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

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

MAY 2009 American Journal of Obstetrics & Gynecology 481

Clinical Opinion
FIGURE
Overlapping role of hypertension, capillary leak, maternal symptoms,
and fibrinolysis/hemolysis in the spectrum of atypical preeclampsia
Blood
Pressure
Symptoms
Sibai. Diagnosis and management of a typical preeclampsia-eclampsia. Am J Obstet Gynecol 2009.
Gestational proteinuria
Gestational proteinuria is defined as uri-
nary protein excretion of ⱖ 300 mg/24-
hour timed collection or persistent pro-
teinuria (ⱖ 1⫹ on dipstick on at least 2
occasions at least 4 hours apart but not ⬎
1 week apart).
Women with new-onset gestational
proteinuria only should be monitored
very closely for early detection of pre-
eclampsia, because the presence of gesta-
tional proteinuria alone may herald the
early manifestation of an impending
preeclampsia. In addition, these women
should be evaluated for potential pre-
existing renal disease (such as chronic
pyelonephritis, lupus nephritis, immu-
noglobulin A nephropathy, and other
nephropathies). Moreover, women with
proteinuria and cardiorespiratory symp-
toms, ascites, or pulmonary edema
should be evaluated for potential cardiac
disease, such as congestive heart failure
and peripartum cardiomyopathy.
Preeclampsia-eclampsia
at < 20 weeks of gestation
Preeclampsia and/or eclampsia that
occurs at ⬍ 20 weeks of gestation has
482 American Journal of Obstetrics & Gynecology MAY 2009
Obstetrics
Capillary
Leak
Fibrinolysis
Hemolysis
been reported with molar or hydropic
degeneration of the placenta with or
without a coexistent fetus. The pres-
ence of hypertension, proteinuria, and
abnormal laboratory tests at ⬍ 20
weeks of gestation may be caused by
lupus nephritis, hemolytic-uremic
syndrome, antiphospholipid antibody
syndrome, or thrombotic thrombocy-
topenic purpura. These women should
be evaluated to rule out the presence of
these disorders. In the absence of other
disease, the patient should be treated
for severe preeclampsia. In addition,
women in whom convulsions develop
in association with hypertension and
proteinuria during the first half of
pregnancy should be considered to
have eclampsia until proven otherwise.
Late postpartum preeclampsia-
eclampsia and hemolysis,
elevated liver enzymes, low
platelets (HELLP) syndrome
Late postpartum preeclampsia-eclampsia
is the development of signs and symptoms
of preeclampsia-eclampsia for the first
time at ⬎ 48 hours, but ⬍ 4 weeks, after
delivery. Based on our experience and re-
www.AJOG.org
view of literature, we recommend that, af-
ter delivery, any woman with a history of
convulsions at ⬎ 48 hours after delivery
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
and control of hypertension and those who
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-
agnosis is spontaneous reversible vascu-
lopathy syndrome or cerebral angiopathy.
Approximately 20-30% of women
with HELLP syndrome experience the
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
laboratory testing to rule out or confirm
the presence of severe preeclampsia or
HELLP syndrome.
The use of intravenous dexametha-
sone to improve maternal outcome in
women with HELLP syndrome in the
postpartum period remains controver-
sial. Almost all studies that have reported
such benefit were retrospective or com-
pared treatment to no treatment in a
limited number of subjects. In contrast,
2 recent multicenter, double-blind, pla-
cebo-controlled trials that evaluated the
administration of intravenous dexa-
methasone in patients with antepartum
and postpartum HELLP syndrome re-
vealed no improvement in maternal lab-
oratory findings, maternal morbidities,
or length of hospital stay.
Conclusion
Preeclampsia is a syndrome that is char-
acterized by heterogenous clinical and
laboratory findings for which the patho-
genesis can differ. We recommend that
health care providers in obstetric prac-
tice maintain a high index of suspicion
for the potential atypical clinical mani-
festations of preeclampsia, irrespective
of gestational age at time of onset or
number of days after delivery.
www.AJOG.org
Treatment of patients with atypical
manifestations of preeclampsia-eclamp-
sia require a well formulated plan that
takes the following items into consider-
ation: maternal risk factors; clinical, lab-
oratory, and imaging findings; and the
time of onset in relation to both gesta-
tional age and delivery.
For pregnancies that are complicated by
hypertension and proteinuria that occurs
at ⱕ 20 weeks of gestation, an ultrasound
scan should be performed to exclude the
diagnosis of molar or partial molar preg-
nancy and uterine artery Doppler velocim-
etry to evaluate uterine artery resistance
and the presence of a notch.
Gestational hypertension or gestational
proteinuria alone may be the first sign of
the subsequent development of pre-
eclampsia. Women in such cases should
have close antenatal follow-up evaluation,
with attention to new onset of symptoms
and regular evaluation (1-2 times/wk) of
platelet count and liver enzymes for early
detection of preeclampsia. Patients with
symptoms and/or abnormal laboratory
tests and women with abnormal ultra-
sound findings should be considered to
have atypical preeclampsia and be treated.
Obstetrics
Patients with gestational proteinuria
should be evaluated for the presence of un-
diagnosed diabetes mellitus (glucose test-
ing), undiagnosed lupus (serology, anti-
bodies, anticardiolipin antibodies, platelet
count), and undergo a metabolic profile,
complete urine analysis, and 24-hour
urine test for creatinine clearance and
quantitative proteinuria.
In cases with hypertension and symp-
toms of headache or blurred vision, with or
without seizures ⬎ 48 hours after delivery,
magnesium sulfate therapy should be ini-
tiated without delay while other possible
causes of the aforementioned symptoms
are being ruled out. If the patient has severe
hypertension alone, antihypertensive ther-
apy should be administered to stabilize
blood pressure to a level ⬍ 150/100 mm
Hg. If the patient’s condition does not re-
spond to such therapy, continues to have
seizures despite magnesium sulfate ther-
apy, or continues to have cerebral symp-
toms, brain imaging with magnetic reso-
nance imaging and angiography, if needed,
should be performed to rule out the pres-
ence of other cerebral disease.
In summary, it is important to widen the
spectrum of the definition of preeclampsia
MAY 2009 American Journal of Obstetrics & Gynecology
Clinical Opinion
to cases that manifest as hypertension
without proteinuria and vice versa. Alter-
nately, one must be careful to avoid over-
diagnosis or misdiagnosis of other preex-
isting conditions (such as undiagnosed
chronic hypertension or renal disease) that
might lead to unnecessary intervention.
Therefore, it is important to obtain a de-
tailed history, to assess for the presence of
symptoms, and to obtain targeted labora-
tory tests, as needed, to confirm the diag-
nosis of atypical preeclampsia.
CLINICAL IMPLICATIONS
 Atypical preeclampsia should be con-
sidered in all pregnant and postpar-
tum patients, even when classic find-
ings are absent.
 All clinicians who treat pregnant or
postpartum patients should under-
stand the clinical manifestation of
atypical preeclampsia and the poten-
tial sequelae of a missed diagnosis.
 Our stepwise approach can be used
for diagnosis and treatment of pa-
tients with atypical features of
preeclampsia. f
483