Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 483–494
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Risk stratification and hierarchy of antenatal care Sarah Vause, MD, FRCOG, Consultant in Fetal and Maternal Medicine a, *, Bernard Clarke, MD, FRCP, FESC, FACC, FRCOG (Hon), Consultant Cardiologist, Honorary Clinical Professor of Cardiology b a
St Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK and Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester b Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester M13 9WL and Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, UK
Keywords: pregnancy heart diseases maternal mortality
Cardiac disease is the leading cause of maternal death in the UK. The triennial maternal mortality reports have repeatedly highlighted failure to recognise the level of risk as a major contributing factor to the deaths of these women. Once the level of risk has been recognised, services then need to be organised in a way that supports the needs of the highest risk women, but avoids unnecessary intervention for women at lower risk. Risk scoring systems and lesion-specific indicators may help predict maternal and neonatal outcomes. Care can then be planned accordingly, to optimise the outcome for the woman and her baby. Ó 2014 Elsevier Ltd. All rights reserved.
Introduction Cardiac disease is the leading cause of maternal death in the UK. The triennial maternal mortality reports have repeatedly highlighted failure to recognise the level of risk as a major contributing factor to the deaths of women undergoing childbirth [1,2]. Risk stratification is important as it can provide women with information preconceptually, allowing them to make an informed choice about whether or not to embark on pregnancy. In early pregnancy, * Corresponding author. Tel.: þ44 0161 276 6426; Fax: þ44 0161 276 6143. E-mail address: [email protected] (S. Vause).
http://dx.doi.org/10.1016/j.bpobgyn.2014.03.004 1521-6934/Ó 2014 Elsevier Ltd. All rights reserved.
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this same information may enable them to opt for a termination of pregnancy if they feel that the risks involved in continuing with the pregnancy are unacceptable. Risk stratification enables antenatal care to be organised so that women are cared for in the most appropriate place, with the mode and timing of delivery planned appropriately. For women with lower risk cardiac problems, appropriate risk stratification can avoid inappropriate intervention and enables their care to be provided by their local team closer to home. Women with higher risk cardiac disease can be transferred to tertiary centres with the facilities and expertise to care for them appropriately. What risks are we predicting? Women with heart disease are prone to maternal cardiac, obstetric, and neonatal complications, and are frequently concerned about the risks to their baby; their partners and family, however, are often more concerned about the risks to the woman herself. A systematic review of the literature relating to women with congenital heart disease showed that cardiac complications occurred in about 11% of women [3]. Women with a Fontan circulation, transposition of the great arteries, or an atrioventricular septal defect, were particularly prone to cardiac arrhythmias. Those with cyanotic congenital heart disease, pulmonary atresia with a ventriculoseptal defect, or Eisenmenger syndrome, were most at risk of developing heart failure. There seems to be a modest increase in the incidence of preeclampsia and thromboembolic disease in women with cardiac disease. From an obstetric perspective, preterm delivery increases (16%), which is partly due to an increased incidence of spontaneous preterm labour or preterm rupture of membranes, and partly iatrogenic in origin [3]. This was particularly evident in those women with more complex, cyanotic congenital heart lesions, or both. Overall, the risk of perinatal mortality was increased four-fold, with the greatest risk in women with Eisenmenger syndrome. Chronic heart disease is also associated with an increased risk of small-for-gestational age fetuses, perinatal mortality, and post-neonatal death [4]. A study from Washington state showed that, when women with chronic heart disease were compared with control women, there were an extra 62 small for gestational age babies per 1000 births. The risk of stillbirth, perinatal death, and postneonatal death was also increased. Although it was suggested that this could be due to higher rates of smoking, diabetes, and hypertension in women with chronic heart disease, this did not seem to fully explain the increase. The investigators also showed a progressive rise over an 18-year period in the numbers of women with chronic heart disease who became pregnant. In some cardiac diseases, the fetus is at increased risk of being affected by the same condition. Clinical geneticists are ideally placed to provide women with information about these risks and their long-term implications. For some conditions, the pathological changes may not manifest in the child until later in life (e.g. Marfan’s syndrome). For other conditions incomplete penetrance of the gene may occur and, although the gene may be inherited, there may not be any phenotypic manifestation. An example of this would be the q22 deletion associated with Di George syndrome, where there is a 50% chance of passing on the gene, but a significant proportion (>25%) of fetuses with the gene will not have congenital heart disease [5]. For some conditions, prenatal diagnostic testing may be technically possible, but detailed discussion is needed to determine whether it would be appropriate and ethical. Prediction of risk in women with heart disease in pregnancy In this section, we initially discuss systems that have been developed to predict the overall risk of adverse maternal cardiac or neonatal outcomes. We then discuss prediction of risk in specific cardiac conditions. Table 1 New York Heart Association Classification. Class Class Class Class
I II III IV
Uncompromised – no limitation to physical activity Slight limitation of physical activity Marked limitation of physical activity Severely compromised at rest
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The New York Heart Association (NYHA) classification is a system that describes functional capacity in people with heart disease, and is often used when describing risk (Table 1). In women with cyanotic congenital heart disease, maternal haemoglobin concentration and maternal oxygen saturations have been shown to be predictive of a poor perinatal outcome [6] (Table 2). Women with Eisenmenger syndrome were excluded from this analysis. Scoring systems Various scoring systems have also been devised to predict the chance of a cardiac complication during pregnancy. The CARPREG score is the most commonly used [7]. The strengths of this scoring system are that it was developed in a prospective multicentre study (which was carried out in Canada). Outcomes of 599 pregnancies in 562 women initially enrolled were reported. It included women with both congenital and acquired heart disease. The limitations of the study were that it excluded women who terminated their pregnancy or miscarried before 20 weeks’ gestation. Although the study used recent pregnancies at the time, recruiting women between October 1994 and November 1999, the data are now old, and treatment of heart disease has changed significantly in this time. The study reported on the risk of serious cardiac events in pregnancy, the sort of events which may deter women from embarking on pregnancy; these were pulmonary oedema, arrhythmia, stroke, cardiac arrest, or cardiac death. The scoring system is simple to use with four predictors, each scoring one point. The four predictors of primary cardiac events were as follows: (1) prior cardiac event (e.g. heart failure, transient ischaemic attack, or stroke before pregnancy) or arrhythmia; (2) baseline NYHA class > II or cyanosis; (3) left heart obstruction (mitral valve area 90 85–90 1
5 27 75
