Obstetrics & Gynecology:
Pregnancy‐Related Mortality From Preeclampsia and Eclampsia
MACKAY, ANDREA P. MSPH; BERG, CYNTHIA J. MD, MPH; ATRASH, HANI K. MD, MPH
Office of Analysis, Epidemiology, and Health Promotion, National Center for Health Statistics, Hyattsville, Maryland, and Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Address reprint requests to: Andrea P. MacKay, MSPH, National Center for Health Statistics, 6525 Belcrest Road, Room 790, Hyattsville, MD 20782. E-mail: email@example.com
Received August 17, 2000. Received in revised form November 28, 2000. Accepted December 7, 2000.
Objective: To examine the role of preeclampsia and eclampsia in pregnancy-related mortality.
Methods: We used data from the Centers for Disease Control and Prevention's Pregnancy Mortality Surveillance System to examine pregnancy-related deaths from preeclampsia and eclampsia from 1979 to 1992. The pregnancy-related mortality ratio for preeclampsia-eclampsia was defined as the number of deaths from preeclampsia and eclampsia per 100,000 live births. Case-fatality rates for 1988–1992 were calculated for preeclampsia and eclampsia deaths per 10,000 cases during the delivery hospitalization, using the National Hospital Discharge Survey.
Results: Of 4024 pregnancy-related deaths at 20 weeks' or more gestation in 1979–1992, 790 were due to preeclampsia or eclampsia (1.5 deaths/100,000 live births). Mortality from preeclampsia and eclampsia increased with increasing maternal age. The highest risk of death was at gestational age 20–28 weeks and after the first live birth. Black women were 3.1 times more likely to die from preeclampsia or eclampsia as white women. Women who had received no prenatal care had a higher risk of death from preeclampsia or eclampsia than women who had received any level of prenatal care. The overall preeclampsia-eclampsia case-fatality rate was 6.4 per 10,000 cases at delivery, and was twice as high for black women as for white women.
Conclusion: The continuing racial disparity in mortality from preeclampsia and eclampsia emphasizes the need to identify those differences that contribute to excess mortality among black women, and to develop specific interventions to reduce mortality from preeclampsia and eclampsia among all women.
Pregnancy-induced or aggravated hypertension is an important complication of pregnancy and a leading cause of pregnancy-related death in the United States. The reported incidence of hypertension, including preeclampsia, eclampsia, and superimposed preeclampsia and eclampsia among all pregnant women varies from approximately 3% to 10%.1–3 Hypertension was reported to account for 15% of all antenatal hospitalizations for pregnancy complications.4 Women who develop preeclampsia or eclampsia during pregnancy are at an increased risk of abruptio placentae, acute renal failure, cerebrovascular and cardiovascular complications, and maternal death.3,5
We used data from the Centers for Disease Control and Prevention's (CDC) Pregnancy Mortality Surveillance System to conduct an analysis of pregnancy-related mortality from preeclampsia and eclampsia. We reviewed all reported pregnancy-related deaths in the United States for 1979–1992 to understand trends in pregnancy-related mortality associated with complications of preeclampsia and eclampsia, to identify risk factors for these deaths, and to calculate case-fatality rates.
Materials and Methods
CDC's Division of Reproductive Health, in collaboration with ACOG and state health departments, conducts ongoing surveillance of pregnancy-related deaths. Health departments in the 50 states, the District of Columbia, and New York City provide CDC with copies of death certificates and, when available, matched birth or fetal death certificates for all identified pregnancy-related deaths. The present analysis includes data from 1979 to 1992, the most recent years for which completed data are available.
Deaths were considered pregnancy-related if they occurred during pregnancy or within 1 year of the termination of pregnancy and resulted from complications of pregnancy itself, a chain of events initiated by pregnancy, or aggravation of an unrelated event by the physiologic effects of pregnancy. Information on all pregnancy deaths was reviewed and coded by clinically experienced epidemiologists for cause of death, contributing conditions of death, and outcome of the pregnancy. Deaths were classified using the system designed in collaboration with the CDC/ACOG Maternal Mortality Study Group. Pregnancy-related mortality ratios were defined as the number of pregnancy-related deaths per 100,000 live births. The number of live births was obtained from public-use tapes maintained by CDC's National Center for Health Statistics.
