Pregnancy and contraception in young women with congenital heart disease: General considerations

Abstract

Young women with heart disease are increasingly being seen in obstetrical referral centres owing, in large part, to the dramatic improvements in survival of young adults with congenital heart disease in recent years. Although pregnancies in most women with heart disease result in favourable outcomes, there are important exceptions that must be recognized. These exceptions pose significant mortality risk to the mother and/or the fetus. The present article outlines cardiovascular adaptations to pregnancy, general outcomes and management considerations for practitioners caring for pregnant young women with congenital heart disease. A lesion-specific review is published in a complementary article.

With some important exceptions, women with congenital heart disease (CHD) can be expected to do well during pregnancy, with little need for medical intervention. Nevertheless, for young women with CHD who are contemplating pregnancy, a preconceptual cardiac evaluation is of great value. At this visit, baseline testing can be arranged, pregnancy-related risk stratification can be established and interventions can be planned before pregnancy when necessary. Medications should be reviewed and, depending on teratogenic potential, discontinued, altered or, if safe, confirmed. A discussion regarding the impact of pregnancy on long-term outcomes of specific forms of CHD should ideally take place before pregnancy; cardiac-related morbidity will have an impact on a woman’s ability to care for her child and, in select cases, an abbreviated life expectancy of the mother should be carefully considered before conception.

In some instances – as will be outlined in the present review (also described in detail in a companion review [1] to be published in the May 2011 issue of Paediatrics & Child Health) – pregnancy imposes a significant risk to the mother with CHD and/or her developing fetus; effective and consistent contraception should be used in these situations (Table 1). In women deemed to be ‘high risk’, termination of pregnancy may itself carry considerable risk to the mother; pregnancy in these situations is best avoided altogether. Age- and circumstance-appropriate counselling regarding contraception and family planning should occur during routine follow-up of all females of child-bearing age, beginning during paediatric care.

TABLE 1.

Risk of maternal morbidity or mortality related to pregnancy in women with congenital heart disease^*

Class 1: No risk	Class 2: Small risk	Class 2 or 3: Risk varies depending on the individual	Class 3: Significant risk	Class 4: Extremely high risk; pregnancy contraindicated
Uncomplicated, small or mild pulmonary stenosis, VSD and PDA Successfully repaired simple lesions, ASD, VSD, PDA, repaired anomalous pulmonary venous drainage Isolated premature atrial or ventricular extrasystoles	Unoperated ASD Repaired tetralogy of Fallot Most arrhythmias	Mild LV impairment Native or tissue valvular heart disease not considered class 4 Marfan syndrome without aortopathy	Mechanical valve Systemic RV (complete TGA postatrial switch, congenitally corrected TGA) Post-Fontan procedure Cyanotic heart disease or other complex lesions	Pulmonary arterial hypertension of any cause Severe systemic ventricular dysfunction (LVEF <30% or NYHA functional class III or IV) Severe left heart obstruction Marfan syndrome with aortic dilation >40 mm Peripartum cardiomyopathy with any residual LV impairment

^*Adapted from reference 29. ASD Atrial septal defect; LV Left ventricle; LVEF LV ejection fraction; NYHA New York Heart Association; PDA Patent ductus arteriosus; RV Right ventricle; TGA Transposition of the great arteries; VSD Ventricular septal defect

PHYSIOLOGY OF THE PARTURIENT

The necessary physiological adaptations to the pregnant state are well established. The peak effect of these changes is generally seen late in the second trimester or early in the third trimester. Specifically, a decrease in total peripheral vascular resistance to 40% to 70% of prepregnancy levels, augmentation in blood volume by 30% to 50% compared with baseline, an increase in mean heart rate by 10 beats/min to 20 beats/min and, ultimately, a 30% to 50% increase in cardiac output can be expected to occur (2–4). Physiological anemia results from an increase in plasma volume that exceeds the increase in red blood cell mass (5,6). The physiological impact of pregnancy on young women with CHD is achieved mainly through decreased afterload mediated by a decline in peripheral vascular resistance and increased preload resulting from factors such as increased blood volume (7).

A specific management plan can be designed for the individual patient when knowledge of the physiological changes relating to normal pregnancy is coupled with an understanding of the pathophysiology of the underlying CHD. The present article provides a general framework for the practitioner caring for women with CHD before, during and/or after pregnancy. Lesion-specific considerations are discussed in the companion review (1).

