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Preeclampsia: Clinical features and diagnosis

Authors: Phyllis August, MD, MPH, Baha M Sibai, MD
Section Editor: Charles J Lockwood, MD, MHCM
Deputy Editor: Vanessa A Barss, MD, FACOG
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2019. | This topic last updated: Jan 28, 2019.
INTRODUCTION
Preeclampsia is a multisystem progressive disorder characterized by the new onset of hypertension

and proteinuria, or of hypertension and significant end-organ dysfunction with or without proteinuria,
in the last half of pregnancy or postpartum (table 1). The disorder is caused by placental and
maternal vascular dysfunction and always resolves after delivery. Although most affected pregnancies
deliver at term or near term with good maternal and fetal outcomes, these pregnancies are at
increased risk for maternal and/or fetal mortality or serious morbidity. In addition, women with
preeclampsia are at increased risk for future cardiovascular disease.
This topic will discuss the clinical features, diagnosis, and differential diagnosis of preeclampsia.
Other important issues related to this disease are reviewed separately:
● (See "Preeclampsia: Pathogenesis".)

● (See "Preeclampsia: Management and prognosis".)
● (See "Early pregnancy prediction of preeclampsia".)
● (See "Preeclampsia: Prevention".)
DEFINITIONS OF PREGNANCY-RELATED HYPERTENSIVE DISORDERS
There are four major hypertensive disorders related to pregnancy [1,2]:
● Preeclampsia – Preeclampsia refers to the new onset of hypertension and proteinuria or

hypertension and significant end-organ dysfunction with or without proteinuria after 20 weeks of
gestation in a previously normotensive woman (table 1). It may also develop postpartum. Severe
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hypertension or signs/symptoms of significant end-organ injury, as listed in the table, represent

the severe end of the disease spectrum (table 2). (See 'Diagnostic criteria' below.)
In 2013, the American College of Obstetricians and Gynecologists removed proteinuria as an

essential criterion for diagnosis of preeclampsia (hypertension plus signs of significant end-organ
dysfunction are sufficient for diagnosis). They also removed massive proteinuria (5 g/24 hours)
and fetal growth restriction as possible features of severe disease because massive proteinuria
has a poor correlation with outcome, and fetal growth restriction is managed similarly whether or
not preeclampsia is diagnosed. Oliguria was also removed as a characteristic of severe disease.
Eclampsia refers to the development of grand mal seizures in a woman with preeclampsia in the
absence of other neurologic conditions that could account for the seizure. (See "Eclampsia".)
HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) probably represents a
subtype of preeclampsia with severe features in which hemolysis, elevated liver enzymes, and
thrombocytopenia are the predominant features, rather than hypertension or central nervous
system or renal dysfunction, although the latter do occur. The majority of patients, but not all,
have hypertension (82 to 88 percent) and/or proteinuria (86 to 100 percent) [3]. Rare patients
have neither; other diagnoses associated with similar laboratory abnormalities should be
excluded before making the diagnosis of HELLP in these atypical patients. Because some
affected patients do not have concurrent hypertension or proteinuria, some authorities have
opined that HELLP syndrome is a separate disorder from preeclampsia. (See "HELLP
syndrome".)
● Chronic/preexisting hypertension – Chronic/preexisting hypertension is defined as

hypertension that antecedes pregnancy or is present on at least two occasions before the 20th
week of gestation or persists longer than 12 weeks postpartum. It can be primary (primary
hypertension, formerly called "essential hypertension") or secondary to a variety of medical
disorders. (See "Overview of hypertension in adults", section on 'Definitions'.)
● Preeclampsia superimposed upon chronic/preexisting hypertension – Superimposed

preeclampsia is defined by the new onset of proteinuria, significant end-organ dysfunction, or
both after 20 weeks of gestation in a woman with chronic/preexisting hypertension. For women
with chronic/preexisting hypertension who have proteinuria prior to or in early pregnancy,
superimposed preeclampsia is defined by worsening or resistant hypertension (especially
acutely) in the last half of pregnancy or development of signs/symptoms of the severe end of the
disease spectrum (table 2).
● Gestational hypertension – Gestational hypertension refers to hypertension (systolic ≥140 and

<160 mmHg, and/or diastolic ≥90 and <110 mmHg) without proteinuria or other signs/symptoms
of preeclampsia-related end-organ dysfunction that develops after 20 weeks of gestation.

Development of proteinuria upgrades the diagnosis to preeclampsia. Development of a systolic
blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg or other features of
severe disease (table 3) upgrades the diagnosis to preeclampsia with severe features.
Some women (10 to 25 percent) with gestational hypertension may ultimately develop signs and
symptoms of preeclampsia. It should resolve by 12 weeks postpartum. If hypertension persists
beyond 12 weeks postpartum, the diagnosis is "revised" to chronic/preexisting hypertension that
was masked by the physiologic decrease in blood pressure that occurs in early pregnancy. If
hypertension resolves postpartum, and if signs and symptoms of preeclampsia have not
developed, the diagnosis can be "revised" to transient hypertension of pregnancy. (See
"Gestational hypertension".)
DIAGNOSTIC CRITERIA
Note: the 2017 changes in the definitions for elevated blood pressure and hypertension in
nonpregnant adults do not affect diagnostic criteria for preeclampsia and other pregnancy-related
hypertensive disorders. (See "Overview of hypertension in adults", section on 'Definitions'.)
Preeclampsia — Professional guidelines generally agree that the diagnosis of preeclampsia should
be made in a previously normotensive woman with the new onset of hypertension (systolic blood
pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg on at least two occasions at least four
hours apart) and proteinuria after 20 weeks of gestation (table 1) [2,4-6]. In the absence of
proteinuria, the diagnosis can still be made if new-onset hypertension is accompanied by signs or
symptoms of significant end-organ dysfunction, as described below. (See 'Accurate assessment of
blood pressure' below.)
Preeclampsia with severe features — A subset of women with preeclampsia are classified as
manifesting the severe end of the preeclampsia spectrum (called "preeclampsia with severe
features," formerly "severe preeclampsia") (table 1). This diagnosis is made after 20 weeks of
gestation in previously normotensive women who develop:
● Systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg and proteinuria (with
or without signs and symptoms of significant end-organ dysfunction).
● Systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg (with or without
proteinuria) and one or more of the following signs and symptoms of significant end-organ
dysfunction:
New-onset cerebral or visual disturbance, such as:

