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Clinical Opinion www. AJOG.

org

OBSTETRICS
Diagnosis and management
of atypical preeclampsia-eclampsia
Baha M. Sibai, MD; Caroline L. Stella, MD

The traditional criterion to confirm a di-


agnosis of preeclampsia is the presence Preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelets
of proteinuric hypertension (new onset syndrome are major obstetric disorders that are associated with substantial maternal and
of hypertension and new onset of pro- perinatal morbidities. As a result, it is important that clinicians make timely and accurate
teinuria at ⬎ 20 weeks of gestation). This diagnoses to prevent adverse maternal and perinatal outcomes associated with these
criterion is appropriate to use in most syndromes. In general, most women will have a classic presentation of preeclampsia
nulliparous women; however, recent (hypertension and proteinuria) at ⬎ 20 weeks of gestation and/or ⬍ 48 hours after
data suggest that, in some women, pre- delivery. However, recent studies have suggested that some women will experience
eclampsia and even eclampsia may de- preeclampsia without ⱖ 1 of these classic findings and/or outside of these time periods.
velop in the absence of either hyperten- Atypical cases are those that develop at ⬍ 20 weeks of gestation and ⬎ 48 hours after delivery
sion or proteinuria. Many of these and that have some of the signs and symptoms of preeclampsia without the usual hypertension
women display other manifestations of or proteinuria. The purpose of this review was to increase awareness of the nonclassic and
preeclampsia, such as the presence of atypical features of preeclampsia-eclampsia. In addition, a stepwise approach toward diagnosis
signs and symptoms or other laboratory and treatment of patients with these atypical features is described.
abnormalities. We will focus on the clinical Cite this article as: Sibai BM, Stella CL. Diagnosis and management of atypical preeclampsia-
entities that comprise atypical preeclamp- eclampsia. Am J Obstet Gynecol 2009;200:481.e1-481.e7.
sia and eclampsia and their management.

Gestational hypertension proteinuria, the syndrome of pre- sion and women with signs and symp-
without proteinuria eclampsia should be considered when toms of end-organ disease with any
Proteinuria in preeclampsia is a manifes- gestational hypertension is present in as- hypertension should be treated as if they
tation of renal involvement that results sociation with persistent symptoms or had severe preeclampsia.
from glomerular endothelial injury (al- when laboratory tests produce abnormal
tered permeability to proteins) and ab- results (Figure). Mild gestational hyper- Capillary leak syndrome
normal tubular handling of filtered pro- tension usually progresses to preeclamp- Recent evidence suggests that in some
teins. Traditionally, proteinuria was sia in 25-50% of cases. patients with preeclampsia, capillary
considered the hallmark for the diagno- Preeclampsia should be considered leak syndrome may manifest itself in the
sis of preeclampsia because it usually de- when gestational hypertension is severe form of a capillary leak (proteinuria, as-
velops after the onset of hypertension because of the associated adverse mater- cites, or pulmonary edema), excessive
and/or symptoms. However, its onset in nal-perinatal outcome that is reported in weight gain, or a spectrum of abnormal
clinical practice may be variable in rela- such cases. In a secondary analysis of hemostasis with multiple organ dysfunc-
tion to hypertension and/or other end- data from 2 multicenter trials, pregnancy tion. These patients usually have the
organ effects. Therefore, its presence outcomes in women with severe gesta- clinical manifestations of atypical pre-
should not be considered mandatory to tional hypertension were compared with eclampsia (ie, proteinuria with or with-
establish the clinical diagnosis of pre- outcomes in women with mild or severe out facial edema, excessive weight gain
eclampsia or eclampsia. In the absence of preeclampsia. This analysis revealed that [⬎ 5 lb/wk], ascites, or pulmonary
severe gestational hypertension is associ- edema in association with abnormal lab-
ated with higher maternal and perinatal oratory values or presence of symptoms)
From the Division of Maternal-Fetal morbidities than those found in mild but without hypertension. Therefore, we
Medicine, Department of Obstetrics and preeclampsia. In these studies, women recommend that women with capillary
Gynecology, University of Cincinnati
with severe gestational hypertension had leak syndrome with or without hyper-
College of Medicine, Cincinnati, OH.
adverse maternal or perinatal outcomes tension be evaluated for platelet, liver en-
0002-9378/free
© 2009 Mosby, Inc. All rights reserved.
that were similar to those outcomes that zyme, and renal abnormalities. They
doi: 10.1016/j.ajog.2008.07.048 were seen in women with severe pre- should also be questioned about symp-
eclampsia. However, the 2 trials included toms of preeclampsia. Women with
Download the full-length only a total of 56 subjects; more data are symptoms and/or abnormal blood test
article at www.AJOG.org needed. Nevertheless, women with un- results should be considered to have
controllable severe gestational hyperten- preeclampsia.

