Abstract
BACKGROUND:
As early life interventions for congenital heart disease improve, more patients are living to adulthood and are considering pregnancy. Scoring and classification systems predict the maternal cardiovascular risk of pregnancy in the context of congenital heart disease, but these scoring systems do not assess the potential subsequent risks following pregnancy. Data on the long-term cardiac outcomes after pregnancy are unknown for most lesion types. This limits the ability of healthcare practitioners to thoroughly counsel patients who are considering pregnancy in the setting of congenital heart disease.
OBJECTIVE:
We aimed to evaluate the association between pregnancy and the subsequent long-term cardiovascular health of individuals with congenital heart disease.
STUDY DESIGN:
This was a retrospective longitudinal cohort study of individuals identifying as female who were receiving care in two adult congenital heart disease centers from 2014 to 2019. Patient data were abstracted longitudinally from a patient age of 15 years (or from the time of entry into the healthcare system) to the conclusion of the study, death, or exit from the healthcare system. The primary endpoint, a composite adverse cardiac outcome (death, stroke, heart failure, unanticipated cardiac surgery, or a requirement for a catheterized procedure), was compared between parous (at least one pregnancy >20 weeks’ gestation) and nulliparous individuals. By accounting for differences in the follow-up, the effect of pregnancy was estimated based on the time to the composite adverse outcome in a proportional hazards regression model adjusted for the World Health Organization class, baseline cardiac medications, and number of previous sternotomies. Participants were also categorized according to their lesion type, including septal defects (ventricular septal defects, atrial septal defects, atrioventricular septal defects, or atrioventricular canal defects), right-sided valvular lesions, left-sided valvular lesions, complex cardiac anomalies, and aortopathies, to evaluate if there is a differential effect of pregnancy on the primary outcome when adjusting for lesion type in a sensitivity analysis.
RESULTS:
Overall, 711 individuals were eligible for inclusion; 209 were parous and 502 nulliparous. People were classified according to the World Health Organization classification system with 86 (12.3%) being classified as class I, 76 (10.9%) being classified as class II, 272 (38.9%) being classified as class II to III, 155 (22.1%) being classified as class III, and 26 (3.7%) being classified as class IV. Aortic stenosis, bicuspid aortic valve, dilated ascending aorta or aortic root, aortic regurgitation, and pulmonary insufficiency were more common in parous individuals, whereas dextro-transposition of the great arteries, Turner syndrome, hypoplastic right heart, left superior vena cava, and other cardiac diagnoses were more common in nulliparous individuals. In multivariable modeling, pregnancy was associated with the composite adverse cardiac outcome (36.4%% vs 26.1%%; hazard ratio, 1.83; 95% confidence interval, 1.25–2.66). Parous individuals were more likely to have unanticipated cardiac surgery (28.2% vs 18.1%; P=.003). No other individual components of the primary outcome were statistically different between parous and nulliparous individuals in cross-sectional comparisons. The association between pregnancy and the primary outcome was similar in a sensitivity analysis that adjusted for cardiac lesion type (hazard ratio, 1.61; 95% confidence interval, 1.10–2.36).
CONCLUSION:
Among individuals with congenital heart disease, pregnancy was associated with an increase in subsequent long-term adverse cardiac outcomes. These data may inform counseling of individuals with congenital heart disease who are considering pregnancy.
Keywords: adult congenital heart disease, aortopathy, maternal aortopathy, maternal congenital heart disease, maternal heart disease, pregnancy with congenital heart disease
Introduction
As early life interventions for congenital heart disease (CHD) improve, a higher proportion of patients are living to adulthood and are considering pregnancy. The physiological changes that occur as part of pregnancy place hemodynamic stress on individuals with CHD.1–6 Scoring and classification systems have been developed to predict the maternal cardiovascular risk of pregnancy in the context of CHD. The most commonly used systems include the modified World Health Organization (WHO) classification, Zwangerschap bij vrouwen met een Aangeboren HARtAfwijking-II (ZAHARA) risk score, Canadian Cardiac Disease in Pregnancy (CARPREG), and CARPREG II scoring systems.7–10 These scoring systems aim to predict the cardiovascular risk associated with a pregnancy but do not assess the potential risks that follow pregnancy.