We included deaths from preeclampsia, eclampsia, and chronic hypertension with superimposed preeclampsia or eclampsia in this analysis. Deaths from complications of preexisting, chronic hypertension not aggravated by pregnancy were excluded. We limited the analysis to women with pregnancies at gestational age 20 weeks or greater. We also reviewed deaths from other causes when preeclampsia or eclampsia was a contributory cause of death.
Race-specific mortality for women classified as other than white or black was not analyzed because of small numbers. We examined live birth order as a proxy for parity. Information on live birth order, reported on birth certificates, was available for deaths associated with live births. Information on prenatal care, available for women who died after a live birth, was assessed by using a modification of the Kotelchuck Prenatal Care Utilization Index,6 which combined “intermediate” and “inadequate” care and added a category for women who received no prenatal care. Deaths from states not reporting one or more of the variables needed to calculate the prenatal care utilization index (timing of first prenatal care visit, number of prenatal care visits, and gestational age) were excluded from the analysis of prenatal care for those years during which they did not report (Texas, 1979; New Mexico, 1979–1985; California, 1979–1988).
We defined preeclampsia-eclampsia case-fatality rates as the number of deaths with preeclampsia or eclampsia as the underlying cause of death per 10,000 cases of preeclampsia or eclampsia during the delivery hospitalization. The numerator was the sum of these deaths from the Pregnancy Mortality Surveillance System for 1988–1992. The estimated number of delivery hospitalizations with a diagnosis of preeclampsia or eclampsia for 1988–1992 was obtained from the National Hospital Discharge Survey, an annual multistage probability sample of discharges from nonfederal, short-stay hospitals in the United States. Cases of preeclampsia or eclampsia at delivery were identified using International Classification of Diseases, Ninth Revision codes; we restricted case selection to hospitalizations that indicated a live birth or stillbirth and preeclampsia, eclampsia, or superimposed preeclampsia or eclampsia (ICD-9 codes 642.3–642.7).
For the 14-year study period, we identified 4024 pregnancy-related deaths to women at 20 weeks' or greater gestation; 790 of these deaths (19.6%) were from complications of preeclampsia or eclampsia. The pregnancy-related mortality ratio for deaths from preeclampsia and eclampsia was 1.5 pregnancy-related deaths per 100,000 live births; the overall pregnancy-related mortality ratio for deaths occurring at 20 weeks' or greater gestation was 7.5/100,000. The most frequent causes of pregnancy-related death were embolism, hemorrhage, and preeclampsia or eclampsia (Table 1).
Approximately half (51%) of preeclampsia-eclampsia deaths were associated with preeclampsia, the remainder with eclampsia. The largest percentage of preeclampsia and eclampsia deaths was attributed to cerebrovascular complications, primarily cerebrovascular hemorrhage (Table 2). Renal or hepatic failure was also frequently listed as the cause of death. Disseminated intravascular coagulation was a contributing condition in 15% of hypertension deaths.
Preeclampsia or eclampsia was a contributing condition of death in 4.5% of pregnancy-related deaths because of other causes of death (185 deaths). Approximately 11% of anesthesia deaths, 7% of cardiomyopathy deaths, and 10% of deaths from abruptio placentae were complicated by preeclampsia or eclampsia.
The risk of death from preeclampsia or eclampsia was higher for older women than for younger women (Table 3). Black women were at a greater risk of such deaths than white women. The disparity in the risk of death between white and black women was greatest among women aged 30 to 34 years, with black women having more than four times the risk of white women. Among all women, the risk of death from preeclampsia or eclampsia was highest after the first and fifth or higher live birth (Table 3); however, more than half of such deaths occurred after the first live birth and less than 8% after the fifth or higher. Although 47% of deaths from preeclampsia or eclampsia occurred during or after the 37th week of gestation, the greatest risk of death was among women with pregnancies at 28 or fewer weeks' gestation (Table 3).
