The Determinant Analysis of Adverse Maternal and Neonatal Outcomes in Pregnancy with Pre-existing Heart Disease

Pregnancy and the peripartum period impose ongoing physiological stress on the cardiovascular system.¹ This syndrome causes several important changes in the body’s blood flow, such as an increase in blood volume, an increase in stroke volume and a decrease in systemic vascular resistance. These changes are meant to meet the needs of both the mother and the foetus. Pregnancy problems are more likely to arise in individuals with a history of heart disease. While most prevalent heart disease conditions are generally well tolerated and yield favourable clinical outcomes during pregnancy, certain conditions pose considerable risks, including maternal mortality and morbidity, characterised by rehospitalisation, heart failure, arrhythmias, thromboembolic events and strokes, as well as foetal/neonatal risks, such as intrauterine death, premature birth, low birthweight and congenital heart disease.

The pregnant women with heart disease experienced a 24% mortality rate, and 13% of cases showed morbidity, primarily due to complications from heart failure. Siu et al. reported maternal and foetal mortality rates of 26.14 and 50.48 per 1,000 pregnancies, respectively, in individuals with a history of heart disease.² The prevalence of pregnancy among patients with a history of heart disease currently affects approximately 0.3–3.5% of all pregnancies. The frequency and prevalence of pregnancy among women with heart disease vary by country, with a notable prevalence of up to 1.4% reported in Western nations. The prevalence of pregnancy complicated by heart disease in Asia ranges from 0.3% to 5.2%.^3–5

The description implies that pregnant women with a history of heart disease are at an increased risk of negative clinical outcomes for both the mother and the foetus. Notwithstanding significant progress in the prognosis and management of heart disease during gestation, clinical outcomes related to the cardiovascular system have not been thoroughly investigated. Due to the heightened incidence of negative clinical outcomes following childbirth, evaluating these outcomes is essential, as they are associated with prognosis and a greater risk of later cardiovascular events in maternal and neonatal adverse outcomes patients within 6 months postpartum.^3–5

Although a meta-analysis and systematic review on maternal clinical outcomes in pregnant women with heart disease in South Asia was conducted in 2022, the findings are restricted to the causes of congenital heart disease (CHD) and rheumatic heart disease, excluding other aetiologies and disregarding all countries, including Indonesia. Information regarding the factors influencing cardiovascular events in neonates and mothers within 6 months postpartum is quite limited. Moreover, no studies have been undertaken on this matter in Indonesia.^2,6

Methods

Study Design

This retrospective cohort study was conducted at Dr. M. Djamil Padang Hospital, a tertiary referral centre, and included pregnant women with pre-existing structural heart disease who were managed during pregnancy and/or admitted for delivery between January 2017 and January 2024. Patients were identified through obstetric and cardiology service records. To provide additional context, a total of 4,097 deliveries, including vaginal deliveries and both emergency and elective caesarean sections, were recorded at Dr. M. Djamil Padang Hospital during the same study period. Of the 193 total deliveries involving cardiac disease, 83 cases were excluded due to incomplete data (n=21), pre-eclampsia/eclampsia (n=38), gestational hypertension (n=5), peripartum cardiomyopathy (n=7), placenta previa or placental abruption (n=9) and moderate-to-severe anaemia (n=3), resulting in 110 eligible cases (56.99%) for final analysis.

Data collected included maternal demographic and clinical characteristics, type and severity of heart disease, echocardiographic parameters, and pregnancy outcomes. Maternal clinical parameters at admission, such as blood pressure, heart rate, respiratory rate and peripheral oxygen saturation, were also recorded. Peripheral oxygen saturation <90% was determined using pulse oximetry and confirmed by medical records. This hypoxia was defined as saturation <90% due to acute heart failure and not in the context of cyanotic congenital heart disease.

We also recorded the use of antihypertensive agents during hospitalisation, including classes such as labetalol, methyldopa and nifedipine, which are considered safe in pregnancy. Notably, while 15% of patients were documented as receiving angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or mineralocorticoid receptor antagonists, these agents were prescribed prior to hospital admission.