A previous retrospective cohort study demonstrated an increased risk for long-term adverse cardiac outcomes among parous individuals when compared with nulliparous individuals in cases with a previous pulmonary valve repair or replacement for a tetralogy of Fallot or a pulmonic stenosis.11 The long-term cardiac outcomes following pregnancy in individuals with other types of CHD remain unknown. Siu et al12 compared the long-term adverse cardiac events in parous patients with CHD to parous patients without CHD. Parous patients with CHD had a higher risk for adverse long-term cardiac events than those without CHD.12 However, the long-term effect of pregnancy on cardiovascular function among patients with CHD remains largely unknown, highlighting the importance of ongoing research in this area to optimize patient counseling on the anticipated cardiac outcomes beyond the immediate peripartum period.
Our objective was to evaluate whether there is an association between pregnancy and long-term cardiac outcomes among individuals with CHD. Importantly, this was performed by simulating a longitudinal cohort with ongoing follow-ups over time and taking into account the timing of the pregnancy on the primary cardiovascular event endpoint.
Materials and Methods
This was a retrospective, longitudinal cohort study of all individuals identifying as female, who had CHD, were ≥15 years, and were followed at the Adult Congenital Heart Disease (ACHD) clinic at the University of Utah Health or Intermountain Healthcare, two tertiary care facilities in Salt Lake City, Utah, which serve the majority of patients with CHD in the state. As part of the standard of practice for quality improvement and patient tracking, any patients with CHD seen in the ACHD clinic at either site are included in a clinical database. Individuals were included in the database if they had a visit to the ACHD clinic from August 2014 (creation of institutional clinical database) through April 2019. All individuals in this database were evaluated for eligibility, which included a cursory electronic medical record review to confirm that the age of the patient was ≥15 years and to confirm the presence of a CHD or aortopathy diagnosis. If these criteria were met, a thorough medical record abstraction was performed by trained healthcare personnel. This project was granted institutional review board exemption by both the University of Utah Health and Intermountain Healthcare. The results are reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines for observational studies.
The primary exposure was pregnancy. For this study, pregnancy was defined as a delivery at ≥20 weeks’ gestation. Individuals with pregnancies who delivered at ≥20 weeks’ gestation were considered parous. Otherwise, individuals were classified as nulliparous. Adoptions were not included. Data regarding the pregnancy history and specific dates of deliveries were abstracted from the electronic medical records. When antepartum records were available, risk classification scores (WHO, CARPREG, CARPREG II, and ZAHARA) for the pregnancy were also abstracted. The WHO classification was preferentially utilized in the analysis for the following two reasons: (1) some patients did not have CARPREG or ZAHARA scores available because they were not under the care of a physician at our ACHD or Maternal-Fetal Medicine clinics during those pregnancies and (2) the WHO classification has predictive capability exceeding that of the other risk stratification scores.7
Once identified, participants were followed longitudinally from 15 years of age (or the time of entry into the healthcare system) until the conclusion of the study, death of the patient, or exit from the healthcare system. The primary outcome was a composite long-term adverse cardiac outcome, which included death, stroke, heart failure, unanticipated cardiac surgery, and the need for a catheterized procedure. These outcomes were chosen a priori based on what were thought to be clinically meaningful endpoints among the authors who are subspecialists in maternal-fetal medicine and ACHD. An age of 15 years was selected as an inclusion criterion for study entry because this is the point at which adult female cardiovascular physiology is considered to have been achieved. Complications and interventions occurring between birth and 15 years of age were collected but not included as an adverse cardiac outcome (eg, surgery at 12 years of age was documented but not noted as part of the composite outcome).