Women who had received no prenatal care had a higher risk of death from preeclampsia or eclampsia than women who had received any prenatal care (Table 3). Among white women the risk of death associated with no prenatal care was 12 times that for adequate care; among black women the risk associated with no care was approximately four times that of adequate care.
The case-fatality rate for deaths from preeclampsia or eclampsia was 6.4 deaths per 10,000 cases at delivery (Table 4); the case-fatality rate for deaths associated with eclampsia (71.6) was strikingly higher than for deaths associated with preeclampsia (3.4). The risk of death for women 35 years and older was more than three times that of women 24 years or younger. Case-fatality rates for black women were twice those for white women; the prevalence of preeclampsia or eclampsia at the delivery hospitalization among black women was 1.4 times that of white women.
The results of this analysis are consistent with findings from previous studies of pregnancy-related mortality in which complications of hypertension were found to be the third leading cause of pregnancy-related death, after hemorrhage and embolism.7 The age-specific mortality ratios for preeclampsia and eclampsia reflect the trend observed in other studies—slightly increased risk for younger women (under 20 years) and markedly increased for older women, especially older black women.7 Hansen8 reported that hypertension is more common and carries an increased risk of death among older pregnant women, contributing to the several-fold increase in overall pregnancy mortality for older women compared with younger women.
Although most women in this analysis died after their first live birth, mortality from preeclampsia or eclampsia is not limited to first pregnancies; 40% of the women who died had a previous live birth. Other studies have found that women with a history of hypertension in a prior pregnancy or with a family history of chronic hypertension are at a greater risk of developing hypertension during pregnancy.9 We could not evaluate the role of these risks, as past medical history and family medical history were not available. Further, we could not evaluate the potentially confounding effects of age and birth order because of relatively small numbers.
The racial disparity in overall pregnancy-related mortality is also seen in hypertension-specific mortality.10–12 The combination of a higher prevalence of preeclampsia and eclampsia among black women and higher case-fatality rates contributed to pregnancy-related mortality rates because of preeclampsia and eclampsia for black women more than three times that of white women.
Women who received no prenatal care were more than seven times as likely to die from complications of preeclampsia or eclampsia as women receiving any prenatal care. Although black and white women who received prenatal care had a lower risk of death than women who received no prenatal care, there was a far greater reduction in the risk of death for white women receiving adequate prenatal care than for black women. This finding may reflect the quality of prenatal care, which is not measured by the Prenatal Care Utilization Index, or may be related to other factors not measurable from the data available. Whereas several studies have suggested that the content of prenatal care may differ for black women and white women,13,14 another study reported that black women receiving prenatal care reported significantly fewer prenatal visits than white women during the 8th and 9th months of pregnancy, those months when preeclampsia onset is most common.15
Although a rare event, onset of severe preeclampsia in the second trimester is associated with a higher risk of maternal and fetal morbidity and mortality.16 We found a dramatic increase in the risk of death for women at 20–32 weeks' gestation compared with women at 36–40 weeks or more. The mortality ratios for black and white women during the second trimester were similar; however, for women at 37–40 weeks' gestation, we found a threefold difference in the risk of death for black women compared with white women. This finding may be a further indication of a disparity in health status and access to and quality of prenatal care.