• - Photopsia (flashes of light) and/or scotomata (dark areas or gaps in the visual field).
- Severe headache (ie, incapacitating, "the worst headache I've ever had") or headache
that persists and progresses despite analgesic therapy.
- Altered mental status.
• Severe, persistent right upper quadrant or epigastric pain unresponsive to medication and
not accounted for by an alternative diagnosis or serum transaminase concentration ≥2 times
upper limit of normal for a specific laboratory, or both.
• <100,000 platelets/microL.
• Progressive renal insufficiency (serum creatinine >1.1 mg/dL [97.3 micromol/L]; some
guidelines also include doubling of serum creatinine concentration in the absence of other
renal disease ).
• Pulmonary edema.
PREVALENCE
In a systematic review, 4.6 percent (95% CI 2.7-8.2) of pregnancies worldwide were complicated by
preeclampsia [7]. The prevalence of preeclampsia in the United States is approximately 3.4 percent,
but 1.5-fold to 2-fold higher in first pregnancies [8]. Variations in prevalence among countries reflect,
at least in part, differences in the maternal age distribution and proportion of nulliparous pregnant
women in the population [9]. (See 'Risk factors' below.)
Prevalence also varies by gestational age. Preeclampsia is less prevalent before 34 weeks of
gestation. In one population-based study, the prevalence before and after 34 weeks was 0.3 and 2.7
percent, respectively [10].
RISK FACTORS
Risk factors for preeclampsia are listed in the table (table 4) and apply to both early-onset and late-
onset disease. The magnitude of risk depends upon the specific factor and is described below for
selected risk factors evaluated in systematic reviews [11,12]. A past history of preeclampsia,
preexisting hypertension, pregestational diabetes, multifetal gestation, chronic kidney disease, and
some autoimmune diseases (antiphospholipid syndrome, systemic lupus erythematosus) carry the
highest relative risk (RR).
● A past history of preeclampsia increases the risk of developing preeclampsia in a subsequent

pregnancy eightfold compared with women without this history (RR 8.4, 95% CI 7.1-9.9) [12].
The severity of preeclampsia strongly impacts this risk. Women with severe features of
preeclampsia in the second trimester are at greatest risk of developing preeclampsia in a
subsequent pregnancy: Rates of 25 to 65 percent have been reported [13-16]. By comparison,
women without severe features of preeclampsia in their first pregnancy develop preeclampsia in
5 to 7 percent of second pregnancies [17,18]. Women who had a normotensive first pregnancy
develop preeclampsia in less than 1 percent of second pregnancies.
● Preexisting medical conditions:
• Pregestational diabetes (RR 3.7, 95% CI 3.1-4.3) [12] – This increase has been related to
a variety of factors, such as underlying renal or vascular disease, high plasma insulin
levels/insulin resistance, and abnormal lipid metabolism [19].
• Chronic hypertension (RR 5.1, 95% CI 4.0-6.5) [12] – Blood pressure ≥130/80 mmHg at
the first prenatal visit has also been reported to increase risk (RR 1.38 to 2.37) [11].
Although chronic hypertension (defined as blood pressure ≥140/90 mmHg) increases the
risk of preeclampsia fivefold compared with women without this risk factor, chronic
hypertension is uncommon in reproductive-aged women and thus accounts for only 5 to 10
percent of preeclampsia cases [20]. Although the American College of Cardiology/American
Heart Association revised their definitions of hypertension in 2017, preliminary data suggest
that women with systolic pressures of 130 to 135 and/or diastolic pressures of 80 to 85
mmHg are also at increased risk for preeclampsia [21].
• Systemic lupus erythematosus (RR 1.8, 95% CI 1.5-2.1) [12].
• Antiphospholipid syndrome (RR 2.8, 95% CI 1.8-4.3) [12].
• Prepregnancy body mass index >25 (RR 2.1, 95% CI 2.0-2.2) and body mass index
(BMI) >30 (RR 2.8, 95% CI 2.6-3.1) [12] – The risk of preeclampsia doubles with each 5 to 7
kg/m2 increase in prepregnancy BMI [22]. This relationship persisted in studies that excluded
women with chronic hypertension, diabetes mellitus, multiple gestations, or after adjustment
for other confounders. Although overweight and obesity increase the risk of preeclampsia
only two- to threefold, overweight and obesity are highly prevalent worldwide and thus
cumulatively account for over 40 percent of preeclampsia cases [20].
• Chronic kidney disease (CKD) (RR 1.8, 95% CI 1.5-2.1) [12] – The risk varies depending
on the degree of reduction of glomerular filtration rate and the presence or absence of
hypertension. In some studies, as many as 40 to 60 percent of women with advanced CKD

(stages 3, 4, 5) were diagnosed with preeclampsia in the latter half of pregnancy [23,24].
● Multifetal pregnancy (RR 2.9, RR 2.6-3.1) [12] – The risk increases with increasing numbers of
fetuses [25].
● First pregnancy (nulliparity) (RR 2.1, 95% CI 1.9-2.4) [12] – It is unclear why the nulliparous
state is consistently found to be a significant predisposing factor for preeclampsia. One theory is
that the immune system of nulliparous women has had limited exposure to paternal antigens,
and this lack of desensitization may play a role in the pathogenesis of the disease. Epidemiologic
data support this theory: Protection from preeclampsia in subsequent pregnancies is either
reduced or eliminated if there is a change in paternity, women using barrier methods of
contraception are at increased risk, and risk is reduced with increased duration of sexual activity
before pregnancy [26]. However, the notion that the risk of preeclampsia is increased in a second
pregnancy with a new partner has been challenged by data suggesting that a longer interval
between pregnancies may be the reason for the increased risk with a new partner [27].
● A family history of preeclampsia in a first-degree relative (RR 2.90, 95% CI 1.70-4.93) [11],
suggesting a heritable mechanism in some cases [28,29]. The occurrence and severity of the
disease appears to be influenced primarily by maternal factors, but the paternal contribution to
fetal genes may have a role in defective placentation and subsequent preeclampsia. (See
"Preeclampsia: Pathogenesis", section on 'Genetic factors'.)
● Prior pregnancy complications associated with placental insufficiency – Fetal growth