Death was ascertained from reports in the electronic medical records. Cross-linkage to death certificates in the state of Utah occurs on an ongoing basis to ensure that the outcome of death is noted in the electronic medical record of the decedent. Stroke was defined as either a hemorrhagic or ischemic stroke based on brain imaging or surgical pathology reports. Heart failure was defined as either a clinical diagnosis of heart failure or a diagnosis of pulmonary edema by a cardiologist. Unanticipated cardiac surgery included surgical procedures that were not considered to be part of the original or planned staged repair of the congenital lesion. Catheterized procedures were defined as cardiac catheter procedures during which an intervention was performed (eg, not limited to diagnostic evaluation only). These procedures were further described as valvular (eg, balloon valvuloplasty) or other (eg, ablation, collateral vessels requiring coiling).
Baseline characteristics were also abstracted and included race, ethnicity, education history, employment status, insurance status, body mass index (BMI), noncardiac medical conditions (type 1 diabetes mellitus, type 2 diabetes mellitus, chronic hypertension, hypercholesterolemia, neurologic disease or seizures, obstructive sleep apnea [OSA], obesity, or other), baseline medications (anticoagulants, antiarrhythmic agents, antihypertensive agents, lipid-lowering agents, diuretics, other, or unknown), and substance use (tobacco, alcohol, or illicit drugs). Information about the specific cardiac lesion was collected and the cardiac lesion types were grouped into septal defects (ventricular septal defect, atrioseptal defect, atrioventricular septal defect, or atrioventricular canal defect), right-sided valvular lesions, left-sided valvular lesions, complex cardiac anomalies, and aortopathies for comparison between parous and nulliparous participants.
Study data were collected and managed using the Research Electronic Data Capture system, a secure, web-based software platform.13,14 To ensure validity of the detailed manual chart abstraction, a random sample of 5% of the charts were abstracted by both of the data abstractors (S.L.S. and L.L.H.) for the primary outcome with 97% agreement (kappa=0.85; 95% confidence interval [CI], 0.66–1.0). One discrepancy was corrected, and the updated data were analyzed.15
A power estimate was performed based on the number of individuals available in an existing clinical database covering a narrower window than the planned study and the 25% pregnancy rate among those individuals. Assuming a similar distribution of people in the clinic and pregnancies over the years of planned data extraction, we expected a total of 262 parous and 787 nulliparous individuals for inclusion between August 2014 and April 2019. We anticipated that 90% of the individuals would have complete data available for chart abstraction. Thus, with a group sample sizes of 236 parous individuals and 708 nulliparous individuals we would have 80% power to detect a difference between the group proportions of 11%. The rate of morbidity among nulliparous individuals was assumed to be 50% under the null hypothesis and 39% under the alternative hypothesis.11 The test statistic that was used is the 2-sided Fisher exact test with an α=.05.
Statistical analysis
Demographic and baseline clinical characteristics were summarized for the nulliparous and parous individuals, with between-group differences tested using a 2-sample t test for continuous variable or an exact chi-square test for categorical characteristics. To test the primary hypothesis that among individuals with CHD, parous individuals will have a higher incidence of subsequent long-term adverse cardiac outcomes than nulliparous individuals, the effect of pregnancy on the time to composite adverse outcome was estimated in a proportional hazards regression model to account for the differential duration of observation. In adjusted modeling, the WHO class, use of cardiac medications, and number of previous sternotomies were included as clinically important covariates. Given the small number of patients categorized as WHO class IV, classes III and IV were combined in the model. Difference in number of years of observation (ie, age) between individuals was accounted for in time-to-event modeling. In a time-varying Cox model, time was modeled as maternal age and pregnancy as a time-varying covariate. Parous subjects were excluded if the dates of their deliveries were unknown given that pregnancy was the primary exposure and survival analysis using a time-to-event methodology necessitates knowledge of the timing of exposure.
