Pregnancy-associated Mortality Research Articles

Pregnancy-associated mortality in Taiwan, 2004–2011

ObjectivePregnancy-associated death is defined by the American College of Obstetricians and Gynecologists as “a death of a woman while pregnant or within 1 year of termination of pregnancy, irrespective of the cause of death.” We sought to determine pregnancy-associated mortality ratio (PAMR) in Taiwan and to compare the cause of death pattern with other countries to assess the national health status of Taiwanese women. Materials and methodsWe linked four nationwide population-based data sets (birth registration, birth notification, National Health Insurance claims, and cause of death mortality) from 2004 to 2011 to identify women aged 15–49 years that died from pregnancy-associated deaths. We then calculated the PAMR and cause of death distribution by maternal age. ResultsA total of 559 pregnancy-associated deaths were identified with an overall PAMR of 36 (deaths per 100,000 live births). The J-shaped age-specific PAMR mortality pattern was noted, in which the PAMR was 32, 25, 24, 36, 71, 143, and 369 for women aged 15–19 years, 20–24 years, 25–29 years, 30–34 years, 35–39 years, 40–44 years, and 45–49 years, respectively. The age-standardized PAMR decreased drastically from 45 in 2004–2005 to 36 in 2006–2007 and 30 in 2008–2009, but leveled off to 33 in 2010–2011. The proportion of indirect causes increased from 2004–2007 to 2008–2011 among women aged 15–29 years and 35–49 years. ConclusionCompared with previous studies, the PAMR of Taiwan is moderate. However, the proportion of external causes of pregnancy-associated deaths in Taiwan is the lowest compared with other regions. Further studies (such as death review) are needed to explore possible preventable factors.

Pregnancy-associated homicide and suicide in 37 US states with enhanced pregnancy surveillance

Pregnant and postpartum women may be at increased risk of violent death including homicide and suicide relative to nonpregnant women, but US national data have not been reported since the implementation of enhanced mortality surveillance. The objective of the study was to estimate homicide and suicide ratios among women who are pregnant or postpartum and to compare their risk of violent death with nonpregnant/nonpostpartum women. Death certificates (n= 465,097) from US states with enhanced pregnancy mortality surveillance from 2005 through 2010 were used to compare mortality among 4 groups of women aged 10-54 years: pregnant, early postpartum (pregnant within 42 days of death), late postpartum (pregnant within 43 days to 1 year of death), and nonpregnant/nonpostpartum. We estimated pregnancy-associated mortality ratios and compared with nonpregnant/nonpostpartum mortality ratios to identify differences in risk after adjusting for potential levels of pregnancy misclassification as reported in the literature. Pregnancy-associated homicide victims were most frequently young, black, and undereducated, whereas pregnancy-associated suicide occurred most frequently among older white women. After adjustments, pregnancy-associated homicide risk ranged from 2.2 to 6.2 per 100,000 live births, depending on the degree of misclassification estimated, compared with 2.5-2.6 per 100,000 nonpregnant/nonpostpartum women aged 10-54 years. Pregnancy-associated suicide risk ranged from 1.6-4.5 per 100,000 live births after adjustments compared with 5.3-5.5 per 100,000 women aged 10-54 years among nonpregnant/nonpostpartum women. Assuming the most conservative published estimate of misclassification, the risk of homicide among pregnant/postpartum women was 1.84 times that of nonpregnant/nonpostpartum women (95% confidence interval, 1.71-1.98), whereas risk of suicide was decreased (relative risk, 0.62, 95% confidence interval, 0.57-0.68). Pregnancy and postpartum appear to be times of increased risk for homicide and decreased risk for suicide among women in the United States.

Pregnancy-Related Cardiovascular Deaths in California

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 P 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.

Pregnancy-related cardiovascular deaths in California: beyond peripartum cardiomyopathy

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. 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. 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. 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.