Cerebral hemorrhage has been reported in as many as 60% of all deaths from eclampsia.17 Seven percent of deaths in this study were attributed to hemolysis, elevated liver enzymes, and low platelet count syndrome, a variant of severe hypertension that results in multiorgan failure, which has cited mortality rates ranging from 2% to 24% of cases.18 Preeclampsia and eclampsia have been associated with an increased risk of abruptio placentae,5 disseminated intravascular coagulation, and acute renal failure.17 Abruptio placentae complicated 4% of the pregnancies of women who died of preeclampsia or eclampsia, more than four times the incidence of abruption at the delivery hospitalization for all women.1
The limitations of this analysis should be considered. Pregnancy-related mortality ratios are underestimated; despite improved ascertainment methods initiated over the study period, more than half of pregnancy-related deaths are not identified through routine surveillance methods.19,20 Preeclampsia and eclampsia are multisystem disorders of unknown etiology; the complex nature of complications may lead to misclassification of the underlying cause of death. Cause of death information was obtained from death certificates; therefore, we could not standardize our definitions. For some women, information about preexisting hypertension or chronic renal disease may not have been provided. Estimates from the National Hospital Discharge Survey are subject to errors associated with the use of medical records, including incorrect diagnoses or coder errors.
Deaths from preeclampsia and eclampsia are often preventable.21 Prenatal care, early detection, and careful monitoring and treatment during pregnancy are essential to prevent serious complications.3 It is important for clinicians to identify women with preexisting hypertensive disorders, a prior history of hypertension, or a family history of hypertension, and to educate women about the early warning signs of preeclampsia. The continuing racial disparity in preeclampsia and eclampsia mortality ratios emphasizes the need to identify those differences that contribute to excess mortality among black women, and to develop specific interventions to reduce mortality from preeclampsia and eclampsia among all women.
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Advances in Chronic Kidney DiseaseNew Developments in the Pathogenesis of PreeclampsiaAdvances in Chronic Kidney Disease
Hypertension ResearchIncreased oxygen free radical production during pregnancy may impair vascular reactivity in preeclamptic womenHypertension Research
Reproduction in Domestic AnimalsWho Let the Dogs In: A Canine Trophoblast Invasion Model for Pre-eclampsiaReproduction in Domestic Animals
American Journal of Obstetrics and GynecologyPerformance of a first-trimester screening of preeclampsia in a routine care low-risk settingAmerican Journal of Obstetrics and Gynecology
Prenatal DiagnosisCan detection of late-onset PE at triage by sflt-1 or PlGF be improved by the use of additional biomarkers?Prenatal Diagnosis
HypertensionFolic Acid Supplementation During Early Pregnancy and the Risk of Gestational Hypertension and PreeclampsiaHypertension
International Journal of Gynecology & ObstetricsErrors in the treatment of hypertensive disorders of pregnancy and their impact on maternal mortalityInternational Journal of Gynecology & Obstetrics
Circulation-Cardiovascular ImagingSubclinical Left Ventricular Dysfunction in Preeclamptic Women With Preserved Left Ventricular Ejection Fraction A 2D Speckle-Tracking Imaging StudyCirculation-Cardiovascular Imaging
Clinical Obstetrics and GynecologyEclampsia: Morbidity, Mortality, and ManagementClinical Obstetrics and Gynecology
Clinical Obstetrics and GynecologyAcute Complications of PreeclampsiaClinical Obstetrics and Gynecology
Current Opinion in Obstetrics and GynecologyHypertensive diseases and eclampsiaCurrent Opinion in Obstetrics and Gynecology
Obstetrics & GynecologyDiagnosis, Prevention, and Management of EclampsiaObstetrics & Gynecology
Obstetrics & GynecologyIncidence and Risk Factors for Stroke in Pregnancy and the PuerperiumObstetrics & Gynecology
Journal of HypertensionLow socioeconomic status is a risk factor for preeclampsia: the Generation R StudyJournal of Hypertension
Obstetrical & Gynecological SurveyVitamin D May Be a Link to Black-White Disparities in Adverse Birth OutcomesObstetrical & Gynecological Survey
Obstetrical & Gynecological SurveyLate Postpartum Eclampsia: Examples and ReviewObstetrical & Gynecological Survey
Obstetrical & Gynecological SurveyPreeclampsia. Part 1: Clinical and Pathophysiologic ConsiderationsObstetrical & Gynecological Survey
Southern Medical JournalPreeclampsia and Eclampsia RevisitedSouthern Medical Journal
© 2001 The American College of Obstetricians and Gynecologists