Given that there may be differences in the outcomes based on cardiac lesion type, we performed a sensitivity analysis in which the cardiac lesion type was included in the multivariable model instead of the WHO class. A test for interaction was first performed for pregnancy and cardiac lesion type. Because there was no significant interaction between the pregnancy and cardiac lesion type, the reported sensitivity analysis model included parity, cardiac lesion type, use of cardiac medications, and the number of previous sternotomies. In a subgroup analysis, we evaluated whether there was a difference in the effect between pregnancy and our primary morbidity endpoint when individuals with Turner syndrome were excluded. We estimated the adjusted Cox proportional hazards model from which our primary endpoint was reported and individuals with Turner syndrome were excluded.
Statistical difference was defined as a 2-sided P value of <.05. All analyses were performed in SAS (SAS Institute Inc, Cary, NC).
Results
In total, 1064 individuals were identified by the institutional clinical database and screened for inclusion. Individuals were most commonly excluded for being younger than 15 years of age or not having a diagnosis of CHD (eg, acquired heart disease such as rheumatic heart disease) (Figure 1). Among otherwise eligible patients, 105 were excluded because of missing dates associated with deliveries (precluding time-to-event analysis), leaving a final sample size of 711 individuals (209 parous and 502 nulliparous).
FIGURE 1. Patient eligibility flow diagram.
IMH, Intermountain Healthcare; UofU, University of Utah Health.
Parous individuals were more commonly older, were followed longitudinally for longer periods of time, had a higher BMI, were partnered or married, and employed than nulliparous individuals (Table 1). The distribution of baseline WHO class did not differ between parous and nulliparous individuals (Table 2). Parous individuals less commonly had a sternotomy before 15 years of age (Table 2). The frequency of cardiac lesion types for the parous and nulliparous individuals is shown in Figure 2. Aortic stenosis, bicuspid aortic valve, dilated ascending aorta or aortic root, aortic regurgitation, and pulmonary insufficiency were more common in parous individuals, whereas dextro-transposition of the great arteries, Turner syndrome, hypoplastic right heart, left superior vena cava, and other cardiac diagnoses were more common among nulliparous individuals (Figure 2).
TABLE 1.
Baseline demographic and clinical characteristics
| Characteristic | All, N=711 | Parous, n=209 | Nulliparous, n=502 | P value |
|---|---|---|---|---|
| Age at first visit (y), mean (SE) | 23.9 (10.1) | 26.3 (10.1) | 22.9 (9.9) | <.001 |
| Age at last visit (y), mean (SE) | 28.9 (10.4) | 32.4 (9.0) | 27.4 (10.6) | <.001 |
| Years followed, mean (SE) | 4.7 (5.3) | 6.1 (5.5) | 4.1 (5.2) | <.001 |
| Current or recent overweight or obese BMI | 330 (48.0) | 111 (54.7) | 219 (45.2) | .024 |
| Hispanic ethnicity | 37 (5.2) | 13 (6.2) | 24 (4.8) | .431 |
| Marital status: partnered or married | 270 (39.1) | 164 (80.0) | 106 (21.9) | <.001 |
| Currently employed | 291 (52.2) | 104 (63.0) | 187 (47.7) | <.001 |
| Noncardiac chronic conditions | ||||
| Type 1 diabetes | 4 (0.6) | 2 (1.0) | 2 (0.4) | .364 |
| Type 2 diabetes | 12 (1.7) | 2 (1.0) | 10 (2.0) | .329 |
| Chronic HTN | 49 (6.9) | 17 (8.1) | 32 (6.4) | .399 |
| Hypercholesterolemia | 25 (3.5) | 9 (4.3) | 16 (3.2) | .461 |
| Neurologic disease or seizures | 26 (3.7) | 4 (1.9) | 22 (4.4) | .11 |
| Obstructive sleep apnea | 34 (4.8) | 4 (1.9) | 30 (6.0) | .021 |
| Obesity | 8 (1.1) | 4 (1.9) | 4 (0.8) | .198 |
| Other chronic conditions | 313 (44.0) | 75 (35.9) | 238 (47.4) | .005 |
Data are presented as number (percentage) unless otherwise stated. Employment was missing for 20% of participants and marital status was missing for 1%. Other chronic conditions included hypothyroidism, asthma or lung disease, cancer, rheumatologic disease, and other or unknown.
