Pregnancy outcome in women with an uncorrected single ventricle: A single-centre experience from South India

Abstract

Background

Women with an uncorrected single ventricle heart are at increased risk of adverse maternal and perinatal outcomes.

Methods

We report our experience of managing pregnant women with uncorrected single ventricles, during the time period 2011 to 2017, in a low-resource setting and compare pregnancy outcome with healthy concurrent controls. Outcomes assessed include the mode of delivery, maternal complications, neonatal death and birth weight.

Results

There were six pregnant women with uncorrected single ventricles who had a total of 14 pregnancies. There was one maternal death in a woman with atrioventricular-septal defect and Eisenmenger syndrome. Caesarean section rates and preterm delivery were similar, whereas perinatal loss and low-birth weight rates were higher among women with a single ventricle compared to healthy controls.

Conclusion

Unplanned pregnancies without prenatal counselling/care pose a challenge to physicians especially in low to middle income countries and with the high risk of morbidity/mortality, pregnancy should be discouraged.

Keywords

Single ventricle arrhythmia Eisenmenger syndrome double outlet right ventricle

Introduction

Survival of women with complex congenital heart disease is improving with the advances in medicine.¹ Univentricular heart or single ventricle accounts for 0.5–1.5% of women with congenital heart disease.^2,3 Survival to adulthood is rare in uncorrected cases, with very few achieving successful pregnancy outcome.^2–13 Systemic and pulmonary circulations originate from the single ventricle where mixing of saturated and desaturated blood occurs, leading to a varying degree of systemic arterial desaturation. Maladaptation to the haemodynamic changes of pregnancy results in an increased risk of maternal and fetal complications.^13,14

Pregnancy is discouraged due to this increased risk of morbidity and mortality as per the modified WHO classification.¹⁵ Unlike high-income countries where these women may receive care in specialized tertiary centres which offer pre-pregnancy counselling and a multidisciplinary team-based approach, in low to middle income countries the majority of the pregnancies are unplanned without any prior optimization of the maternal cardiac status. Regional centres are consulted or referral occurs when complications develop.¹⁶ This situation poses a challenge to the multidisciplinary team. Here we report our experience of management of women with a single ventricle who all, with the exception of one, had unplanned pregnancies, and compare them with healthy controls.

Materials and methods

All women with a diagnosis of an uncorrected single ventricle admitted during the time period from 2011 to 2017 to Women and Children Hospital, Jawaharlal Institute of Medical Education & Research (JIPMER), Puducherry, India, from an ongoing study of pregnancy outcome in women with congenital heart disease were included in the study. Cases were defined as those with both atria or a common atrium completely or almost completely draining into a single ventricle on either side. For each pregnancy in a woman with single ventricle (case), four women matched for age (±2 years), without a diagnosis of heart disease were included as controls (n = 56). We collected demographic details (such as age, parity), medical (age at diagnosis, primary diagnosis, medication if any received and echocardiographic details) and obstetric details (whether she received pre-pregnancy counselling, gestational age at delivery, mode of delivery, neonatal outcome, birth weight and details of neonatal complications). Outcomes compared were mode of delivery, maternal mortality, neonatal death and low birth weight. The study was approved by the Institute Ethics Committee (Human Studies).

Statistical analysis

We performed statistical analysis using STATA 13.1 software (Stata Corp 13.1, Texas, USA). Continuous and categorical outcomes were presented as means (standard error) and frequency (percentage), respectively. Comparison of the outcomes were done using either Chi-square test, Student’s t-test or Kruskal–Wallis test as appropriate. Statistical significance was determined by a p-value less than 0.05.