are specific to certain conditions would not be predicted by such scoring systems; for example, the risk of aortic dissection in Marfan’s syndrome. Perhaps the most importance message to take from both of these studies is which risk factors are of most important in predicting outcome. It is then important for the clinician to take other comorbidities or obstetric risk factors into account when trying to provide realistic counselling about the risks involved in a pregnancy. Cardiopulmonary exercise testing In pregnancy, cardiac output increases. It is therefore reasonable to consider whether a cardiopulmonary exercise test, which mimics this increase in cardiac output, could predict whether a woman will be able to mount an appropriate haemodynamic response in pregnancy, and whether it would predict pregnancy outcome. Lui et al. [10] studied 83 women with congenital heart disease (89 pregnancies), who had a cardiopulmonary exercise test either before pregnancy or during the first trimester. One or more adverse cardiac events occurred in 18% (heart failure in 14%, and sustained arrhythmia in 7%). The investigators found that failure to raise heart rate to expected levels during the test was associated with cardiac events in pregnancy and adverse fetal or neonatal outcomes. In particular, a chronotropic index ([peak heart rate-resting heart rate]/[220-age-resting heart rate]) of less than 0.8 was associated with such events. Peak oxygen consumption was not correlated with outcome in this study. Ohuchi et al. [11] performed a similar study, again in women with congenital heart disease. They concurred that the heart rate response was predictive of maternal cardiac events but also found that peak oxygen uptake correlated with poor fetal or neonatal outcomes. A peak heart rate of less than 150 beats per minute, a peak oxygen consumption of less than 25 ml/kg/min, or both, were predictors of maternal cardiac events, and a peak oxygen consumption of less than 26.2 ml/kg/min predicted an adverse neonatal outcome. Specific lesions The above risk stratification systems relate to either all women with heart disease in pregnancy, or women with any form of congenital heart disease in pregnancy. In the next section we will look at risk stratification in specific conditions. Aortopathy and aortic dissection None of the above scoring systems would predict the risk of dissection in women with aortopathy. Therefore, disease-specific risk prediction is needed. In the most recent maternal mortality report in the UK covering maternal deaths in between 2003 and 2005, aortic dissection accounted for seven out of 53 cardiac deaths [1]. Research shows that women in whom Marfan syndrome, Ehlers Danlos Type IV, a bicuspid aortic valve, who may have an associated aortopathy, Turner’s syndrome, and coarctation of the aorta are at particular risk, of dissection in pregnancy. The risk is higher in older women and women who suffer from hypertension. Family history of aortic dissection is particularly relevant in women with Marfan’s syndrome. For women with Marfan syndrome, the risk of dissection increases with increasing aortic root size, and has been found to be 1% in women with an aortic root less than 4 cm in diameter, and 10% if the aortic root is greater than 4 cm in diameter [12]. However, 4 cm should not be seen as an absolute cut off for defining risk, as pregnant women are at particular risk as the aorta increased in size during
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pregnancy, even if the aortic root measures less than 4 cm [13,14]. A recent Dutch study suggested that a figure of 4.5 cm could be used, as no aortic dissections occurred in women without previous aortic dissection and an aortic root diameter less than or equal to 45 mm [15]. Similar figures are not available for women with non-Marfan aortopathy. In women with Ehlers Danlos syndrome the aorta may dissect without any antecedent increase in size. Previous peripartum cardiomyopathy All women with a previous peripartum cardiomyopathy are at high risk of recurrence in a subsequent pregnancy (30–50%), and should be referred to a specialist joint obstetric cardiac service. Those at highest risk are the women whose ejection fraction did not return to normal after the index pregnancy. A study by Elkayam et al. [16] compared women whose ejection fraction had normalised (>50%) with those in whom it had not and showed that the women whose ejection fraction had not normalised were at higher risk in a subsequent pregnancy of developing symptoms of heart failure (44% v 21%), dying (19% v 0%) and delivering before 37 weeks (37% v 11%). In the most recent UK maternal mortality report, deficiencies in the care of women with previous peripartum cardiomyopathy were described, and emphasis was placed on counselling to make women aware of the risks of recurrence or deterioration in subsequent pregnancies [2]. The lack of clinicians’ awareness and knowledge of the risks was also highlighted, and the report stated that ‘it is crucial to refer women with previous cardiomyopathy to specialist units with joint clinics where both the obstetricians and cardiologists are familiar with the expected changes of pregnancy.’ Mitral valve disease Mitral regurgitation is much better tolerated in pregnancy than mitral stenosis. As valve area remains unchanged during pregnancy (unlike valve gradient), it can be used as a tool to risk stratify a woman, whenever she presents [17]. The severity of mitral stenosis has been shown to correlate with maternal and fetal outcomes with a mitral valve area of 1.5 cm2 or less, carrying a 78% chance of heart failure and a 33% chance of arrhythmias [18]. Aortic valve disease Aortic regurgitation is much better tolerated in pregnancy than aortic stenosis. The risk of complications during pregnancy is related to the severity of the gradient across the aortic valve. Good left ventricular function, normal heart rate, and blood pressure responses during an exercise test are predictors of good maternal and fetal outcomes [19]. Mechanical prosthetic valves Women with mechanical prosthetic valves in situ have a maternal mortality risk, which has been estimated between 1 and 4% [20]. The level of risk is influenced by the type of prosthetic valve, the position of the valve (mitral valves are more prone to thrombosis than aortic valves), and compliance with anticoagulation treatment during pregnancy [21]. The underlying pathology which led to the valve replacement should also be considered when assessing risk. Women with congenital heart disease who have required prosthetic valve replacement often have complex cardiac lesions and may experience other cardiac complications such as arrhythmias. Small sized valves are often used if the valve replacement occurs in childhood, resulting in a functional stenosis in the adult, particularly with the increased cardiac output of pregnancy. Intravenous drug users who develop endocarditis and require prosthetic valve replacement may continue to have chaotic lifestyles and be poorly compliant with treatment. Other factors such as smoking, poor intravenous access, poor diet, and social issues increase the obstetric and neonatal risks (see also Chapter 4). Debate continues on which anticoagulant regimen is better in pregnancy, and whether low molecular weight heparin is as efficacious as warfarin, but this is outwith the scope of this chapter.
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Tetralogy of Fallot Usually, women with Tetralogy of Fallot tolerate pregnancy well. Those with severe pulmonary regurgitation are at highest risk of complications, which can include right ventricular failure (1.6%); arrhythmias (6.5%); preterm labour (18%), and small for gestational age babies (19%) [22]. Transposition of the great arteries The risks for women during pregnancy depend on the type of surgery the woman has undergone. In atrial switch procedures (operations such as a Mustard or Senning procedure), the right ventricle supplies the systemic circulation. These women are prone to develop arrhythmias and heart failure during pregnancy. About 38% will deteriorate in pregnancy and, in 12%, this will be a permanent deterioration in cardiac function [23]. Over the past 30 years, arterial switch procedures have been carried out in preference to the atrial switch described above. In this operation, the great arteries are switched around, so that the left ventricle supplies the systemic circulation. As this is a more modern operation, only small numbers of pregnancies have been reported [24]. It is thought that these women could potentially be prone to myocardial ischaemia and aortic root dilatation in pregnancy. Fontan All women with a Fontan type circulation are at high risk of maternal and fetal complications in pregnancy. Within this group, it is difficult to predict which women are at higher risk, as only small case studies have been reported [25]. They were also under-represented in the cohorts studied by Siu et al. [7] and Drenthen et al. [9] when developing their scoring systems, as many were advised against pregnancy. Pulmonary hypertension All women with pulmonary hypertension are at high risk of maternal mortality. Bedard et al. [26] carried out a systematic review of the literature and found 48 papers describing outcomes in 73 parturients who delivered between 1997 and 2007. An overall mortality rate of 25% was reported, but this was lowest (17%) in the women with idiopathic pulmonary hypertension and highest (33%) in women who had developed pulmonary hypertension secondary to an underlying medical condition. In women with congenital heart disease, it was 28%. Hierarchy of antenatal care The aim of an obstetric cardiac service is to provide women with appropriate co-ordinated multidisciplinary care, by clinicians with the appropriate level of expertise, in a setting where the appropriate facilities are co-located to support the woman and her baby around the time of delivery. For a woman with a low-risk condition, care can be provided by her local obstetrician, cardiologist, and community midwife, in her local hospital. Women with high-risk cardiac conditions will require care from a specialised obstetric cardiac team in a tertiary referral hospital, with obstetric, cardiology, cardiac surgery, specialised anaesthetic, intensive care, fetal medicine, and neonatal facilities all co-located. Other disciplines may also need to provide input, such as haematology, perfusionists, genetics, dentistry, reproductive and sexual health (abortion services and contraception). For women with low-risk conditions, appropriate referral pathways need to be in place so that care can be escalated promptly should the woman’s condition deteriorate during pregnancy, or should she develop other medical or obstetric co-morbidities.