BMI, body mass index; HTN, hypertension; SE, standard error.
TABLE 2.
Baseline cardiac status of study population
| Characteristic | Classification | All, N=711 (%) | Parous, n=209 (%) | Nulliparous, n=502 (%) | P value |
|---|---|---|---|---|---|
| Baseline WHO class | None | 85 (12.1) | 29 (13.9) | 56 (11.4) | .36 |
| WHO I | 86 (12.3) | 24 (11.5) | 62 (12.6) | ||
| WHO II | 76 (10.9) | 23 (11.0) | 53 (10.8) | ||
| WHO II–III | 272 (38.9) | 90 (43.1) | 182 (37.1) | ||
| WHO III | 155 (22.1) | 37 (17.7) | 118 (24.0) | ||
| WHO IV | 26 (3.7) | 6 (2.9) | 20 (4.1) | ||
| Current or most recent WHO class | None | ||||
| WHO I | 86 (12.3) | 29 (13.9) | 57 (11.6) | .35 | |
| WHO II | 86 (12.3) | 25 (12.0) | 61 (12.4) | ||
| WHO II–III | 73 (10.4) | 19 (9.1) | 54 (11.0) | ||
| WHO III | 271 (38.8) | 88 (42.3) | 183 (37.3) | ||
| WHO IV | 160 (22.9) | 44 (21.2) | 116 (23.6) | ||
| Number of WHO class changes | Zero | 671 (97.0) | 197 (96.1) | 474 (97.3) | .319 |
| 1 | 19 (2.7) | 8 (3.9) | 11 (2.3) | ||
| 2 | 2 (0.3) | 0 (0.0) | 2 (0.4) | ||
| Baseline cardiac medications | Any | 226 (31.8) | 61 (29.2) | 165 (32.9) | .337 |
| Anticoagulants | 120 (16.9) | 31 (14.8) | 89 (17.7) | .348 | |
| Antiarrhythmics | 51 (7.2) | 10 (4.8) | 41 (8.2) | .111 | |
| Antihypertensive agents | 127 (17.9) | 32 (15.3) | 95 (18.9) | .252 | |
| Diuretic | 35 (4.9) | 9 (4.3) | 26 (5.2) | .624 | |
| Sternotomies before 15 y of age | 0 | 371 (52.2) | 116 (55.5) | 255 (50.8) | .045 |
| 1 | 204 (28.7) | 66 (31.6) | 138 (27.5) | ||
| 2–3 | 113 (15.9) | 24 (11.5) | 89 (17.7) | ||
| >3 | 23 (3.2) | 3 (1.4) | 20 (4.0) | ||
| Cardiac diagnosesa | Septal defects (ASD/VSD/AVSD/AVCD) | 96 (14.3) | 26 (12.7) | 70 (15.0) | .336 |
| Valvular lesions of the right heart | 38 (5.6) | 16 (7.8) | 22 (4.7) | ||
| Valvular lesions of the left heart | 81 (12.0) | 27 (13.2) | 54 (11.5) | ||
| Aortopathies | 87 (12.9) | 30 (14.6) | 57 (12.2) | ||
| Complex congenital lesions | 371 (55.1) | 106 (51.7) | 265 (56.6) |
WHO I: Uncomplicated, small or mild pulmonary stenosis, patent ductus arteriosus, or mitral valve prolapse. Successfully repaired simple atrial septal defects, ventricular septal defects, patent ductus arteriosus, or total anomalous pulmonary venous repair. Isolated premature atrial contractions or premature ventricular contractions.