Improving Outcomes of Preeclampsia in California: From Review of Maternal Death to Quality Care Collaboratives

Childbearing Poster Presentation Objective To describe characteristics of women in California who died from preeclampsia/eclampsia in 2002 to 2004, identify contributing factors and quality improvement opportunities, and report on process and outcome measures from a multihospital, statewide learning collaborative that implemented a Maternity Care Improvement Preeclampsia Toolkit. Design In 2004, the California Maternal, Child and Adolescent Health Division developed an enhanced surveillance method to identify maternal deaths from administrative data; women's abstracted medical records were reviewed by an expert committee to determine causes of death and opportunities for prevention. Setting Data were collected as part of the California Pregnancy-Associated Mortality Review (CA-PAMR) and from CA-PAMR committee determination after case review. Data collection included classification of pregnancy-relatedness, contributing factors, and quality improvement opportunities. Learning Collaborative participants submitted process and outcomes measures related to the implementation of the Preeclampsia Toolkit. Sample Cases of pregnancy-related deaths (145) from preeclampsia/eclampsia in California between 2002 and 2004 from 26 hospitals in a statewide learning collaborative. Methods Mixed methods analysis was conducted of the CA-PAMR data; Learning Collaborative data were analyzed using frequency and trend charts. Results After case review, 145 maternal deaths from 2002 to 2004 were determined to be pregnancy-related. Preeclampsia was the second leading cause of death accounting for 17% of all pregnancy-related deaths in 2002 to 2004. The women who died from preeclampsia in California from 2002 to 2004 were more likely to be Hispanic, multiparous, and have normal body mass index (BMI) compared to women who died of other pregnancy-related causes. Nearly all ( n = 24/25) of these deaths were determined to have some degree of preventability, with half having a good-to-strong chance. Analysis of the opportunities to improve quality and reduce preventable maternal deaths revealed themes related to the need for recognition and response to clinical triggers (i.e., warning signs) in clinical status and care coordination. Learning collaborative participants reported increased levels of awareness and education regarding the importance of treating severe hypertension in pregnant women as a result of debriefing activity. Sites improved methods for medical chart documentation and coding, and overall data quality improvements as they apply to women with hypertensive disorders, including preeclampsia. Conclusion/Implications for Nursing Practice Implementation of the Preeclampsia Toolkit in the multihospital, statewide Learning Collaborative is intended to reduce rates of severe maternal morbidity and prolonged postpartum length of stay. Learning Collaborative participants who adopted the Toolkit showed measurable improvement in the ability of their sites to respond to this leading cause of pregnancy-related morbidity and mortality.

Fibrinogen, an endogenous ligand of Toll-like receptor 4, activates monocytes in pre-eclamptic patients

Pre-eclampsia (PE) remains the leading cause of pregnancy-associated mortality and morbidity, urging the need for a better understanding of its aetiology and pathophysiological progression. A key characteristic of PE is a systemic, exaggerated, inflammatory condition involving abnormal cytokine levels in serum, altered immune cell phenotype and Th1/Th2-type immunological imbalance. However, it is unknown how this heightened inflammatory condition manifests. We previously reported increased expression of the lipopolysaccharide receptor, Toll-like receptor 4 (TLR4), on monocytes from PE patients compared with normotensive, pregnant patients (NP). This upregulation of TLR4 on PE monocytes was accompanied by a hyper-responsiveness to bacterial TLR4 ligands. To determine whether non-microbial, endogenous TLR4 ligands also activate monocytes from PE patients, we investigated the expression of host-derived TLR4 ligands and the response of monocytes to these endogenous ligands. Plasma levels of fibrinogen – but not fibronectin or heparan sulphate – were higher in PE patients than in NP. Exposure to fibrinogen was associated with significantly increased production of inflammatory cytokines by monocytes from PE patients. Interestingly, this effect was not observed with NP monocytes. Our findings suggest that the fibrinogen-TLR4 axis might play an important role in the atypical activation of monocytes observed in PE patients that may contribute to the exaggerated inflammatory condition.