Results

During the study period, there were six pregnant women with an uncorrected single ventricle, with 14 pregnancies. Among these six women, three had double outlet right ventricle (DORV) with ventricular septal defect (VSD), two had atrioventricular canal defect (AVCD) and one had a single ventricle of left ventricular morphology with transposition of the great vessels (Figure 1). Details regarding the maternal characteristics are shown in Table 1. Among these six women, only one with DORV with VSD (Patient 5) received counselling and prenatal care. She had four pregnancies and had three first trimester spontaneous miscarriages before having a term pregnancy that resulted in a livebirth. Among the two with AVCD, one (Patient 1) died following delivery at 26 weeks (as discussed later in results), and the other (Patient 2) developed complete heart block following her second delivery (presented with syncopal attacks) and a permanent single chamber ventricular pacemaker was placed. Both these women had severe pulmonary hypertension (mean pulmonary artery pressure (mPAP) during right heart catheterisation was 90 and 110 mmHg respectively) and were on sildenafil therapy. One (Patient 4) among the three with DORV was diagnosed during pregnancy when she presented with heart failure and cyanosis. Another one with DORV (Patient 6) was diagnosed with severe pulmonary hypertension (mPAP 70 mmHg) on cardiac catheterisation and was started on sildenafil.

Figure 1.

Anatomy of single ventricle defects. (a) Complete atrioventricular canal defect; (b) double outlet right ventricle with ventricular septal defect; (c) single ventricle with transposition of the great arteries. Ao: aorta; PA: pulmonary artery; RA: right atrium; LA: left atrium.

Table 1.

The maternal characteristics.

Characteristics	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6
Cardiac lesion	AVCD unbalanced	AVCD unbalanced	Single ventricle (LV morphology) with TGA	DORV with subpulmonic VSD	DORV with subpulmonic VSD with severe PS	DORV with subpulmonic VSD
Age at diagnosis	6 years	15 years	At birth	21 years (during pregnancy)	7 years	10 years
Pulmonary hypertension	Yes	Yes	No	No	No	Yes
Symptoms at presentation	Cyanosis	Breathlessness, cyanosis	Cyanosis	Breathless, palpitations	Cyanosis	Breathlessness, cyanosis
SpO₂	70.0%	86%	78%	85%	76%	80%
Medications	Sildenafil, furosemide, aspirin	Furosemide, sildenafil	Aspirin, furosemide	Aspirin, furosemide	Aspirin	Aspirin, sildenafil
Number of pregnancies (outcome)	1 (preterm/neonatal loss)	3 (3 term live births)	3 (1 termination of pregnancy, 1 each of preterm and term live births)	1 (preterm live birth)	4 (3 terminations of pregnancy and 1 preterm live birth)	1 (term live birth)
Cardiac complications	Pulmonary oedema, cardiac arrest following arrhythmia	Pacemaker inserted at 19 years for CHB	None	None	None	Pulmonary oedema

AVCD: atrioventricular canal defect; CHB: complete heart block; TGA: transposition of the great vessels; DORV: double outlet right ventricle; VSD: ventricular septal defect; PS: pulmonary stenosis; LA: left atrium.

Four pregnancies in women with an uncorrected single ventricle resulted in first trimester miscarriage, whereas pregnancy continued beyond 20 weeks in the remainder (n = 10). Age at pregnancy was comparable with the controls (n = 56) who did not have any heart disease (20.4 ± 3.0 years vs. 21.7 ± 2.2 years, p = 0.113). Median gestational age at delivery was lower among pregnancies in women with a single ventricle compared to the controls (36.1 (range: 24–38.5) weeks vs. 39.2 (range: 28.4 – 41.3) weeks, p = 0.009). Caesarean section rates (20.0% vs. 7.1%, p = 0.193), preterm delivery (40.0% vs. 23.2%, p = 0.264) were comparable with those who did not have heart disease. Among the 10 pregnancies which continued beyond 20 weeks, two were complicated with intrauterine growth restriction. Among the two women with a single ventricle who underwent caesarean section, one was an elective caesarean section in view of intrauterine growth restriction with absent end diastolic flow and the other was done in view of heart disease, whereas fetal distress was the reason in the control group. There were three perinatal losses (30.0%, one still-birth and two neonatal death) in those women with single ventricle compared to one neonatal death (2.6%) in those without cardiac disease (p = 0.005). One of the neonatal deaths was due to suspected cyanotic heart disease (fetal echocardiogram was not done and the death occurred prior to neonatal imaging). Neonatal echocardiography was done in six babies born to women with a single ventricle and was reported as normal. Mean birth weight was lower in babies born to women with single ventricle compared to the controls (1819.0 ± 232.8 g vs. 2543.0 ± 86.5 g, p = 0.002). The majority of the infants were low birth weight (80.0%) compared to 34.2% (n = 13) among the controls (p = 0.009). No women in the study had post-partum haemorrhage. Wound infection following caesarean section occurred in a woman with DORV, which was managed with antibiotics.