restriction (RR 1.4, 95% CI 0.6-3.0), abruption (RR 2.0, 95% CI 1.4-2.7), or stillbirth (RR 2.4,
95% CI 1.7-3.4) [12].
● Advanced maternal age (maternal age ≥35 RR 1.2, 95% CI 1.1-1.3 and ≥40 RR 1.5, 95% CI
1.2-2.0) [12] – Older women tend to have additional risk factors, such as diabetes mellitus and
chronic hypertension, that predispose them to developing preeclampsia.
Whether adolescents are at higher risk of preeclampsia is more controversial [30]; a systematic
review did not find an association [11]. (See "Effects of advanced maternal age on pregnancy".)
● Use of assisted reproductive technology is a risk factor in large cohort studies (pooled rate
6.2 percent, 95% CI 4.7-7.9; RR 1.8, 95% CI 1.6-2.1) [12]. However, multivariate logistic
regression analysis attenuates this association and propensity analysis further weakens it [31].
Of note, women who smoke cigarettes have a lower risk of preeclampsia than nonsmokers. (See
"Cigarette and tobacco products in pregnancy: Impact on pregnancy and the neonate", section on
'Preeclampsia'.)
OVERVIEW OF PATHOPHYSIOLOGY
The pathophysiology of preeclampsia likely involves both maternal and fetal/placental factors.
Shallow placentation and failure to remodel the spiral arteries of the decidua and myometrium early in
pregnancy, weeks to months before development of clinical manifestations of the disease, have been
well documented [32,33]. Failure to establish an adequate uteroplacental blood flow can result in
relatively hypoxic trophoblast tissue, which may promote an exaggerated state of oxidative stress in
the placenta [34]. This appears to alter placental villous angiogenesis, leading to poor development of
the fetoplacental vasculature and abnormal vascular reactivity. Placental secretion of antiangiogenic
factors (sFlt-1 and endoglin) that bind vascular endothelial growth factor and placental growth factor
in the maternal circulation appears to result in widespread maternal vascular dysfunction, leading to
hypertension, proteinuria, and the other clinical manifestations of preeclampsia [35,36]. (See
"Preeclampsia: Pathogenesis".)
Some authorities have characterized preeclampsia as early onset (<34 weeks of gestation) and late
onset (≥34 weeks of gestation). The clinical features overlap, but the spectrum of disease and
outcomes differ: Early-onset disease has been associated with more severe placental and
maternal/fetal clinical findings and, in turn, poorer maternal/fetal outcomes [37,38]. For this reason, it
has been hypothesized that the two phenotypes have different origins and pathophysiologies
[37,39,40]. However, these differences can also be explained by biological variation in the disease
process.
SCREENING
Screening for traditional risk factors for preeclampsia is of value at the first prenatal visit to identify
women at high risk of developing the disease, as these women are offered low-dose aspirin therapy
to reduce their risk of developing the disease. (See "Early pregnancy prediction of preeclampsia",
section on 'Universal routine blood pressure measurement in pregnancy' and "Preeclampsia:
Prevention", section on 'Candidates'.)
All pregnant women are at risk for preeclampsia, and evidence supports routinely screening for the
disorder by measuring blood pressure at all provider visits throughout pregnancy [41,42]. (See
'Accurate assessment of blood pressure' below.)
The value of any laboratory or imaging test for screening and subsequent intervention has not been
established. This includes using results from maternal Down syndrome screening (biochemical
markers [eg, Quad screen] or cell-free DNA) for prediction of preeclampsia risk. (See "Early
pregnancy prediction of preeclampsia".)
It is customary to test for proteinuria at each prenatal visit; however, this practice has not been
rigorously evaluated and proven to improve outcomes [42]. We suggest performing a urinalysis to test
for proteinuria at the first prenatal visit to establish a baseline and, given the possibility for false-
positives and false-negatives, repeating the test in asymptomatic normotensive patients on at least
one subsequent prenatal visit. In contrast, testing for proteinuria should be performed in women with
hypertension as proteinuria changes the diagnosis to preeclampsia. Once a diagnosis of
preeclampsia is established, testing for proteinuria is no longer diagnostically or prognostically useful.
(See "Proteinuria in pregnancy: Evaluation and management of nephrotic syndrome" and "Proteinuria
in pregnancy: Evaluation and management of nephrotic syndrome", section on 'Qualitative' and
"Proteinuria in pregnancy: Evaluation and management of nephrotic syndrome", section on
'Quantitative'.)
CLINICAL PRESENTATION
Most affected patients are nulliparous or at high risk for the disease. Most present with new-onset
hypertension and proteinuria at ≥34 weeks of gestation, sometimes during labor [43,44].
Approximately 10 percent of affected women develop these signs and symptoms at <34 weeks of
gestation (ie, early-onset preeclampsia) [43] and rarely as early as 20 to 22 weeks. In approximately
5 percent of preeclampsia cases, the signs and symptoms are first recognized postpartum (ie,
postpartum preeclampsia), usually within 48 hours of delivery [45-47].
The degree of maternal hypertension and proteinuria as well as the presence/absence of other
clinical manifestations of the disease (described below) are highly variable [48]. Approximately 25
percent of affected women develop one or more of the following nonspecific symptoms, which
characterize the severe spectrum of the disease and signify the need for urgent evaluation and
possible delivery:
● Persistent and/or severe headache

● Visual abnormalities (scotomata, photophobia, blurred vision, or temporary blindness [rare])
● Upper abdominal or epigastric pain
● Altered mental status
● Dyspnea, retrosternal chest pain
Epigastric pain may be the presenting symptom of preeclampsia; thus, a high index of suspicion is
important to make a timely diagnosis of preeclampsia rather than gastroesophageal reflux in women
who call their provider with this symptom, since reflux is common in pregnant women, especially at
night.
Atypical presentations are described separately. (See 'Rare and atypical presentations' below.)
PATIENT EVALUATION
All pregnant women with new onset hypertension or worsening hypertension after 20 weeks gestation
should be evaluated for preeclampsia. Women with severe hypertension or symptoms suggestive of
severe disease, such as cerebral or visual symptoms, epigastric pain, or dyspnea, require
hospitalization for initial maternal and fetal evaluation and management. Asymptomatic women with
nonsevere hypertension may be followed closely as outpatients provided they are seen frequently
and the maternal and fetal status is stable. The decision to monitor women in the hospital versus in
an outpatient setting should be made on a case-by-case basis, taking into consideration both medical
and social issues. (See "Preeclampsia: Management and prognosis".)
Accurate assessment of blood pressure — Blood pressure is obtained after at least five minutes of
rest, with the patient sitting with feet on the ground and legs uncrossed or in a semi-reclining position
with her back supported. Whether sitting or in semi-Fowler, the arm should be supported and at heart
level. Measurement of blood pressure in left lateral recumbency, on the left arm, does not differ
substantially from blood pressure that is recorded in the sitting position, and may be used if a seated
blood pressure is not feasible [49]. Choose an appropriately sized cuff: length 1.5 times upper arm
circumference or a cuff with a bladder that encircles at least 80 percent of the upper arm. Use a large
adult cuff in women with an upper-arm circumference of 35 to 44 cm, and use a thigh cuff if the upper-
arm circumference is 45 to 52 cm. If an automated device is used, it should have been validated in a
pregnant population [50]. If an auscultatory method is used, the first audible sound (Korotkoff I) is the
systolic pressure and the disappearance of sound (Korotkoff V) is the diastolic pressure [51].
However, if sounds are audible with the cuff deflated, which can happen in pregnant women, then
Korotkoff IV (abrupt muffling) should be used [49]. Caffeine or nicotine within 30 minutes of
measurement can increase readings. Additional details regarding accurate assessment of blood
pressure are reviewed separately. (See "Blood pressure measurement in the diagnosis and
management of hypertension in adults".)
Routine laboratory evaluation — Pregnant women with suspected preeclampsia due to