Abstract 18851: Cardiovascular Disease: The Leading Cause of Pregnancy-Related Death in California 2002-2005

Introduction: The California Pregnancy-Associated Mortality Review (CA-PAMR) was started in 2006 by the California Department of Health, Maternal, Child, and Adolescent Health Division in response to rising rates of maternal mortality with the goal of understanding and reducing maternal morbidity and mortality. Methodology: CA-PAMR uses an enhanced surveillance methodology to identify and investigate maternal deaths, as described previously. An expert committee reviewed medical records to determine pregnancy-related deaths, their clinical causes, contributing factors and opportunities for quality improvement. Results: From 2002-2005, there were 2,147,492 live births and 732 women died while pregnant or within 1 year of pregnancy. Among them, 207 were determined to be pregnancy-related: 53 were from cardiovascular disease (CVD) and two-thirds (n=33) of those from cardiomyopathy (CMP). Compared to women who died from non-cardiac causes, women who died from any CVD were twice as likely to be African-American (39% vs. 17%, p&lt;.01) and obese (BMI&gt;30) (42% vs. 26%, p&lt;.05), and had documented substance abuse during pregnancy (27% vs. 10%, p&lt;.01) and to die ≥ 42 days postpartum (31% vs. 6%, p&lt;.01). Almost a quarter (22%) of CVD deaths had a concomitant diagnosis of hypertension or preeclampsia. Similarly, the CMP deaths were three times as likely to be African-American (46% vs. 18%, p&lt;.01), twice as likely to be obese (47% vs 27%, p&lt;.05), four times as likely with substance abuse (37% vs. 9%, p&lt;.01), and to die ≥ 42 days postpartum (46% vs. 5%, p&lt;.01). Concomitant diagnosis of hypertension or preeclampsia occurred in 30% of CMP deaths. Overall, for those diagnosed before death (n=29), the mean time from symptom onset to diagnosis was 26 days (range=0, 223 days) and from diagnosis to death was 79 days (range 0, 347 days). Patient and health care provider factors were identified as having contributed to 86% and 71% of the deaths respectively, and 30% of the CVD deaths were considered potentially preventable. Conclusion: Medical expert review of maternal deaths has provided additional insight into CVD deaths that occur during or after pregnancy. Earlier recognition and referral of a symptomatic patient by obstetric providers may help prevent serious morbidity and mortality.

California Pregnancy-Associated Mortality Review: Mixed Methods Approach for Improved Case Identification, Cause of Death Analyses and Translation of Findings

After several decades of declining rates, maternal mortality climbed in California from a three-year moving average of 9.4 deaths per 100,000 live births in 1999-2001 to a high of 14.0 deaths per 100,000 live births in 2006-2008 (p < 0.001). The Maternal, Child and Adolescent Health Division of the California Department of Public Health developed a mixed method approach to identify and investigate maternal deaths to inform prevention strategies. This paper describes the methodology of the California Pregnancy-Associated Mortality Review (CA-PAMR) and its advantages for improved surveillance, cause of death analysis, and translation of findings. From 2002 to 2004, 1,598,792 live births occurred in California and 555 women died while pregnant or within one year of pregnancy. A screening algorithm identified cases for review that were likely to be pregnancy-related. Medical records were then abstracted and reviewed by a multidisciplinary committee to determine cause of death, contributing factors, and opportunities for quality improvement. Mixed methods were used to analyze, synthesize and translate Committee recommendations for improved care. Of 211 cases selected for review, 145 deaths were determined to be pregnancy-related. CA-PAMR methods corrected misclassification of cases and more accurately identified the leading causes of death. Cardiovascular disease emerged as the leading cause of pregnancy-related deaths (20%), and African-American women were disproportionately represented among cardiovascular deaths. Overall, the chance to prevent the fatal outcome appeared good or strong in 40% of cases reviewed. The CA-PAMR methodology resulted in additional case finding, improved accuracy of the causes of pregnancy-related deaths, and evidence to guide development of prevention and quality improvement efforts.

