Objective
Maternal mortality rates rose markedly from 2002 to 2006 in California, prompting an in-depth maternal mortality review in a state that comprises one twelfth of the US birth cohort. Cardiovascular disease has emerged as the leading cause of pregnancy-related death in the United States. The primary aim of this analysis was to describe the incidence and type of cardiovascular disease as a cause of pregnancy-related mortality in California. The secondary aims were to describe racial/ethnic and socioeconomic disparities, risk factors, birth outcomes, timing of death and diagnosis, and signs and symptoms of cardiovascular disease and identify contributing factors.
Study Design
The California Pregnancy-Associated Mortality Review retrospectively examined a case series of 64 cardiovascular pregnancy-related deaths from 2002 through 2006. Two cardiologists independently reviewed complete inpatient and outpatient medical records including laboratory, radiology, electrocardiogram, chest X-ray, echocardiograms, and autopsy findings for each cardiovascular death and classified cause of death by type of cardiovascular disease. Demographic data, racial disparities, risk factors, signs and symptoms, timing of diagnosis and death, birth outcomes, and contributing factors were analyzed using bivariate comparisons with noncardiovascular pregnancy-related deaths and population-based data.
Results
Among 2,741,220 California women who gave birth, 864 died while pregnant or within 1 year of pregnancy; 257 of the deaths were deemed pregnancy related, and of these, 64 (25%) were attributed to cardiovascular disease. There were 42 deaths caused by cardiomyopathy, and the pregnancy-related mortality rate from cardiomyopathy was 1.54 per 100,000 births. Dilated cardiomyopathy existed in 29 cases, of which 15 met the definition of peripartum cardiomyopathy. Women with cardiovascular disease were more likely than women who died from noncardiovascular causes to be African-American (39.1% vs 16.1%; P < .01) and more likely to use illicit substances (23.7% vs 9.4%; P < .01). Thirty-seven percent were obese and 20% had a concomitant diagnosis of hypertension or preeclampsia during pregnancy. Health care decisions in the diagnosis or treatment of cardiovascular disease during and after pregnancy contributed to the fatal outcomes.
Conclusion
African-American race, substance use, and obesity were risk factors for pregnancy-related cardiovascular disease mortality. Chronic disease prevention and better recognition and response to cardiovascular disease during pregnancy are needed to reduce maternal mortality.
Cardiovascular disease (CVD) is increasingly recognized as a frequent cause of pregnancy-related morbidity and mortality worldwide and is surpassing other medical causes of pregnancy-related mortality in developed countries. United Kingdom obstetrical surveillance reported heart disease as a leading cause of maternal deaths from 2010 to 2012 with an incidence of 2.25 deaths per 100,000 live births. United States surveillance data show an increase in cardiovascular pregnancy-related deaths with 3.48 deaths per 100,000 live births from 1998 to 2005 to 4.23 cardiovascular deaths during 2006-2010.
Cardiomyopathy contributed to nearly 12% of pregnancy-related deaths for a rate of 0.88 deaths per 100,000 live births during 2006-2009. CVD in pregnancy encompasses a spectrum of cardiac diagnoses with a preponderance of cardiomyopathy. In particular, peripartum cardiomyopathy presents in the last month of pregnancy or within the first 5 months postpartum. Obese African-American women of non-Hispanic origin are particularly at risk for cardiomyopathy. Additionally, more than one third of intensive care unit admissions in pregnancy and postpartum are related to cardiac disease.
The California Pregnancy-Associated Mortality Review (CA-PAMR) was initiated in 2006 in response to rising rates of maternal mortality and retrospectively investigates maternal deaths statewide to inform prevention and quality improvement strategies. The primary objective of this analysis is to describe the incidence and type of CVD as a cause of pregnancy-related mortality. The secondary objectives are as follows: (1) to describe disparities in risk based on race/ethnicity and socioeconomic status; (2) to identify risk factors; (3) to measure birth outcomes; (4) to describe the timing of death and diagnosis; (5) to describe signs and symptoms of CVD identified during pregnancy; and (6) to identify contributing factors.
Materials and Methods
Women who died while pregnant or within a year of delivery were identified by linkage of birth, fetal death, and maternal death certificates. When data sources (death certificates and autopsy and toxicology reports) suggested the death may be pregnancy related, defined as deaths directly related to the physiological changes in pregnancy or causes aggravated by the pregnancy or its management, medical records were reviewed by the CA-PAMR Committee.
