Mary M. Canobbio
•Advances in medical and surgical arenas have created a larger pool of women of childbearing age with heart disease
•Congenital heart disease is the most frequently encountered type of cardiac disorder in pregnancy and must be managed by a multidisciplinary team with appropriate expertise in adult congenital heart disease
•The modified WHO risk classification is the more widely used and is the simplest risk scoring scale
•Pregnancy is not recommended for women in modified WHO risk category IV
•Contraceptive counseling should be an integral part of the clinical management of females with cardiac history who are of childbearing age
The number of reproductive age women who are born with or develop heart disease is steadily growing, and with each decade the numbers continue to increase. While the exact numbers are unknown, advances in both medical and surgical arenas have created a larger pool of women of childbearing age with heart disease. Consequently, questions regarding pregnancy become an important issue for all providers who care for patients with heart disease, including congenital heart disease (CHD), acquired cardiac disorders, and those following cardiac transplant. In order to ensure their safety, it is imperative these patients undergo preconception counseling regardless of their desire to become pregnant; that they understand the actual or potential risk to them and to their fetus and the importance of avoiding an unplanned pregnancy. For cardiac and obstetrical providers, a number of risk scoring scales have been developed to help guide management. The importance of using risk assessment models to advise patients on the risk of pregnancy is reviewed.
Scope of the Problem
In the developed world, while prevalence rates are low, cardiovascular disease is the most common cause of maternal mortality [1–5]. CHD, which affects 0.8%–1.5% of the population, is the most frequently encountered cardiac disorder in obstetrics . While the majority of women with simple CHD will tolerate pregnancy well, those with moderate to complex lesions that have been surgically repaired in childhood may present with residual effects of their surgical procedure as they grow older. It is therefore difficult to categorize these patients based solely on their primary defect, because many may be at risk for developing complications such as ventricular dysfunction, arrhythmias, or thromboembolic events. For women with complex CHD who have undergone surgical repair, such as univentricular circulation (Fontan palliation) or transposition of great arteries (Mustard, Senning), or those with cyanotic heart disease, the risk of developing complications during and after delivery is higher [7–13]. For women who remain cyanotic (O2 saturation ≤85%), with or without pulmonary hypertension, or those with critical left ventricular outflow tract obstruction (gradients >60 mmHg) or severe ventricular function pregnancy is not advisable .
While CHD is more prevalent, those with acquired heart disease carry a higher risk of mortality during childbirth [7,14]. These include women with ischemic heart disease, aortopathies, various cardiomyopathies, hypertensive disorders, and valvular heart disease, particularly requiring anticoagulation. In addition, over the past 2–3 decades, the number of children undergoing heart transplant has risen and consequently the number of these young women now and in future will be seeking to become pregnant. Today, transplanted female patients represent approximately 20% of overall cardiac transplants population, 25% of which are reported to be between the ages of 18–39 years [15,16]. While successful pregnancies have been reported, the majority experience complications such as hypertensive disorders of pregnancy, prematurity, graft rejection, and/or infection [17,18].
The task of advising females regarding the safety of pregnancy has been challenging until recently. After almost three decades, the body of literature in this field has moved from expert opinion and case reporting to cumulative data reported from multicenter studies and international registries [8,19]. As result, we now have growing evidence-based data that permits us to advise patients regarding the safety of carrying a pregnancy. Less clear is the potential risk pregnancy poses to long-term survival of patients with complex cardiac lesions. Reports regarding long-term outcomes in patients with CHD indicate that for the majority of patients, the effects of pregnancy resolve within the first year after delivery, while for others it may be longer, but may not have a lasting effect on long-term survival [7,9].
Estimating Maternal and Fetal Risk
While the information regarding pregnancy outcomes across the spectrum of various cardiac disorder is growing, it remains a challenge to assign risk solely on the basis of their cardiac lesion. Therefore, in order to determine maternal risk, the patients must be evaluated against a number of parameters (Table 4.1) that include not only maternal primary disorder, but also any residual effects associated with the primary defect, such as diminished ventricular function, history of arrhythmias, and any prior surgical or procedural interventions . A thorough review of the past medical history should also include the presence of any noncardiac comorbidities that may influence pregnancy, such as thyroid disease, diabetes, and history of use of recreational drugs, alcohol, and cannabis products, particularly those with tetrahydrocannabinol (THC), which passes through the placenta . The history must also take into account a number of social factors such as history of medical compliance, geographical distance to doctor’s office and hospital as well the patient’s spousal and extended family support. The latter is of particular concern for the patient considered high risk in the event that post-delivery clinical problems arise making it difficult for the patient to care for her infant.