WHO II: Unoperated atrial septal defects or ventricular septal defects. Repaired tetralogy of Fallot. Most arrhythmias.
WHO II–III: Mild left ventricular impairment. Hypertrophic obstructive cardiomyopathy. Native tissue valvular heart disease not class I or IV. Marfan without aortic dilation. Bicuspid aortic valve aortopathy with aortic diameter of <45 mm. Repaired aortic coarctation.
WHO III: Mechanical valve. Systemic right ventricle. Fontan. Unrepaired cyanotic heart disease. Other complex congenital heart diseases. Marfan syndrome with aortic diameter of 40 to 45 mm. Bicuspid aortic valve aorta of 45 to 50 mm.
WHO IV: Pulmonary arterial hypertension of any cause. Severe left ventricular dysfunction ejection fraction <30, the New York Heart Association class III to IV. Previous peripartum cardiomyopathy with residual impaired left ventricular function. Severe mitral stenosis. Severe symptomatic aortic stenosis. Marfan syndrome with aortic diameter >45 mm. Bicuspid aortic valve with aortic diameter >50 mm. Native severe coarctation.7
ASD, atrial septal defects; AVCD, atrioventricular canal defects; AVSD, atrioventricular septal defects; VSD, ventricular septal defects; WHO, World Health Organization.
A total of 16 individuals with cardiac diagnoses not categorized were excluded from this comparison.
FIGURE 2. Frequency of cardiac lesion types in parous and nulliparous patients.
“Other cardiac diagnoses” include any congenital cardiac condition not otherwise listed.
When comparing the medical comorbidities among parous and nulliparous individuals, parous individuals were less likely to have OSA and other chronic conditions (Table 1).
Overall, in the unadjusted cross-sectional analyses, 207 (29.1%) participants met the primary endpoint, of which 76 (36.4%) were parous and 131 (26.1%) were nulliparous individuals (P=.006) (Table 3). Parous individuals were more likely to have unanticipated cardiac surgery (28.2% vs 18.1%; P=.003). No other individual components of the primary outcome were statistically different between parous and nulliparous individuals in cross-sectional comparisons (Table 3). When using time-to-event methodology, pregnancy was associated with the primary endpoint of long-term adverse cardiac outcomes (hazard ratio [HR], 1.83; 95% CI, 1.25–2.66). A higher risk for the primary endpoint was also associated with cardiac medication use at baseline (HR, 1.73; 95% CI, 1.29–2.33) and sternotomy before the age of 15 years (HR, 2.08; 95% CI, 1.53–2.83). All point estimates for WHO class II to IV vs class I (referent) cases were in the expected direction with significant differences noted for classes II vs I and class III to IV vs I (Figure 3). A simple (unadjusted) Kaplan-Meier survival analysis revealed a median time (years) to an event of 48.4 years (40.9–53.7 years) for nulliparous subjects and 44.1 years (36.4–57.3 years) for parous subjects.
TABLE 3.
Unadjusted rates of primary and secondary endpoints without time-to-event methodology
| Characteristic | All, N=711 (%) | Parous, n=209 (%) | Nulliparous, n=502 (%) | P value |
|---|---|---|---|---|
| Composite endpoint | 207 (29.1) | 76 (36.4) | 131 (26.1) | .006 |
| • Heart failure | 25 (3.5) | 9 (4.3) | 16 (3.2) | .461 |
| • Death | 7 (1.0) | 0 (0.0) | 7 (1.4) | .086 |
| • Stroke | 9 (1.3) | 2 (1.0) | 7 (1.4) | .635 |
| • Unanticipated cardiac surgery | 150 (21.1) | 59 (28.2) | 91 (18.1) | .003 |
| • Catheterized procedure, valvular | 27 (3.8) | 7 (3.3) | 20 (4.0) | .687 |
| • Catheterized procedure, othera | 92 (12.9) | 27 (12.9) | 65 (12.9) | .991 |
Other procedures include ablation for arrhythmia or coiling of collateral vessels.
