Predicting Adverse Outcomes in Women with Severe Pre-eclampsia

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The reason pre-eclampsia matters so much to maternity care providers is that adverse maternal and perinatal events cluster around the diagnosis of proteinuric gestational hypertension. While that is true, most pre-eclampsia is mild and evanescent, resolving rapidly postpartum. Therefore, every effort must be made to identify those women at greatest personal risk, and those bearing fetuses at greatest risk, so that they can be offered closer surveillance and lower thresholds for the use of effective interventions, such as delivery and the use of MgSO4. Conversely, as delivery remote from term can increase perinatal risks and as liberal MgSO4 use is associated with maternal morbidity, it may be as important to identify those women who have “mild” disease and bear little personal and/or fetal actuarial risk. For women with “mild” disease at presentation, expectant management remote from term or nonuse of MgSO4 would be appropriate. Through the PIERS (Pre-eclampsia Integrated Estimate of RiSk) model research program, we have determined that most criteria for “severe” disease perform poorly when operationalized to predict adverse maternal and/or perinatal outcomes. However, with standardized assessment and surveillance of women with suspected and confirmed pre-eclampsia it is possible to lower maternal risks both within individual institutions and across regions. In addition, the PIERS group developed, and is currently validating, 2 outcome prediction models (full-PIERS and mini-PIERS) that we hope will provide an evidence base for the definition of “severe” disease and guide clinical decision-making, especially remote from term when potential perinatal gains are so great.

Introduction

The reason pre-eclampsia matters so much to maternity care providers is that adverse maternal and perinatal events cluster around the diagnosis of proteinuric gestational hypertension. While this is true, most pre-eclampsia is mild and evanescent, resolving rapidly postpartum. Therefore, every effort must be made to identify those women at greatest personal risk, and those bearing fetuses at greatest risk. Once identified, these women can be offered closer surveillance and lower thresholds for the use of effective interventions, such as delivery and the use of MgSO4. Conversely, as delivery remote from term can increase perinatal risks1 and as liberal MgSO4 use is frequently associated with maternal morbidity,2 it may be as important to identify those women who have “mild” disease and bear little personal and/or fetal actuarial risk. For women with “mild” disease at presentation, expectant management remote from term or nonuse of MgSO4 would be appropriate.

It is also increasingly apparent that, other than the presence of a placenta, there is no single root cause for the maternal syndrome of pre-eclampsia across the spectrum of severity.3 The maternal syndrome appears to be triggered variably through a multihit process, where genetic predisposition, pre-existing renal disease or metabolic syndrome, chronic infectious and inflammatory states, and fetal growth potential (eg, macrosomia, multiple pregnancy) exist. These factors all modulate the maternal response to a placenta that may, or may not, be adequately formed during the first half of pregnancy where the interaction between maternal innate immune surveillance and invading cytotrophoblast plays a central role. Poor placentation appears to be most important in early onset pre-eclampsia (<34 weeks' gestation at onset), with other maternal and fetal factors acting as modifiers, whereas, at term, factors other than the adequacy of placentation appear to contribute more strongly.3

Whatever the inciting cause or causes, the result appears to be a complex soup of cellular, subcellular, and suspended components. Derived from the maternal (eg, activated leukocytes) and fetal (eg, trophoblast debris) compartments that exit the intervillous space of the placenta, this complex soup interacts primarily with the systemic maternal endothelium.3

The outcome of these complex interactions is a maternal syndrome of hypertension, glomerular endotheliosis and proteinuria, and systemic inflammation that we term pre-eclampsia—in a minority of cases this syndrome is severe and potentially life-threatening.

This article confines its focus to the prediction of severe and potentially life-threatening adverse outcomes in women, and, too a smaller extent, their fetuses, with suspected or confirmed pre-eclampsia, and not to the prediction of the diagnosis of pre-eclampsia during the first and/or second trimesters.

Section snippets

Current Classification and Evaluation of Pre-Eclampsia

Guidelines for the diagnosis, classification, and management of pre-eclampsia have been produced by the Canadian Hypertension Society (CHS; 1997),4 the U.S. National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy (NHBPEP; 2000),5 the Australasian Society for the Study of Hypertension in Pregnancy (2000),6 and the Society of Obstetricians and Gynaecologists of Canada (2008).3

These publications classify pre-eclampsia as being either mild or severe. Mild

The PIERS Program of Research

The PIERS program of research was initiated to develop an evidence-based framework by which clinicians can better define the maternal risks associated with the diagnosis of pre-eclampsia and the other hypertensive disorders of pregnancy. The ultimate goal is to develop and promulgate a clinical PIERS score that will not only guide clinical practice, especially as it relates to decisions around expectant management, but also have utility in selecting women for, and describing outcomes in,

Management of Pre-Eclampsia Pregnancies

Currently, management of pre-eclampsia is guided primarily by clinical impression rather than by evidence-based criteria of disease severity. The definitive treatment for pre-eclampsia is always delivery for the mother, but this is not always the best option for the fetus. Evidence from randomized controlled trials (RCTs) has shown that, remote from term, pregnancy prolongation by expectant therapy (delaying delivery until compelled by either maternal or fetal condition) decreases serious

Predictors of Adverse Outcomes Associated with Pre-Eclampsia—The Role for National Guidelines

At present, it is extremely difficult to identify which mothers with pre-eclampsia are at increased risk of developing adverse maternal complications, and this risk cannot be graded. Hypertension and proteinuria are commonly recognized risk factors for adverse maternal or perinatal outcome in pre-eclampsia pregnancies, and, as such, are often used to differentiate between “mild” and “severe” disease.3, 4, 5, 6, 16 Both heavy proteinuria and severe maternal hypertension are listed as “adverse

Single Site Experience

Through the PIERS project design of using primarily a continuous quality improvement approach, we chose to assess the incidence of combined adverse maternal and perinatal outcomes in women with pre-eclampsia before and after introducing standardized assessment and surveillance at BC Women's Hospital and Health Centre.18

This study was a preintervention (retrospective) compared with a postintervention (prospective) cohort comparison in a single-tertiary, perinatal unit that included women

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