Highlights
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Among 1,108 pregnant women with cardiac disease, there were high rates of adverse neonatal outcomes (33.7%).
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Women with pulmonary hypertension, hypertensive disease, congenital heart disease, and cardiomyopathy had the highest risk of an adverse neonatal outcomes.
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Structural heart disease as assessed by echocardiography was not associated with adverse neonatal outcomes in the total study population and in a subgroup of women with congenital heart disease.
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In the congenital heart disease subgroup, single ventricle palliation, a CARPREG II score > 4, and the presence of an adverse cardiac outcome during pregnancy was associated with an adverse neonatal outcome.
Abstract
Women with cardiac disease have worse neonatal outcomes compared to women without cardiac disease; risk factors are not well-defined. We hypothesized that structural heart disease, as assessed by echocardiography, is a noninvasive metric for abnormal hemodynamics and an unfavorable maternal-fetal environment. We assessed the association between echocardiographic markers of structural heart disease in women with cardiac disease and a primary endpoint of adverse neonatal outcomes operationalized as neonates with small-for-gestational-age birth weight, preterm delivery, neonatal intensive care unit/transition care unit admission, or neonatal/fatal demise. Women with cardiac disease who delivered at a tertiary care center between 2014 and 2022 were included. Echocardiographic parameters and neonatal outcomes were collected. A subgroup analysis was performed among women with congenital heart disease (CHD). Among 1,108 women, maternal diagnoses of pulmonary hypertension (OR 5.7, 95% CI 1.8–18.6), hypertensive disease (OR 3.8, 95% CI 2.4–6.2), CHD (OR 2.2, 95% CI 1.3–3.8), and cardiomyopathy (OR 2.0, 95% CI 1.1–3.8) were associated with the primary endpoint. Peak tricuspid regurgitation velocity was associated with the primary endpoint (OR 1.9, 95% CI 1.2–3.1). Biventricular function and severity of valvular disease were not associated with the primary endpoint in the total study population and in the CHD subgroup. In conclusion, maternal cardiac diagnosis is associated with adverse neonatal outcomes. Structural heart disease as assessed by echocardiography was not predictive of adverse neonatal outcomes. Large-scale studies are needed to identify drivers of adverse neonatal outcomes in women with cardiac disease.
Introduction
The prevalence of maternal cardiac disease during pregnancy is increasing. Risk assessment models for predicting adverse outcomes in women with cardiac disease focus largely on adverse maternal cardiac and obstetric outcomes. ,, However, women with cardiac disease, including those with congenital heart disease (CHD), also have worse neonatal outcomes, including higher rates of neonates with small-for-gestational-age birth weights and preterm delivery, compared to women without cardiac disease. Risk factors for adverse neonatal outcomes among women with cardiac disease are not well-defined though likely include poor hemodynamics, abnormal placental development, or genetics. A more complete understanding of predictors of adverse neonatal outcomes is necessary to counsel women with cardiac disease as part of preconception risk stratification. Moreover, understanding drivers of adverse neonatal outcomes will guide clinicians to care for their patients through pregnancy and reduce the probability of these events. We hypothesized that structural heart disease as assessed by echocardiography is a noninvasive surrogate for abnormal maternal hemodynamics and an unfavorable maternal-fetal environment. In this study, we sought to identify echocardiographic predictors of adverse neonatal outcomes in a large cohort of women with both acquired heart disease and CHD.
Methods
Data source and study population
Patients with pre-existing cardiac disease who became pregnant and delivered at Columbia University Irving Medical Center/New York Presbyterian Hospital between 2014 and 2022 were included in this study. Patients ≥ 18 years of age were retrospectively chosen for this study if they had an echocardiogram at our institution during pregnancy. If a patient had multiple deliveries during this time period, only the first delivery at our center was included in this study. Patient characteristics, imaging results, maternal, obstetric and neonatal outcomes were collected and managed using an institutional database. Our Institutional Review Board’s approval and waiver of consent was granted for this retrospective study.
Demographics, comorbid conditions as well as maternal, obstetric and fetal outcomes were obtained from chart review from the index delivery admission. Maternal cardiac disease was categorized into broad categories based on review of ICD-9 and ICD-10 codes, as well as manual review of the cardiovascular and obstetric notes in the electronic medical record. Maternal cardiac disease categories were: arrhythmias, coronary artery disease, aortopathy, cardiomyopathy, valvular heart disease, pulmonary hypertension, CHD, hypertensive disease, and other (women with nonspecific cardiac symptoms [i.e., palpitations, shortness of breath, or chest pain] without documented arrhythmia or structural heart disease). Cardiomyopathy included those with current or previous systolic dysfunction, hypertrophic cardiomyopathy, restrictive cardiomyopathy. Bicuspid aortic valve disease and pulmonic stenosis was classified as CHD. Mitral valve prolapse was classified as valvular heart disease. Patients with valve replacements were categorized based on their initial cardiac pathology (e.g., those with rheumatic heart disease requiring valve replacement were included in valvular heart disease, and those with bicuspid aortic valve requiring valve intervention were included in CHD). For those with CHD, maternal cardiac disease was further categorized into more specific subtypes based on the type of congenital heart defect, including: right heart lesion (Tetralogy of Fallot, pulmonary valve disease, Ebstein’s anomaly), left heart lesion (coarctation of the aorta or other left heart obstructive lesion, congenital aortic or mitral valve disease), shunt lesions (atrial septal defect, ventricular septal defect, anomalous pulmonary venous return), transposition of the great arteries, and single ventricle palliation.