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Guidelines for stratification of antenatal care The 2011 European Society for Cardiology guidelines suggest a system for stratifying risk and give an example of its application [27]. This can be further extended to stratification of the care the woman will need during pregnancy and around the time of delivery (Table 4). Organisation of antenatal care Many lessons relating to risk awareness and provision of care for women with cardiac problems in pregnancy can be learnt from the triennial confidential enquiries into maternal mortality in the UK. The most recent UK maternal mortality report [2] made clear recommendations that referrals to specialist services (such as an obstetric cardiac service) should be made immediately and prioritised as urgent. It stressed that not all maternity units are able or equipped to care for pregnant women with major complications, but such services should be accessible to all, and referrals should be made. It was also highlighted that some centres did not have experience of the management of some of the less common types of conditions seen in pregnancy. For example, some tertiary centre clinicians may have great expertise in ischaemic heart disease, but not in caring for a pregnant woman with congenital heart disease. It was also recommended that providers and commissioners should consider developing protocols to specify which medical conditions mandate at least a consultant review in early pregnancy, and that this agreement should take place via local maternity networks. Failure of clinicians to recognise important symptoms, failure to examine the patient adequately (particularly failure to listen to the heart), or failure to interpret electrocardiograms correctly [1], have resulted in failure to recognise risk and refer or escalate care. A lack of knowledge of potential complications of conditions such as peripartum cardiomyopathy has resulted in inappropriate risk stratification and women not being referred to specialist services [2]. Preconceptual care Ideally, all women of reproductive age with known cardiac disease should have preconceptual assessment, discussion of the potential risks involved in pregnancy, and a provisional outline given about the plan for care. This should be a multidisciplinary consultation with an obstetrician, cardiologist, and midwife present. The preconceptual assessment should not be viewed as a ‘one off’ appointment. Further assessments may be needed if there is a long interval between the initial preconceptual assessment and the time a woman decides to embark on pregnancy as her clinical status may have changed. The purpose of the preconceptual appointment is to provide a woman with a realistic view of the maternal and fetal risks involved in pregnancy and allow optimisation of her clinical condition before embarking on pregnancy [28]. Discussion should also include advice on appropriate contraception, as some women may choose not to embark on pregnancy if they perceive the risks are too great. Information about how to access obstetric cardiac services once pregnant, or how to access appropriate termination of pregnancy services is also important [1]. Referral to a clinical geneticist may be appropriate for women with genetically inherited conditions to enable women to understand the risks to the fetus and whether prenatal diagnosis is available. Antenatal care Unfortunately, not all women have preconceptual counselling, as young women are frequently lost to follow up at the time of transition between children and adult services. They then re-present to obstetric services when pregnant, often in a different hospital from where they had their cardiac care as a child. Although some women know many details of their condition and previous care, some have little knowledge of it, particularly if operations were carried out when they were very young. Information about when and where previous surgery was carried out can often be obtained from parents. It is then important to trace clinical details from previous hospitals to risk accurately during the current pregnancy; for example, the type of surgery undertaken for correction of Transposition of the Great Arteries.
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Table 4 Modified World Health Organization classification of maternal cardiovascular risk: principles and examples of application (European Society of Cardiology guidelines [27]). Class
Principle
Example of application
Suggested pattern of care
WHO I
No detectable increased risk of maternal mortality and no/mild increase in morbidity.
Care locally (secondary care and community midwife).
WHO II
Small increased risk of maternal mortality or moderate increase in morbidity. Significantly increased risk of maternal mortality or severe morbidity. Expert counselling required. If pregnancy is decided upon, intensive specialist cardiac and obstetric monitoring needed throughout pregnancy, childbirth, and the puerperium.
Uncomplicated, small or mild pulmonary stenosis patent ductus arteriosus mitral valve prolapse Successfully repaired simple lesions (atrial or ventricular septal defect, patent ductus arteriosus, anomalous pulmonary venous drainage); atrial or ventricular ectopic beats (isolated). WHO II (if otherwise well and uncomplicated) Unoperated atrial or ventricular septal defect; repaired tetralogy of Fallot; most arrhythmias. WHO II–III (depending on individual) Mild left ventricular impairment; hypertrophic cardiomyopathy; native or tissue valvular heart disease not considered WHO I or IV; Marfan syndrome without aortic dilatation; aorta 50 mm in aortic disease associated with bicuspid aortic valve; and native severe coarctation.
WHO III
WHO IV
Extremely high risk of maternal mortality or severe morbidity; pregnancy contraindicated. If pregnancy occurs termination should be discussed. If pregnancy continues, care as for class III.
Seen each trimester at tertiary centre but could deliver locally. Regular review at tertiary centre. Individualised plans for delivery depending on clinical condition, facilities and expertise in local hospital. Cared for at tertiary centre and reviewed at least monthly. Delivery in tertiary centre with ideally with all facilities co-located.
Advised against pregnancy and offered termination – but if continues cared for at tertiary centre and reviewed at least monthly. Delivery in tertiary centre with ideally with all facilities co-located.
NYHA, New York Heart Association; WHO, World Health Organization.
Some practical considerations need to be overcome when planning care for women. Antenatal care should lead seamlessly into planning delivery and postpartum care. It is, therefore, important that the woman has met the team in the hospital where her delivery takes place beforehand, and that the team of clinicians has had the time to assess her and gather the relevant information to formulate a multidisciplinary care plan for delivery. This is difficult if women present for care late in pregnancy, especially if the severity of the woman’s condition has not been recognised by the local team previously. Clearly defined referral pathways, with easy access to the team at the specialist centre, are vitally important.
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Fetal considerations Although the health and wellbeing of the mother always takes priority over fetal considerations, antenatal care for the woman with heart disease also needs to optimise the outcome for the fetus. Some of the more complex cardiac conditions, for example Fontan circulations, carry a high risk of miscarriage, growth restriction, and preterm delivery [9]. For women with inherited cardiac conditions, there will be a risk of the fetus inheriting the disorder; in autosomal dominant conditions such as Marfan syndrome, this risk will be one in two women. Although testing may be technically possible, it can be questioned whether this is ethically appropriate for some conditions. Consultation with a clinical geneticist can be helpful in arranging long-term follow up, and for arranging testing of the baby, child, or young adult at the relevant age. All women with structural congenital heart disease have an increased chance of having a fetus with congenital heart disease. In the UK population, an overall recurrence risk of 4.1% has been found [29]. The recurrence risk varies with the type of lesion in the mother, with heterotaxia, conotruncal defects, atrioventriculoseptal defects, and outflow tract abnormalities having the highest recurrence risks [30]. A fetal echocardiography should, therefore, be arranged in a Fetal Medicine Unit for all women with structural congenital heart disease. It should be remembered that the risks of congenital heart disease in the fetus are still present even if the woman has had her defect repaired, has no residual defect, and is now at low risk from cardiac complications herself (e.g. a woman with a repaired ventricular septal defect). Women with heart disease may be taking teratogenic or fetotoxic drugs (Table 5). An assessment needs to be made whether these can be discontinued or changed, or whether the maternal risks are such that they should be continued during the pregnancy, accepting the increased risk to the fetus [31,32]. If the drugs are continued, the fetus should be monitored for any adverse effects; for example, intracranial haemorrhage with warfarin, which could result in termination of pregnancy being offered. Poor fetal growth may be a problem in women with congenital or acquired heart disease. In women with congenital heart disease, those with cyanotic heart disease, Eisenmenger syndrome, Transposition of the Great Arteries, pulmonary atresia with ventriculoseptal defect, or Fontan type circulation, are at particular risk [3]. In women with acquired heart disease, it is often the underlying comorbidities, such as hypertension, which are associated with poor placental function and poor fetal growth [33]. Smoking, which is associated with ischaemic heart disease, has a strong dose-dependent association with fetal growth restriction [34]. If women with these conditions are not already taking aspirin, it should be commenced as early in pregnancy as possible. A recent meta-analysis of five trials, with 414 women at risk of pre-eclampsia, has shown that, when aspirin was started at 16 weeks of gestation or less, the relative risk of having a small for gestational age infant was 0.47 (95% CI 0.30 to 0.74), and the number needed to treat was 9 (95% CI 5.0 to 17.0) [35]. A high index of suspicion for fetal growth problems and clinical monitoring, supplemented where necessary with ultrasound monitoring, is needed in women with either congenital or acquired heart disease. Premature delivery also occurs more frequently in women with heart disease. This may be either due to the increased risk of spontaneous preterm labour or because iatrogenic preterm delivery is needed for maternal or fetal reasons. Women with Transposition of the Great Arteries and Fontan Table 5 Examples of drugs with adverse fetal effects. Drug
Teratogenic effect
Fetotoxic effect
ACE inhibitors Angiotensin II receptor blockers Statins
Ossification disorders of fetal skull. Ossification disorders of fetal skull.
Nephrotoxic effect leading to oligohydramnios. Nephrotoxic effect leading to oligohydramnios.
No conclusive evidence [28].
Beta blockers
No evidence of teratogenicity.