The committee determined causation of pregnancy-related cardiovascular deaths by ascribing the cause as either cardiomyopathy or other cardiovascular disease, similar to national reporting. Through consensus, the committee also identified contributing factors related to health care providers, health care facilities, or patient circumstances and the degree to which the death might have been prevented.
Health care provider factors included actions involving diagnosis, treatment, and communication processes. Facility factors included systems-level processes involving policies, nursing knowledge, or infrastructure. Patient factors included circumstances, risk factors, or health behaviors contributing to the cause of death.
Preventability was assessed by whether specific and feasible actions, had they been implemented, might have changed the course of the woman’s trajectory and led to a nonfatal outcome, as measured on a 4-part continuum: strong, good, some, or no chance. Examples of specific and feasible actions included failure to evaluate the cause of severe shortness of breath and anxiety in a postpartum woman and apparent lack of communication and care coordination among obstetrics and cardiology around a diagnosis of Marfan syndrome.
For this analysis, in 2013, 2 cardiologist members of the CA-PAMR Committee (A.B.H. and E.F.) independently re-reviewed the available series of CVD cases from 2002 to 2006 to confirm CVD causes of death and further classify cardiomyopathy and other CVD subtypes per the criteria listed in Table 1 . In cases of discordant coding, the cases were discussed to seek consensus, and if still discordant, a third cardiologist was consulted to adjudicate.
| Terms | Definition |
|---|---|
| California birth cohort | Women with a live birth or fetal loss within the calendar year |
| Pregnancy-associated mortality cohort | Women who died while pregnant or within 1 y postpartum from any cause |
| Pregnancy-related death | Death from causes directly related to the physiological changes in pregnancy or causes aggravated by the pregnancy or its management |
| Cardiovascular pregnancy-related death | Death in which cardiovascular disease, which is caused or aggravated by pregnancy, is the initiating or critical pathological event leading to death |
| Type of cardiomyopathy | Hx/S/S, ECHO, and AUT |
| Dilated cardiomyopathy | Hx/S/S: rales, S3 gallop, pulmonary edema on CXR ECHO: LV ejection fraction less than 40%; LV wall thickness ≤1.2 cm; dilated LV AUT: enlarged heart; increased chamber dimensions, wall thickness <1.5 cm, no identifiable structural heart disease |
| Peripartum | Hx/S/S: development of congestive heart failure in the last month of pregnancy or within 5 mo postpartum, absence of preexisting cardiac dysfunction, absence of a determinable cause of cardiomyopathy, and ECHO: documented LV systolic dysfunction |
| Nonperipartum (secondary to drug and/or alcohol use) | Hx/S/S: documented substance or alcohol use, by positive toxicology screen ± well-documented history |
| Nonperipartum (secondary to infection (eg, acute myocarditis) | Hx/S/S: clinical history of recent respiratory or other infection; AUT: inflammatory cells (lymphocytes) on microscopy |
| Subtype could not be determined | Hx/S/S: outside window for peripartum cardiomyopathy but had no other features to suggest etiology |
| Hypertrophic heart disease, including cardiomyopathy | Hx/S/S: S4 gallop, systolic murmur; pulmonary edema on CXR ECHO: LV ejection fraction ≥40%; LV wall thickness ≥1.2 cm AUT: increased heart weight; normal chamber dimensions, wall thickness ≥1.5 cm |
| Primary, potential | Hx/S/S: no documented family history but no cause for secondary hypertrophy |
| Secondary, hypertension | Hx/S/S: documented blood pressures ≥140/90 mm Hg |
| Secondary, drug use | Hx/S/S: documented history of methamphetamine or cocaine, by positive toxicology screen ± well-documented history |
| Secondary, valve disease | ECHO: significant valve abnormality |
| Etiology could not be determined | Hx/S/S: inadequate documentation for presence of secondary causes and no known family history |
Case data were analyzed using IBM SPSS Statistics version 20.0 (IBM Corp, New York, NY). Demographic variables (age, race, payer source) were derived from the maternal death certificate. Adequacy of prenatal care was calculated using a well-established index, based on 2 independent measures: initiation of care and frequency of visits. Substance use, body mass index, parity, CVD-related clinical variables, and timing of diagnoses were collected from the medical record; heart weight was collected from the autopsy.