All patients included in this study underwent echocardiography during pregnancy. Echocardiogram results were collected from the first echo obtained during pregnancy. The interpretation of images were all performed at the study institution by attending Cardiologists with dedicated subspecialty echocardiography training. Echocardiographic variables included were left ventricular ejection fraction (%), interventricular septum thickness (cm), left ventricular posterior wall thickness (cm), left ventricular end diastolic diameter (cm), left ventricular end systolic diameter (cm), right ventricular function (normal, mildly reduced, moderately reduced, severely reduced), right ventricular size (normal, mildly dilated, moderately dilated, severely dilated), tricuspid regurgitation peak velocity (m/s), degree of left ventricular outflow tract or valvar aortic stenosis (none, mild stenosis, moderate stenosis, severe stenosis), degree of aortic regurgitation (none, mild regurgitation, moderate regurgitation, severe regurgitation), degree of mitral stenosis (none, mild stenosis, moderate stenosis, severe stenosis), degree of mitral regurgitation (none, mildly regurgitation, moderate regurgitation, severe regurgitation), degree of pulmonic stenosis (none, mild stenosis, moderate stenosis, severe stenosis), degree of pulmonic regurgitation (none, mildly regurgitation, moderate regurgitation, severe regurgitation), and degree of tricuspid regurgitation (none, mild regurgitation, moderate regurgitation, severe regurgitation). Left ventricular function and right ventricular function were determined by qualitative assessment.
Primary outcome
The primary outcome was a composite of adverse neonatal outcomes, including fetal death (in utero), neonatal death (within index delivery hospitalization), preterm delivery (<37 weeks gestational age), small-for-gestational-age birth weight (<10 th percentile), and admission to transition care unit or neonatal intensive care unit (NICU) following delivery. Preterm delivery included planned preterm delivery to balance maternal and fetal wellbeing in women with high risk cardiac lesions, spontaneous preterm delivery, and preterm delivery induced for fetal indications.
Secondary outcomes
We assessed APGAR scores and the presence of CHD or other congenital anomaly in the neonate as secondary outcomes. We also assessed for adverse OB events as a secondary outcome. Adverse obstetric outcomes included pregnancy-induced hypertension, postpartum hemorrhage (defined as estimated blood loss >1,000 ml), placental abruption, or maternal intensive care unit admission during pregnancy. Adverse cardiac outcomes were recorded in the CHD subgroup, and defined as any of the following: maternal death or cardiac arrest, sustained arrhythmia requiring treatment, heart failure (defined as pulmonary edema, right-sided heart failure requiring diuretic treatment), stroke or transient ischemic attack, cardiac thromboembolism, or nonobstetric indication for intensive care unit admission.
Statistical analysis
Baseline characteristics of patients were summarized using means and standard deviations (SD) for continuous variables, and median and interquartile range (IQR) for ordinal variables. Frequencies and percentages were used for categorical variables. Among the total study cohort, characteristics and echocardiographic parameters were compared between the categories of maternal cardiac disease. ANOVA under the assumption of unequal variance was used to examine the existence of significant differences of continuous variables. Pearson’s Chi-Squared test and Fisher’s exact test were used to compare categorical variables. A logistic regression model was used to determine risk factors for adverse neonatal outcomes and adverse obstetric outcomes. Odds ratios (OR) and 95% confidence intervals (CI) were reported. A subgroup analysis was performed among the CHD cohort. A p-value <0.05 was considered to be significant. All analyses were carried out using R Statistical Software (version 2023.0.3.0+386; R Foundation for Statistical Computing, Vienna, Austria).