To assess risk stratification and predictive performance for adverse maternal cardiac events, we applied four validated risk models: the modified WHO (mWHO) stratification, CARPREG II score, ZAHARA score and DEVI score. The discriminative ability of each model was evaluated using receiver operating characteristic (ROC) curve analysis. Ethical approval was obtained from the institutional review board.

Statistical Analysis

Data were analysed using IBM SPSS Statistics version 29.0 (IBM Corporation). Continuous variables were summarised as mean ± SD, while categorical variables were expressed as frequencies and percentages. Group comparisons were performed using the χ² test or Fisher’s exact test, as appropriate. Multivariate logistic regression was used to identify independent predictors of adverse maternal and neonatal outcomes. Results were reported as OR with 95% CI. The discriminative performance of significant predictors and the final logistic regression model was assessed using ROC curve analysis. The area under the curve (AUC) was calculated to determine predictive accuracy. The optimal cutoff value was derived using Youden’s index, with corresponding sensitivity and specificity reported. A p-value <0.05 was considered statistically significant.

Results

Maternal Characteristics of the Study Subjects

A study was performed on the medical records of pregnant women with a history of cardiac disease at Dr. M. Djamil Padang Hospital from January 2017 to January 2024. Out of 193 pregnant women with cardiac disease, 83 were excluded for not meeting the research requirements, resulting in 110 patient cases included in the study. The univariate analysis is presented in Supplementary Table 1.

The mean age of patients was 30.52 ± 6.00 years. None of the patients had a history of smoking. The most common cardiac condition was valvular heart disease (28%), of which 78% were rheumatic in origin. Among congenital heart diseases, acyanotic types predominated (60%), with atrial septal defect and ventricular septal defect being the most frequent, accounting for 33.4%. Among patients with arrhythmia, the distribution was relatively even: 35% bradyarrhythmias, 30% supraventricular arrhythmias (AF and supraventricular tachycardia) and 35% ventricular arrhythmias (premature ventricular contraction).

Upon admission, clinical assessment revealed that in patients with cyanotic heart disease, the average initial maternal peripheral oxygen saturation was 84%. Meanwhile, among patients with heart conditions other than cyanotic heart disease, two patients (2%) had maternal peripheral oxygen saturation <90% on admission due to acute heart failure. Of the patients with heart failure, 22% were classified as functional class III–IV. A total of 21% of cases were classified as mWHO class III or IV, and 21.8% had a CARPREG score >2 on admission. According to obstetric statistics, 99% of patients had singleton pregnancies, with more than half of deliveries occurring at term (55.4%). The majority of deliveries (85.4%) were by caesarean section, with more than half classified as emergencies (54%).

Adverse Maternal and Neonatal Outcomes

A total of 30 patients (27.2%) encountered adverse maternal outcomes within 6 months postpartum. When calculated against the total cohort (n=110), the event rates were 10% for mortality, 8.2% for heart failure, 4.5% for arrhythmia, 3.6% for re-hospitalisation and 0.9% for thromboembolism. Simultaneously, adverse neonatal outcomes were observed in 63 patients (57.3%) of the total cohort, with event rates of 5.4% for neonatal mortality, 16.4% for low Apgar scores, 28.2% for prematurity, 6.4% for low birthweight and 0.9% for congenital cardiac disease (Tables 1 and 2). The bivariate analysis of maternal clinical outcomes in this study revealed that cyanotic heart disease (p=0.041) was a determinant of adverse neonatal outcomes (Table 3). Multivariate logistic regression analysis using the backward method revealed that moderate-to-severe left heart obstruction (OR 16.211; 95% CI [2.725–73.836]; p=0.015) and ejection fraction values <40% (OR 14.184; 95% CI [1.712–153.507]; p=0.002) are the most significant predictors of adverse maternal outcomes within 6 months postpartum (Table 4). The logistic regression study using the backward technique revealed factors influencing adverse neonatal outcomes in pregnancies complicated by heart disease, in which CHD cyanosis (OR 8.449, 95% CI [1.030–69.328]; p=0.047) was a determinant of unfavourable neonatal outcomes.