The California birth cohort is comprised of women who gave birth or had a fetal death, as reported on California birth and fetal death certificates, and provides a population-based comparison of child-bearing women in the same time frame. Comparisons were also made to CA-PAMR pregnancy-related deaths from causes other than CVD for risk factors and clinical characteristics. Statistical significance was determined using the Pearson χ 2 test of independence for categorical variables, and independent t tests and nonparametric Mann Whitney tests were conducted for continuous variables. A paired-samples t test was conducted for an analysis of average heart weight in CVD cases compared with the average heart weight of nonpregnant women.
All CA-PAMR protocols were approved by the Committee for the Protection of Human Subjects of the State of California and comply with the Health Insurance Portability and Accountability Act. The Stanford University and Public Health Institute Institutional Review Boards exempted analysis of deidentified data on deceased persons.
Results
Incidence and type of CVD
From 2002 to 2006, there were 2,741,220 California women who gave birth or had a fetal demise and 864 women who died while pregnant or within 1 year of pregnancy. Initial screening yielded 344 cases for committee review, and 257 were subsequently determined to be pregnancy related by the CA-PAMR Committee. Among the pregnancy-related deaths, nearly a quarter (n = 64) were due to CVD, for an incidence rate of 2.35 CVD deaths per 100,000 live births.
Among the CVD deaths, two-thirds (n = 42) met criteria for cardiomyopathy (1.54 cardiomyopathy deaths per 100,000 live births) and 22 deaths were from other cardiovascular causes ( Figure 1 ). Among the cardiomyopathy deaths, 29 (69%) were from dilated cardiomyopathy (1.06 dilated cardiomyopathy deaths per 100,000 live births) and 10 (24%) were associated with hypertrophic heart disease (HHD) (0.37 HHD deaths per 100,000 live births).
Of the 29 dilated cardiomyopathy cases, 24 deaths had sufficient documentation to determine whether they met the case definition of peripartum cardiomyopathy ( Table 1 ), and 15 deaths were attributed to this etiology. Five of the 10 deaths from HHD were determined to be secondary to hypertension, substance use, or valve disease. Two cases were potentially primary hypertrophic cardiomyopathy, and in 3 cases, the etiology could not be determined. The most frequent diagnoses among the other cardiovascular category (n = 22) were pulmonary hypertension (n = 7) and aortic dissection (n = 5).
Racial/ethnic and socioeconomic disparities of all CVD pregnancy-related deaths
Women who died from CVD were more likely than those who died of non-CVD causes to be African-American (39.1% vs 16.1%; P < .01) ( Table 2 ). The CVD pregnancy-related mortality rate for African-Americans was more than 8 times higher than that for whites (17.1; 95% confidence interval [CI], 10.4–23.7 vs 2.0; 95% CI, 1.0–3.0 per 100,000 live births, respectively). CVD type did not significantly vary by race/ethnicity. Women who died from CVD were more likely than the California birth cohort to have public insurance (62.5% vs 47%, respectively, P < .01) and were significantly less likely than the California birth cohort to have had adequate prenatal care ( P < .05) ( Table 2 ).
| Characteristic | All CVD deaths, n (%) (n = 64) | Non-CVD deaths, n (%) (n = 193) | California birth cohort, n (%) (n = 2,741,220) |
|---|---|---|---|
| Age, y | |||
| <20 | 3 (4.7) | 12 (6.2) | 257,301 (9.4) |
| 20–34 | 46 (71.9) | 115 (59.6) | 2,014,092 (73.5) |
| ≥35 | 15 (23.4) | 66 (34.2) | 469,102 (17.1) |
| Race/ethnicity | |||
| White, non-Hispanic | 16 (25.0) | 50 (25.9) | 793,780 (29.0) |
| Hispanic | 21 (32.8) | 91 (47.2) | 1,391,656 (50.9) |
| African-American, non-Hispanic | 25 (39.1) | 31 (16.1) a | 146,536 (5.4) a |
| All other/unknown or missing | 2 (3.1) | 19 (9.8) | 401,701 (14.7) |
| Payer source for delivery | |||
| Medi-Cal/other government | 40 (62.5) | 106 (54.9) | 1,289,446 (47.0) a |
| Private/other | 24 (37.5) | 87 (45.1) | 1,451,774 (52.9) |
| Adequacy of prenatal care | |||
| Less than adequate care | 23 (37.7) | 50 (27.0) | 663,542 (25.0) a |
| Adequate or better care | 38 (62.3) | 135 (73.0) | 1,993,835 (75.0) |
| Missing information (excluded from analysis) | 3 (4.7) | 8 (4.1) | 67,589 (2.5) |
a χ 2 analysis compared all CVD deaths with non-CVD deaths and with the California birth cohort ( P < .05).
