The leading causes of pregnancy-related mortality had differing distributions of maternal age, parity, and gestational age at delivery (Table 2). Of the California birth cohort, 41% were 30 years or older compared with 67% of preeclampsia deaths, 75% of hemorrhage deaths, and 78% of amniotic fluid embolism deaths (P<.001), whereas the age distribution of women who died of cardiovascular disease and venous thromboembolism mirrored that of the California birth cohort.
Women who died of preeclampsia were more likely than women who died of the other four causes to be primiparous (44% compared with 21%, P<.01) but their rate of primiparity was similar to the California birth cohort. Women who died from hemorrhage, venous thromboembolism, and amniotic fluid embolism were more likely to be grand multiparous than the California birth cohort (P<.01). Women who died of preeclampsia (61%), hemorrhage (50%), venous thromboembolism (40%), and cardiovascular disease (32.6%) were more likely to have delivered preterm (less than 37 weeks of gestation) than the California birth cohort (11%) (P<.001). Almost all (94%) who died from amniotic fluid embolism delivered at term, differing from the other four causes (P<.05).
Women who died were significantly more likely to be obese (BMI 30 or higher) before pregnancy than the Maternal Infant Health Assessment population (30% compared with 16%, respectively, P<.05) (Fig. 1). An even greater difference was found in the percent of extremely obese (BMI 40 or higher) women (10% compared with 2%, P<.05). Women who died of cardiovascular disease were more likely to be obese than those who died of preeclampsia or amniotic fluid embolism (P<.05). Women who died of venous thromboembolism were more likely to be obese than those who died of preeclampsia, hemorrhage, and amniotic fluid embolism (P<.01). At the time of delivery, of the 58% obese women who died from venous thromboembolism, half were extremely obese.
The median time interval between delivery and death varied by cause (Fig. 2). Amniotic fluid embolism and hemorrhage deaths were more likely than venous thromboembolism and cardiovascular disease deaths to occur during labor or within 1 day of delivery (P<.05). Cardiovascular disease deaths occurred significantly later (median 9 days) than amniotic fluid embolism, hemorrhage, and preeclampsia deaths (P<.001) largely as a result of cardiomyopathy deaths, which occurred up to 5 months postpartum. The short time interval from delivery to death for women with preeclampsia reflected the high percentage of these deaths with hypertension-related hemorrhagic stroke (58%). The extreme outliers represented women with multiorgan failure or brain injury, which resulted in prolonged hospitalization before death.
Cesarean delivery was the most frequent mode of delivery among the five leading causes of pregnancy-related death (67%) (Table 2), as would be expected because more than half of the cesarean deliveries were emergent or perimortem. The exception was among patients with venous thromboembolism, in whom 64% were repeat cesarean deliveries, only two were emergent, and none were perimortem. Of the women with BMIs 40 or higher who died of venous thromboembolism, 89% delivered by cesarean (n=14).
With the exception of amniotic fluid embolism, the frequency of labor induction was similar among the major causes of pregnancy-related mortality. Of the women who died of amniotic fluid embolism, 53% were induced compared with 21% of women who died from the other major causes (P<.01).
For hemorrhage deaths, the underlying processes were evenly attributed to placental issues (previa, accreta, and retained placenta) (35%), uterine lacerations or rupture (35%), and atony, with or without coagulopathy (30%).
Overall, 41% of pregnancy-related deaths had a good-to-strong chance of preventability, and nearly 90% had at least “some” chance; however, the leading causes showed considerable variation (Fig. 3). Hemorrhage and preeclampsia were significantly more likely than cardiovascular disease and amniotic fluid embolism deaths to have had a good-to-strong chance of preventability, estimated at 70% and 60%, respectively. No amniotic fluid embolism deaths had a good-to-strong chance, differing from all other causes of death (P<.001), but 83% of amniotic fluid embolism deaths had at least some chance of preventability.
The California Pregnancy-Associated Mortality Review Committee identified specific contributing factors to guide quality improvement opportunities. Each patient may have had multiple contributing factors. Health care provider factors were the most common type of contributor identified for all five leading causes of death (Fig. 4A) and were particularly common for preeclampsia and hemorrhage, consistent with their higher degree of preventability. The most common health care provider factor was delayed response to clinical warning signs followed by ineffective care. Of note, among women who died from venous thromboembolism after cesarean delivery, only one received any form of mechanical or medical prophylaxis.
Hemorrhage was associated with the most facility factors identified (Fig. 4B), with inadequate staff knowledge (42%), systems issues (ie, lack of massive transfusion protocols) (30%), and coordination of care (ie, delays in blood product administration) (30%) the most common specific factors.
Patient-related factors, particularly underlying medical conditions and obesity, were most commonly identified among cardiovascular disease and venous thromboembolism cases (Fig. 4C). The leading patient factors among preeclampsia deaths were delays in seeking care (42%), underlying medical conditions (39%), and presumed lack of knowledge regarding the severity of a symptom or condition (39%). Frequent patient factors among hemorrhage deaths were delays in seeking care (40%) and refusal of blood products among Jehovah's Witness adherents (20%).