Results
Patient characteristics
Patient characteristics and baseline echocardiographic parameters are described in Table 1 . Among the 1,108 women composing the study population, the average age was 33.4 ± 6.4 years. Four hundred and 5 (36.6%) women had hypertensive heart disease, 195 (17.6%) women had CHD, 195 (17.6%) women had pre-existing arrhythmic disease, 78 (7.0%) women had a cardiomyopathy, 71 (6.4%) women had valvular heart disease, 14 (1.3%) women had pulmonary hypertension, 11 (1.0%) women had coronary artery disease, 8 (0.7%) women had an aortopathy, and 131 (11.8%) women were categorized as other (women with nonspecific cardiac symptoms without documented arrhythmia or structural heart disease). Six patients had a mechanical valve (based on initial cardiac pathology, 4 patients with a mechanical valve were included in the valvular heart disease cohort, and 2 patients with a mechanical valve were included in the CHD cohort). Over half the study population (55.9%) had experienced a prior miscarriage or abortion.
Table 1
Baseline characteristics and baseline echocardiographic parameters of the study population
| Baseline characteristics | Total study cohort (N = 1108) |
|---|---|
| Age, years (mean (SD)) | 33.4 (6.4) |
| Race (n (%)) | |
| African American | 232 (22.4) |
| Asian | 45 (4.3) |
| Caucasian | 427 (41.2) |
| Other/Unknown | 332 (32.1) |
| Ethnicity (n (%)) | |
| Hispanic | 435 (39.5) |
| Not Hispanic | 450 (40.9) |
| Unknown | 215 (19.5) |
| Tobacco use (n (%)) | |
| Current smoker | 4 (0.4) |
| Former smoker | 27 (2.4) |
| Never smoker | 1,078 (97.2) |
| Maternal cardiac disease (n (%)) | |
| Aortopathy | 8 (0.7) |
| Arrhythmia | 195 (17.6) |
| CHD | 78 (7.0) |
| Coronary artery disease | 195 (17.6) |
| Hypertensive disease | 405 (36.6) |
| Other | 131 (11.8) |
| Pulmonary hypertension | 14 (1.3) |
| Valvular disease | 71 (6.4) |
| Prior pregnancy (n (%)) | 746 (69.0) |
| Prior abortion or miscarriage (n (%)) | 527 (55.9%) |
| Baseline echocardiographic variables | |
| Left ventricular ejection fraction, % (mean (SD)) | 59.4 (5.4) |
| Left ventricular interventricular septum, cm (mean (SD)) | 0.9 (0.2) |
| Left ventricular posterior wall, cm (mean (SD)) | 0.9 (0.2) |
| Left ventricular end diastolic diameter, cm (mean (SD)) | 4.6 (0.5) |
| Left ventricular end systolic diameter, cm (mean (SD)) | 3.1 (0.5) |
| Right ventricular size (n (%)) | |
| Normal | 980 (92.0) |
| Mildly dilated | 54 (5.1) |
| Moderately dilated | 24 (2.3) |
| Severely dilated | 7 (0.7) |
| Right ventricular function (n (%)) | |
| Normal | 1,044 (97.4) |
| Mildly dilated | 25 (2.3) |
| Moderately dilated | 2 (0.2) |
| Severely dilated | 1 (0.1) |
| Degree of aortic stenosis (n (%)) | |
| No stenosis | 1,076 (98.2) |
| Mild stenosis | 11 (1.0) |
| Moderate stenosis | 7 (0.6) |
| Severe stenosis | 2 (0.2) |
| Degree of aortic regurgitation (n (%)) | |
| No regurgitation | 1,002 (91.5) |
| Mild regurgitation | 78 (7.1) |
| Moderate regurgitation | 14 (1.3) |
| Severe regurgitation | 1 (0.1) |
| Degree of mitral stenosis (n (%)) | |
| No stenosis | 1,085 (98.7) |
| Mild stenosis | 7 (0.6) |
| Moderate stenosis | 5 (0.5) |
| Severe stenosis | 2 (0.2) |
| Degree of mitral regurgitation (n (%)) | |
| No regurgitation | 839 (76.3) |
| Mild regurgitation | 227 (20.7) |
| Moderate regurgitation | 30 (2.7) |
| Severe regurgitation | 3 (0.3) |
| Degree of pulmonic stenosis (n (%)) | |
| No stenosis | 1,044 (95.8) |
| Mild stenosis | 30 (2.8) |
| Moderate stenosis | 12 (1.1) |
| Severe stenosis | 4 (0.4) |
| Degree of pulmonic regurgitation (n (%)) | |
| No regurgitation | 876 (80.4) |
| Mild regurgitation | 188 (17.2) |
| Moderate regurgitation | 14 (1.3) |
| Severe regurgitation | 12 (1.1) |
| Degree of tricuspid stenosis (n (%)) | |
| No stenosis | 1,108 (100.0) |
| Degree of tricuspid regurgitation (n (%)) | |
| No regurgitation | 760 (69.7) |
| Mild regurgitation | 313 (28.7) |
| Moderate regurgitation | 15 (1.4) |
| Severe regurgitation | 2 (0.2) |
| Tricuspid regurgitation peak velocity, m/s (mean (SD)) | 2.4 (0.5) |
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