hypertension and proteinuria or hypertension and signs and symptoms associated with the severe
end of the disease spectrum (eg, headache, visual symptoms, epigastric pain, pulmonary edema)
should have a complete blood count, serum creatinine level, liver chemistries (LDH, AST, ALT), and
urinary protein determination (protein:creatinine ratio or 24-hour urine protein) [2].
Coagulation studies (prothrombin time, partial thromboplastin time, fibrinogen) are not routinely
obtained but are indicated in patients with additional complications, such as abruptio placentae,
severe bleeding, or severe liver dysfunction.
Assessment of fetal status — Fetal status is assessed concurrently with the maternal evaluation or
post-diagnosis, depending on the degree of concern when the mother is evaluated. At a minimum, a
nonstress test or biophysical profile is performed. Ultrasound is indicated to evaluate amniotic fluid
volume and estimate fetal weight given the increased risk for oligohydramnios and fetal growth
restriction.
Indications for neurology consultation — The neurology service should be consulted to evaluate
women with neurological deficits/abnormal neurological examination, ocular signs and symptoms, or
a severe persistent headache that does not respond to a dose of acetaminophen and initial routine
management of preeclampsia.
The complaint of the sudden onset of severe headache ("worst headache of my life") is sufficiently
characteristic of subarachnoid hemorrhage that this diagnosis should prompt neurology consultation
and consideration of imaging. The headache is lateralized in 30 percent of patients and may or may
not be associated with a brief period of altered consciousness, collapse, nausea or vomiting,
preretinal subhyaloid hemorrhages, and meningismus. (See "Clinical manifestations and diagnosis of
aneurysmal subarachnoid hemorrhage".)
Measurement of angiogenic factors — In the future, measurement of urinary or plasma

antiangiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and angiogenic factors such
as placental growth factor (PlGF) or their ratios may be useful for distinguishing preeclampsia from
other hypertensive-proteinuric disorders (see "Preeclampsia: Pathogenesis", section on 'sFlt-1,
VEGF, PlGF'). This test is commercially available in some countries but is still considered
investigational and should be limited to patients in research studies [52-54].
What remains to be determined is whether, and in what circumstances, measurement of these

angiogenic-related factors could be clinically useful and improve patient outcomes. One particular
scenario that is clinically challenging is determining whether a woman with signs of preeclampsia,
such as an increase in blood pressure or a slightly elevated level of urinary protein, requires medical
intervention, such as hospitalization or even delivery. A biomarker test that improved our ability to
predict patients who require or do not require a higher degree of medical intervention would be
helpful.
A prospective, multicenter, international observational study (PROGNOSIS) attempted to derive and

validate a serum sFlt-1:PlGF ratio that would predict the absence or presence of preeclampsia in the
short term in women who already had signs suggestive of preeclampsia, such as an increase in blood
pressure and/or proteinuria [55]. The study included 500 women with singleton pregnancies at 24 to
36+6 weeks of gestation with suspected preeclampsia based on one or more of the following: new
increase in blood pressure but less than 140/90 mmHg, new proteinuria but less than 2+ dipstick,
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preeclampsia-related laboratory findings but not meeting criteria for HELLP syndrome (hemolysis,
elevated liver enzymes, low platelets), preeclampsia-related symptoms (edema, headache, visual
changes, sudden weight gain). Although the authors concluded that an sFlt-1:PlGF ratio cutoff of 38
or lower using a specific automated commercial assay had a negative predictive value (no
preeclampsia in the next seven days) of 99.3 percent (95% CI 97.9-99.9), with sensitivity of 80
percent (95% CI 51.9-95.7) and specificity of 78.3 percent (95% CI 74.6-81.7), we question the
clinical usefulness of this conclusion since the women enrolled in the study appeared to have a
clinical profile of mild disease and the prevalence of preeclampsia was quite low in this group. The
positive predictive value of a ratio above 38 for the diagnosis of preeclampsia within four weeks was
only 36.7 percent in the next four weeks (95% CI 28.4-45.7) with a sensitivity of 66.2 percent (95%
CI, 54.0-77.0) and specificity of 83.1 percent (95% CI, 79.4-86.3). Whether this ratio will be helpful in
reducing iatrogenic morbidity due to over-diagnosis in women with suggestive signs of preeclampsia
is unclear. Further exploration of this test is warranted, including determining whether the cut-off
varies among laboratories and patient populations, the best interval for repeat testing, and how this
information affects clinical outcomes and costs. The latter can only be answered with a randomized
trial.
SPECTRUM OF DISEASE
Potential clinical findings
Hypertension — All patients with preeclampsia have hypertension. It is generally the earliest
clinical finding of preeclampsia and the most common clinical clue to the presence of the disease.
The blood pressure usually rises gradually, reaching the hypertensive range (defined as ≥140/90
mmHg) sometime in the third trimester, often after the 37th week of gestation [43]. Blood pressures
are often around 135/85 mmHg in the one to two weeks before reaching the hypertensive range.
However, in some women, hypertension develops rapidly or before 34 weeks of gestation or
postpartum.
Pheochromocytoma is a rare cause of hypertension during pregnancy and may be difficult to

distinguish from preeclampsia. (See 'Pheochromocytoma' below.)
Epigastric pain — Epigastric pain, when present, is a cardinal symptom of the severe end of the
disease spectrum. It is characterized by severe constant pain that often begins at night, usually
maximal in the low retrosternum or epigastrium, but may radiate to the right hypochondrium or back
[56]. Nausea and vomiting sometimes also occur. On examination, the liver may be tender to
palpation due to stretching of Glisson capsule from hepatic swelling or bleeding.
Liver rupture or hemorrhage is rare but should be suspected when there is sudden onset of right
upper quadrant pain associated with a decrease in blood pressure. (See "HELLP syndrome", section
on 'Management of hepatic complications'.)
Acute pancreatitis is a rare complication of preeclampsia [57] and can mimic the epigastric pain of
preeclampsia [58]. (See 'Medical and surgical disorders associated with elevated blood pressure,
headache, and/or abdominal pain' below.)
Neurologic
Headache — Headache, when present, is another feature of the severe end of the disease
spectrum. It may be temporal, frontal, occipital, or diffuse [59,60]. The pain usually has a throbbing or
pounding quality but may be piercing. Although not pathognomonic, a feature that suggests
preeclampsia-related headache rather than another type of headache is that it persists despite
administration of over-the-counter analgesics, and it may become severe (ie, incapacitating, "the
worst headache of my life"). However, resolution of the headache with analgesics does not exclude
the possibility of preeclampsia.
The mechanism for headache, as well as other cerebrovascular symptoms of preeclampsia, is poorly
understood. Cerebral edema and ischemic/hemorrhagic changes in the posterior hemispheres
observed on computed tomography and magnetic resonance imaging help to explain, but do not fully
account for, the clinical findings [61,62]. These findings may result from generalized endothelial cell
dysfunction, leading to vasospasm of the cerebral vasculature in response to severe hypertension, or
they may result from loss of cerebrovascular autoregulation, leading to areas of both vasoconstriction
and forced vasodilation. Thus, they could represent a form of posterior reversible
leukoencephalopathy syndrome (PRES) [63-65]. PRES is typically associated with severe
hypertension but can also occur with rapid increases in blood pressure in patients with endothelial
damage [66]. (See "Reversible posterior leukoencephalopathy syndrome" and "Eclampsia", section
on 'Clinical findings'.)
Acetaminophen is commonly used to treat headache. Doses ≤2 g/day can be administered to women
with mild hepatic or renal insufficiency, but it is contraindicated in patients with severe hepatic
insufficiency.
Visual symptoms — Visual symptoms, when present, are also symptoms of the severe end of
the disease spectrum. They are caused, at least in part, by retinal arteriolar spasm [67]. Symptoms
include blurred vision, photopsia (flashing lights or sparks), and scotomata (dark areas or gaps in the
visual field) [68-70]. Diplopia or amaurosis fugax (blindness in one or both eyes) may also occur.
Visual disturbances in preeclampsia may also be manifestations of PRES [65].
Cortical blindness is rare and typically transient [71]. Blindness related to retinal pathology, such as
retinal artery or vein occlusion, retinal detachment, optic nerve damage, retinal artery spasm, and
retinal ischemia may be permanent [72].
Stroke — Stroke leading to death or disability is the most serious complication of

