Valvular heart disease (VHD) accounts for significant morbidity and mortality during pregnancy, with limited data to guide cardio-obstetric risks. This is a retrospective cohort study describing maternal, obstetric, and fetal outcomes of Kaiser Permanente Northern California members with VHD during pregnancies between 2010 and 2021. Adult patients with moderate to severe native VHD and/or previous valve interventions were included. There were 242,066 eligible pregnancies in the study period, 89 (0.04%) of which were complicated by clinically significant VHD: 25 with pulmonary stenosis/regurgitation, 40 with aortic/mitral regurgitation, 18 with aortic/mitral stenosis, and 6 with mixed/other VHD. Forty-eight had native VHD, and 41 had previous percutaneous/surgical valve intervention. Adverse maternal outcomes were rare in pulmonary stenosis/regurgitation patients, but preeclampsia/eclampsia was observed in 20%, and C-section in 36%. In those with aortic/mitral regurgitation, congestive heart failure hospitalizations occurred in 10%, preeclampsia/eclampsia in 22.5%, preterm delivery in 25%, and C-section in 32.5%. In those with aortic/mitral stenosis, 5.6% had congestive heart failure hospitalizations, 22% had C-section, 22% were preterm with 27.8% infants requiring neonatal intensive care unit stay. One maternal death occurred in a patient with MR with concomitant long QT syndrome. In this contemporary pregnancy cohort, regurgitant lesions were most prevalent and associated with significant maternal morbidity. In conclusion, this study highlights that left-sided valvular regurgitant lesions during pregnancy, in addition to stenotic lesions, are associated with significant morbidity.
Cardiovascular disease remains the leading cause of maternal mortality, accounting for 26.5% of pregnancy deaths in the United States. Valvular heart disease (VHD) in particular accounts for 30% to 50% of cardiac disease in pregnancy, , largely due to medical advancements that have allowed more patients with congenital heart disease to reach childbearing age. While regurgitant lesions may be better tolerated hemodynamically during pregnancy, stenotic valves traditionally are thought to result in greater morbidity, due to the poorly tolerated effects of greater blood volume and higher heart rate during pregnancy.
Impact on maternal, obstetric, and fetal outcomes
Regurgitant valves have a significant adverse impact on maternal health: 23% to 30% of pregnant patients with moderate or severe mitral valve regurgitation (MR) have been shown to develop congestive heart failure (CHF). Valvular regurgitation is also associated with adverse fetal events, with 31% of pregnant patients with MR experiencing premature birth, small for gestational age, respiratory distress syndrome, intraventricular hemorrhage, and/or fetal or neonatal death.
Pregnant patients with stenotic valvular lesions suffer from high rates of decompensated CHF, arrhythmias, and hospitalizations, even if asymptomatic previous to pregnancy. The highest rate of hospitalizations is seen in patients with severe, symptomatic aortic or mitral stenosis. ,, Those with severe aortic stenosis (AS) have higher rates of cesarean section and shorter pregnancy duration. ,, Stenotic valve disease is also associated with fetal growth restriction, low birth weight, and up to a 40% increase in risk of preterm delivery. , Fetal morbidity also correlates with MS or AS severity. The highest rates of adverse fetal events occur in patients with bioprosthetic valves with left-sided structural valve dysfunction.
Current risk calculators and preconception counseling have led to increased caution in pursuing pregnancy in those with severe left-sided stenotic lesions and typically identify individuals with regurgitant lesions as safe to proceed with pregnancy. In this study, we aim to describe further maternal, obstetric, and fetal outcomes of patients with clinically significant VHD during pregnancy from a large, integrated health system across a 12-year period, in an era of multidisciplinary cardio-obstetric counseling. We hope this study provides further insight into risk stratification in an understudied, high-risk population.