Warfarin
Warfarin embryopathy – nasal hypoplasia and epiphysial dysplasia.
Concerns about effect on brain myelination and neurodevelopment but no conclusive evidence. Lower birth weight when atenolol used in pregnancy [29], but no evidence of adverse effects with other beta blockers. Intracranial haemorrhage, microcephaly.
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circulation have a higher incidence of preterm pre-labour rupture of membranes [36]. Those with Ehlers Danlos syndrome seem to be at increased risk of cervical incompetence and preterm prelabour rupture of membranes. It has been postulated that this is due to the inherited collagen defect, and the risk seems to be higher when the fetus is also affected [37]. Delivery planning One of the main reasons for antenatal risk stratification of women with heart disease is to ensure that delivery occurs in a planned way, with the most appropriate personnel and facilities available. For low-risk women, this may be in their local hospital, but, for women with more complex heart disease, it will be in a specialist centre. Maternal mortality reports [1,2] and the Royal College of Obstetricians and Gynaecologists’ Good Clinical Practice guidelines [38] have stressed the need for written multidisciplinary care plans for delivery. Obstetric, cardiac, anaesthetic, and fetal considerations will all inform decisions about the mode, timing, and place of delivery. These decisions will be made antenatally, and should involve the woman, her family, and all members of the multidisciplinary team. The plan should include personnel who need to be notified on admission, planned mode of delivery, management of the second and third stages, place of delivery, and plans for the postnatal care. An important part of the care plan is to anticipate complications and contingency plan for these; for example, spontaneous preterm labour or postpartum haemorrhage. The care plan should also highlight what the main risks would be for that particular woman during delivery. An example of a care plan is given in the Royal College of Obstetricians and Gynaecologists’ Good Practice guideline on Cardiac Disease and Pregnancy [35]. Where possible, vaginal delivery should be the aim, as it is associated with less blood loss and infection risk compared with caesarean delivery [27]. Caesarean section also increases the risk of venous thrombosis and thromboembolism. Caesarean section should therefore be reserved for those women who are unable to safely increase cardiac output during labour, or where there are obstetric indications for cesarean section, for example placenta previa. Women who may need delivery by caesarean section are those with cyanosis, reduced ejection fraction, dilated aortic root, severe mitral or aortic stenosis, pulmonary hypertension, or ischaemia. None of these indications are absolute, and patient choice and previous obstetric history will influence the decision. A particular concern when aiming for a vaginal delivery would be whether a baby of a woman could be delivered sufficiently quickly if she required a category 1 cesarean section. (A category 1 cesarean section is carried out when there is a threat to the life of the mother or fetus, and most hospitals would aim for a decision to delivery interval of less than 30 min). This contingency should be planned for antenatally. The woman would need to be informed that, if this situation arose, her health would be prioritised over that of the fetus, and that a longer time may be needed to anesthetise her safely. This may, therefore, influence decisions about the place and mode of delivery. For women with complex heart conditions, there is a possibility that other disciplines may be required around the time of delivery (e.g. cardiac anesthetic support, cardiac surgery, or vascular perfusion services). Such women require delivery in a unit where these services are co-located. Postpartum care Women who are stratified as high risk antenatally are still likely to be at high risk in the postpartum period. Cardiac output is at its highest immediately after delivery, and many complications such as heart failure and dissection occur at this time. Plans for management of the woman in the immediate postpartum period should be made antenatally by the multidisciplinary team, and included within the care plan. Conclusion Increasing numbers of women with heart disease are embarking on pregnancy, and cardiac disease is the leading cause of maternal death in the UK. Providing appropriate care for this group of women is challenging, as it needs to meet the complex clinical needs of the woman, together with her emotional and psychosocial needs and the clinical needs of her fetus. Those at lower risk of complications should
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be cared for in their own local unit, whereas women with more complex needs will require specialist care from a multidisciplinary team experienced in dealing with cardiac disease in pregnancy. Risk stratification is, therefore, necessary to ensure women receive the appropriate pattern of antenatal care. It is also important that networks of hospitals, with clear pathways for referral and escalation of care, are developed so that women with heart disease in pregnancy can be supported through pregnancy and afterwards, and the best outcomes for the woman and her baby achieved.
Practice points Services for women with heart disease in pregnancy should be organised within networks so that all women have access to an appropriate level of care, with high-risk women being referred to specialist obstetric cardiac services. Recognised pathways, to facilitate referral to specialist obstetric cardiac services and to enable prompt escalation of care if complications occur, should be developed. All women with known or suspected congenital or acquired cardiac, aortic disease, or both, should be referred to an obstetric cardiac service in a specialist centre for pre-pregnancy risk assessment and counselling. This may include referral to clinical genetics. Women with previous peripartum cardiomyopathy are at high risk of recurrence, and should be referred to specialist obstetric cardiac services for preconceptual counselling and for care during subsequent pregnancies. In women with prosthetic heart valves, the underlying pathology that led to the valve replacement is likely to affect management in pregnancy. There should be a high index of suspicion for fetal growth problems in women with heart disease in pregnancy.
Research agenda A qualitative study to understand womens perception of risk and how information is best presented during preconceptual discussions. A study of outcomes in women with non-Marfan aortopathy in pregnancy. A study of maternal and fetal outcomes in women with prosthetic valves using different thromboprophylaxis regimens. Large cohort studies of specific cardiac lesions to provide outcome data and information about risk prediction.
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*[7] Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001;104:515–21. [8] Jastrow N, Meyer P, Khairy P, et al. Prediction of complications in pregnant women with cardiac diseases referred to a tertiary center. Int J Cardiol 2011;151:209–13. *[9] Drenthen W, Boersma E, Balci A, et al. Predictors of pregnancy complications in women with congenital heart disease. Eur Heart J 2010;31:2124–32. [10] Lui GK, Silversides CK, Khairy P, et al. Alliance for Adult Research in Congenital Cardiology (AARCC). Heart rate response during exercise and pregnancy outcome in women with congenital heart disease. Circulation 2011;123:242–8. [11] Ohuchi H, Tanabe Y, Kamiya C, et al. Cardiopulmonary variables during exercise predict pregnancy outcome in women with congenital heart disease. Circ J 2013;77:470–6. [12] Lipscomb KJ, Smith JC, Clarke B, et al. Outcome of pregnancy in women with Marfan’s syndrome. Br J Obstet Gynaecol 1997;104:201–6. [13] Pyeritz RE. Maternal and fetal complications of pregnancy in the Marfans syndrome. Am J Med 1981;71:784–90. [14] Immer FF, Bansi AG, Immer-Bansi AS, et al. Aortic dissection in pregnancy: analysis of risk factors and outcome. Ann Thorac Surg 2003;76:309–14. [15] Meijboom LJ, Vos FE, Timmermans J, et al. Pregnancy and aortic root growth in the Marfan syndrome: a prospective study. Eur Heart J 2005;26:914–20. [16] Elkayam U, Tummala PP, Rao K, et al. Maternal and fetal outcomes of subsequent pregnancies in women with peripartum cardiomyopathy. N Engl J Med 2001;344:1567–71. [17] Silversides CK, Colman JM, Sermer M, et al. Cardiac risk in pregnant women with rheumatic mitral stenosis. Am J Cardiol 2003;91:1382–5. [18] Hameed A, Karaalp IS, Tummala PP, et al. The effect of valvular heart disease on maternal and fetal outcome of pregnancy. J Am Coll Cardiol 2001;37:893–9. [19] Silversides CK, Colman JM, Sermer M, et al. Early and intermediate term outcomes of pregnancy with congenital aortic stenosis. Am J Cardiol 2003;91:1386–9. [20] Reimold SC, Rutherford JD. Valvular heart disease in pregnancy. N Engl J Med 2003;349:52–9. [21] McLintock C. Anticoagulant therapy in pregnant women with mechanical prosthetic heart valves: no easy option. Thromb Res 2011;127(Suppl. 