preeclampsia/eclampsia and is responsible for approximately 36 percent of pregnancy-associated
stroke [73]. Most strokes in this setting are hemorrhagic and preceded by severe headache and
severe and fluctuating blood pressure levels. Eclamptic seizures occur in some, but not all, cases.
Risk factors for hemorrhagic stroke in women with preeclampsia include persistent severe
hypertension associated with significant headache and/or seizures. Lowering blood pressure may
reduce the risk; however, criteria for persistent hypertension and timing of initiation of acute
antihypertensive therapy (after 15 minutes, 30 minutes, or >60 minutes) are unclear. (See
"Cerebrovascular disorders complicating pregnancy", section on 'Preeclampsia, eclampsia, and
HELLP'.)
Generalized hyperreflexia — Hyperreflexia is a common finding. Sustained ankle clonus may

be present.
Seizure — Seizure in a preeclamptic woman upstages the diagnosis to eclampsia. Eclamptic

seizures develop in 1 in 400 women with preeclampsia without severe features and 1 in 50 women
with preeclampsia with severe features. Histopathologic correlates include brain hemorrhage,
petechiae, edema, vasculopathy, ischemic damage, microinfarcts, and fibrinoid necrosis [74,75].
Neuroimaging consistent with posterior reversible encephalopathy syndrome may be seen [76]. (See
"Eclampsia".)
Pulmonary edema — Pulmonary edema is a feature of the severe end of the disease spectrum,
and was observed in approximately 10 percent (6/63) of these cases in a prospective study [77]. The
symptom complex of dyspnea, chest pain, and/or decreased (≤93 percent) oxygen saturation by
pulse oximetry is predictive of adverse maternal outcome (maternal death and hepatic, central
nervous system, renal, cardiorespiratory, and hematological morbidities) [78].
The etiology of pulmonary edema in preeclampsia is multifactorial [79-82]. Excessive elevation in

pulmonary vascular hydrostatic pressure combined with decreased plasma oncotic pressure may
produce pulmonary edema in some women, particularly in the postpartum period. However, not all
preeclamptic patients with pulmonary edema demonstrate this phenomenon. Other causes of
pulmonary edema are capillary leak, left heart failure, acute severe hypertension, and iatrogenic
volume overload.
Oliguria — Contraction of the intravascular space secondary to vasospasm leads to worsening

renal sodium and water retention [83]. Oliguria in preeclampsia with severe features results from
intrarenal vasospasm and a 25 percent reduction in glomerular filtration rate. Transient oliguria (less
than 100 mL over 4 hours) is common in labor or the first 24 hours of the postpartum. Urine output
may decrease to <500 mL/24 hours in women at the severe end of the disease spectrum. (See
"Acute kidney injury in pregnancy", section on 'Preeclampsia with or without HELLP'.)
Rarely, women with preeclamptic hepatic disease have developed polyuria due to transient diabetes
insipidus of pregnancy. The mechanism in these cases is decreased degradation of vasopressinase
due to hepatic dysfunction. (See "Polyuria and diabetes insipidus of pregnancy".)
Peripheral edema — Many pregnant women have edema, whether or not they have
preeclampsia. However, sudden and rapid weight gain (eg, >5 lb/week [2.3 kg]) and facial edema are
more common in women who develop preeclampsia; thus, these findings warrant diagnostic
evaluation for the disease. Peripheral edema in preeclampsia may be due to capillary leaking or
represent "overfill" edema.
Abruptio placentae — Abruption occurs in less than 1 percent of pregnancies with preeclampsia
without severe features but 3 percent of those with severe features [84]. (See "Placental abruption:
Pathophysiology, clinical features, diagnosis, and consequences" and "Placental abruption:
Management".)
Potential laboratory findings
● Proteinuria – Proteinuria in preeclampsia can be defined as any of the following [2]:
• ≥0.3 g protein in a 24-hour urine specimen. The completeness of the 24-hour urine collection
can be estimated from creatinine excretion, which should be 15 to 20 mg/kg (133 to 177
micromol/kg) of lean bodyweight in women. (See "Assessment of urinary protein excretion
and evaluation of isolated non-nephrotic proteinuria in adults", section on '24-hour versus
spot urine collection'.)
• Random urine protein:creatinine ratio ≥0.3 mg protein/mg creatinine (some clinicians opt to
confirm presence of ≥0.3 g protein with a 24-hour collection).
• Protein ≥2+ (30 mg/dL) on a paper test strip dipped into a fresh, clean voided midstream
urine specimen (only if one of the above quantitative methods is not available).
Proteinuria generally increases as preeclampsia progresses, but increased urinary protein

excretion may be a late finding [85,86]. It usually remains <5 g/day, but levels >10 g/day may be
seen. Preeclampsia is the most common cause of severe proteinuria in pregnant women.
Proteinuria is due, in part, to impaired integrity of the glomerular filtration barrier and altered
tubular handling of filtered proteins (hypofiltration) leading to increased nonselective protein
excretion [87]. Both size and charge selectivity of the glomerular barrier are affected [88]. Using
special studies, podocyturia (urinary excretion of podocytes) has been observed in patients with
preeclampsia [89,90]. Urinary shedding of podocytes may indicate podocyte loss from the
glomerulus, which may lead to a disruption of the glomerular filtration barrier and consequent
proteinuria. Deficient vascular endothelial growth factor signaling appears to account, at least in
part, for these findings. (See "Preeclampsia: Pathogenesis", section on 'Role of systemic
endothelial dysfunction in clinical findings'.)
The urine protein concentration in a spot sample is measured in mg/dL and is divided by the
urine creatinine concentration, also measured in mg/dL. This value can be used to estimate the
24-hour protein excretion (calculator 1) [91-99]. Measurement of proteinuria is discussed in detail
separately. (See "Proteinuria in pregnancy: Evaluation and management of nephrotic
syndrome".)
● Elevated creatinine – The physiologic increase in glomerular filtration rate (GFR) during a
normal pregnancy results in a decrease in serum creatinine concentration, which falls by an
average of 0.4 mg/dL (35 micromol/L) to a range of 0.4 to 0.8 mg/dL (35 to 70 micromol/L). The
serum creatinine concentration in women with preeclampsia generally remains in this range or
only slightly elevated. A creatinine level >1.1 mg/dL (97.3 micromol/L) concentration indicates the
severe end of the disease spectrum. Some guidelines also include doubling of the patient's
baseline creatinine in the absence of other renal disease as indicative of the severe end of the
disease spectrum. Although creatinine levels remain <1.5 mg/dL (133 micromol/L) in most
patients, preeclampsia is the most common cause of acute kidney injury in pregnancy. (See
"Acute kidney injury in pregnancy", section on 'Preeclampsia with or without HELLP'.)
The rise in serum creatinine is due primarily to a fall in GFR; renal plasma flow also decreases,
but to a lesser degree.
● Decreased platelet count – A platelet count less than 150,000/microL occurs in approximately
20 percent of patients with preeclampsia [2]. The severe end of the disease spectrum is
characterized by a platelet count less than 100,000/microL.
Thrombocytopenia is the most common coagulation abnormality in preeclampsia.

