After years of decline, the frequency of maternal mortality in the United States has begun to increase.1 Consequently, several professional organizations devoted to maternal health held a meeting in 2012 to determine methods to help improve maternal outcomes.2 One concern was the lack of a standardized metric to identify women who experience significant maternal morbidity. This absence hinders both 1) investigation into etiologies of the events that result in severe morbidity; and 2) evidence-based quality improvement initiatives. Correspondingly, the group called for research that would help to develop a standardized measure of severe maternal morbidity that could be used as the foundation for surveillance and continuous quality improvement.
The development of such a measure is a goal that has been shared by others. Geller et al3 identified those with very severe morbidity by validating an arithmetical scoring system that took into account whether a woman had an unanticipated surgical intervention, was intubated for more than 12 hours postpartum, received a transfusion more than three units, was admitted to the intensive care unit, or experienced organ failure. However, this measure only has been explored in two studies, both of which were performed in single centers with relatively few patients analyzed.4,5
The purpose of the present study was to estimate the frequency of severe maternal morbidity in a large multicenter obstetric population using the system of Geller et al4 and to identify its underlying etiologies, associated factors, and whether a scoring system could be developed to predict its occurrence.
PATIENTS AND METHODS
Between 2008 and 2011, investigators at 25 medical centers belonging to the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network assembled an obstetric cohort in which detailed information was collected by trained and certified nurses on patient characteristics, intrapartum events, pregnancy outcomes, and postpartum courses of women who delivered at their institutions. Full details of the study design and technique of data collection for the Assessment of Perinatal Excellence cohort have been described previously.6 Institutional review board approval was obtained at all centers under a waiver of informed consent.
The present analysis included all women in the Assessment of Perinatal Excellence cohort. Women were given a score according to the classification system developed by Geller et al.4 This system assigns points according to whether a parturient had an unanticipated surgical intervention (1 point), was intubated for more than 12 hours (2 points), received a red blood cell transfusion of greater than three units (3 points), was admitted to the intensive care unit (4 points), or had failure of at least one organ system (5 points). Points are then summated, and those women with 8 or more points are classified as having had severe morbidity. For the present analysis, organ failure was defined as any one of the following: cardiopulmonary arrest, cardiac dysfunction (eg, cardiomyopathy), adult respiratory distress syndrome, pulmonary edema, disseminated intravascular coagulation, transfusion of platelets, stroke, subdural hematoma, postpartum serum creatinine greater than 2.0, or postpartum serum aspartate transaminase greater than 1,000 IU/L. Also, women were considered to fulfill the intubation criterion if they were intubated on at least 1 day given that data for length of intubation were collected in day, not hour, increments.
Women who experienced severe morbidity were identified and the overall frequency in the cohort was determined. Their abstracted data were further reviewed by one of the investigators (W.A.G.) to determine the primary etiology of their morbid outcome. Etiologic categories included: hemorrhage, infection, hypertensive disorders of pregnancy, nonhypertensive and noninfectious cardiopulmonary complications, trauma, iatrogenic complications, and preexisting maternal medical conditions.
We then investigated which patient factors were independently associated with severe morbidity using multivariable logistic regression to generate odds ratios and 95% confidence intervals. Model selection and internal validation was performed using k-fold crossvalidation in which the cohort was randomly divided into 10 equal parts and logistic regression models, using backward selection, were generated using every possible combination of nine of the 10 sets.7 Variables with P<.05 were retained, and each of the 10 subsamples was used for validation. A risk score was developed using methods similar to Rassi et al.8 Each coefficient from the final multivariable model was divided by the smallest coefficient and rounded to the nearest integer. The area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative likelihood ratios (with 95% confidence intervals [CIs]) were then calculated. All tests were two-tailed and P<.05 was used to define statistical significance. No imputation for missing data was performed. Analyses were performed using SAS software.
During the study period, 115,502 women delivered. After excluding seven maternal deaths, 115,495 were included in this analysis. Of the 115,495, 0.5% (n=619) had an unanticipated surgical intervention, 0.1% (n=136) were intubated on at least 1 day, 0.3% (n=323) received a blood transfusion of greater than three units, 0.6% (n=735) were admitted to the intensive care unit, and 0.6% (n=709) had at least one organ system fail. The summative point totals, as determined by the system of Geller et al,4 are provided in Table 1. Three hundred thirty-two women (2.9/1,000 births, 95% CI 2.6–3.2) had a point total of eight or more and thus were classified as having had severe morbidity.
Postpartum hemorrhage was responsible for almost half of severe morbidity (n=158 [47.6%]). Hypertensive complications (n=68 [20.5%]), acute cardiopulmonary complications (cardiomyopathy, arrest, acute respiratory distress syndrome, pulmonary edema) (n=63 [19.0%]), infection (n=20 [6.0%]), preexisting maternal medical conditions (n=8 [2.4%]), venous thromboembolism (n=4 [1.2%]), trauma (n=4 [1.2%]), acute neurologic complications (n=3 [0.9%]), iatrogenic events (anaphylaxis, surgical visceral injury) (n=2 [0.6%]), and pregnancy-specific conditions (acute fatty liver, amniotic fluid embolism) (n=2 [0.6%]) accounted for the remainder.