There was one maternal death (Patient 1) in the study. This 19-year-old primigravida was admitted with heart failure and cyanosis at 25 weeks. At the age of six years, she had been diagnosed with an AVCD and found to have Eisenmenger syndrome following cardiac catheterization. She was under regular follow-up until 15 years of age. She and her parents were counselled regarding her condition and the risks of future pregnancy, and were advised against it. Subsequently, she was lost to follow-up and married her maternal cousin. She conceived, as the social and the familial pressures were high, in spite of the risks involved. She stopped her medications without medical advice due to the concerns from the family regarding teratogenic effects of medications (sildenafil). She was admitted to the intensive care unit. She was managed medically with diuretics and was restarted on sildenafil therapy. She had preterm labour at 26 weeks and delivered a 480 g infant, after a labour of six hours. She was given opioid analgesia during labour. On the second post-partum day, she had a syncopal attack during micturition and sustained a sudden cardiac arrest due to ventricular fibrillation from which she could not be revived. The baby expired within few hours of birth due to complications of extreme prematurity.

Discussion

Univentricular heart is a rare form of cyanotic congenital heart disease where the reported survival to adulthood is unusual. This condition is described based on the atrioventricular connection, with both atria completely or almost completely drain into a single ventricle of right, left or intermediate morphology.^13,16,17 This results in total mixing of systemic and pulmonary venous return, leading to cyanosis. The aorta and pulmonary artery may arise from this single chamber; although in some cases it may arise from a rudimentary outflow chamber which is incapable of supporting either systemic or pulmonary circulation. Aorta may be anterior (malposition), posterior or on either side of the pulmonary artery.^16–18

Changes in pregnancy and the maternal–fetal risk

With advances of care more women with a single ventricle are surviving to reproductive age. There is therefore a need to understand the physiological changes which increases the risk in pregnancy and puerperium. Maternal and neonatal complications are increased in these women, with corrective surgery reported in the literature to reduce the risks.^19–20 The rise in cardiac output and the reduction in the systemic vascular resistance accompanying pregnancy can result in increasing maternal hypoxemia, cyanosis and polycythemia due to an increase in right to left shunting. The presence of pulmonary hypertension, ventricular dysfunction and functional class III/IV are associated with adverse maternal outcome.^13–15,21 Pulmonary hypertension can lead to reduced oxygen saturation, increased right to left shunting and polycythemia. These changes increase the risk of complications in pregnancy.¹³ In women with a single ventricle, systemic oxygen saturation is dependent upon the extent of mixing and in most cases, in the absence of pulmonary outflow obstruction or hypertension, the oxygen saturation remains above 80%. In this study, all women had resting saturations below 90%. Patient 1 had AVSD and no right ventricular outflow stenosis but had cardiac complications and reduced pulmonary oxygenation secondary to elevated pulmonary vascular resistance. Oxygen saturation of Patients 3 and 4 were below 80%; however, there were no adverse outcomes attributed to lower saturation levels.

Maternal complications include pre-eclampsia, embolism, thrombosis, pulmonary oedema and arrhythmias.^4,13 In the present series, there were two women with pulmonary oedema which was managed medically. However, none in the present series were diagnosed with pre-eclampsia. Women with pulmonary hypertension were treated with sildenafil and one of them died as a result of an arrhythmic episode following delivery. Fetal complications include miscarriages, preterm births, low birth weight and cardiac anomalies.^4,13 There were four miscarriages and three perinatal losses among 14 pregnancies, suggesting a higher risk of pregnancy losses (7/14) in women with a single ventricle, although the incidence of preterm birth and the low birth weight were higher than the low-risk control group.