3):S56–60. [22] Balci A, Drenthen W, Mulder BJM, et al. Pregnancy in women with corrected tetralogy of Fallot: occurrence and predictors of adverse events. Am Heart J 2011;161:307–13. [23] Guedes A, Mercier LA, Leduc L, et al. Impact of pregnancy on the systemic right ventricle after a Mustard operation for transposition of the great arteries. J Am Coll Cardiol 2004;44:433–7. [24] Tobler D, Fernandes SM, Wald RM, et al. Pregnancy outcomes in women with transposition of the great arteries and arterial switch operation. Am J Cardiol 2010;106:417–20. [25] Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Pregnancy and delivery in women after Fontan palliation. Heart 2006; 92:1290–4. [26] Bedard E, Dimopoulos K, Gatzoulis MA. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension? Eur Heart J 2009;30:256–65. *[27] The Task Force on the management of cardiovascular diseases during pregnancy of the European Society of Cardiology (ESC). ESC guidelines on the management of cardiovascular diseases during pregnancy. Eur Heart J 2011;32:3147–97. *[28] Vause S, Thorne S, Clarke B. Preconceptual counseling for women with heart disease. In: Steer PJ, Gatzoulis MA, Baker P, editors. Consensus views arising from the 51st Study Group Heart Disease in Pregnancy. Heart disease and pregnancy. London: RCOG Press; 2006. [29] Burn J, Brennan P, Little J, et al. Recurrence risks in offspring of adults with major heart defects: results from first cohort of British collaborative study. Lancet 1998;351:311–6. [30] Øyen N, Poulsen G, Boyd HA, et al. Recurrence of congenital heart defects in families. Circulation 2009;120:295–301. [31] Winterfeld U, Allignol A, Panchaud A, et al. Pregnancy outcome following maternal exposure to statins: a multicentre prospective study. BJOG 2013;120:463–71. [32] National Institute for Health and Clinical Excellence. Hypertension in pregnancy: the management of hypertensive disorders during pregnancy (NICE clinical guideline 107). London: NICE; 2010. [33] Allen VM, Joseph KS, Murphy KE, et al. The effect of hypertensive disorders in pregnancy on small for gestational age and stillbirth: a population based study. BMC Pregnancy Childbirth 2004;4:17–25. [34] McCowan LM, Dekker GA, Chan E, et al. Spontaneous preterm birth and small for gestational age infants in women who stop smoking early in pregnancy: prospective cohort study. BMJ 2009;338:b1081. [35] Bujold E, Roberge S, Lacasse Y, et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy. Obstet Gynecol 2010;116:402–14. [36] Nitsche JF, Phillips SD, Rose CH, et al. Pregnancy and delivery in patients with Fontan circulation a case report and review of obstetric management. Obstet Gynecol Surv 2009;64:608–14. [37] Anuma EA, Hill LD, Pandya A, et al. Connective tissue and related disorders and preterm birth: clues to genes contributing to prematurity. Placenta 2009;30:207–15. [38] Royal College of Obstetrics and Gynaecology. Cardiac disease in pregnancy. Good practice No 13 RCOG; 2011.
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Risk stratification and hierarchy of antenatal care Sarah Vause, MD, FRCOG, Consultant in Fetal and Maternal Medicine a, *, Bernard Clarke, MD, FRCP, FESC, FACC, FRCOG (Hon), Consultant Cardiologist, Honorary Clinical Professor of Cardiology b a
St Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK and Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester b Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester M13 9WL and Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, UK
Keywords: pregnancy heart diseases maternal mortality
Cardiac disease is the leading cause of maternal death in the UK. The triennial maternal mortality reports have repeatedly highlighted failure to recognise the level of risk as a major contributing factor to the deaths of these women. Once the level of risk has been recognised, services then need to be organised in a way that supports the needs of the highest risk women, but avoids unnecessary intervention for women at lower risk. Risk scoring systems and lesion-specific indicators may help predict maternal and neonatal outcomes. Care can then be planned accordingly, to optimise the outcome for the woman and her baby. Ó 2014 Elsevier Ltd. All rights reserved.
Introduction Cardiac disease is the leading cause of maternal death in the UK. The triennial maternal mortality reports have repeatedly highlighted failure to recognise the level of risk as a major contributing factor to the deaths of women undergoing childbirth [1,2]. Risk stratification is important as it can provide women with information preconceptually, allowing them to make an informed choice about whether or not to embark on pregnancy. In early pregnancy, * Corresponding author. Tel.: þ44 0161 276 6426; Fax: þ44 0161 276 6143. E-mail address: [email protected] (S. Vause).
http://dx.doi.org/10.1016/j.bpobgyn.2014.03.004 1521-6934/Ó 2014 Elsevier Ltd. All rights reserved.
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this same information may enable them to opt for a termination of pregnancy if they feel that the risks involved in continuing with the pregnancy are unacceptable. Risk stratification enables antenatal care to be organised so that women are cared for in the most appropriate place, with the mode and timing of delivery planned appropriately. For women with lower risk cardiac problems, appropriate risk stratification can avoid inappropriate intervention and enables their care to be provided by their local team closer to home. Women with higher risk cardiac disease can be transferred to tertiary centres with the facilities and expertise to care for them appropriately. What risks are we predicting? Women with heart disease are prone to maternal cardiac, obstetric, and neonatal complications, and are frequently concerned about the risks to their baby; their partners and family, however, are often more concerned about the risks to the woman herself. A systematic review of the literature relating to women with congenital heart disease showed that cardiac complications occurred in about 11% of women [3]. Women with a Fontan circulation, transposition of the great arteries, or an atrioventricular septal defect, were particularly prone to cardiac arrhythmias. Those with cyanotic congenital heart disease, pulmonary atresia with a ventriculoseptal defect, or Eisenmenger syndrome, were most at risk of developing heart failure. There seems to be a modest increase in the incidence of preeclampsia and thromboembolic disease in women with cardiac disease. From an obstetric perspective, preterm delivery increases (16%), which is partly due to an increased incidence of spontaneous preterm labour or preterm rupture of membranes, and partly iatrogenic in origin [3]. This was particularly evident in those women with more complex, cyanotic congenital heart lesions, or both. Overall, the risk of perinatal mortality was increased four-fold, with the greatest risk in women with Eisenmenger syndrome. Chronic heart disease is also associated with an increased risk of small-for-gestational age fetuses, perinatal mortality, and post-neonatal death [4]. A study from Washington state showed that, when women with chronic heart disease were compared with control women, there were an extra 62 small for gestational age babies per 1000 births. The risk of stillbirth, perinatal death, and postneonatal death was also increased. Although it was suggested that this could be due to higher rates of smoking, diabetes, and hypertension in women with chronic heart disease, this did not seem to fully explain the increase. The investigators also showed a progressive rise over an 18-year period in the numbers of women with chronic heart disease who became pregnant. In some cardiac diseases, the fetus is at increased risk of being affected by the same condition. Clinical geneticists are ideally placed to provide women with information about these risks and their long-term implications. For some conditions, the pathological changes may not manifest in the child until later in life (e.g. Marfan’s syndrome). For other conditions incomplete penetrance of the gene may occur and, although the gene may be inherited, there may not be any phenotypic manifestation. An example of this would be the q22 deletion associated with Di George syndrome, where there is a 50% chance of passing on the gene, but a significant proportion (>25%) of fetuses with the gene will not have congenital heart disease [5]. For some conditions, prenatal diagnostic testing may be technically possible, but detailed discussion is needed to determine whether it would be appropriate and ethical. Prediction of risk in women with heart disease in pregnancy In this section, we initially discuss systems that have been developed to predict the overall risk of adverse maternal cardiac or neonatal outcomes. We then discuss prediction of risk in specific cardiac conditions. Table 1 New York Heart Association Classification. Class Class Class Class
I II III IV
Uncompromised – no limitation to physical activity Slight limitation of physical activity Marked limitation of physical activity Severely compromised at rest