Risk factors for pregnancy-related CVD deaths
Women who died from CVD had a higher frequency of documented substance use than women who died from non-CVD causes (23.7% vs 9.4%; P < .01) ( Table 3 ). When self-reported alcohol and tobacco use were included, the proportion of any substance use during pregnancy or the postpartum period rose to 32.8% among women with CVD deaths compared with 16.1% among non-CVD pregnancy-related deaths ( P < .01). The most prevalent underlying conditions among women who died from CVD were obesity (37.5%) based on prepregnancy body mass index (BMI) and hypertension. One fifth of the women who died from CVD (20.3%) had a concomitant diagnosis of hypertension (n = 8) or preeclampsia (n = 4), which was slightly more than the non-CVD deaths (16.6%). No differences in parity were noted ( Table 3 ).
| Variable | Cardiovascular pregnancy-related deaths | Noncardiovascular pregnancy-related deaths, n (%) (n = 193) | |||
|---|---|---|---|---|---|
| All CVD, n (%) (n = 64) | Cardiomyopathy deaths a (n = 42) | Other CVD, n (%) (n = 22) | |||
| Dilated cardiomyopathy, n (%) (n = 29) | Hypertrophic heart disease, n (%) (n = 10) | ||||
| Substance use b | |||||
| Amphetamines or cocaine | 7 (10.9) | 4 (13.8) | 2 (20.0) | 1 (4.5) | 15 (7.8) |
| Marijuana, opioids | 8 (12.5) | 8 (27.6) | — | — | 2 (1.0) c |
| Any of the drugs listed previously | 14 (27.3) | 11 (39.3) | 2 (25.0) | 1 (5.0) | 17 (9.4) c |
| Alcohol | 10 (16.9) | 7 (24.1) | 2 (20.0) | 1 (4.5) | 7 (3.6) c |
| Tobacco | 15 (25.0) | 6 (20.7) | 4 (40.0) | 3 (15.0) | 24 (12.4) c |
| Prepregnancy BMI, kg/m 2 d | |||||
| Underweight or normal (<25) | 19 (29.7) | 8 (27.6) | 2 (20.0) | 9 (40.9) | 76 (41.3) |
| Overweight (25.0–29.9) | 21 (32.8) | 7 (24.1) | 4 (40.0) | 8 (36.4) | 61 (33.1) |
| Obese 1 (30.0–34.9) | 11 (17.2) | 7 (24.1) | 1 (10.0) | 3 (13.6) | 22 (11.4) |
| Obese 2 (35.0–39.9) | 6 (9.4) | 4 (13.8) | — | 1 (4.5) | 6 (3.3) a |
| Obese 3 (≥40.0) | 7 (10.9) | 3 (10.3) | 3 (30.0) | 1 (4.5) | 19 (10.3) |
| Parity e | |||||
| 1 | 16 (25.0) | 6 (20.7) | 3 (30.0) | 6 (27.3) | 60 (31.1) |
| 2–3 | 33 (51.6) | 14 (48.3) | 7 (70.0) | 11 (50.0) | 89 (46.2) |
| ≥4 | 15 (23.4) | 9 (31.0) | — | 5 (22.7) | 43 (22.6) |
| Hypertensive disease, including preeclampsia | 13 (20.3) | 7 (24.1) | 4 (40.0) | 2 (9.1) | 32 (16.6) |
a There were 3 cardiomyopathy deaths whose subtypes were unable to be determined. As a result, not all values presented in the dilated cardiomyopathy and hypertrophic cardiomyopathy add up to (all) cardiomyopathy deaths (n = 42)
b Autopsy toxicology reports were data source for amphetamine, cocaine, marijuana, and opioid drug use. Alcohol and tobacco use obtained from self-reported data in medical records. Any substance use includes women with multiple substance use and will not equal the total of individual substances used
c χ 2 analysis compared all CVD deaths with non-CVD deaths ( P < .05)
d BMI calculated as: weight (pounds)/[height (inches)] 2 × 703. BMI data were missing for 9 of the women who died of non-CVD, and these cases were excluded from analysis. Thus, the total n does not sum to 193 and denominators for the BMI categories varied for non-CVD deaths
e Parity of 1 comprises the birth/fetal demise associated with this pregnancy-related death.