FIGURE 3. Primary endpoint comparison using time-to-event methodology.
*Other includes patients with CHD that did not fit into the WHO classification system
CHD, congenital heart disease; CI, confidence interval; WHO, World Health Organization.
The frequency of each cardiac lesion type in nulliparous and parous individuals was reported (Table 2). There was no significant difference in cardiac lesion type between nulliparous and parous individuals (P=.336). In a sensitivity analysis in which cardiac lesion type was considered as a covariate instead of the WHO class, the HR for the association between pregnancy and the composite outcome remained similar in magnitude (HR, 1.61; 95% CI, 1.10–2.36). In the subgroup analysis that assessed if there was a difference in the effect between pregnancy and the primary endpoint among individuals with Turner syndrome, it was determined that there were 30 individuals in our cohort with a diagnosis of Turner syndrome, none of which were categorized as parous. The rate of the primary endpoint was higher those individuals without Turner syndrome than among individuals with Turner syndrome (30% vs 10%; P=.0219). When subjects with Turner syndrome were excluded from a sensitivity model, the risk for the primary adverse cardiac outcome remained similar (HR, 1.81; 95% CI, 1.24–2.65).
Comment
Principal findings
Among individuals with CHD, when using the time-to-event methodology, pregnancy was associated with a higher risk for long-term composite adverse cardiac outcomes including death, stroke, heart failure, unanticipated cardiac surgery, and the need for a catheterized procedure. The observed association persisted after adjusting for differences in the baseline characteristics, including the WHO class, use of cardiac medications, and number of previous sternotomies. In a sensitivity analysis that included the type of cardiac lesion instead of the WHO class, the association between pregnancy and adverse long-term cardiac outcomes remained similar in magnitude. These findings are important in counseling a growing population of reproductive-aged individuals with CHD who are considering pregnancy.
Results in the context of what is known
Previous studies have evaluated highrisk demographic and clinical characteristics and created algorithms for approximation of the risk for a cardiac event during pregnancy.7–10 The CARPREG II system, for example, uses a points-based system with 10 independent predictors of primary maternal cardiac events to approximate the proportion of patients that could be expected to experience a cardiac event during pregnancy. Although these studies are helpful in counseling patients about the pregnancy-related risks, they do not explore the long-term effects of the cardiac stress of pregnancy.10
A previous study evaluated the cardiac outcomes subsequent to pregnancy among individuals with a specific lesion type, namely pulmonary valve anomalies.11 Similarly, these investigators found an association between pregnancy and adverse cardiac outcomes. Our findings are consistent with the Metz et al11 findings that demonstrate that adverse cardiac outcomes are more frequent among parous than nulliparous subjects across other lesion types.11
Another previous study demonstrated that parous patients with CHD had higher rates of an adverse cardiac event than parous patients without CHD. Our findings are consistent with that study showing a similar rate of cardiac events in parous patients with CHD (33.1% [Siu study] vs 36.4% [our data]).12
Clinical implications
Although other studies have described the risks associated with pregnancy itself among individuals with CHD, our study provides additional information on the cardiovascular risks after pregnancy.
Research implications
Future studies that prospectively follow individuals with CHD across a lifetime would overcome the limitations of our analysis and further elucidate the relationship between pregnancy and subsequent adverse cardiac events.
Strengths and limitations
The strengths of this study include that it was conducted at two large referral centers that provide the majority of care to individuals with CHD in the region. In addition, the Utah state population is relatively stable.16 As such, individuals are likely to continue to be followed clinically on an ongoing basis in one of these healthcare systems. Detailed medical record abstraction was performed across many years to simulate longitudinal follow-up of individuals with CHD over time for cardiac events, thereby strengthening the study design of this retrospective cohort study. Detailed medical record abstraction was performed by trained medical professionals and evaluated for agreement, which was demonstrated to be excellent.