Methods
This is a retrospective cohort study of Kaiser Permanente Northern California (KPNC) members with clinically significant VHD during pregnancy from 2010 to 2021. The KPNC population is demographically representative of the larger community from which membership is drawn. This study was reviewed and approved by the KPNC Regional Institutional Review Board.
Study population
The study population included patients who were 18 or older with pregnancy onset between January 1, 2010 and December 31, 2021, with at least 1 year of membership before pregnancy and maintained membership until the end of their pregnancy. Patients who had a first-trimester miscarriage or termination of pregnancy were excluded. ICD-9 and ICD-10 codes were initially applied to identify members with VHD during pregnancy, and a 2-physician chart review (including one attending cardiologist) of echocardiography and cardiac MRI data was performed to verify valvular lesion severity and study inclusion. Individuals were included if they had moderate or greater native VHD or repaired/replaced valves with less than moderate residual disease. Valve severity was defined according to the American Society of Echocardiography guideline criteria. , For individuals with multiple pregnancies during the study period, only the first pregnancy was included.
Outcomes
Maternal outcomes were collected from pregnancy initiation to 12 months postpartum, including sustained ventricular tachycardia or supraventricular tachycardia, CHF exacerbation requiring emergency department visit or hospitalization, myocardial infarction, and maternal death. Obstetric outcomes included preeclampsia/eclampsia, preterm delivery (defined as before 37 weeks of gestation), cesarean section delivery, need for emergent cesarean section delivery, and postpartum hemorrhage (defined as blood loss of ≥500 mL within 24 hours for spontaneous vaginal delivery or ≥1,000 mL within 24 hours for C-section). Fetal outcomes included abnormal birth weight (based on Fenton weight percentile), low appearance, pulse, grimace, activity and respiration (APGAR) score (<7), neonatal intensive care unit (NICU) stay, pregnancy loss (defined as 13–20 weeks of gestation), and fetal demise (defined as greater than 20 weeks of gestation).
Data collection and statistical analysis
Demographic and clinical characteristics were extracted from the electronic health record and KP Division of Research databases, including: age, self-identified race/ethnicity, hemoglobin A1c, substance use, hypertension, diabetes mellitus, valve position, and valve type. Maternal, obstetric, and fetal outcomes, in addition to VHD severity, were identified using procedure and diagnosis codes and from KPNC pregnancy outcomes databases and subsequently validated by chart review. We conducted a descriptive analysis of adverse maternal, obstetric, and fetal outcomes in pregnancies complicated by VHD, stratified by lesion, valve type, and disease severity.
Results
Of 242,066 pregnancies studied in a 10-year period, 89 had clinically significant VHD (0.04%). Of these, 25 (28.1%) had pulmonary stenosis/regurgitation (PS/PR), 40 (44.9%) had aortic/mitral regurgitation (AR/MR), 18 (20.2%) had aortic/mitral stenosis (AS/MS), and 6 (6.7%) had mixed/other VHD. Before pregnancy, 48 (53.9%) had native VHD and 41 (46.1%) had previous valve intervention. Baseline characteristics are presented in Table 1 , stratified by type of valvular disease. The average age of patients was 32.2 years, of whom 31.5% were White, followed by Hispanic at 16.9%. Across all valve types, 6 patients reported illicit drug use, 4 patients had a history of hypertension, and 1 patient had diabetes before pregnancy.