MAY 2009 American Journal of Obstetrics & Gynecology 481


Clinical Opinion Obstetrics www.AJOG.org

view of literature, we recommend that, af-


FIGURE
ter delivery, any woman with a history of
Overlapping role of hypertension, capillary leak, maternal symptoms,
convulsions at ⬎ 48 hours after delivery
and fibrinolysis/hemolysis in the spectrum of atypical preeclampsia
who is hypertensive and has either protein-
uria or symptoms of preeclampsia should
be considered eclamptic while other causes
are being ruled out. Patients who do not
improve rapidly after control of seizures
Blood Capillary and control of hypertension and those who
Pressure Leak have localized findings on neurologic ex-
amination should be evaluated aggres-
sively with neurodiagnostic tests. In the
presence of unexplained blindness or other
neurologic deficits, another differential di-
Symptoms agnosis is spontaneous reversible vascu-
lopathy syndrome or cerebral angiopathy.
Fibrinolysis Approximately 20-30% of women
with HELLP syndrome experience the
Hemolysis
manifestations for the first time at ⬎ 48
hours after delivery. Thus, women who
experience signs and symptoms that are
consistent with HELLP syndrome for the
first time after delivery should undergo
prompt medical evaluation that includes
Sibai. Diagnosis and management of a typical preeclampsia-eclampsia. Am J Obstet Gynecol 2009. laboratory testing to rule out or confirm
the presence of severe preeclampsia or
HELLP syndrome.
Gestational proteinuria been reported with molar or hydropic The use of intravenous dexametha-
Gestational proteinuria is defined as uri- degeneration of the placenta with or sone to improve maternal outcome in
nary protein excretion of ⱖ 300 mg/24- without a coexistent fetus. The pres- women with HELLP syndrome in the
hour timed collection or persistent pro- ence of hypertension, proteinuria, and postpartum period remains controver-
teinuria (ⱖ 1⫹ on dipstick on at least 2 abnormal laboratory tests at ⬍ 20 sial. Almost all studies that have reported
occasions at least 4 hours apart but not ⬎ weeks of gestation may be caused by such benefit were retrospective or com-
1 week apart). lupus nephritis, hemolytic-uremic pared treatment to no treatment in a
Women with new-onset gestational syndrome, antiphospholipid antibody limited number of subjects. In contrast,
proteinuria only should be monitored syndrome, or thrombotic thrombocy- 2 recent multicenter, double-blind, pla-
very closely for early detection of pre- topenic purpura. These women should cebo-controlled trials that evaluated the
eclampsia, because the presence of gesta- be evaluated to rule out the presence of administration of intravenous dexa-
tional proteinuria alone may herald the these disorders. In the absence of other methasone in patients with antepartum
early manifestation of an impending disease, the patient should be treated and postpartum HELLP syndrome re-
preeclampsia. In addition, these women for severe preeclampsia. In addition, vealed no improvement in maternal lab-
should be evaluated for potential pre- women in whom convulsions develop
oratory findings, maternal morbidities,
existing renal disease (such as chronic in association with hypertension and
or length of hospital stay.
pyelonephritis, lupus nephritis, immu- proteinuria during the first half of
noglobulin A nephropathy, and other pregnancy should be considered to
Conclusion
nephropathies). Moreover, women with have eclampsia until proven otherwise.
Preeclampsia is a syndrome that is char-
proteinuria and cardiorespiratory symp-
Late postpartum preeclampsia- acterized by heterogenous clinical and
toms, ascites, or pulmonary edema
eclampsia and hemolysis, laboratory findings for which the patho-
should be evaluated for potential cardiac
elevated liver enzymes, low genesis can differ. We recommend that
disease, such as congestive heart failure
platelets (HELLP) syndrome health care providers in obstetric prac-
and peripartum cardiomyopathy.
Late postpartum preeclampsia-eclampsia tice maintain a high index of suspicion
Preeclampsia-eclampsia is the development of signs and symptoms for the potential atypical clinical mani-
at < 20 weeks of gestation of preeclampsia-eclampsia for the first festations of preeclampsia, irrespective
Preeclampsia and/or eclampsia that time at ⬎ 48 hours, but ⬍ 4 weeks, after of gestational age at time of onset or
occurs at ⬍ 20 weeks of gestation has delivery. Based on our experience and re- number of days after delivery.