Our study has limitations. Data were collected retrospectively and, at times, only limited obstetrical history was available without a date of delivery, which led to the exclusion of some otherwise eligible participants. The majority of the cohort was of White race, potentially limiting the generalizability of the findings. In addition, because of the nature of our medical record abstraction, we were unable to determine whether subjects who were nulliparous made the decision to not become pregnant intentionally, whether they were counseled against pursuing pregnancy because of their cardiac or other conditions, or whether they experienced infertility. Parous patients were, on average, followed for a longer period of time (6.1 years vs 4.1 years). However, differential follow-ups were accounted for using a survival analysis methodology and our modeled results demonstrated differences between groups despite accounting for differential follow-ups. Finally, with the multitude of cardiac diagnoses that exist, we were unable to analyze each lesion type separately because of insufficient sample sizes among the various subsets.
Conclusions
Our findings may inform counseling regarding the potential long-term implications of pregnancy in a growing population of reproductive-aged individuals with CHD. In addition, because the risk varies by baseline characteristics and lesion type, these data provide an opportunity for more individualized counseling.
AJOG at a Glance.
Why was this study conducted?
An increasing number of individuals with congenital heart disease are surviving into adulthood and many are pursuing pregnancy. Although calculators and algorithms exist to predict the risk for cardiac events during pregnancy, little data related to the effects of pregnancy on long-term cardiac outcomes exist. Given the increased cardiac work during pregnancy, it is plausible that pregnancy could have long-term effects on cardiac function.
Key findings
Pregnancy was associated with a higher risk for a long-term composite adverse cardiac outcome among individuals with congenital heart disease who were followed longitudinally.
What does this add to what is known?
This study provides information that extends beyond predicting cardiac events during pregnancy itself by evaluating adverse cardiac outcomes subsequent to delivery. These data can be used for tailored counseling of individuals with congenital heart disease about the anticipated effects of pregnancy on long-term cardiac outcomes.
Acknowledgments
This study was supported, in part, by funding from the National Institutes of Health to the University of Utah Center for Clinical and Translational Sciences (under grant number 8UL1TR000105 [formerly UL1RR025764]) and by the Short-Term Training: Students in Health Professional Schools grant from the National Heart, Lung, and Blood Institute (under grant number T35 HL007744).
Footnotes
The authors report no conflict of interest.
The findings from this study were presented in poster format at the 40th annual pregnancy meeting of the Society for Maternal-Fetal Medicine, Grapevine, TX, February 5–8, 2020.
Contributor Information
Drs Shannon L. Son, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, UT; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Intermountain Healthcare, Salt Lake City, UT.
Drs Lauren L. Hosek, University of Utah School of Medicine, Salt Lake City, UT.
Miranda C. Stein, University of Utah School of Medicine, Salt Lake City, UT.
Amanda A. Allshouse, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, UT.
Drs Anna B. Catino, University of Utah Health, Division of Cardiology, Salt Lake City, UT.
Drs Arvind K. Hoskoppal, University of Utah Health, Division of Cardiology, Salt Lake City, UT; Division of Cardiology, Intermountain Healthcare, Salt Lake City, UT.
Daniel A. Cox, University of Utah Health, Division of Cardiology, Salt Lake City, UT; Division of Cardiology, Intermountain Healthcare, Salt Lake City, UT.
Kevin J. Whitehead, University of Utah Health, Division of Cardiology, Salt Lake City, UT; Division of Cardiology, Intermountain Healthcare, Salt Lake City, UT.
Ian M. Lindsay, University of Utah Health, Division of Cardiology, Salt Lake City, UT; Division of Cardiology, Intermountain Healthcare, Salt Lake City, UT.
Sean Esplin, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, UT; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Intermountain Healthcare, Salt Lake City, UT.
Torri D. Metz, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, UT; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Intermountain Healthcare, Salt Lake City, UT.
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