Microangiopathic endothelial injury and activation result in formation of platelet and fibrin thrombi
in the microvasculature. Accelerated platelet consumption leads to thrombocytopenia; immune
mechanisms may also play a role [100].
● Hemolysis – Schistocytes and helmet cells on the peripheral blood smear (picture 1A-B)
suggest microangiopathic hemolysis, which is a finding in severe disease. Elevation in the serum
indirect bilirubin level also suggest hemolysis, whereas elevations in lactate dehydrogenase are
usually related to liver dysfunction.
● Hemoconcentration – Hemoconcentration may result from contraction of the intravascular

space secondary to vasospasm, as well as capillary leaking. Hematocrit typically increases.
When both hemolysis and hemoconcentration occur concurrently, the effects on hematocrit may
negate each other, resulting in a normal value. (See "Thrombocytopenia in pregnancy" and
"Preeclampsia: Pathogenesis" and "Maternal adaptations to pregnancy: Hematologic changes".)
● Coagulation studies – The prothrombin time, partial thromboplastin time, and fibrinogen
concentration are not affected by preeclampsia, unless there are additional complications, such
as severe thrombocytopenia [101], abruptio placentae, severe bleeding, or severe liver
dysfunction [102].
● Liver chemistries – Liver function tests are normal, except at the severe end of the disease
spectrum, which is characterized by elevated transaminase levels (twice the upper limit of normal
for the local laboratory).
Elevation in the serum indirect bilirubin level suggests hemolysis.
Abnormalities in liver chemistries are due to reduced hepatic blood flow, potentially resulting in
ischemia and periportal hemorrhage. Periportal and sinusoidal fibrin deposition and
microvesicular fat deposition also occur and may affect hepatocyte function [103,104].
● Hyperuricemia – The association between hyperuricemia and preeclampsia has been known for
decades. The cause is most likely related to a reduction in GFR. However, the increase in serum
uric acid is often greater than expected for mild reductions in GFR, leading to the hypothesis that
decreased tubular secretion or increased reabsorption in the proximal renal tubules plays a role
[105]. Although meta-analyses published in 2006 concluded that uric acid levels are not an
accurate predictor of complications associated with preeclampsia [106,107], this issue remains
controversial. Data from an ongoing international prospective study of women admitted to the
hospital with preeclampsia showed that serum uric acid corrected for gestational age is clinically
useful in predicting adverse perinatal, but not maternal, outcomes [108].
● Other
• Urine sediment – The urine sediment is typically benign.
• Lipids – Women with preeclampsia appear to have changes in lipid metabolism resulting in
higher total cholesterol and triglyceride levels than normotensive pregnant women [109,110].
• Neutrophilia – The white blood count may be slightly higher in preeclampsia due to
neutrophilia.
• Hypocalciuria – Hypocalciuria in women with preeclampsia has been attributed to increased

tubular reabsorption of calcium [111-113].
• Troponin – Preeclampsia is not associated with elevated troponin levels in the absence of
cardiac disease [114]. A very small subgroup of women with severe preeclampsia may
develop myocardial damage or global diastolic dysfunction [115]. Therefore, troponin I levels
should be obtained when clinically indicated, such as when the patient complains of chest
pain suggestive of myocardial ischemia or new electrocardiogram changes are observed
[116,117].
Potential sonographic findings
● Fetal ultrasound – Preeclampsia that develops clinically before term may be associated with
suboptimal fetal growth due to reduced uteroplacental perfusion [118] (see 'Overview of
pathophysiology' above). Fetal growth restriction may be accompanied by oligohydramnios due
to redistribution of the fetal circulation away from the kidneys and toward more vital organs,
particularly the brain (see "Oligohydramnios"). In contrast, preeclampsia that develops clinically
at term tends to be associated with fetal growth that is appropriate for gestational age and normal
amniotic fluid volume. In some cases, the fetus may be large for gestational age [119-124].
Fetal anatomy is usually normal. However, three population-based studies have reported a
relationship between fetal congenital cardiac defects and maternal preeclampsia, particularly
preterm preeclampsia [125-127]. It has been hypothesized that characteristics of the maternal
cardiovascular system impair adequate adaption to the vascular load of pregnancy, and this may
be the primary mechanism leading to the development of preeclampsia [128]. Shared angiogenic
imbalance in the mother and fetus may explain the increased risk of congenital heart disease in
the offspring of these women.
Fetal hydrops of any etiology is an uncommon cause of preeclampsia-like symptoms. (See

'Mirror syndrome' below.)
● Uterine and umbilical artery Doppler – Increased impedance to flow in the uterine arteries due
to uteroplacental maldevelopment is manifested by elevation of the pulsatility index accompanied
by uterine artery notching on uterine artery Doppler velocimetry. However, this finding is neither
sensitive nor specific for preeclampsia. (See "Early pregnancy prediction of preeclampsia",
section on 'Uterine artery Doppler velocimetry'.)
Increased resistance in the placental vasculature is reflected by rising Doppler indices of the
umbilical artery. Absent and reversed end diastolic flow are the most severe abnormalities and
associated with a poor perinatal outcome. (See "Doppler ultrasound of the umbilical artery for
fetal surveillance".)
● Maternal hemodynamic imaging studies – Preeclampsia can be associated with a highly