Ectopic Pregnancy Mortality—Florida, 2009–2010

Mortality rates for ectopic pregnancy in the United States decreased from 1.15 deaths per 100,000 live births during 1980–1984 to 0.50 during 2003–2007. This decline in the ectopic pregnancy mortality ratio has been attributed to improvements in diagnosis and treatment modalities, as well as increased access to early care of women with signs and symptoms of ectopic pregnancy. The present report discussed data showing a nearly 5-fold increase in the ectopic pregnancy mortality ratio in Florida between 1999–2008 and 2009–2010. The Florida Pregnancy-Associated Mortality Review subcommittee identified 13 ectopic pregnancy deaths that occurred in that state during the 10-year period from 1999 to 2008 and 11 during 2009–2010. This represented an increase in the mortality ratio from 0.6 deaths per 100,000 live births during 1999 to 2008 (which is similar to the national rate) to 2.5 during 2009 to 2010. Compared with 1999 to 2008, ectopic pregnancy deaths in Florida during 2009 to 2010 were more likely to have occurred in women who collapsed, presumably from hemorrhage associated with acute tubal rupture. Limited data based on information provided by household and family members and electronic medical records showed that most of these women received no health care before collapse. Six of the 8 women who collapsed during 2009 to 2010 tested positive at autopsy for use of illicit drugs. Therefore, the increased mortality appeared to be associated with delays in seeking health care and to illicit drug use among pregnant women. This report highlights the need for state-based pregnancy-related mortality surveillance to guide public health actions with the aim of preventing future deaths among women with ectopic pregnancy. Based on these findings, the Florida’s Florida Pregnancy-Associated Mortality Review committee recommends increased awareness among both pregnant women and health care providers about the importance of early access to care and the health risks associated with illicit drug use during pregnancy.

Pregnancy-Related Deaths Due to Pulmonary Embolism: Findings from Two State-Based Mortality Reviews

This report presents findings from two state-based pregnancy-related reviews of deaths due to pulmonary embolism to describe prevalence, risk factors, and timing of symptoms and fatal events (N=46). We examined the utility of state-based maternal mortality review teams as a means to gain more complete data on maternal deaths from which guidelines for prevention and intervention can be developed. The Florida Pregnancy-Associated Mortality Review Team and Virginia Maternal Mortality Review Team collaborated on findings from 9years of pregnancy-related mortality review conducted in each state. Pregnancy-related deaths due to pulmonary embolism occurring within 42days of pregnancy between 1999 and 2007 in Florida and Virginia were identified. Retrospective review of records was conducted to obtain data on timing of the fatal event in relation to the pregnancy, risk factors, and the presence and timing of symptoms suggestive of pulmonary embolism. Forty-six cases of pregnancy-related death due to pulmonary embolism were identified. The combined pregnancy-related mortality ratio (PRMR) was 1.6/100,000 live births. The PRMR for patients undergoing cesarean section delivery was 2.8 compared to 0.2 among those with vaginal deliveries (95% CI=1.8-4.2 and 0.1-0.5 respectively). Women aged 35 and older had the highest PRMR at 2.6/100,000 live births. BMI over 30kg/m(2) and presence of chronic conditions were frequently identified risk factors. One in five decedents (21.7%) reported at least two symptoms suggestive of pulmonary embolism in the days before death. This combined state-based maternal death review confirms age over 35years, obesity, and the presence of chronic conditions are risk factors for pregnancy-related mortality due to venous thromboembolism in the US. Expanding and standardizing the process of state-based reviews offers the potential for reducing pregnancy-related mortality in the US.

Monocyte Subpopulations from Pre-Eclamptic Patients Are Abnormally Skewed and Exhibit Exaggerated Responses to Toll-Like Receptor Ligands

The leading cause of pregnancy-associated mortality and morbidity is pre-eclampsia (PE). Although information regarding the etiology of this disease is scant, its pathophysiology is characterized by abnormal placentation, endothelial dysfunction as well as an exaggerated inflammatory response. Clinical evidence also indicates that the abundance of many immune cells at the feto-maternal interface and in the circulation of PE patients is abnormal, when compared with normal pregnant (NP) controls. In addition, the phenotype and function of some of these cells is altered. To further characterize the systemic effects of PE on circulating cells, we analyzed monocytic subpopulations in NP and PE patients by flow cytometry. We found that non-classical CD14lowCD16+ monocytes are significantly increased in women with PE and they display irregular expression of several chemokine receptors and antigen presentation molecules. The most striking phenotypic difference among the cell surface molecules was the marked upregulation of TLR4 expression, where both CD14highCD16+ and CD14lowCD16+ monocytes demonstrated higher levels than their NP counterparts. Stimulation of PE monocytes with TLR ligands resulted in profound secretion of various cytokines in comparison with NP controls. These data suggest that PE monocytes are hyper-responsive to TLR ligands and this may contribute to exacerbation of the disease.