Receiver Operating Characteristic Analysis for All Maternal Outcomes

Based on the overall analysis (Figure 1A), the mWHO stratification emerged as the most reliable predictive model for identifying all adverse maternal outcomes, defined as the combined maternal morbidity and mortality. This model achieved the highest AUC of 0.48 on the ROC analysis, indicating its discriminative ability among the evaluated scoring systems. Despite other models performing better at specific thresholds, mWHO provided a balanced sensitivity and specificity, making it a tool for early risk stratification.

Receiver Operating Characteristic Analysis for Mortality

In the second analysis focusing on mortality prediction (Figure 1B), the DEVI score demonstrated the best performance among all evaluated models. This is supported by the visual ROC curve analysis, where the DEVI curve shows the largest AUC (0.71), indicating its strongest discriminative ability.

Receiver Operating Characteristic Analysis for Morbidity

When focusing on maternal morbidity alone, mWHO again demonstrated the best performance, with an AUC of 0.66 (Figure 1C). It proved to be an effective model for identifying patients at risk of complications, supporting its potential application in clinical decision-making.

Discussion

This study involved pregnant women with heart disease, with a mean age of 30.52 ± 6.00 years. Most had been diagnosed before pregnancy, and the most common type was valvular heart disease (28%), predominantly caused by rheumatic heart disease (87.5%). Echocardiographic evaluation showed that 13.6% had moderate-to-severe left-sided valvular stenosis, 7.5% had a left ventricular ejection fraction <40 and 4.5% had impaired right ventricular function. Anticoagulant use was reported in 3.6% of patients, mainly among those with severe mitral stenosis or mechanical valves, although none received oral doses >5 mg during the first trimester. Cardiac medications, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and mineralocorticoid receptor antagonists, were administered to 15.4% of patients before hospital admission.

Nearly all cases (99%) were singleton pregnancies, with the majority delivered via caesarean section (85.4%). Among these, six out of 95 caesarean deliveries (6.3%) were performed primarily due to maternal cardiac concerns, such as decompensated heart failure, cyanotic heart disease or significant arrhythmia, while the remainder were based on obstetric considerations, including previous caesarean delivery, transverse foetal presentation, suspected foetal demise or foetal distress.

Adverse maternal outcomes within 6 months postpartum were observed in 27.2% of patients, including mortality (10%), heart failure (8.2%), arrhythmia (4.5%), rehospitalisation (3.6%) and thromboembolic events (0.9%). Meanwhile, 57.3% experienced adverse neonatal outcomes, such as preterm birth (28.2%), low Apgar scores (16.4%), low birthweight (6.4%), neonatal death (5.4%) and congenital heart disease (0.9%), particularly among those with chronic hypertension or congenital heart disease.

The majority of valvular heart disease cases in this study were caused by rheumatic heart disease (87.5%), with 32% of patients experiencing moderate-to-severe mitral or aortic stenosis, which serves as a major risk factor for left ventricular obstruction and cardiovascular complications during pregnancy. Additionally, 9.6% of patients had prosthetic valves, further increasing the risk of cardiovascular events.

Among patients with congenital heart disease, 40% presented with cyanotic conditions, including defects, such as tetralogy of Fallot, double outlet right ventricle and ventricular septal defect with bidirectional shunting. The remaining 60% had acyanotic conditions, predominantly atrial septal defect and ventricular septal defect, with several having undergone corrective interventions. These cardiac abnormalities, combined with a diverse arrhythmia profile (35% bradycardia, 30% supraventricular and 35% ventricular arrhythmias), highlight the complexity of risk in this population, and underscore the need for specialised monitoring and management throughout pregnancy and the postpartum period.