Maternal Factors to Assess in Estimating Pregnancy Risk
•Primary cardiac defect (acyanotic vs. cyanotic)
•Genetic disorder (22q deletion, Turner syndrome, Marfan syndrome)
•Integrity of prosthetic valves
•Patency of baffles/conduits
•Medications (e.g., ACE inhibitors, anticoagulants)
•Comorbidities (e.g., diabetes, thyroid dysfunction)
•Presence of devices (pacemaker, internal defibrillator)
•Residual and/or sequelae associated with the lesion/surgery
•Access to medical center with experience in managing cardiac patients
•History of compliance
Source: Adapted from Canobbio MM. Prog Pediatr Cardiol. 2004;19:1–3.
CARPREG II Predictors of Adverse Events in Pregnant Women with Heart Disease
Source: From Silversides CK et al. J Am Coll Cardiol. 2018;71:2419–30. With permission.
Maternal Risk Assessment
Maternal risk assessment is based on several factors as outlined above. Several predictors have been described and more recently various risk assessment models have been validated for use in pregnancy.
1.Functional capacity: Maternal functional capacity using the New York Heart Association (NYHA) classification has traditionally been used as a predictor of maternal and fetal prognosis. Thus women who enter the pregnancy in NYHA class I and II were reported to have a maternal mortality rate of less than 1% (0.4%) while class III–IV patients could have a rate that ranged from 5%–15%. A major limitation of this system, however, is that assessments are based upon subjective assessment rather than clinical data.
2.Risk scoring scales: Over the last two decades, a number of pregnancy risk scoring scales have been developed to better predict the likelihood of developing cardiac complications during pregnancy.
a.CARPREG: The first risk scoring system for women with various forms of heart disease was the Cardiac Disease in Pregnancy risk index (CARPREG), a population-based study that assesses the risk of an adverse maternal event on the basis of four specific indicators (Table 4.2) . Each indicator is awarded one point each for poor functional status (NYHA >II), cyanosis (<90%), left ventricular (LV) systolic dysfunction, left heart obstruction, and history of cardiac events prior to pregnancy including arrhythmias, stroke, or pulmonary edema . Thus a risk index score of 0 is estimated at a 5% risk, but a risk index of 1 rises to 27%, and at a risk index of >1, the likelihood of adverse event is 75%. For the past two decades this has been the most widely used index despite reported limitations, including that it was event-directed versus lesion-specific, thus excluding patients born with congenital heart disease, with pulmonary hypertension, and prosthetic valves .
Pregnancy Risk Stratification Methods
Risk Stratification Index
WHO classification: Index score in 4 areas for women with heart disease includes acquired and congenital
I.No detectable increase of maternal mortality and no/mild increase in morbidity
II.Small increase of maternal mortality or moderate increase in morbidity
III.Significant increased risk of maternal mortality or morbidity
WHO categories range from very low risk (Class I) to highest risk (Class IV)
CARPREG I: Index score for women with heart disease
Pre-pregnancy history of cardiac events (heart failure, stroke) or arrhythmias: 1 point
Baseline NYHA functional class >II or cyanosis: 1 point
Left heart obstruction: 1 point
Mitral valve area: <2 cm2
Aortic valve area: <1.52
Reduced systemic ventricular function (ejection fraction <40%): 1 point
CARPREG I risk score for each CARPREG predictor:
0 point: 5%
1 point: 27%
>1 point: 75%
ZAHARA: Index score for congenital heart disease
Prior arrhythmias: 1.5
NYHA class >II: 0.75
Left heart obstruction: 2.5
(Peak aortic gradient >50 mmHG, aortic valve area <1.0 cm2)
Cardiac medications before pregnancy: 1.5
Moderate/severe systemic AV valve regurgitation: 0.75
Moderate/severe subpulmonary regurgitation: 0.75
Mechanical valve prosthesis: 4.5
Cyanotic heart disease: 1.0
ZAHARA: Highest number of the 8 risk factors/or total number of points: 13
Each factor is individually weighted from 0.75 to 4.5 points. A score of >3.51 points carries the highest risk category of 70% risk of developing a cardiac event
b.ZAHARA: The ZAHARA (Zwangerschap bij vrouwen met een Aangeboredn HARtAfwijking-II) classification, a second retrospective study, was designed for patients with CHD, but also included patients with mechanical prosthetic valves. In addition, it identified additional predictors, such as use of cardiac medications before pregnancy, and unrepaired cyanotic heart disease, to develop a pregnancy risk score  (Table 4.2).