Patient characteristics, stratified by the occurrence of severe morbidity, are presented in Table 2. Patient factors significantly and independently associated with severe morbidity, along with odds ratios and 95% CIs, are presented in Table 3. The presence of placenta accreta was the characteristic most strongly associated with severe morbidity, although multiple other associated factors such as preterm delivery, antenatal anticoagulant or cigarette use, hypertension, diabetes mellitus, abruptio placentae, and prior cesarean delivery also were identified.
The number of points that each characteristic contributed to the risk score is presented in Table 3. Point totals ranged from 0 to 24 with higher point totals indicating greater frequency of severe maternal morbidity (Table 4). The area under the receiver operating characteristic curve for the risk score model was 0.80 (95% CI 0.77–0.83). Sensitivity, specificity, and likelihood ratios for the various risk score cutoff points are also presented (Table 4).
In this study, we have used the scoring system developed by Geller et al4 to characterize the frequency of and factors associated with severe morbidity in a 25-hospital consortium.6 Our results demonstrate that, between 2008 and 2011, severe morbidity occurred in 2.9 per 1,000 women who gave birth. Postpartum hemorrhage and hypertensive disorders of pregnancies together accounted for more than two-thirds of the primary underlying causes of severe morbidity. Additionally, the probability of experiencing severe morbidity was related to multiple well-defined patient characteristics.
The observed frequency is slightly lower than that estimated in other reports from developed countries. Wen et al,9 using Canadian administrative data, found that severe maternal morbidity occurred in 0.44% of deliveries. Zwart et al,10 analyzing data from a prospective study between 2004 and 2006, estimated that 0.71% of women giving birth experienced severe maternal morbidity in The Netherlands. Callaghan et al11 studied the National Inpatient Sample to estimate severe maternal morbidity among American women and derived an estimate of 1.5% for the years 2008–2009.
These previous studies differ from the current analysis in several important aspects. Both the Canadian and American estimates were derived from administrative data sets, in which the codes are limited in their scope, entered primarily for billing, and, as Callaghan et al note, subject to errors of omission and commission.9,11 Also, the definition of severe morbidity in all of these studies was based on the occurrence of a predefined event such as eclampsia or blood transfusion.9–11 However, determining morbidity through such a system could miss women who had severe morbidity because of other diagnoses or causes. These approaches also may be too sensitive; although it is likely that a woman who has received a blood transfusion has experienced some morbidity, it may not have been severe.
Our analysis, in contrast, estimated the frequency of severe morbidity from a data set that was derived from direct chart abstraction and was specifically constructed for research purposes. We used a system that was developed and validated specifically for the purpose of identifying women with the gravest obstetric morbidity. This system is not dependent on any single factor or diagnosis for identification, but on a constellation of adverse outcomes that could be the end result of any serious untoward or precipitating event.
The use of such a system allows insight into the etiologies that are contributing to severe morbidity. Such knowledge is important from a public health perspective in terms of knowing where to focus prevention and treatment efforts. Our data support the concept that postpartum hemorrhage and hypertensive disease of pregnancy are responsible for a large portion of severe maternal morbidity and underscore that the continued pursuit of best-practice care for these conditions may also yield substantial benefits in terms of decreasing the most severe maternal outcomes.12,13
Our data also allow insight into the patient factors that are associated with severe morbidity. These factors as well as the risk score derived from them could be used to help quantify the level of risk a woman has for a severely morbid outcome. It should be noted, however, that this quantification does not allow precise identification of women who will and will not have severe maternal morbidity. Because of the very low prevalence of severe morbidity, as indicated by Table 4, even with a prediction system with a receiver operating characteristic area under the curve of 0.80, a cutoff point that identifies women with a high risk of severe morbidity will simultaneously miss identifying most women who experience severe morbidity. For example, although a score of at least 19 results in a positive predictive value for severe maternal morbidity of 39%, this cutoff will not identify 93% of women who will experience severe morbidity. Conversely, a cutoff of 5 will result in 67% of women destined to have severe maternal morbidity being identified but a positive predictive value of only 0.93%. Thus, it is not evident that this prediction model could be used to effectively identify and change the clinical care of individual women.
Nevertheless, as maternal morbidity and mortality increase in frequency in the United States, the need to better understand their risks and causes increases in importance. Without the ability to measure and analyze these outcomes, the potential for systems improvement is compromised.2 Severe morbidity as defined in this analysis was approximately 50 times as frequent as maternal mortality in our population and could be used more readily to track outcomes and to be incorporated into quality improvement initiatives. Our analysis illustrates the importance of gaining a national consensus on a standard definition of severe maternal morbidity to allow standardized surveillance.
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