The Contribution of Heart Disease to Pregnancy-Related Mortality According to the Pregnancy Mortality Surveillance System

The objective of this study was to demonstrate the increasing importance of heart disease as a cause of pregnancy-related mortality in Hawaii and the rest of the United States. Hawaii's Department of Public Health identified all pregnancy-associated death certificates from 1991 to 2007. Hospital records and autopsy reports were reviewed to determine whether deaths were pregnancy-related. From 1991 to 2007, Hawaii registered 156 deaths occurring within 1 year of pregnancy, which represented 4.2% of the total number of women who died in the same 17 to 46 years age group and 9.0% of the total number of women who died in the same 17 to 34 years age group. The pregnancy-related mortality ratio was 22.4 and the pregnancy-associated mortality ratio was 50. The leading cause of pregnancy-associated mortality was heart disease (20.5%) followed by cancer (18.6%) and suicide/homicide (12.2%). Pregnancy-related deaths (n=70) were attributed to heart disease (45.7%) followed by sepsis (14.2%) and hemorrhage (12.9%). The new Hawaii death certificate beginning in 2006 increased the detection of both pregnancy-related and -associated deaths. Heart disease is the most common cause of pregnancy-related mortality in Hawaii, and with improved ascertainment, may be determined to be the most common cause of pregnancy-related mortality in the rest of the United States.

The Comparative Safety of Legal Induced Abortion and Childbirth in the United States

To assess the safety of abortion compared with childbirth. We estimated mortality rates associated with live births and legal induced abortions in the United States in 1998-2005. We used data from the Centers for Disease Control and Prevention's Pregnancy Mortality Surveillance System, birth certificates, and Guttmacher Institute surveys. In addition, we searched for population-based data comparing the morbidity of abortion and childbirth. The pregnancy-associated mortality rate among women who delivered live neonates was 8.8 deaths per 100,000 live births. The mortality rate related to induced abortion was 0.6 deaths per 100,000 abortions. In the one recent comparative study of pregnancy morbidity in the United States, pregnancy-related complications were more common with childbirth than with abortion. Legal induced abortion is markedly safer than childbirth. The risk of death associated with childbirth is approximately 14 times higher than that with abortion. Similarly, the overall morbidity associated with childbirth exceeds that with abortion. II.

The contribution of heart disease to pregnancy-related mortality according to the pregnancy mortality surveillance system

The objective of this study was to demonstrate the increasing importance of heart disease as a cause of pregnancy-related mortality in Hawaii and the rest of the United States. Hawaii's Department of Public Health identified all pregnancy-associated death certificates from 1991 to 2007. Hospital records and autopsy reports were reviewed to determine whether deaths were pregnancy-related. From 1991 to 2007, Hawaii registered 156 deaths occurring within 1 year of pregnancy, which represented 4.2% of the total number of women who died in the same 17 to 46 years age group and 9.0% of the total number of women who died in the same 17 to 34 years age group. The pregnancy-related mortality ratio was 22.4 and the pregnancy-associated mortality ratio was 50. The leading cause of pregnancy-associated mortality was heart disease (20.5%) followed by cancer (18.6%) and suicide/homicide (12.2%). Pregnancy-related deaths (n=70) were attributed to heart disease (45.7%) followed by sepsis (14.2%) and hemorrhage (12.9%). The new Hawaii death certificate beginning in 2006 increased the detection of both pregnancy-related and -associated deaths. Heart disease is the most common cause of pregnancy-related mortality in Hawaii, and with improved ascertainment, may be determined to be the most common cause of pregnancy-related mortality in the rest of the United States.

Effectiveness of Pregnancy Check Boxes on Death Certificates in Identifying Pregnancy-Associated Mortality

Information that would allow the identification of women who were pregnant at the time of death or within the year preceding death has historically been underreported on death certificates. As a result, the magnitude of the problem of pregnancy-associated mortality is underestimated. To improve the identification of these deaths, check boxes for reporting pregnancy status have been added to death certificates in a number of states. We used multiple external data sources to determine whether check boxes have been effective in identifying pregnancy-associated deaths. We collected data on deaths occurring among pregnant or recently pregnant women residing in Maryland during the years 2001-2008 using multiple data sources. We determined the percentage of these deaths that could be identified through check boxes placed on death certificates. Overall, 64.5% of pregnancy-associated deaths were identified through pregnancy check boxes on death certificates, including 98.1% of maternal deaths-defined as deaths occurring during pregnancy or within 42 days of delivery from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes-and 46.7% of deaths from nonmaternal causes, such as homicide, suicide, accidents, and substance abuse. Check boxes on death certificates are effective in identifying pregnancy-associated deaths resulting from maternal causes. However, they are far less effective in identifying deaths resulting from nonmaternal causes, such as homicide, accidental death, and substance abuse, which represent three of the four leading causes of pregnancy-associated death in Maryland.

