

Wittemore and colleagues (12), which reported only the offspring of affected mothers, ascertained many malformations (such as ventricular septal defects that closed spontaneously) that were missed in other series. These differences in ascertainment did affect the total numbers, but even when the authors removed such cases from the data set (33), there was still a substantial difference between mother and father in terms of risk to the infant for congenital heart disease. Nora and Nora (32) have argued that all of these findings lead to the conclusion that some cases of congenital heart disease are inherited by cytoplasmic inheritance. They point out that there are several other disorders known to be mediated by defects in mitochondrial genes. Although provocative, this suggestion remains unproved; it would be strengthened by finding cases in which a defect was inherited in a pseudodominant manner only through women. A final suggestion is that the trait in question is really a susceptibility to a teratogen or teratogens that act on the heart. This susceptibility might be enhanced if both mother and fetus shared the trait. It seems likely that more than one of these possible mechanisms is responsible for recurrent congenital heart disease in the general population. In addition, several cases certainly represent true "sporadic" events, with no increase in recurrence risk over the background.

tricles, valvular atresia, septal defects (34) (Figures 4, 5) and anomalies of the great vessels, such as the tetralogy of Fallot, and transposition of the great vessels. Fetal M-mode echocardiography is useful in establishing the type of fetal arrhythmias and measuring the sizes of ventricles, valves, and vessels. Ventricular measurements are important to distinguish, for example, left ventricular hypoplasia from the right ventricular dilatation associated with fetal heart failure. Doppler echocardiography has been useful in some cases to show the changing blood flow patterns in complex heart lesions, and color flow Doppler is being evaluated for a possible role in identifying complex fetal congenital heart disease. Any patient having a thorough fetal cardiac evaluation should have the fetus examined for other anomalies as well. This is especially indicated when congenital heart disease of the fetus is identified, as the mere presence of this disease in the fetus does not guarantee that the remainder of the phenotype will be like that of the mother. In addition, consideration should be given to genetic amniocentesis. In one study (35), 34% of fetuses with congenital heart disease were found to be aneuploid. Although a family history of congenital heart disease was not the only reason for referral in these patients, such patients were a major part of the group. Use of Medications in Pregnancy Congenital heart disease in the mother may necessitate the use of various drugs. The prescribing physician may be asked about the effect of these drugs on the fetus in pregnancy and lactation. Relatively little information exists concerning the teratogenic risk of cardiac drugs; therefore recommendations must be made on the basis of uncontrolled studies, case reports, and animal data. With the few exceptions outlined below, most authorities do not recommend changing or dis-

Prenatal Diagnosis of Congenital Heart Disease Many anatomic defects can be diagnosed in the fetus with the use of various ultrasonographic techniques (34). The ultrasonographer is aided by the fluid environment of the fetus and by the fact that the fetal bones are more penetrable to soundwaves than are adult bones (34) (Figures 2, 3). Three sonographic techniques are used. Direct imaging with two-dimensional sonography visualizes major structural aberrations, including hypoplastic ven-


Figure 3. Fetal aortic arch. Head to right, longitudinal image. LA = left atrium; RA = right atrium; R P A = right pulmonary artery; AO arch = aortic arch. From Reed and colleagues (34); reproduced with permission from Alan R. Liss, Inc.

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Figure 4. Fetal ventricular septal defect. Spine posterior, transverse image. RV = right ventricle; RA = right atrium; LV = left ventricle; LA = left atrium; VSD = ventricular septal defect. From Reed and colleagues (34); reproduced with permission from Alan R. Liss, Inc.

continuing necessary drugs during pregnancy (30, 36). Even fewer data are available regarding breast feeding. Reported studies typically involve drug excretion in the milk after a single dose and not under steadystate conditions. From theoretic considerations, it has been predicted that about 2 % of the maternal drug dose is transferred to the fetal gastrointestinal tract (37). In most cases, breast feeding can be safely managed by keeping the mother under observation and checking the drug levels in the infant (38). Anticoagulants are sometimes indicated in patients with congenital heart disease. The difficulty of managing anticoagulants in pregnancy is an argument for using bioprosthetic heart valves in young women. Of the various anticoagulants commonly used, only heparin (which does not cross the placenta) has not been associated with an unacceptable level of fetal risk. Warfarin, in particular, has been associated both with a specific syndrome, warfarin embryopathy (29), when given during the first trimester, and with a continued risk for fetal wastage, neurologic damage, and bleeding events when used later in gestation. Some disagreement exists as to whether to begin heparin before conception. In a patient who can easily become pregnant, doing so seems the best course. Long-term heparin use is, however, associated with osteopenia, and there is no compelling evidence that early embryonic exposure to warfarin is teratogenic. A patient being treated for infertility might therefore be permitted to conceive on warfarin and then be switched immediately to heparin. All patients on anticoagulants should, of course, be instructed to report any missed menses immediately. Aspirin use is discouraged in pregnancy as it may be associated with teratogenicity and fetal intracranial hemorrhage in labor and because it may prolong pregnancy and labor (36). Other anticoagulants have not