Management of labour and delivery

A multidisciplinary team approach, with cardiologist, obstetrician, anaesthetist and neonatologist in the management in labour and delivery can help to optimize the outcomes.^14,15,22 All cases in this study received care from a multidisciplinary team. Wang et al.¹³ reviewing the literature of pregnancy outcome in women with a single ventricle (from 1963 to 2015) reported that the majority of women were delivered by caesarean section under epidural or general anaesthesia. In our series, caesarean section was done under general anaesthesia in two women and the majority of the women delivered vaginally. All women had normal ventricular function in the study and tolerated the labour and delivery well in spite of two women having pulmonary hypertension. Follow-up visits in pregnancy and re-admission will be guided by the risk stratification and the development of maternal or fetal complications.

Pre-conception counselling

Pregnant women with uncorrected single ventricle will be under World Health Organization Class III/IV of maternal risk (depending on the presence or absence of pulmonary hypertension) due to the high risk of maternal and fetal complications compared to general low-risk women.^13–15 Management of these women should be planned and the pregnancy risks involved be explained during the visits in the pre-conception period. The need for early booking in pregnancy must be emphasized, to evaluate the cardiac function and perform risk stratification which will guide further management. In women with severe pulmonary hypertension or significant ventricular dysfunction, pregnancy should be discouraged and termination of early in first trimester should be offered, if unplanned pregnancy occurs.^13–15,22

Challenges in low to middle income countries

In low to middle income countries, most of these women have unplanned pregnancies without any prenatal counselling or evaluation. In the present series, only one woman (Patient 5) had prenatal care and counselling, whereas the one who had AVCD with severe pulmonary hypertension (Patient 1) who was advised against pregnancy did not report to hospital until she had heart failure due to the fear of discouraging pregnancy if she attended hospital early. In addition to missing the antenatal visits, she stopped all her medications due to concerns of teratogenicity. Booking in pregnancies are delayed due to either cultural/social beliefs about motherhood or pressure from the family to have a child (as in our case who died from her illness), and the proximity of expert centres to their villages. As there are no routine neonatal screening programmes for congenital heart disease in most of these countries, it poses a further challenge to the treating team when the diagnosis is made during pregnancy (Patient 4) and optimal evaluation of the lesion is not performed or possible due to concerns of risk to the fetus.

Despite advances in care, women with a single ventricle are at increased risk of maternal or fetal complications. In spite of the risks involved and counselling against conception, women embark on the ‘unplanned’ journey of motherhood due their own desire or pressure from family to have a child; perhaps more in low to middle income countries. In the absence of risk factors such as ventricular dysfunction, pulmonary hypertension and worsening of functional class, a successful outcome may result if appropriate multidisciplinary care is provided. In contrast to the high-income countries where many women with these conditions undergo pre-conceptional counselling and risk stratification in early pregnancy, unplanned pregnancies in these women in low to middle income countries pose an additional challenge to the treating team.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

The authors assert that all procedures performed in this study were done with the ethical standards set by the Institute Scientific Advisory and Ethical committee (Human Studies), in accordance with the 1964 Helsinki declaration and its later amendments. Waiver of consent and the protocol of the ongoing study on ‘Pregnancy outcome in women with congenital heart disease’ was approved by the Institute ethics committee (Human studies) (No. JIP/IEC/2016/1105).

Informed consent

Not applicable as waiver of consent was approved by Institute Ethics Committee.

Guarantor

AK.

Contributorship

AK was involved in designing, writing the draft and approved the final version. AR and JB were involved in designing, collection and revision of the manuscript. AAP was involved in designing the study, analysis, reviewed, revised and approved the manuscript. NP and SS were involved in designing, revision of the manuscript. All authors reviewed and approved the final draft.

Acknowledgements

None.

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