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The New York Heart Association (NYHA) classification is a system that describes functional capacity in people with heart disease, and is often used when describing risk (Table 1). In women with cyanotic congenital heart disease, maternal haemoglobin concentration and maternal oxygen saturations have been shown to be predictive of a poor perinatal outcome [6] (Table 2). Women with Eisenmenger syndrome were excluded from this analysis. Scoring systems Various scoring systems have also been devised to predict the chance of a cardiac complication during pregnancy. The CARPREG score is the most commonly used [7]. The strengths of this scoring system are that it was developed in a prospective multicentre study (which was carried out in Canada). Outcomes of 599 pregnancies in 562 women initially enrolled were reported. It included women with both congenital and acquired heart disease. The limitations of the study were that it excluded women who terminated their pregnancy or miscarried before 20 weeks’ gestation. Although the study used recent pregnancies at the time, recruiting women between October 1994 and November 1999, the data are now old, and treatment of heart disease has changed significantly in this time. The study reported on the risk of serious cardiac events in pregnancy, the sort of events which may deter women from embarking on pregnancy; these were pulmonary oedema, arrhythmia, stroke, cardiac arrest, or cardiac death. The scoring system is simple to use with four predictors, each scoring one point. The four predictors of primary cardiac events were as follows: (1) prior cardiac event (e.g. heart failure, transient ischaemic attack, or stroke before pregnancy) or arrhythmia; (2) baseline NYHA class > II or cyanosis; (3) left heart obstruction (mitral valve area 90 85–90 1
5 27 75
are specific to certain conditions would not be predicted by such scoring systems; for example, the risk of aortic dissection in Marfan’s syndrome. Perhaps the most importance message to take from both of these studies is which risk factors are of most important in predicting outcome. It is then important for the clinician to take other comorbidities or obstetric risk factors into account when trying to provide realistic counselling about the risks involved in a pregnancy. Cardiopulmonary exercise testing In pregnancy, cardiac output increases. It is therefore reasonable to consider whether a cardiopulmonary exercise test, which mimics this increase in cardiac output, could predict whether a woman will be able to mount an appropriate haemodynamic response in pregnancy, and whether it would predict pregnancy outcome. Lui et al. [10] studied 83 women with congenital heart disease (89 pregnancies), who had a cardiopulmonary exercise test either before pregnancy or during the first trimester. One or more adverse cardiac events occurred in 18% (heart failure in 14%, and sustained arrhythmia in 7%). The investigators found that failure to raise heart rate to expected levels during the test was associated with cardiac events in pregnancy and adverse fetal or neonatal outcomes. In particular, a chronotropic index ([peak heart rate-resting heart rate]/[220-age-resting heart rate]) of less than 0.8 was associated with such events. Peak oxygen consumption was not correlated with outcome in this study. Ohuchi et al. [11] performed a similar study, again in women with congenital heart disease. They concurred that the heart rate response was predictive of maternal cardiac events but also found that peak oxygen uptake correlated with poor fetal or neonatal outcomes. A peak heart rate of less than 150 beats per minute, a peak oxygen consumption of less than 25 ml/kg/min, or both, were predictors of maternal cardiac events, and a peak oxygen consumption of less than 26.2 ml/kg/min predicted an adverse neonatal outcome. Specific lesions The above risk stratification systems relate to either all women with heart disease in pregnancy, or women with any form of congenital heart disease in pregnancy. In the next section we will look at risk stratification in specific conditions. Aortopathy and aortic dissection None of the above scoring systems would predict the risk of dissection in women with aortopathy. Therefore, disease-specific risk prediction is needed. In the most recent maternal mortality report in the UK covering maternal deaths in between 2003 and 2005, aortic dissection accounted for seven out of 53 cardiac deaths [1]. Research shows that women in whom Marfan syndrome, Ehlers Danlos Type IV, a bicuspid aortic valve, who may have an associated aortopathy, Turner’s syndrome, and coarctation of the aorta are at particular risk, of dissection in pregnancy. The risk is higher in older women and women who suffer from hypertension. Family history of aortic dissection is particularly relevant in women with Marfan’s syndrome. For women with Marfan syndrome, the risk of dissection increases with increasing aortic root size, and has been found to be 1% in women with an aortic root less than 4 cm in diameter, and 10% if the aortic root is greater than 4 cm in diameter [12]. However, 4 cm should not be seen as an absolute cut off for defining risk, as pregnant women are at particular risk as the aorta increased in size during
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pregnancy, even if the aortic root measures less than 4 cm [13,14]. A recent Dutch study suggested that a figure of 4.5 cm could be used, as no aortic dissections occurred in women without previous aortic dissection and an aortic root diameter less than or equal to 45 mm [15]. Similar figures are not available for women with non-Marfan aortopathy. In women with Ehlers Danlos syndrome the aorta may dissect without any antecedent increase in size. Previous peripartum cardiomyopathy All women with a previous peripartum cardiomyopathy are at high risk of recurrence in a subsequent pregnancy (30–50%), and should be referred to a specialist joint obstetric cardiac service. Those at highest risk are the women whose ejection fraction did not return to normal after the index pregnancy. A study by Elkayam et al. [16] compared women whose ejection fraction had normalised (>50%) with those in whom it had not and showed that the women whose ejection fraction had not normalised were at higher risk in a subsequent pregnancy of developing symptoms of heart failure (44% v 21%), dying (19% v 0%) and delivering before 37 weeks (37% v 11%). In the most recent UK maternal mortality report, deficiencies in the care of women with previous peripartum cardiomyopathy were described, and emphasis was placed on counselling to make women aware of the risks of recurrence or deterioration in subsequent pregnancies [2]. The lack of clinicians’ awareness and knowledge of the risks was also highlighted, and the report stated that ‘it is crucial to refer women with previous cardiomyopathy to specialist units with joint clinics where both the obstetricians and cardiologists are familiar with the expected changes of pregnancy.’ Mitral valve disease Mitral regurgitation is much better tolerated in pregnancy than mitral stenosis. As valve area remains unchanged during pregnancy (unlike valve gradient), it can be used as a tool to risk stratify a woman, whenever she presents [17]. The severity of mitral stenosis has been shown to correlate with maternal and fetal outcomes with a mitral valve area of 1.5 cm2 or less, carrying a 78% chance of heart failure and a 33% chance of arrhythmias [18]. Aortic valve disease Aortic regurgitation is much better tolerated in pregnancy than aortic stenosis. The risk of complications during pregnancy is related to the severity of the gradient across the aortic valve. Good left ventricular function, normal heart rate, and blood pressure responses during an exercise test are predictors of good maternal and fetal outcomes [19]. Mechanical prosthetic valves Women with mechanical prosthetic valves in situ have a maternal mortality risk, which has been estimated between 1 and 4% [20]. The level of risk is influenced by the type of prosthetic valve, the position of the valve (mitral valves are more prone to thrombosis than aortic valves), and compliance with anticoagulation treatment during pregnancy [21]. The underlying pathology which led to the valve replacement should also be considered when assessing risk. Women with congenital heart disease who have required prosthetic valve replacement often have complex cardiac lesions and may experience other cardiac complications such as arrhythmias. Small sized valves are often used if the valve replacement occurs in childhood, resulting in a functional stenosis in the adult, particularly with the increased cardiac output of pregnancy. Intravenous drug users who develop endocarditis and require prosthetic valve replacement may continue to have chaotic lifestyles and be poorly compliant with treatment. Other factors such as smoking, poor intravenous access, poor diet, and social issues increase the obstetric and neonatal risks (see also Chapter 4). Debate continues on which anticoagulant regimen is better in pregnancy, and whether low molecular weight heparin is as efficacious as warfarin, but this is outwith the scope of this chapter.
