WHO I (no increased risk of maternal mortality, mild increased risk of maternal morbidity)
Uncomplicated, small, or mild
Pulmonary valve stenosis
Patent ductus arteriosus
Mitral valve prolapse
Successfully repaired simple lesions
Atrial septal defect
Ventricular septal defect
Patent ductus arteriosus
Anomalous pulmonary venous drainage
WHO II (small increased risk of maternal mortality, moderate increased risk of maternal morbidity)
Unoperated atrial or ventricular septal defect
Repaired tetralogy of Fallot
WHO II–III (depending on individual)
Mild left ventricular impairment
Native or tissue valvular heart disease not considered WHO I or IV
Marfan syndrome without aortic dilatation
Aorta <45 mm in aortic disease associated with bicuspid aortic valve
Repaired coarctation
WHO III (significantly increased risk of maternal mortality or severe morbidity)
Mechanical valve
Systemic right ventricle
Fontan circulation
Cyanotic heart disease (unrepaired)
Other complex congenital heart disease
Aortic dilatation 40–45 mm in Marfan syndrome
Aortic dilatation 45–50 mm in aortic disease associated with bicuspid aortic valve
WHO IV (extremely high risk of maternal mortality or severe morbidity, pregnancy contraindicated)
Pulmonary arterial hypertension of any cause
Severe systemic ventricular dysfunction (LVEF <30 %, New York Heart Association functional (NYHA) III–IV)
Previous peripartum cardiomyopathy with any residual impairment of left ventricular function
Severe mitral stenosis, severe symptomatic aortic stenosis
Marfan syndrome with aorta dilated >45 mm
Aortic dilatation >50 mm in aortic disease associated with bicuspid aortic valve
Native severe coarctation
In the past decade, various predictors of adverse maternal cardiac outcome have been identified, and two widely used prediction models, CARPREG and ZAHARA, have been developed (Table 3.2) [8, 24, 25, 47–49]. These risk scores assign points when specific risk predictors are present, and the total of points gathered gives an indication of maternal cardiovascular risk during pregnancy. The CARPREG and ZAHARA risk scores have been validated in several studies and appear helpful in predicting maternal cardiac risk [1, 8, 22, 28, 38]. However, in both risk scores, several high-risk populations were underrepresented and because of that several important risk factors were not identified (i.e., dilated aorta and pulmonary arterial hypertension). Recent studies comparing the CARPREG, ZAHARA, and modified WHO risk class indicate that the latter is superior to the CARPREG and ZAHARA risk scores in identifying patients at high risk of cardiovascular complications [1, 28, 38]. Therefore, it should be advised to use the modified WHO risk classification in preconception counseling of women with CHD.
Table 3.2
Risk predictors for adverse maternal and neonatal outcome
Maternal outcome | Risk points |
CARPREG a | |
Prior cardiac event (heart failure, stroke/transient ischemic attack) or arrhythmia | 1.0 |
Baseline NYHA functional class >II or cyanosis | 1.0 |
Left heart obstruction (mitral valve area (MVA) <2 cm2, aortic valve area (AVA) <1.5 cm2, or peak left ventricular outflow tract gradient (LVOT) >30 mmHg) | 1.0 |
Reduced systemic ventricular systolic function (ejection fraction <40 %) | 1.0 |
ZAHARA b | |
History of arrhythmias | 1.5 |
Use of cardiac medication before pregnancy | 1.5 |
Baseline NYHA functional class ≥2 | 0.75 |
Left heart obstruction (peak aortic gradient >50 mmHg or AVA <1.5 cm2 or mitral valve area <2.0 cm2) | 2.5 |
Moderate/severe systemic atrioventricular valve regurgitation | 0.75 |
Moderate/severe pulmonary atrioventricular valve regurgitation | 0.75 |
Mechanical valve prosthesis | 4.25 |
Repaired or unrepaired cyanotic heart disease | 1.0 |
Other studies | |
Smoking history | |
Severe pulmonary valve regurgitation/depressed subpulmonary ventricular ejection fraction | |
Mechanical valve prosthesis | |
Subpulmonary ventricular dysfunction (TAPSE <16 mm) | |
Use of cardiac medication | |
Use of anticoagulation | |
Pulmonary hypertension | |
Dilatation subpulmonary ventricle | |
Neonatal outcome | |
CARPREG | |
NYHA functional class <II or cyanosis | |
Heparin/warfarin during pregnancy | |
Smoking | |
Multiple gestation | |
Left heart obstruction (mitral valve area <2 cm2, aortic valve area <1.5 cm2 or peak left ventricular outflow tract gradient >30 mmHg) | |
ZAHARA | |
Multiple gestation | |
Smoking | |
Repaired or unrepaired cyanotic heart disease | |
Mechanical valve prosthesis | |
Use of cardiac medication before pregnancy | |
Table 3.2 displays an overview of various identified predictors prior to pregnancy. The use of cardiac medication prior to pregnancy is most likely a surrogate marker for severity of heart disease. This may also be the case for the predictor cyanotic heart disease (corrected and uncorrected), which probably reflects the greater complexity of the underlying lesion.