GLOBAL RISK ASSESSMENT

Maternal risk

Comprehensive evaluation of a woman with CHD who is contemplating pregnancy includes a thorough history, and a detailed physical examination including upper and lower extremity blood pressures, measurement of oxygen saturation at rest (and with exertion when appropriate) and assessment of dysmorphology. Evaluation should also include a 12-lead electrocardiogram and a detailed transthoracic echocardiogram.

A maternal risk score, based on data from a prospective multicentre study (8), may be applied to determine the likelihood of developing an adverse cardiac event during pregnancy. Independent predictors of pregnancy-related cardiac complications have been identified and include poor functional class (New York Heart Association functional class of greater than II) or cyanosis, systemic ventricular systolic dysfunction, left heart obstruction and a previous adverse cardiac event (Table 2). The overall risk of developing a cardiac-related complication during pregnancy is low (5%) if no predictors are present, intermediate (27%) if one predictor is present, and high (75%) if more than one predictor is present. Global risk stratification, as described above, should be used in conjunction with lesion-specific estimates (1) and the highest risk estimate should be used to guide management (9).

TABLE 2.

Risk factors for maternal cardiac adverse events during pregnancy^*

Adverse maternal cardiac events	Risk factors
Pulmonary edema	General†
Arrhythmia Stroke	Poor functional class (New York Heart Association functional class III or IV) or cyanosis
Death	Systemic ventricular ejection fraction <40%
	Left heart obstruction (mitral valve area <2 cm2, aortic valve area <1.5 cm2, peak left ventricular outflow gradient >30 mmHg)
	Cardiac event (arrhythmia, stroke, pulmonary edema) before pregnancy
	Lesion specific
	As discussed in the text

^*Adapted from references 8 and 9;

^†The general risk factors can be used to create a maternal risk index for adverse cardiac events related to pregnancy: zero risk factors, less than 5% risk; one risk factor, approximately 27% risk; two or more risk factors, 75% risk

In a subsequent single-centre retrospective study, the aforementioned global predictors of risk were again validated, and subpulmonary ventricular dysfunction and severe pulmonary regurgitation were identified as additional predictors of adverse cardiac outcome (10). In a recent, large meta-analysis of the outcome of pregnancies in women with CHD (11), important pregnancy-related complications were seen in 11% of pregnancies; the most frequently encountered cardiac problems were clinically significant heart failure and arrhythmia (predominantly supraventricular) at a prevalence of 4.9% and 4.5%, respectively.

Fetal-neonatal risk

Women with CHD and compromised cardiovascular status are at increased risk for adverse fetal and/or neonatal events, which may be related, at least in part, to insufficient uteroplacental perfusion. In a prospective, controlled study of pregnant women with heart disease, adverse fetal-neonatal events (prematurity, low birth weight, respiratory distress syndrome, intraventricular hemorrhage, and fetal or neonatal death) were associated with identified cardiovascular risk factors – namely poor maternal functional class, cyanosis and left heart obstruction (Table 3). The risk for neonatal complications was found to be further increased in women with heart disease who had established obstetrical risk factors or a multiple-gestation pregnancy, who smoked or who received anticoagulant therapy (12). In a large, recent meta-analysis (11) of pregnancy outcome in women with CHD, the risk of having premature or small-for-gestational-age children was increased. Premature delivery occurred in 16% of pregnancies and was substantially higher in those with cyanotic and/or complex CHD. The overall mortality rate in offspring in that cohort was 4%, and was related to the increased risk of prematurity and the overall recurrence risk of CHD (11).

TABLE 3.

Risk factors for neonatal cardiac adverse events during pregnancy^*

Adverse neonatal cardiac events	Risk factors
Premature birth	Cardiac
Small-for-gestational-age birth weight Respiratory distress syndrome Intraventricular hemorrhage	Poor maternal functional class (New York Heart Association functional class III or IV) or cyanosis   Maternal left heart obstruction (mitral valve area <2 cm2, aortic valve area <1.5 cm2, peak left ventricular outflow gradient >30 mmHg)
Fetal or neonatal death	General   Maternal age <20 years or >35 years   Anticoagulant therapy   Smoking during pregnancy   Multiple-gestation pregnancy Obstetrical   Premature delivery/premature membrane rupture   Incompetent cervix   Caesarean section   Intrauterine growth retardation   Bleeding at >12 weeks’ gestation   Febrile illness   Uterine/placental abnormalities

^*Adapted from references 8, 9 and 12

A genetic or syndromic anomaly with autosomal dominant inheritance in a parent (such as a 22q11 deletion or Holt-Oram syndrome) can confer up to a 50% risk of recurrence in the offspring. In the absence of an identifiable anomaly with Mendelian inheritance, the risk of CHD recurrence in the fetus is approximately 6%, compared with the background population risk of approximately 0.8% (13,14). The type of CHD seen in offspring can differ altogether from the lesion seen in the mother (15). The risk of CHD recurrence in offspring varies depending on the lesion and, in some reports, is as low as 0.6% in association with maternal transposition of the great arteries (11) and as high as 18% in the presence of maternal left ventricular outflow tract obstruction (16).