Birth outcomes
Among the 64 women who died from CVD, there were 60 live births and 4 fetal deaths. The average gestational age at the time of delivery was 36.9 weeks (range, 23.3–42.0 weeks; median, 38.4 weeks). The cesarean delivery rate was 53.1% in the CVD group vs 68.6% in the non-CVD group ( P < .05), with the maternal condition as the most common indication for cesarean delivery within both groups.
Timing of CVD pregnancy-related deaths and diagnosis
Among all CVD pregnancy-related deaths, 1 (1.6%) occurred prior to delivery and 70.3% occurred in the early postpartum period (ie, 42 or fewer days from delivery). Deaths among women with CVD, however, were more likely to occur beyond the 6 week postpartum period compared with women with non-CVD deaths (29.7% vs 7.3%; P < .001). Only 5% of other cardiovascular deaths occurred in the late postpartum period compared with 40% of all cardiomyopathy deaths and 55% of dilated cardiomyopathy deaths ( Table 4 ).
| Variable | Cardiovascular pregnancy-related deaths | Noncardiovascular pregnancy-related deaths, n (%) (n = 193) | |||
|---|---|---|---|---|---|
| All CVD, n (%) (n = 64) | Cardiomyopathy deaths (n = 42) a | Other CVD, n (%) (n = 22) | |||
| Dilated cardiomyopathy, n (%) (n = 29) | Hypertrophic heart disease, n (%) (n = 10) | ||||
| Time to death from birth or fetal demise | |||||
| Mean, d | 56 | 112 | 12 | 7 | 12 b |
| Median, d | 9.0 | 67.0 | 6.5 | 2 | 2 |
| Mode, d | 0 | 0 | 0 | 0 | 0 |
| Range (upper, lower) | (0, 340) | (0, 340) | (0, 64) | (0, 53) | (0, 255) |
| Early (≤42 d postpartum) | 45 (70.3) | 13 (44.8) | 9 (90.0) | 21 (95.5) | 179 (92.7) b |
| Late (>42 d postpartum) | 19 (29.7) | 16 (55.2) | 1 (10.0) | 1 (4.5) | 14 (7.3) b |
| Timing of CVD diagnosis | |||||
| Preexisting disease | 2 (3.1) | — | — | 2 (9.1) | N/A |
| Prenatal period | 5 (7.8) | 1 (3.4) | 1 (10) | 3 (13.6) | N/A |
| At labor and delivery | 4 (6.3) | 3 (10.3) | — | 1 (4.5) | N/A |
| Postpartum period | 22 (34.4) | 17 (58.6) | — | 5 (22.7) | N/A |
| Postmortem | 31 (48.4) | 8 (27.6) | 9 (90) | 11 (50.0) | N/A |
| Autopsy performed | |||||
| Yes | 44 (68.8) | 16 (55.2) | 9 (90.0) | 17 (77.3) | 103 (53.4) b |
| Heart weight a | |||||
| Heart weight data available | 40 (62.5) | 16 (55.2) | 8 (80) | 14 (63.6) | Data not available |
| Heart weight mean, g | 443 | 458 | 463 | 424 | Data not available |
| Exceeded normal heart weight, based on body weight c | 100% | 100% | 100% | 100% | Data not available |
| Identified as pregnancy related on death certificate d | |||||
| Yes | 33 (51.6) | 13 (44.8) | 4 (40.0) | 15 (68.2) | 156 (80.8) b |
| No | 31 (48.4) | 16 (55.2) | 6 (60.0) | 7 (31.8) | 37 (19.2) |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