Two studies thus far investigated the role of increased natriuretic peptide levels in the prediction of cardiovascular complications during pregnancy [24, 49]. Women with cardiovascular complications during pregnancy had higher natriuretic peptide levels compared to women without. More research is required in this field, but natriuretic peptides might provide a valuable tool to identify patients at highest risk of complications when they are already pregnant, as well as to identify women with the lowest risk.
3.4.2 Neonatal Risk
The CARPREG and ZAHARA studies identified predictors of adverse neonatal outcome [8, 47], and data from the European Registry on Pregnancy and Cardiac Disease (ROPAC) indicate that high-modified WHO risk class is associated with adverse offspring outcome, such as low birth weight and premature birth (Fig. 3.1). However, recent validation showed that all three risk assessment strategies failed to accurately identify the risk to the offspring [1].
Fig. 3.1
Information required for cardiovascular risk assessment during pregnancy in women with congenital heart disease
3.5 Preconception Investigations
Several investigations should be done in order to gather the required information for a full risk assessment (Fig. 3.1). Ideally, these investigations should be performed before pregnancy, otherwise as early as possible during the first trimester. Risk assessment begins with exploring the medical history of the patient. History and clinical assessment are essential in the evaluation of women with CHD who desire to become pregnant, in order to evaluate if the patient is symptomatic (dyspnea or palpitations) or cyanotic or had previous cardiovascular events. Taking a good history and performing an accurate clinical assessment provide instant information about patient well-being and the presence of long-term complications, such as hypertension. It also provides an important reference point, in case deterioration occurs during pregnancy.
Echocardiography is an essential tool in the evaluation of cardiac performance. In particular ventricular and valvular function should be assessed, and lesion-specific investigations should be performed (i.e., aortic diameters, signs of re-coarctation, baffle leakage, etc.). These all give important insights in cardiac function and are important to make a good risk assessment. Stress echocardiography using bicycle ergometry may add in the evaluation of patients with valve dysfunction and in patients with reduced systemic ventricular function.
Exercise capacity testing is recommended before pregnancy to assess the functional capacity, chronotropic, and blood pressure response and to identify exercise-induced arrhythmias [13]. Liu et al. found in a population with mainly complex congenital heart disease that abnormal chronotropic response correlated with adverse maternal and neonatal pregnancy outcome [29]. Comparable results were reported by Ohuchi et al. In this study not only peak heart rate but also peak oxygen uptake during exercise testing was associated with maternal and neonatal outcome [37].
Electrocardiography provides valuable information concerning the presence of conduction disorders, which are common in certain types of, mainly complex, congenital heart disease. In patients known with previous arrhythmia or those reporting symptoms of palpitations, Holter monitoring should be performed.
Other imaging modalities, such as magnetic resonance imaging (MRI) or computed tomography (CT), can be useful in situations where echocardiography is not sufficient and are particularly useful for evaluation of aortic disease. There is no place for routine cardiac catheterization as preconception investigation. However, catheterization can be helpful when interventions are necessary before pregnancy and should be done before pregnancy when pulmonary arterial hypertension is suspected, since pulmonary arterial hypertension is a contraindication for pregnancy. All imaging modalities using radiation are relatively contraindicated during early pregnancy [13].