The performance of transabdominal fetal echocardiography is an accepted clinical practice for women with structural CHD, and is best performed at 18 to 22 weeks’ gestation (17). Fetal echocardiography not only allows for early counselling and decision making for the expectant parents but, in some forms of CHD, the outcome of a fetus with an antenatal diagnosis of CHD is improved relative to an infant with the same cardiac lesion diagnosed postnatally (18,19). Although most major structural and functional cardiac diseases can reliably be excluded with fetal echocardiography (20,21), some forms of CHD cannot be definitively diagnosed (22). In a prospective review (22) of 276 infants at our centre who had undergone both fetal echocardiography and postnatal paediatric cardiac assessment, we found that fetal echocardiography accurately diagnosed all major forms of CHD; shunt lesions and minor valve abnormalities that were missed on fetal echocardiography were reliably diagnosed with careful paediatric cardiac assessment. The limitations of fetal echocardiography may be explained by features inherent in the fetal circulation (ie, presence of an atrial-level shunt and ductus arteriosus), cardiac morphogenesis (ie, normal presence of muscular ventricular septal defects during cardiac development) and the limitations of current ultrasound technology (ie, difficulties with visualization of some lesions such as minor valvular abnormalities, small septal defects or anomalies of venous return).

High-risk lesions that may preclude pregnancy

A select number of maternal cardiac conditions are associated with high maternal morbidity and mortality rates. In such circumstances, pregnancy should be discouraged indefinitely or until corrective surgery can be performed. These conditions include severe pulmonary hypertension; severe left heart obstructive lesions including aortic stenosis (irrespective of symptoms); Marfan syndrome with aortic root enlargement; and systemic ventricular dysfunction (8,10,23–26).

MANAGEMENT OF LABOUR AND DELIVERY

In our centre, the mode of delivery in women with CHD is vaginal unless obstetrical indications for caesarean delivery exist. Cardiac indications for caesarean section include a risk of aortic dissection (ie, Marfan syndrome with dilated aortic root) or significant bleeding risk (ie, warfarin within two weeks of delivery). To optimally coordinate care for the complex cardiac patient in advance of labour and delivery, we have found that a ‘patient care conference’ involving all members of the medical team is invaluable because a detailed management plan can be discussed and documented. Modification of labour is often employed using early epidural to attenuate hemodynamic responses to pain and an assisted second stage to limit or avoid maternal expulsive efforts. In the presence of intracardiac shunts, bubble trap filters should be added to all intravenous lines. Invasive cardiac monitoring is generally determined on a case-by-case basis and, aside from arterial pressure lines, is rarely used. Endocarditis prophylaxis during delivery is currently not mandated (27). The hemodynamic changes related to pregnancy, labour and delivery may not return to baseline for weeks or months after delivery. In some patient populations, such as those with Eisenmenger syndrome, the risk of mortality is highest in the first few weeks after delivery; therefore, extended postpartum observation of these women is prudent.

CONTRACEPTION

Discussions regarding family planning should begin during childhood, before a young woman approaches childbearing age. Contraception should be individually tailored to the patient; any personal preference, and the efficacy and safety of each method should be considered. Factors to be considered that relate directly to a woman’s cardiac condition include the risk of thrombosis with estrogen-containing products, risk of endocarditis, vagal response with insertion of an intrauterine device and maternal risk in the event of contraceptive failure. All barrier methods have a significant failure rate and are, therefore, not an optimal strategy for a population of women in whom pregnancy is best avoided.

Efficacy rates for combined estrogen and progesterone oral contraceptive pills are extremely high, nearing 99.5% if optimally administered (28). Newer modes of delivery for combined hormonal contraception include a vaginal ring, a contraceptive patch and an injectable preparation, all with similarly high efficacy rates (29). However, women with CHD who are at particular risk for thromboembolic events (ie, presence of cyanosis and an obligatory right-to-left intracardiac shunt, pulmonary hypertension, Fontan circulation, sustained arrhythmias, mechanical heart valves and/or significant ventricular dysfunction) should avoid estrogen-containing contraception due to the increased risk of arterial and venous thrombosis (Table 4). It should be noted that anticoagulation with warfarin does not completely protect against the thrombogenic effects of estrogen (30). The risk of estrogen-related thromboembolism is further increased by traditional cardiovascular risk factors such as smoking, hypertension, diabetes and obesity (30).