While both CARPREG I and ZAHARA, have been recognized as important risk assessment systems, they each are limited to their study population, and the retrospective and small sample size nature of the study, but have identified significant predictors for maternal and fetal risk that can impact pregnancy outcomes. These include prior cardiac events, left heart obstruction (mitral valve area <2 cm2, aortic valve area <1.5 cm2, peak left ventricular outflow tract gradient >30 mmHg), and reduced systemic ventricular systolic function and baseline NYHA functional class >II [14,23].
c.Modified World Health Organization (WHO) risk classification: The modified WHO risk classification is the more widely used and simplest risk scoring scale being used. A large validated prospective study, it integrates all known maternal cardiovascular risk predictors plus varying forms of heart disease, and takes into account medical history that includes comorbidities as well as functional class . Recommended by the European Society of Cardiology (ESC) as the most reliable method of risk assessment to determine pregnancy risk of women with heart disease, it is made up of four categories, the WHO class I, which indicates low risk, WHO class II, intermediate risk, WHO class III, high risk, and WHO class IV, indicates pregnancy is contraindicated because of extreme high risk (Table 4.3) [6,7,21,24,26].
Modified WHO Classification of Maternal Cardiovascular Risk
Pregnancy Risk Category
Maternal Risk Factors
No detectable increase in maternal mortality and no/mild increase in morbidity risk
Maternal cardiac event rate 5.7%–10.5%
Uncomplicated small/mild pulmonary stenosis, PDA, mitral valve prolapse
Successfully repaired simple lesions (ASD, VSD, PDA, anomalous pulmonary venous drainage)
Atrial or ventricular ectopic beats, isolated
Small increase in maternal mortality and moderate increase in morbidity risk
Maternal cardiac event rate 2.5%–5%
(If otherwise well and uncomplicated)
Unoperated ASD, VSD
Moderate increase in maternal mortality morbidity risk
Maternal cardiac event rate 10%–19%
Mild LV impairment
Native or tissue valvular disease (not considered risk category I or IV)
Marfan syndrome without aortic dilation
Aortic dilation <45 mm in bicuspid aortic valve aortopathy
Significantly increased maternal mortality or severe morbidity risk
Expert counseling required
In the event of pregnancy, intensive specialist cardiac and obstetric monitoring needed throughout pregnancy, childbirth and the puerperium
Maternal cardiac event rate 9%–27%
Cyanotic heart disease (unrepaired)
Other complex CHD
Aortic dilation 40–45 mm in Marfan syndrome
Aortic dilation 45–50 mm in bicuspid aortic valve aortopathy
Extremely high maternal mortality or severe morbidity risk
Pregnancy is contraindicated
In the event of pregnancy, termination should be discussed
If pregnancy continues, care should follow class III recommendations
Maternal cardiac event rate 40–100%
Pulmonary arterial hypertension (of any cause)
Severe systemic ventricular dysfunction (LV ejection fraction <30%, NYHA class III–IV)
Previous peripartum cardiomyopathy with any residual impairment of LV function
Severe mitral stenosis, severe symptomatic aortic stenosis
Aortic dilation >45 mm in Marfan syndrome
Aortic dilation >50 mm in bicuspid aortic valve aortopathy
Native severe coarctation
Source: Modified from Regitz-Zagrosek V et al. Eur Heart J Eur Heart J. 2018;39:3165–241; Canobbio MM et al. Circulation. 2017;135:e50–8; Thorne S et al. Heart. 2006;92:1520–5; Jastrow N et al. Int J Cardiol. 2011;151(2):209–13.
Abbreviations: AS, aortic stenosis; ASD, atrial septal defect; LV, left ventricle; NYHA, New York Heart Association; PDA, patient ductus arteriosus; RV, right ventricle; TOF, tetralogy of Fallot; VSD, ventricular septal defects; WHO, World Health Organizations.