Thrombophilia and pregnancy complications

Venous thromboembolism is the leading cause of pregnancy-associated morbidity and mortality. Women with thrombophilia have an increased risk of VTE in pregnancy and puerperium. In individuals with hereditary thrombosis risk factors a relative risk of pregnancy associated VTE ranging from 3.4 to 15.2 has been found. Women with previous VTE have an approximately 3.5-fold increased risk of recurrent VTE during pregnancy compared to non-pregnant periods. Data on the association of thrombophilia and pregnancy loss and pre-eclampsia are conflicting. Besides an established association with antiphospholipid antibodies, available data suggest associations for antithrombin deficiency, hyper-homo-cysteinemia, factor V Leiden, prothrombin G20210A variation and protein S-deficiency. A contribution of thrombophilia to the risk of pre-eclampsia is less well established. A limited number of prospective studies did not reveal an increased risk of pregnancy complications in unselected women with thrombosis risk factors. Data of only one controlled trial on the prevention of pregnancy loss with low molecular weight heparin (LMWH) are available, which revealed a strikingly positive effect. Thrombophilia screening might be justified in women with pregnancy loss and treatment with LMWH might be considered in those with pregnancy loss and thrombophilia. Further prospective studies and controlled interventional trials are urgently needed.

CHANG AND BERG RESPOND TO HORON

We appreciate Horon’s interest in pregnancy-associated mortality and her work in this important area of women’s health. For the years of our study, we requested reporting areas (health departments in the 50 states, the District of Columbia, and New York City) to send us deidentified death certificates and, for those deaths after a live birth or stillbirth, matching birth or fetal death certificates. We also asked for certificates for deaths that occurred during pregnancy or within 1 year after pregnancy. We have no choice but to rely on the methods used by each reporting area to determine whether a death (including a death because of homicide) is pregnancy-associated. As stated in our discussion, the cause of death on death certificates is the most common way of ascertaining pregnancy-associated deaths. Next is computerized linking of deaths among women of reproductive age with birth certificates and fetal death certificates; we believe this system is used in about half the reporting areas. Maryland is fortunate to be able to also use medical examiners reports to ascertain additional cases. We know our numbers underestimate the overall magnitude of pregnancy-associated mortality. However, to produce a national picture of the risk factors associated with death during or shortly after pregnancy, we used the only sources of information available on pregnancy-associated deaths. We hope that our article and Horon’s letter will encourage states to use multiple methods to identify pregnancy-associated deaths and to use the information to develop appropriate interventions for the period around pregnancy to prevent mortality from all causes.

UNDERREPORTING OF PREGNANCY-ASSOCIATED DEATHS

In the March issue of the Journal, Chang et al. call attention to the finding that homicide is a leading cause of death among pregnant and postpartum women.1 However, their findings substantially underestimate the magnitude of the problem, because data on pregnancy-associated deaths collected by the Centers for Disease Control and Prevention’s Division of Reproductive Health (DRH) through the Pregnancy Mortality Surveillance System are incomplete. To collect data for the Pregnancy Mortality Surveillance System, the DRH asks states to voluntarily send death certificates for all maternal deaths, that is, deaths resulting from medical causes related to the pregnancy that occur during pregnancy or within 42 days of delivery or termination of pregnancy. The DRH also asks states to send information on pregnancy-associated deaths, that is, deaths from any cause that occur during pregnancy or within a year of delivery or termination of pregnancy. This would include homicides. Because it is impossible to identify all pregnancy-associated deaths with only the information contained on death certificates, and few states use additional sources of data to identify pregnancy-associated deaths,2 the information reported to the DRH is incomplete. Our Maryland study showed that only a small proportion of pregnancy-associated deaths can be identified from death certificates alone and that comprehensive identification of pregnancy-associated deaths requires collection of data from additional sources, including medical examiners’ records and linkage of death records with birth and fetal death records.3 Medical examiners’ records are a critical source of information on homicides that occur among women who are pregnant at the time of death, but Maryland may be the only state that routinely reviews medical examiners’ records for this purpose. Linkage of death records with birth and fetal death records is important in identifying homicides among postpartum women, but few states routinely link these records at all and even fewer do so for a full year following pregnancy. Further evidence of underreporting in Chang’s study is that their reported pregnancy-associated homicide rate of 1.7 per 100000 live births is substantially lower than rates cited in other reports. The pregnancy-associated homicide rate in Maryland was found to be 10.5 per 100000 live births when death records, linkage of records, and medical examiner records were used to identify deaths.3 Using only death certificates and linked records to identify deaths, Parsons and Harper4 in North Carolina and Nannini et al.5 in Massachusetts found rates of 7.2 and 3.5, respectively. Both states and the Centers for Disease Control and Prevention must improve their efforts to collect complete and accurate data on pregnancy-associated deaths. This is a critical step in the prevention of pregnancy-associated mortality from all causes.