TABLE 4.

Combined hormonal contraception use in women with congenital heart disease^*

Class 1: Always useable	Class 2: Broadly useable	Class 3: Caution if used	Class 4: Use contraindicated
Minor valve disease (ie, bicuspid aortic valve with normal function or mild pulmonary stenosis)	Tissue prosthetic valve lacking class 3 or 4 features Uncomplicated mild aortic or mitral valve disease	Thrombotic risk (even on warfarin):   Mechanical valve (bileaflet)   Previous thromboembolism   Atrial arrhythmia	Thrombotic risk (even on warfarin):   Mechanical valve (Starr-Edwards†, Bjork-Shiley‡)   Any tricuspid valve
Repaired coarctation of the aorta with no aneurysm and no hypertension	Most arrhythmias other than atrial fibrillation or flutter Uncomplicated Marfan syndrome	Dilated left atrium >4 cm Risk of paradoxical embolism:   Potential reversal of left-to-right shunt (ie, unoperated atrial septal defect)	Pulmonary hypertension of any cause   Left ventricular dysfunction (ejection fraction <30%)
Simple lesions repaired in childhood with no residual sequelae	Congenital heart disease lacking any class 3 or 4 features Small left-to-right shunt not reversible with physiological manoeuvres (ie, small ventricular septal defect) Previous cardiomyopathy with full recovery		Fontan circulation   Previous coronary arteritis (ie, Kawasaki disease) Risk of paradoxical embolism:   Cyanotic heart disease   Pulmonary arteriovenous malformations

^*Modified from reference 29;

^†Edwards Lifesciences, USA (discontinued);

^‡Pfizer Inc, USA

The possible interaction between hormonal contraception and additional medications should be considered. Estrogen and progesterone can individually affect the metabolism of warfarin, necessitating heightened surveillance of anticoagulation efficacy (30). Because of reports of combined oral contraceptive failure with concurrent antibiotic use (even over the short term), an additional method of contraception is recommended in such circumstances (31). Bosentan, an endothelin antagonist used in the treatment of pulmonary hypertension, can decrease the efficacy of some hormonal preparations, and additional contraceptive precautions may be necessary in women with pulmonary hypertension (32).

Progestin-only contraceptive methods, which include oral, injectable and implantable formulations, do not increase the risk of thromboembolism and are, therefore, commonly used when estrogen-containing products are deemed unsafe. The older-generation progestin-only pills, or ‘mini pills’, have considerably lower efficacy compared with combined oral contraceptive pills, and are associated with high uterine breakthrough bleeding rates. A relatively new form of progestin-only pill containing desogestrel (Cerazette, Organon, UK) has significantly lower failure rates than older progestin-only pills and similar efficacy to combined oral contraceptive preparations (30,33). Alternatively, an intramuscular injection of progesterone every three months is highly efficacious and low-dose progestin implants can be inserted in the subcutaneous tissue of the inner surface of the upper arm to provide reliable contraceptive protection for three to five years (29,31).

Intrauterine devices, although highly effective, may carry particular risk for some women with CHD. Bacteremia may occur, particularly at the time of insertion, which may result in bacterial endocarditis. Additionally, during instrumentation of the cervix, a vasovagal reaction can occur in up to 5% of women, and the drop in preload may have deleterious effects on women with a Fontan circulation or pulmonary vascular obstructive disease (30). Generally, intrauterine devices must be replaced every three to five years. A relatively new intrauterine device containing levonorgestrel (Mirena, Bayer Inc, Canada) may be more efficacious than sterilization (30).

Female sterilization is achieved through ligation of the Fallopian tubes or intratubal stent implantation (Essure, Conceptus Inc, USA). As an irreversible procedure, this method of contraception may be the desired approach for situations in which the risk of pregnancy is exceedingly high. Intratubal device insertion can be successfully achieved hysteroscopically without anesthesia (34), making such an approach attractive for women in whom the risk associated with general anesthesia may be high (ie, Eisenmenger syndrome) or if laparoscopy will be poorly tolerated due to the need for abdominal insufflation with carbon dioxide (ie, Fontan circulation) (29,30).