been fully studied. Heparin is not excreted into breast milk, and warfarin treatment of nursing mothers has not been shown to affect clotting times in their infants (36). Aspirin should probably be avoided during breast feeding (38). Diuretics are generally discouraged in pregnancy because they may interfere with the physiologic volume expansion of pregnancy (39). In addition, thiazides have been associated with maternal and fetal thrombocytopenia (36). Diuretics given during lactation may interfere with milk production. Methyldopa has been used extensively in pregnancy without any significant fetal effect. Hydralazine has also been used in many cases without a reported teratogenic effect. Propranolol has been reported to be associated with intrauterine growth retardation, neonatal hypoglycemia, and a blockage of the usual fetal heart rate response to movement (40). Although some of these effects may be related to the condition for which the drug was prescribed, it should be used with caution. All of these drugs are compatible with breast feeding as long as the newborn is checked carefully. Among drugs used to control rhythm disorders, digoxin, lidocaine, and quinidine have been used in pregnancy without affecting the fetus (30, 36). Although verapamil, used in a limited number of pregnancies, crosses the placenta (41), no teratogenic effects have been reported. Digoxin (42), procainamide (43), quinidine (44), and verapamil (41) have been used to control fetal heart rate in cases of fetal tachyarrhythmias with some success and without fetal harm. Few data are available concerning the effect of maternal use of these drugs on the breast-feeding infant. In general, indicated drugs should not be withheld in pregnancy. If a choice of drugs is available, older, better-studied drugs may be preferable, unless they are found to be unsafe. Maternal ill health is usually more dangerous to the fetus than most of these medications. In the care of a patient with cardiac disease, other exposures are occasionally an issue. Influenza vaccine may be used in pregnancy, because it is an inactivated

Figure 5. Fetal atrial septal defect. Spine posterior, transverse image. ASD = atrial septal defect. From Reed and colleagues (34); reproduced with permission from Alan R. Liss, Inc.

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virus, in circumstances that would mandate its use in a nonpregnant person. Necessary roentgenograms may be done although radiation use should be delayed, if possible, until after the first trimester and a lead abdominal shield should be used when appropriate. Exposure of the fetus from a chest film is 0.3 to 4.3 mrad (45), and total fetal exposures of less than 1 rad are probably not significant (30). Radiopaque dyes used in imaging procedures are not of concern in pregnancy. Ultrasonography is thought to be safe at all stages of pregnancy. Radioisotope studies should be discouraged in pregnancy because the isotope may concentrate in the fetus and the fetal effect is unknown. Acknowledgments: The authors thank Annette V. Terzian, UCLA School of Medicine, for editorial assistance. Requests for Reprints: Roy M. Pitkin, MD, Department of Obstetrics and Gynecology, UCLA School of Medicine, Los Angeles, CA 900241740. Current Author Addresses: Drs. Pitkin, Koos, and Beall: Department of Obstetrics and Gynecology, UCLA School of Medicine, Los Angeles, CA 90024-1740. Dr. Perloff: Departments of Medicine and Pediatrics, UCLA School of Medicine, Los Angeles, CA 90024-1679.