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Tetralogy of Fallot Usually, women with Tetralogy of Fallot tolerate pregnancy well. Those with severe pulmonary regurgitation are at highest risk of complications, which can include right ventricular failure (1.6%); arrhythmias (6.5%); preterm labour (18%), and small for gestational age babies (19%) [22]. Transposition of the great arteries The risks for women during pregnancy depend on the type of surgery the woman has undergone. In atrial switch procedures (operations such as a Mustard or Senning procedure), the right ventricle supplies the systemic circulation. These women are prone to develop arrhythmias and heart failure during pregnancy. About 38% will deteriorate in pregnancy and, in 12%, this will be a permanent deterioration in cardiac function [23]. Over the past 30 years, arterial switch procedures have been carried out in preference to the atrial switch described above. In this operation, the great arteries are switched around, so that the left ventricle supplies the systemic circulation. As this is a more modern operation, only small numbers of pregnancies have been reported [24]. It is thought that these women could potentially be prone to myocardial ischaemia and aortic root dilatation in pregnancy. Fontan All women with a Fontan type circulation are at high risk of maternal and fetal complications in pregnancy. Within this group, it is difficult to predict which women are at higher risk, as only small case studies have been reported [25]. They were also under-represented in the cohorts studied by Siu et al. [7] and Drenthen et al. [9] when developing their scoring systems, as many were advised against pregnancy. Pulmonary hypertension All women with pulmonary hypertension are at high risk of maternal mortality. Bedard et al. [26] carried out a systematic review of the literature and found 48 papers describing outcomes in 73 parturients who delivered between 1997 and 2007. An overall mortality rate of 25% was reported, but this was lowest (17%) in the women with idiopathic pulmonary hypertension and highest (33%) in women who had developed pulmonary hypertension secondary to an underlying medical condition. In women with congenital heart disease, it was 28%. Hierarchy of antenatal care The aim of an obstetric cardiac service is to provide women with appropriate co-ordinated multidisciplinary care, by clinicians with the appropriate level of expertise, in a setting where the appropriate facilities are co-located to support the woman and her baby around the time of delivery. For a woman with a low-risk condition, care can be provided by her local obstetrician, cardiologist, and community midwife, in her local hospital. Women with high-risk cardiac conditions will require care from a specialised obstetric cardiac team in a tertiary referral hospital, with obstetric, cardiology, cardiac surgery, specialised anaesthetic, intensive care, fetal medicine, and neonatal facilities all co-located. Other disciplines may also need to provide input, such as haematology, perfusionists, genetics, dentistry, reproductive and sexual health (abortion services and contraception). For women with low-risk conditions, appropriate referral pathways need to be in place so that care can be escalated promptly should the woman’s condition deteriorate during pregnancy, or should she develop other medical or obstetric co-morbidities.
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Guidelines for stratification of antenatal care The 2011 European Society for Cardiology guidelines suggest a system for stratifying risk and give an example of its application [27]. This can be further extended to stratification of the care the woman will need during pregnancy and around the time of delivery (Table 4). Organisation of antenatal care Many lessons relating to risk awareness and provision of care for women with cardiac problems in pregnancy can be learnt from the triennial confidential enquiries into maternal mortality in the UK. The most recent UK maternal mortality report [2] made clear recommendations that referrals to specialist services (such as an obstetric cardiac service) should be made immediately and prioritised as urgent. It stressed that not all maternity units are able or equipped to care for pregnant women with major complications, but such services should be accessible to all, and referrals should be made. It was also highlighted that some centres did not have experience of the management of some of the less common types of conditions seen in pregnancy. For example, some tertiary centre clinicians may have great expertise in ischaemic heart disease, but not in caring for a pregnant woman with congenital heart disease. It was also recommended that providers and commissioners should consider developing protocols to specify which medical conditions mandate at least a consultant review in early pregnancy, and that this agreement should take place via local maternity networks. Failure of clinicians to recognise important symptoms, failure to examine the patient adequately (particularly failure to listen to the heart), or failure to interpret electrocardiograms correctly [1], have resulted in failure to recognise risk and refer or escalate care. A lack of knowledge of potential complications of conditions such as peripartum cardiomyopathy has resulted in inappropriate risk stratification and women not being referred to specialist services [2]. Preconceptual care Ideally, all women of reproductive age with known cardiac disease should have preconceptual assessment, discussion of the potential risks involved in pregnancy, and a provisional outline given about the plan for care. This should be a multidisciplinary consultation with an obstetrician, cardiologist, and midwife present. The preconceptual assessment should not be viewed as a ‘one off’ appointment. Further assessments may be needed if there is a long interval between the initial preconceptual assessment and the time a woman decides to embark on pregnancy as her clinical status may have changed. The purpose of the preconceptual appointment is to provide a woman with a realistic view of the maternal and fetal risks involved in pregnancy and allow optimisation of her clinical condition before embarking on pregnancy [28]. Discussion should also include advice on appropriate contraception, as some women may choose not to embark on pregnancy if they perceive the risks are too great. Information about how to access obstetric cardiac services once pregnant, or how to access appropriate termination of pregnancy services is also important [1]. Referral to a clinical geneticist may be appropriate for women with genetically inherited conditions to enable women to understand the risks to the fetus and whether prenatal diagnosis is available. Antenatal care Unfortunately, not all women have preconceptual counselling, as young women are frequently lost to follow up at the time of transition between children and adult services. They then re-present to obstetric services when pregnant, often in a different hospital from where they had their cardiac care as a child. Although some women know many details of their condition and previous care, some have little knowledge of it, particularly if operations were carried out when they were very young. Information about when and where previous surgery was carried out can often be obtained from parents. It is then important to trace clinical details from previous hospitals to risk accurately during the current pregnancy; for example, the type of surgery undertaken for correction of Transposition of the Great Arteries.
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Table 4 Modified World Health Organization classification of maternal cardiovascular risk: principles and examples of application (European Society of Cardiology guidelines [27]). Class
Principle
Example of application
Suggested pattern of care
WHO I
No detectable increased risk of maternal mortality and no/mild increase in morbidity.
Care locally (secondary care and community midwife).
WHO II
Small increased risk of maternal mortality or moderate increase in morbidity. Significantly increased risk of maternal mortality or severe morbidity. Expert counselling required. If pregnancy is decided upon, intensive specialist cardiac and obstetric monitoring needed throughout pregnancy, childbirth, and the puerperium.
Uncomplicated, small or mild pulmonary stenosis patent ductus arteriosus mitral valve prolapse Successfully repaired simple lesions (atrial or ventricular septal defect, patent ductus arteriosus, anomalous pulmonary venous drainage); atrial or ventricular ectopic beats (isolated). WHO II (if otherwise well and uncomplicated) Unoperated atrial or ventricular septal defect; repaired tetralogy of Fallot; most arrhythmias. WHO II–III (depending on individual) Mild left ventricular impairment; hypertrophic cardiomyopathy; native or tissue valvular heart disease not considered WHO I or IV; Marfan syndrome without aortic dilatation; aorta 50 mm in aortic disease associated with bicuspid aortic valve; and native severe coarctation.
WHO III
WHO IV
Extremely high risk of maternal mortality or severe morbidity; pregnancy contraindicated. If pregnancy occurs termination should be discussed. If pregnancy continues, care as for class III.
Seen each trimester at tertiary centre but could deliver locally. Regular review at tertiary centre. Individualised plans for delivery depending on clinical condition, facilities and expertise in local hospital. Cared for at tertiary centre and reviewed at least monthly. Delivery in tertiary centre with ideally with all facilities co-located.
Advised against pregnancy and offered termination – but if continues cared for at tertiary centre and reviewed at least monthly. Delivery in tertiary centre with ideally with all facilities co-located.
NYHA, New York Heart Association; WHO, World Health Organization.
Some practical considerations need to be overcome when planning care for women. Antenatal care should lead seamlessly into planning delivery and postpartum care. It is, therefore, important that the woman has met the team in the hospital where her delivery takes place beforehand, and that the team of clinicians has had the time to assess her and gather the relevant information to formulate a multidisciplinary care plan for delivery. This is difficult if women present for care late in pregnancy, especially if the severity of the woman’s condition has not been recognised by the local team previously. Clearly defined referral pathways, with easy access to the team at the specialist centre, are vitally important.