This report demonstrates the clinical heterogeneity among pregnancy-related deaths in California and has important implications for medical and public health efforts. This is a large study examining U.S. pregnancy-related mortality analysis with both enhanced ascertainment and full medical record reviews. We identified significant differences among the five leading causes of pregnancy-related death when compared with each other or with the California birth population for race, age, parity, gestational age, BMI, timing of death, induction, and delivery method. Our findings point to specific actions to improve clinical recognition and response for each cause of death described subsequently.
Cardiovascular disease was the most common cause of pregnancy-related death in California. This is consistent with recent U.S. and U.K. analyses but differs from France, where obstetric hemorrhage is most prevalent.3,15,16 Race and obesity were strong risk factors for cardiovascular disease deaths, whereas advanced maternal age was not. The cardiovascular disease pregnancy-related mortality rate for African American women was nearly 10 times higher than any other racial or ethnic group, and women who died of cardiovascular disease were more than three times as likely to be obese than the California population. African American and obese women seeking preconception care should be counseled on how to moderate their cardiovascular disease risk, including attaining a healthy weight before pregnancy.
Preeclampsia deaths were most common among foreign-born Hispanic and African American women and were associated with early gestational age, consistent with studies demonstrating the increased severity of early-onset preeclampsia.17 This cause of death was deemed one of the most preventable, with high rates of delayed response to symptoms and vital signs, ineffective control of hypertension, inadequate staff knowledge around blood pressure management, misdiagnosis, and lack of continuity of care. Patient factors included lack of understanding of warning signs and delays in seeking care. These findings reinforce the ongoing work to promote better clinical recognition and response to preeclampsia and eclampsia. Recently, the California Maternal Quality Care Collaborative, Hospital Corporation of America, and the American College of Obstetricians and Gynecologists released guidelines and quality improvement tool kits with standardized approaches to recognize and treat severe hypertension and to increase awareness of atypical clinical presentations and patient education.17–19
Hemorrhage deaths occurred among women who were significantly older, multiparous, of normal weight, and who had premature births. In this study, 35% of hemorrhage deaths were related to placental complications compared with 16% found in an earlier national study.9 We found high rates of preventability among hemorrhage deaths, similar to other research.6 We identified very high rates of health care provider factors, including delayed response to clinical warning signs, ineffective medication, and inadequate blood product utilization. Hemorrhage deaths had the highest rates of facility contributing factors. U.K. and French reviews noted 66% of hemorrhage cases involved suboptimal care among health care providers and facilities.15,16 Recent studies indicate that standardized approaches to obstetric hemorrhage reduce serious morbidity.20,21
Venous thromboembolism pregnancy-related mortality rates were highest in African American women, obese women, and among women who had repeat cesarean deliveries. Half of the venous thromboembolism deaths were highly preventable, with strong improvement opportunities related to appropriate venous thromboembolism prophylaxis and improved responses to clinical warning signs. The United Kingdom noted a similar relationship with obesity and cesarean delivery, whereas France noted 61% had suboptimal care.15,16 Currently, the U.S. maternity care and safety community is discussing recommendations for additional approaches for prevention of venous thromboembolism based on risk factors beyond universal sequential compression devices at cesarean delivery.4
Women who died from amniotic fluid embolism presented largely in their 30s, were more likely to be multiparas, and to have term births. Other population-based reviews also found amniotic fluid embolisms to be less common among first births.22,23 Our findings differ from earlier studies in that we found no association between amniotic fluid embolism deaths and obesity nor with risk factors such as forceps delivery, multiple gestation, or placenta previa.24
Labor induction is a controversial risk factor for amniotic fluid embolism; several studies note a positive association,22,23 whereas others do not.24,25 With access to the full medical record, we found that 53% of women who died from amniotic fluid embolism were induced, twice that of any other cause and much higher than the population induction rate (21.5%).26 These cases presented catastrophically, with the shortest time to death among all causes. However, recent studies of amniotic fluid embolism survivors suggest that massive transfusion protocols with copious coagulation factors and intensive cardiovascular support may improve survival rates.25
Our study has limitations. Despite California having more than 500,000 annual births and subsequently a relatively large cohort of deaths over the 4-year study period, small numbers have limited statistical power when analyzing specific causes or performing multivariate analysis. Access to medical records was a major strength; however, judgments on preventability, contributing factors, and improvement opportunities were limited to information documented in the chart. Such data do not provide a full picture of patient and health care provider perspectives on decision-making, quality care, or the role of social determinants in health care utilization. We also had limited information on hospital-level data such as policies, procedures, or staffing, which may have contributed to some deaths.
State maternal mortality reviews identify public health and clinical efforts to reduce pregnancy-related mortality and morbidity. These reviews are valuable even in states with low numbers of maternal deaths to identify locally important improvement opportunities and develop ongoing surveillance.5 Our findings illustrate the need for public health interventions aimed at helping all women understand and recognize their risks and attain optimal prepregnancy health and weight. These findings also underscore the need for focused approaches to improve care such as hospital-based safety bundles for hemorrhage, preeclampsia, and venous thromboembolism prevention as well as comprehensive programs for patient education, communication, and teamwork development. Reversing increases in maternal mortality and severe morbidity requires the combined efforts of public health, clinical and hospital leaders, and their institutions.
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© 2015 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.
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