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17. Tanaka T, Miyakoshi Y. Pregnancy and delivery following cardiac operations. Jpn Circ J. 1986;50:918-22. 18. Perloff JK, Rosove MH, Child JS, Wright GB. Adults with cyanotic congenital heart disease: hematologic management. Ann Intern Med. 1988;109:406-13. 19. Khazin AF, Hon EH, Hehre FW. Effects of maternal hyperoxia on the fetus. I. Oxygen tension. Am J Obstet Gynecol. 1971;109:628-37. 20. Willcourt RJ, King JC, Queenan JT. Maternal oxygen administration and the fetal transcutaneous P 0 2 . Am J Obstet Gynecol. 1983;146:714-5. 21. Katz M, Pinko A, Lurio S, Pak I. Outcome of pregnancy in 110 patients with organic heart disease. J Reprod Med. 1986;31:343-7. 22. Clark SL. Structural cardiac disease in pregnancy. In: Clark SL, Phelan JP, Cotton DB, eds. Critical Care in Obstetrics. Oradell, New Jersey: Medical Economics Books; 1987:92-113. 23. Sugrue D, Blake S, Troy P, MacDonald D. Antibiotic prophylaxis against infective endocarditis after normal delivery-is it necessary? Br Heart J. 1980;44:499-502. 24. Gall SA. Prevention of infection: immunization and antimicrobial prophylaxis. In: Gleicher N, ed. Principles of Medical Therapy in Pregnancy. New York: Plenum Medical Book Company; 1985:42332. 25. Shulman ST, Amren DP, Bosno AL, et al. Prevention of Bacterial Endocarditis. A statement for health professionals by the Committee on Rheumatic Fever and Infective Endocarditis of the Council on Cardiovascular Disease in the Young. Circulation. 1984;70:1123A7A. 26. Roberts SL, Chestnut DH. Anesthesia for the obstetric patient with cardiac disease. Clin Obstet Gynecol. 1987;30:601-10. 27. Hendricks CH, Brenner WE. Cardiovascular effects of oxytocic drugs used post partum. Am J Obstet Gynecol. 1970;108:751-60. 28. Johns DW, Ayers CR, Carey RM. The dopamine agonist bromocriptine induces hypotension by venous and arteriolar dilation. / Cardiovasc Pharmacol. 1984;6:582-7. 29. Jones KL. Smith's Recognizable Patterns of Human Malformation. 4th ed. Philadelphia: W.B. Saunders Company; 1988:224-5, 272, 276, 470-1, 491-9, 502-5, 508-11, 545. 30. Shepard TH. Catalog of Teratogenic Agents. 5th ed. Baltimore: Johns Hopkins University Press; 1986:342, 344-5, 489-95. 31. Nora JJ, Nora AH. Update on counseling the family with a first-degree relative with a congenital heart defect. Am J Med Genet. 1988;29:137-42. 32. Nora J J, Nora AH. Maternal transmission of congenital heart diseases: new recurrence risk figures and the questions of cytoplasmic inheritance and vulnerability to teratogens. Am J Cardiol. 1987;59:459-63. 33. Wittemore R, Wells J A, Castellsague-Pique X, Holabird NA. Congenital heart defects in the progeny of affected mothers versus fathers [Abstract]. Circulation. 1988;78:II396. 34. Reed KL, Anderson CF, Shenker L. Fetal Echocardiography: An Atlas. New York: Alan R. Liss; 1988:47-101, 103, 109. 35. Copel J A, Cullen M, Green J J, Mahoney MJ, Hobbins JC, Kleinman CS. The frequency of aneuploidy in prenatally diagnosed congenital heart disease: an indication for fetal karyotyping. Am J Obstet Gynecol. 1988;158:409-13. 36. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 2d ed. Baltimore: Williams & Wilkins; 1986:26-31, 80-3, 106-9, 142-4, 457. 37. Rivera-Calimlim L. The significance of drugs in breast milk. Pharmacokinetic considerations. Clin Perinatol. 1987;14:51-70. 38. The transfer of drugs and other chemicals into human breast milk. Committee on Drugs, American Academy of Pediatrics. Pediatrics. 1983;72:375-83. 39. Sibai BM, Grossman RA, Grossman HG. Effects of diuretics on plasma volume in pregnancies with long-term hypertension. Am J Obstet Gynecol. 1984;150:831-5. 40. Rubin PC. Current concepts: beta-blockers in pregnancy. N Engl J Med. 1981;305:1323-6. 41. Wolff F, Breuker KH, Schlensker KH, Bolte A. Prenatal diagnosis and therapy of fetal heart rate anomalies: with a contribution on the placental transfer of verapamil. J Perinat Med. 1980;8:203-8. 42. Golichowski AM, Caldwell R, Hartsough A, Peleg D. Pharmacologic cardioversion of intrauterine supraventricular tachycardia. A case report. J Reprod Med. 1985;30:139-44. 43. Dumesic DA, Silverman NH, Tobias S, Golbus MS. Transplacental cardioversion of fetal supraventricular tachycardia with procainamide. N Engl J Med. 1982;307:1128-31. 44. Guntheroth WG, Cyr DR, Mack LA, Benedetti T, Lenke RR, Petty CN. Hydrops from reciprocating atrioventricular tachycardia in a 27-week fetus requiring quinidine for conversion. Obstet Gynecol. 1985;66:29S-33S. 45. Lione A. Ionizing radiation and human reproduction. Reproductive Toxicology. 1987; 1:3-16.

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Pregnancy and congenital heart disease.

Congenital heart disease as a complicating factor in pregnancy has assumed increasing clinical importance because improved techniques of surgical repa...
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