Table 1
Demographic and clinical characteristics for patients with VHD
| All Patients | PS/PR | AR/MR | AS/MS | |
|---|---|---|---|---|
| n = 89 (%) | n = 25 (28.1) | n = 40 (44.9) | n = 18 (20.2) | |
| Mean age (SD) | 32.2 (6.0) | 30.1 (5.7) | 33.0 (5.7) | 33.4 (6.7) |
| Race/Ethnicity, n (%) | ||||
| Black | 12 (13.5) | 2 (8.0) | 5 (12.5) | 3 (16.7) |
| Filipino | 6 (6.7) | 0 | 3 (7.5) | 1 (5.6) |
| Hispanic | 15 (16.9) | 6 (24.0) | 2 (5.0) | 7 (38.9) |
| Other Asian/Pacific Islander | 14 (15.7) | 5 (20.0) | 5 (12.5) | 3 (16.7) |
| South Asian | 4 (4.5) | 1 (4.0) | 3 (7.5) | 0 |
| White | 28 (31.5) | 7 (28.0) | 17 (42.5) | 3 (16.7) |
| Other/Unknown | 10 (11.2) | 4 (16.0) | 5 (12.5) | 1 (5.6) |
| Never used tobacco before pregnancy, n (%) | 78 (87.6) | 22 (88.0) | 35 (87.5) | 17 (94.4) |
| Alcohol use before pregnancy, n (%) | ||||
| Yes | 35 (39.3) | 14 (56.0) | 15 (37.5) | 4 (22.2) |
| No | 43 (48.3) | 7 (28.0) | 21 (52.5) | 12 (66.7) |
| Missing | 11 (12.4) | 4 (16.0) | 4 (10.0) | 2 (11.1) |
| Severity of VHD , n (%) | ||||
| Previous valve intervention without residual disease | 25 (28.1) | 9 (36.0) | 9 (22.5) | 5 (27.8) |
| Moderate | 38 (42.7) | 13 (52.0) | 16 (40.0) | 6 (33.3) |
| Severe | 26 (29.2) | 3 (12.0) | 15 (37.5) | 7 (38.9) |
| Etiology, n (%) | ||||
| Congenital | 37 (41.6) | 25 (100.0) | 4 (10.0) | (44.4) |
| Rheumatic | 16 (18.0) | 0 | 5 (12.5) | 8 (44.4) |
| Other | 36 (40.4) | 0 | 31 (77.5) | 2 (11.1) |
| Presence of bioprosthetic or mechanical valve (%) | 15 (16.8) | 5 (20.0) | 4 (10.0) | 3 (16.7) |
| Mean LVEF/SVEF (SD) | 60.9 (4.7) | 59.0 (3.5) | 61.3 (5.1) | 62.8 (3.4) |
Most adverse outcomes in native and bioprosthetic valve patients were obstetric (58.3% vs 85.7%), followed by fetal (35.4% vs 42.9%), then maternal (12.5% vs 21.4%) ( Table 2 ). There was 1 patient with a mechanical valve for AS/MS, who had both an adverse maternal and obstetric outcome.
Table 2
Outcomes during pregnancy to 12 months postpartum, comparing native to non-native valves
|
Native
n = 48 (53.9%) |
Non-native valves
n = 41 (46.1%) |
Non-native valve types | ||||
|---|---|---|---|---|---|---|
|
Bioprosthetic
n = 14 |
Mechanical
n = 1 |
Surgically repaired
n = 15 |
Percutaneously repaired
n = 11 |
|||
| Valve position, n (%) | ||||||
| AR/MR | 28 (58.3) | 12 (29.3) | 4 (28.6) | 0 | 8 (53.3) | 0 |
| AS/MS | 9 (18.8) | 9 (22.0) | 2 (14.3) | 1 (100.0) | 5 (33.3) | 1 (9.1) |
| PS/PR | 8 (16.7) | 17 (41.5) | 5 (35.7) | 0 | 2 (13.3) | 10 (90.9) |
| Mixed/Other | 3 (6.3) | 3 (7.3) | 3 (21.4) | 0 | 0 | 0 |
| Adverse outcomes, n (%) | ||||||
| Maternal | 6 (12.5) | 3 (7.3) | 3 (21.4) | 0 | 0 | 0 |
| Obstetric | 28 (58.3) | 29 (70.7) | 12 (85.7) | 1 (100.0) | 10 (66.7) | 6 (54.5) |
| Fetal | 17 (35.4) | 17 (41.5) | 6 (42.9) | 0 | 6 (40.0) | 5 (45.5) |
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