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Fetal considerations Although the health and wellbeing of the mother always takes priority over fetal considerations, antenatal care for the woman with heart disease also needs to optimise the outcome for the fetus. Some of the more complex cardiac conditions, for example Fontan circulations, carry a high risk of miscarriage, growth restriction, and preterm delivery [9]. For women with inherited cardiac conditions, there will be a risk of the fetus inheriting the disorder; in autosomal dominant conditions such as Marfan syndrome, this risk will be one in two women. Although testing may be technically possible, it can be questioned whether this is ethically appropriate for some conditions. Consultation with a clinical geneticist can be helpful in arranging long-term follow up, and for arranging testing of the baby, child, or young adult at the relevant age. All women with structural congenital heart disease have an increased chance of having a fetus with congenital heart disease. In the UK population, an overall recurrence risk of 4.1% has been found [29]. The recurrence risk varies with the type of lesion in the mother, with heterotaxia, conotruncal defects, atrioventriculoseptal defects, and outflow tract abnormalities having the highest recurrence risks [30]. A fetal echocardiography should, therefore, be arranged in a Fetal Medicine Unit for all women with structural congenital heart disease. It should be remembered that the risks of congenital heart disease in the fetus are still present even if the woman has had her defect repaired, has no residual defect, and is now at low risk from cardiac complications herself (e.g. a woman with a repaired ventricular septal defect). Women with heart disease may be taking teratogenic or fetotoxic drugs (Table 5). An assessment needs to be made whether these can be discontinued or changed, or whether the maternal risks are such that they should be continued during the pregnancy, accepting the increased risk to the fetus [31,32]. If the drugs are continued, the fetus should be monitored for any adverse effects; for example, intracranial haemorrhage with warfarin, which could result in termination of pregnancy being offered. Poor fetal growth may be a problem in women with congenital or acquired heart disease. In women with congenital heart disease, those with cyanotic heart disease, Eisenmenger syndrome, Transposition of the Great Arteries, pulmonary atresia with ventriculoseptal defect, or Fontan type circulation, are at particular risk [3]. In women with acquired heart disease, it is often the underlying comorbidities, such as hypertension, which are associated with poor placental function and poor fetal growth [33]. Smoking, which is associated with ischaemic heart disease, has a strong dose-dependent association with fetal growth restriction [34]. If women with these conditions are not already taking aspirin, it should be commenced as early in pregnancy as possible. A recent meta-analysis of five trials, with 414 women at risk of pre-eclampsia, has shown that, when aspirin was started at 16 weeks of gestation or less, the relative risk of having a small for gestational age infant was 0.47 (95% CI 0.30 to 0.74), and the number needed to treat was 9 (95% CI 5.0 to 17.0) [35]. A high index of suspicion for fetal growth problems and clinical monitoring, supplemented where necessary with ultrasound monitoring, is needed in women with either congenital or acquired heart disease. Premature delivery also occurs more frequently in women with heart disease. This may be either due to the increased risk of spontaneous preterm labour or because iatrogenic preterm delivery is needed for maternal or fetal reasons. Women with Transposition of the Great Arteries and Fontan Table 5 Examples of drugs with adverse fetal effects. Drug
Teratogenic effect
Fetotoxic effect
ACE inhibitors Angiotensin II receptor blockers Statins
Ossification disorders of fetal skull. Ossification disorders of fetal skull.
Nephrotoxic effect leading to oligohydramnios. Nephrotoxic effect leading to oligohydramnios.
No conclusive evidence [28].
Beta blockers
No evidence of teratogenicity.
Warfarin
Warfarin embryopathy – nasal hypoplasia and epiphysial dysplasia.
Concerns about effect on brain myelination and neurodevelopment but no conclusive evidence. Lower birth weight when atenolol used in pregnancy [29], but no evidence of adverse effects with other beta blockers. Intracranial haemorrhage, microcephaly.
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circulation have a higher incidence of preterm pre-labour rupture of membranes [36]. Those with Ehlers Danlos syndrome seem to be at increased risk of cervical incompetence and preterm prelabour rupture of membranes. It has been postulated that this is due to the inherited collagen defect, and the risk seems to be higher when the fetus is also affected [37]. Delivery planning One of the main reasons for antenatal risk stratification of women with heart disease is to ensure that delivery occurs in a planned way, with the most appropriate personnel and facilities available. For low-risk women, this may be in their local hospital, but, for women with more complex heart disease, it will be in a specialist centre. Maternal mortality reports [1,2] and the Royal College of Obstetricians and Gynaecologists’ Good Clinical Practice guidelines [38] have stressed the need for written multidisciplinary care plans for delivery. Obstetric, cardiac, anaesthetic, and fetal considerations will all inform decisions about the mode, timing, and place of delivery. These decisions will be made antenatally, and should involve the woman, her family, and all members of the multidisciplinary team. The plan should include personnel who need to be notified on admission, planned mode of delivery, management of the second and third stages, place of delivery, and plans for the postnatal care. An important part of the care plan is to anticipate complications and contingency plan for these; for example, spontaneous preterm labour or postpartum haemorrhage. The care plan should also highlight what the main risks would be for that particular woman during delivery. An example of a care plan is given in the Royal College of Obstetricians and Gynaecologists’ Good Practice guideline on Cardiac Disease and Pregnancy [35]. Where possible, vaginal delivery should be the aim, as it is associated with less blood loss and infection risk compared with caesarean delivery [27]. Caesarean section also increases the risk of venous thrombosis and thromboembolism. Caesarean section should therefore be reserved for those women who are unable to safely increase cardiac output during labour, or where there are obstetric indications for cesarean section, for example placenta previa. Women who may need delivery by caesarean section are those with cyanosis, reduced ejection fraction, dilated aortic root, severe mitral or aortic stenosis, pulmonary hypertension, or ischaemia. None of these indications are absolute, and patient choice and previous obstetric history will influence the decision. A particular concern when aiming for a vaginal delivery would be whether a baby of a woman could be delivered sufficiently quickly if she required a category 1 cesarean section. (A category 1 cesarean section is carried out when there is a threat to the life of the mother or fetus, and most hospitals would aim for a decision to delivery interval of less than 30 min). This contingency should be planned for antenatally. The woman would need to be informed that, if this situation arose, her health would be prioritised over that of the fetus, and that a longer time may be needed to anesthetise her safely. This may, therefore, influence decisions about the place and mode of delivery. For women with complex heart conditions, there is a possibility that other disciplines may be required around the time of delivery (e.g. cardiac anesthetic support, cardiac surgery, or vascular perfusion services). Such women require delivery in a unit where these services are co-located. Postpartum care Women who are stratified as high risk antenatally are still likely to be at high risk in the postpartum period. Cardiac output is at its highest immediately after delivery, and many complications such as heart failure and dissection occur at this time. Plans for management of the woman in the immediate postpartum period should be made antenatally by the multidisciplinary team, and included within the care plan. Conclusion Increasing numbers of women with heart disease are embarking on pregnancy, and cardiac disease is the leading cause of maternal death in the UK. Providing appropriate care for this group of women is challenging, as it needs to meet the complex clinical needs of the woman, together with her emotional and psychosocial needs and the clinical needs of her fetus. Those at lower risk of complications should
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be cared for in their own local unit, whereas women with more complex needs will require specialist care from a multidisciplinary team experienced in dealing with cardiac disease in pregnancy. Risk stratification is, therefore, necessary to ensure women receive the appropriate pattern of antenatal care. It is also important that networks of hospitals, with clear pathways for referral and escalation of care, are developed so that women with heart disease in pregnancy can be supported through pregnancy and afterwards, and the best outcomes for the woman and her baby achieved.
Practice points Services for women with heart disease in pregnancy should be organised within networks so that all women have access to an appropriate level of care, with high-risk women being referred to specialist obstetric cardiac services. Recognised pathways, to facilitate referral to specialist obstetric cardiac services and to enable prompt escalation of care if complications occur, should be developed. All women with known or suspected congenital or acquired cardiac, aortic disease, or both, should be referred to an obstetric cardiac service in a specialist centre for pre-pregnancy risk assessment and counselling. This may include referral to clinical genetics. Women with previous peripartum cardiomyopathy are at high risk of recurrence, and should be referred to specialist obstetric cardiac services for preconceptual counselling and for care during subsequent pregnancies. In women with prosthetic heart valves, the underlying pathology that led to the valve replacement is likely to affect management in pregnancy. There should be a high index of suspicion for fetal growth problems in women with heart disease in pregnancy.
Research agenda A qualitative study to understand womens perception of risk and how information is best presented during preconceptual discussions. A study of outcomes in women with non-Marfan aortopathy in pregnancy. A study of maternal and fetal outcomes in women with prosthetic valves using different thromboprophylaxis regimens. Large cohort studies of specific cardiac lesions to provide outcome data and information about risk prediction.
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