Pregnancy-associated mortality after birth, spontaneous abortion, or induced abortion in Finland, 1987-2000

ObjectiveTo test the hypothesis that pregnant and recently pregnant women enjoy a “healthy pregnant women effect,” we compared the all natural cause mortality rates for women who were pregnant or within 1 year of pregnancy termination with all other women of reproductive age. Study designThis is a population-based, retrospective cohort study from Finland for a 14-year period, 1987 to 2000. Information on all deaths of women aged 15 to 49 years in Finland (n=15,823) was received from the Cause-of-Death Register and linked to the Medical Birth Register (n=865,988 live births and stillbirths), the Register on Induced Abortions (n=156,789 induced abortions), and the Hospital Discharge Register (n=118,490 spontaneous abortions) to identify pregnancy-associated deaths (n=419). ResultsThe age-adjusted mortality rate for women during pregnancy and within 1 year of pregnancy termination was 36.7 deaths per 100,000 pregnancies, which was significantly lower than the mortality rate among nonpregnant women, 57.0 per 100,000 person-years (relative risk [RR] 0.64, 95% CI 0.58-0.71). The mortality was lower after a birth (28.2/100,000) than after a spontaneous (51.9/100,000) or induced abortion (83.1/100,000). We observed a significant increase in the risk of death from cerebrovascular diseases after delivery among women aged 15 to 24 years (RR 4.08, 95% CI 1.58-10.55). ConclusionOur study supports the healthy pregnant woman effect for all pregnancies, including those not ending in births.

Enhanced Surveillance for Pregnancy-Associated Mortality—Maryland, 1993–1998

ContextDeaths occurring among women who are pregnant or who have had a recent pregnancy have a devastating impact on the family and community. It is important to understand the magnitude and causes of pregnancy-associated mortality so that comprehensive strategies can be formulated to prevent such deaths.ObjectiveTo ascertain the number and causes of pregnancy-associated deaths using enhanced surveillance techniques.Design, Setting, and SubjectsRetrospective, cross-sectional analysis of death certificate data of reproductive-age women, live birth and fetal death records, and medical examiner records in Maryland during 1993-1998.Main Outcome MeasureNumber of pregnancy-associated deaths, defined as death from any cause during pregnancy or within 1 year of delivery or pregnancy termination, by source of data and cause of death.ResultsA total of 247 pregnancy-associated deaths were ascertained. Twenty-seven percent (n = 67) were identified through cause-of-death information obtained from death certificates, 70% (n = 174) through linkage of death records with birth and fetal death records, and 47% (n = 116) through review of medical examiner records. Homicide was the leading cause of pregnancy-associated death (n = 50; 20%), and cardiovascular disorders were the second-leading cause (n = 48; 19%).ConclusionsIn this Maryland sample, comprehensive identification of pregnancy-associated deaths was accomplished only after collecting information from multiple sources and including all deaths occurring up to 1 year after delivery or pregnacy termination. This enhanced pregnancy mortality surveillance led to the disturbing finding that a pregnant or recently pregnant woman is more likely to be a victim of homicide than to die of any other cause. By broadening pregnancy mortality to include all possible causes, previously neglected factors may assume increased importance in prenatal and postpartum care.