variable hemodynamic profile, including cardiac failure [129-133]. Changes in cardiac function
and morphology may be seen on echocardiography at an asymptomatic early stage and
progress with increasing disease severity [134]. Preeclampsia does not affect the myocardium
directly, but the heart responds to physiological changes induced by the disease. Left ventricular
ejection fraction usually remains within normal limits [135], but reductions in longitudinal,
circumferential, and radial systolic strain have been observed [136]. The decrement in left
ventricular performance has been attributed to a physiologic response to increased afterload
[129,135,136], but other factors may play a role since systolic strain was depressed in
preeclamptic patients compared with pregnant women with nonproteinuric hypertension and
similar resting blood pressure [136].
The high afterload in preeclampsia is associated with elevated cardiac filling pressures, reflected
by fourfold higher concentrations of natriuretic peptides in women with preeclampsia compared
with pregnant women who are normotensive or who have chronic hypertension [130].
Intravascular volume may be reduced in preeclampsia, especially with severe features [137].
There is no evidence of underfilling of the arterial circulation; rather, the reduced volume appears
to be a consequence of vasoconstriction from enhanced responses to vasoactive substances;
however, this issue has not been conclusively resolved.
Potential histologic findings
● Placenta – Abnormalities in the placenta are believed to be a critical feature of the preeclampsia
syndrome; however, many findings are nonspecific. In blinded studies, the pooled prevalence of
villous lesions in preeclamptic and normal pregnancies was 42 and 19 percent, respectively, and
the pooled prevalence of vascular lesions was 39 and 10 percent, respectively [138].
The parenchymal finding most characteristically associated with preeclampsia on routine

hematoxylin and eosin staining is acute atherosis (ie, fibrinoid necrosis of the vessel wall with an
accumulation of lipid-laden "foamy" macrophages and a mononuclear perivascular infiltrate).
Cytotrophoblast invasion of the interstitial uterine compartment is frequently shallow, with
incomplete invasion and remodeling of spiral arteries in many places [139]. This maldevelopment
of the uteroplacental circulation can result in reduced placental perfusion, leading to placental
infarcts, villous hypoplasia, and, in some cases, the clinical sequelae of intrauterine growth
restriction. Research studies using more advanced techniques (eg, special stains) have
described additional findings (eg, reduced uterine natural killer cells in decidua).
Placental histology is described in detail separately. (See "The placental pathology report",
section on 'Preeclampsia'.)
● Kidney – The renal histologic changes described in women with preeclampsia who have had
kidney biopsies, and in autopsy specimens obtained from women who died of eclampsia, are
termed "glomerular endotheliosis." Light and electron microscopy of glomerular endotheliosis
show endothelial cell swelling, loss of fenestrations, and occlusion of capillary lumens (picture
2A-C) [140]. Foot process effacement is not a prominent feature, despite marked proteinuria.
Glomerular endotheliosis shares some histologic features with nonpreeclamptic thrombotic

microangiopathies [140], except thrombi are rare in preeclampsia (although fibrin deposition may
be observed by immunofluorescence microscopy). Rarely, it may be present without proteinuria
and in nonpregnant women [141,142].
DIFFERENTIAL DIAGNOSIS
When evaluating women for possible preeclampsia, it is generally safer to assume that new-onset
hypertension in pregnancy is due to preeclampsia, even if all the diagnostic criteria are not fulfilled
and the blood pressure is only mildly elevated, since preeclampsia may progress to eclampsia or
other severe forms of the disease in a short period of time.
Preexisting hypertension versus preeclampsia — In a prospective study, maternal blood pressure

gradually fell after 6 weeks of gestation, reached a nadir between weeks 16 and 20, and then
gradually increased to prepregnancy levels by term [143]. Because of the reduction in blood pressure
that typically occurs early in pregnancy, a woman with preexistent hypertension may be normotensive
when first seen by the obstetrical provider. Later in pregnancy when her blood pressure returns to its
prepregnancy baseline, she may appear to be developing preeclampsia if there are no documented
prepregnancy blood pressure measurements.
In this setting, a variety of factors can be helpful in establishing the likely diagnosis:
● Hypertension occurring before the 20th week is usually due to preexisting hypertension rather
than to preeclampsia.
● Proteinuria is usually present and increases with time in preeclampsia, occasionally reaching the
nephrotic range; by comparison, protein excretion is usually absent or less than 1 g/day in
hypertensive nephrosclerosis [17]. (See "Clinical features, diagnosis, and treatment of

hypertensive nephrosclerosis".)
● Preeclampsia is more common in nulliparas than in multiparas.
● Preeclampsia is more common in older (>40 years) nulliparas, although these women are also
more likely to have preexisting hypertension, as are older multiparous women. (See 'Risk factors'
above.)
Superimposed preeclampsia — Reproductive age women with primary (essential) hypertension

typically have no or mild proteinuria, so severe proteinuria suggests development of superimposed
preeclampsia. In women with chronic/preexisting hypertension who have proteinuria prior to or in
early pregnancy, superimposed preeclampsia is difficult to diagnose definitively, but should be
suspected when there is a significant worsening of hypertension (especially acutely) in the last half of
pregnancy or development of signs/symptoms associated with the severe end of the disease
spectrum.
An elevated uric acid level may help to distinguish superimposed preeclampsia from primary
hypertension [2,144,145].
Exacerbation of preexisting renal disease — Superimposed preeclampsia frequently develops in

women with preexisting primary or secondary renal disease [146,147]. However, worsening
hypertension and proteinuria in a woman with preexisting renal disease may also represent an
exacerbation of the underlying disease or the physiological effects of pregnancy. The ability to
accurately distinguish among these possibilities is important as management and complications are
different.
Significant clues to the diagnosis of preeclampsia with severe features are the presence of systemic
manifestations of the disorder, such as thrombocytopenia; increased serum levels of
aminotransferases; and visual symptoms (table 2) [148]. Onset of disease in the first half of
pregnancy suggests exacerbation of underlying renal disease rather than preeclampsia.
Laboratory evidence suggestive of exacerbation of renal disease includes the presence of findings
specific for disease activity (eg, low complement levels in a patient with systemic lupus
erythematosus, urinalysis consistent with a proliferative glomerular disorder [red and white cells
and/or cellular casts]). An active urine sediment is not a feature of preeclampsia. (See "Pregnancy in
women with nondialysis chronic kidney disease" and "Pregnancy in women with diabetic kidney
disease".)
Antiphospholipid syndrome — Hypertension, proteinuria, thrombocytopenia, and other signs of