Preconception investigations might reveal that an intervention (i.e., valve interventions, aortic root replacement, and stent placement for re-coarctation) is indicated. It is advised to perform such interventions before pregnancy is actively pursued, since this may reduce cardiovascular risk during pregnancy [13].
3.6 Medication and Devices
The ROPAC registry indicated that cardiac medication is used during one third of the pregnancies in women with cardiac disease [43]. A careful review of all medication used should be performed, since several cardiovascular medications are contraindicated during pregnancy. Whenever possible, these medications should be discontinued or should be switched to an alternative which is safe during pregnancy. When medication is indicated, taking the lowest effective dose can be of benefit for both mother and fetus.
It should be noticed that, although some medications are not recommended by the pharmaceutical industry during pregnancy, the benefit to the mother (especially in case of emergency) may outweigh the potential harmful effects for the fetus, and the drug should then not be withheld from the mother [13].
Until December 2014, the US Food and Drug Administration (FDA) classification was widely used to describe the fetal risks of drugs during pregnancy and breastfeeding:
Category A: Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
Category B: Animal reproduction studies have failed to demonstrate a risk to the fetus, but there are no adequate and well-controlled studies in pregnant women, or animal reproduction studies have shown an adverse effect that was not confirmed in controlled studies in women.
Category C: Either animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans or studies in women or animals are not available. Potential benefits may warrant the use of the drug in pregnant women despite potential risks.
Category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant the use of the drug in pregnant women despite potential risks.
Category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in the use of the drug in pregnant women clearly outweigh potential benefits.
Because there were major concerns with this classification, it has been replaced by a narrative summary on the risk of each drug during pregnancy and lactation, together with a discussion of the available data. However, in the literature and in the current guidelines, the FDA classification is still widely used. Large databases are available on the Internet, where recommendations for a specific drug can be found (www.embryotox.de; www.safefetus.com; www.lareb.nl).
3.6.1 Beta-Blockers
Beta-blockers are important drugs to modify pregnancy-associated risk of cardiovascular complications (i.e., risk of arrhythmia, prevention of aortic dissection in patients with Marfan syndrome) [13]. They constitute two thirds of the cardiac medication used during pregnancy [43]. A large meta-analysis concluded that there is no increased risk of major congenital anomalies associated with beta-blocker use during the first trimester [57]. However, organ-specific analyses showed a possible small increased risk of cardiovascular defects, cleft lip/palate, and neural tube defects. Various studies indicated an association between the usage of beta-blockers and fetal growth restriction though causality is uncertain [11, 33, 35, 43]. However, beta-blockers should only be discontinued if fetal risk outweighs maternal benefit. Given the wide experience with labetalol and metoprolol during pregnancy, these are preferred, and changing to these medications should be considered before pregnancy. It should be noted that beta-blockers have been associated with hypoglycemia, bradycardia, and hypotension in the neonate; therefore, close observation of neonates exposed to beta-blockers is necessary postpartum.
3.6.2 Angiotensin-Converting Enzyme (ACE) Inhibitors/Angiotensin Receptor Blockers (ARBs)
ACE inhibitors and ARBs are teratogenic and therefore contraindicated during pregnancy [13]. In women using these drugs, it is wise to introduce an evaluation period before pregnancy without the drugs, in order to see the effect on cardiac function when the patient is not pregnant. If cardiac function remains stable after cessation of the drug (and left ventricular ejection fraction >30 %), pregnancy can be pursued, but close follow-up of cardiac function is warranted.
3.6.3 Antiarrhythmic Agents
ESC guidelines state that beta-blockers and digoxin are the preferred choice for the treatment of arrhythmias [13]. Women who use digoxin can continue this during pregnancy since it is safe for the fetus, though it is less effective during strenuous exercise (as pregnancy is considered to be), and dosing can be difficult because of altered pharmacokinetics during pregnancy. Procainamide is safe during pregnancy and no teratogenic effects were reported for flecainide. However, switching to beta-blockers should be considered for women using these drugs. Sotalol has similar concerns for the fetus as other beta-blockers but can be used during pregnancy when necessary.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