Pregnancy is a naturally hypercoagulable state due to increased procoagulant factors (fibrinogen) and decreased anticoagulant activity (free protein S, antithrombin). These changes alter coagulation parameters (prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, etc.), making pregnancy-specific reference ranges essential.⁷ While hypercoagulability helps prevent haemorrhage during delivery, it also increases the risk of serious complications, such as disseminated intravascular coagulation and postpartum haemorrhage, especially when associated with placental abruption, HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome or infections.⁸ In such cases, haemostatic therapies, such as fresh frozen plasma, fibrinogen concentrate, tranexamic acid and recombinant factor VIIa, may be lifesaving.^9–11

Although only 3.6% of pregnant patients use anticoagulants, mainly those with mechanical heart valves or severe mitral stenosis, this raises concerns. Vitamin K antagonists can cross the placenta in the first trimester and may cause embryopathy. Even though high doses (>5 mg) were not used in the study, evidence supports switching to heparin between 6 and 12 weeks to reduce foetal risk.^7,8,12–18

Multivariate logistic regression revealed that moderate-to-severe left heart obstruction (OR 16.211; p=0.015) and ejection fraction <40% (OR 14.184; p=0.002) were strong predictors of adverse maternal outcomes within 6 months postpartum, while cyanotic CHD (OR 8.449; p=0.047) was a key risk factor for poor neonatal outcomes. Both left heart obstruction and reduced ejection fraction reflect impaired cardiac output, which compromises maternal organ perfusion and increases the risk of cardiac decompensation during pregnancy and the postpartum period.^19,20 Meanwhile, cyanotic CHD leads to chronic hypoxemia due to the mixing of deoxygenated blood into systemic circulation, which in pregnancy results in reduced placental and foetal oxygenation.^21,22 This diminished oxygen and blood flow to the fetoplacental unit can lead to intrauterine growth restriction, prematurity and other perinatal complications.²³ These findings highlight that reduced cardiac output and inadequate maternal oxygenation play a central role in determining adverse outcomes for both mother and baby.

In this study, the mWHO stratification showed the most consistent and reliable performance in predicting overall adverse maternal outcomes, with the highest AUC among all models. It effectively distinguished between high- and low-risk patients for both mortality and morbidity. For mortality specifically, the DEVI score achieved the highest AUC (0.71), indicating superior ability to identify patients at highest risk of death, although it involves more complex variables. For morbidity alone, mWHO again performed best, making it the most practical tool for early detection of non-fatal maternal complications.

In contrast, ZAHARA and CARPREG II showed lower AUC values and Youden indices across all outcomes, likely due to differences in population characteristics during their development. ZAHARA, for example, was derived from European cohorts with congenital heart disease, while DEVI was developed in India with distinct inclusion criteria and healthcare settings. Notably, DEVI, as a model from an Asian context, showed strong potential for mortality prediction and may serve as a useful complementary tool in similar settings.^24–27 The mWHO stratification demonstrated good predictive ability for cardiac complications, with an AUC of 0.71 (95% CI [0.67–0.76]). Globally, it has shown moderate performance (c-statistic 0.711), performing better in developed (0.726) than in developing countries (0.633).²⁸

This study provides practical guidance for managing pregnant women with heart disease in Asia, where both congenital and acquired conditions are common. The WHO functional classification emerged as a reliable and easy-to-use tool for predicting both maternal and neonatal outcomes, particularly for early identification of patients at risk of major morbidity and mortality. The DEVI score, while offering strong sensitivity for mortality prediction, has limited specificity, suggesting its optimal use in combination with WHO for more accurate risk stratification and clinical decision-making. Their use is crucial for reducing maternal and neonatal morbidity and mortality, particularly during the high-risk postpartum period.

Limitations

Several limitations of this study must be acknowledged. First, the relatively small sample size and single-centre design may limit the generalisability of the findings. Second, this study is a retrospective analysis using existing medical records; hence, it is limited by deficiencies in data completeness, particularly with antenatal care information.

Conclusion

This study revealed that moderate-to-severe left heart obstruction and a reduced ejection fraction of <40% were the most significant factors influencing adverse maternal outcomes. Meanwhile, cyanotic CHD was the most important determinant of adverse neonatal outcomes.

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