482 American Journal of Obstetrics & Gynecology MAY 2009


www.AJOG.org Obstetrics Clinical Opinion

Treatment of patients with atypical Patients with gestational proteinuria to cases that manifest as hypertension
manifestations of preeclampsia-eclamp- should be evaluated for the presence of un- without proteinuria and vice versa. Alter-
sia require a well formulated plan that diagnosed diabetes mellitus (glucose test- nately, one must be careful to avoid over-
takes the following items into consider- ing), undiagnosed lupus (serology, anti- diagnosis or misdiagnosis of other preex-
ation: maternal risk factors; clinical, lab- bodies, anticardiolipin antibodies, platelet isting conditions (such as undiagnosed
oratory, and imaging findings; and the count), and undergo a metabolic profile, chronic hypertension or renal disease) that
time of onset in relation to both gesta- complete urine analysis, and 24-hour might lead to unnecessary intervention.
tional age and delivery. urine test for creatinine clearance and Therefore, it is important to obtain a de-
For pregnancies that are complicated by quantitative proteinuria. tailed history, to assess for the presence of
hypertension and proteinuria that occurs In cases with hypertension and symp- symptoms, and to obtain targeted labora-
at ⱕ 20 weeks of gestation, an ultrasound toms of headache or blurred vision, with or tory tests, as needed, to confirm the diag-
scan should be performed to exclude the without seizures ⬎ 48 hours after delivery, nosis of atypical preeclampsia.
diagnosis of molar or partial molar preg- magnesium sulfate therapy should be ini-
nancy and uterine artery Doppler velocim- tiated without delay while other possible
etry to evaluate uterine artery resistance causes of the aforementioned symptoms
CLINICAL IMPLICATIONS
and the presence of a notch. are being ruled out. If the patient has severe
Gestational hypertension or gestational hypertension alone, antihypertensive ther-  Atypical preeclampsia should be con-
proteinuria alone may be the first sign of apy should be administered to stabilize sidered in all pregnant and postpar-
the subsequent development of pre- blood pressure to a level ⬍ 150/100 mm tum patients, even when classic find-
eclampsia. Women in such cases should Hg. If the patient’s condition does not re- ings are absent.
have close antenatal follow-up evaluation, spond to such therapy, continues to have  All clinicians who treat pregnant or
with attention to new onset of symptoms seizures despite magnesium sulfate ther- postpartum patients should under-
and regular evaluation (1-2 times/wk) of apy, or continues to have cerebral symp- stand the clinical manifestation of
platelet count and liver enzymes for early toms, brain imaging with magnetic reso- atypical preeclampsia and the poten-
detection of preeclampsia. Patients with nance imaging and angiography, if needed, tial sequelae of a missed diagnosis.
symptoms and/or abnormal laboratory should be performed to rule out the pres-  Our stepwise approach can be used
tests and women with abnormal ultra- ence of other cerebral disease. for diagnosis and treatment of pa-
sound findings should be considered to In summary, it is important to widen the tients with atypical features of
have atypical preeclampsia and be treated. spectrum of the definition of preeclampsia preeclampsia. f

MAY 2009 American Journal of Obstetrics & Gynecology 483