significant end-organ dysfunction can be seen in antiphospholipid syndrome (APS). Antiphospholipid
antibody testing is not indicated in all women with severe preterm preeclampsia but should be
considered in those in whom APS is suspected based on additional findings. The absence of
laboratory evidence of antiphospholipid antibodies excludes this diagnosis. (See "Clinical
manifestations of antiphospholipid syndrome" and "Diagnosis of antiphospholipid syndrome".)
In a prospective study, 11.5 percent of 148 women who delivered before 36 weeks because of
preeclampsia or placental insufficiency tested positive for antiphospholipid antibodies (aPL; 76
percent had lupus anticoagulant, 41 percent had anticardiolipin, 24 percent had anti-beta-2-
glycoprotein I); antibodies were present in 1.4 percent of matched controls with uncomplicated
pregnancies [149]. Confirmatory testing was positive in 80 percent of women who had repeat testing.
Limitations of the study were that only 53 percent of aPL-positive women underwent confirmatory
testing, 18 percent of patients were on heparin (almost all prophylactic dosing), and 50 patients were
delivered at 34 to 36 weeks, which is inconsistent with international classification criteria for APS
(delivery prior to 34 weeks of gestation).
Although women with preterm preeclampsia or placental insufficiency are more likely to have aPL
antibodies than women with uncomplicated pregnancies, we do not routinely test these women in the
absence of thrombosis and other characteristics of APS since most women with this obstetric history
alone would be treated with low-dose aspirin and not anticoagulated in future pregnancies anyway.
(See "Antiphospholipid syndrome: Pregnancy implications and management in pregnant women" and
"Preeclampsia: Prevention", section on 'Low-dose aspirin'.)
AFLP, TTP, HUS, SLE — Although preeclampsia/HELLP (hemolysis, elevated liver enzymes, low
platelets) is the most common cause of hypertension, thrombocytopenia, liver abnormalities, and
renal abnormalities in pregnant women, the following conditions should be considered and excluded,
if possible. Laboratory findings in these disorders are compared in the tables (table 5A-B).
● Acute fatty liver of pregnancy (AFLP) – Anorexia, nausea, and vomiting are common clinical
features of AFLP. Low-grade fever can be present in AFLP but does not occur in
preeclampsia/HELLP. AFLP is associated with more serious liver dysfunction: hypoglycemia,
elevations in serum ammonia, and disseminated intravascular coagulation are common features,
while unusual in preeclampsia/HELLP. AFLP is also usually associated with more significant
renal dysfunction compared with preeclampsia/HELLP. (See "Acute fatty liver of pregnancy".)
● Thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS) – Although

neurologic abnormalities and acute renal failure are often seen in TTP and HUS, respectively,
distinguishing among related thrombotic microangiopathy syndromes may be challenging. An
approach to the patient suspected of having TTP or HUS, including urgent interventions before
the diagnosis is established, is presented separately. (See "Approach to the patient with
suspected TTP, HUS, or other thrombotic microangiopathy (TMA)".)
● Exacerbation of systemic lupus erythematosus (SLE) – Flares of SLE are likely to be associated
with hypocomplementemia and increased titers of anti-DNA antibodies; by comparison,
complement levels are usually, but not always, normal or increased in preeclampsia. Acute-
onset, accelerated hypertension is more likely to be due to preeclampsia than a lupus flare. (See
"Pregnancy in women with systemic lupus erythematosus".)
Pheochromocytoma — Pheochromocytoma is a rare cause of hypertension during pregnancy and

may be difficult to distinguish from preeclampsia because hypertension and headache occur with both
disorders. Symptoms of pheochromocytoma that help to make this distinction include generalized
sweating, palpitations, tremor, pallor, dyspnea, generalized weakness, and panic attack-type
symptoms. Antepartum diagnosis is important because intrapartum maternal and fetal mortality is
high without appropriate treatment. (See "Clinical presentation and diagnosis of pheochromocytoma",
section on 'Pheochromocytoma in pregnancy'.)
Medical and surgical disorders associated with elevated blood pressure, headache, and/or
abdominal pain — Patients with migraine, pancreatitis, cholecystitis, gastritis, gastroesophageal
reflux, peptic ulcer disease, appendicitis, hepatitis, or other causes of cerebral or abdominal pain may
develop elevated blood pressures and/or other signs/symptoms associated with preeclampsia. These
patients can usually be distinguished from patients with preeclampsia with severe features by taking a
detailed history, performing a thorough physical examination, and obtaining relevant laboratory
studies (table 6A-E). (See individual topic reviews on each disorder.)
Mirror syndrome — Fetal hydrops from any cause (nonimmune or immune) can result in maternal
symptoms identical to those seen in preeclampsia before or after 20 weeks of gestation. This disorder
is called mirror or Ballantyne syndrome and resolves without delivery if hydrops resolves. (See
"Nonimmune hydrops fetalis", section on 'Mirror syndrome'.)
RARE AND ATYPICAL PRESENTATIONS
Onset <20 weeks — Preeclampsia prior to 20 weeks of gestation is usually associated with a
complete or partial molar pregnancy (see "Hydatidiform mole: Epidemiology, clinical features, and
diagnosis"). Rarely, characteristic signs and symptoms before 20 weeks have been attributed to
preeclampsia with severe features after other disorders with similar findings (eg, lupus nephritis,
thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, antiphospholipid syndrome, acute
fatty liver of pregnancy) were excluded. It may also be associated with fetal hydrops. (See 'Differential
diagnosis' above.)
Severe features of preeclampsia without hypertension — It is uncommon for women to exhibit the
severe features of preeclampsia without hypertension, but this may be observed in 15 percent of
patients with HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), which some
consider a variant of preeclampsia and others consider a separate disorder, and in some patients with
eclampsia (a possible sequelae of preeclampsia). It is possible that in such patients, blood pressure
is increased above a lower baseline but does not meet diagnostic criteria for hypertension. (See
"Eclampsia", section on 'Can eclampsia be predicted and prevented?' and "HELLP syndrome".)
Isolated hypertension — Women with new onset of mild hypertension but no other criteria for
preeclampsia or an underlying disease associated with hypertension are given the diagnosis of
gestational hypertension. These women should be followed closely, since 15 to 25 percent will
subsequently develop the full diagnostic criteria for preeclampsia. (See "Gestational hypertension",
section on 'Risk of progression to preeclampsia'.)
Isolated proteinuria — Isolated gestational proteinuria may be an early manifestation of

preeclampsia [150], although this is not well described and we are unaware of prospective studies
describing this finding. In a retrospective study of 95 pregnant women with new-onset isolated
proteinuria who were followed to term, 13 developed preeclampsia during pregnancy and 8
developed preeclampsia postpartum [151].
Onset or exacerbation of symptoms >2 days postpartum — Delayed postpartum preeclampsia

can be defined as signs and symptoms of the disease leading to readmission more than two days but
less than six weeks after delivery [47], although various other definitions have been used. Signs and
symptoms can be atypical; for example, the patient may have thunderclap headaches alternating with
mild headaches or intermittent hypertension. Other etiologies for the signs and symptoms should be
considered, such as cerebral vasoconstriction syndrome or impending stroke [152-155]. Risk factors
for delayed postpartum preeclampsia appear to be similar to those for preeclampsia during
pregnancy [47,156,157], but some patients have no risk factors.
In a retrospective cohort study including 152 patients with delayed postpartum preeclampsia, 63.2
percent had no antecedent diagnosis of hypertensive disease in the current pregnancy, whereas 18.4
percent had preeclampsia, 9.2 percent had chronic hypertension, 4.6 percent had gestational
hypertension, and 4.6 percent had preeclampsia superimposed on chronic hypertension during the
peripartum period [47]. Of these patients, 14.5 percent developed postpartum eclampsia.
NATURAL HISTORY/COURSE OF DISEASE
Preeclampsia can be a progressive disease. Although most women develop signs of the disease in
late pregnancy with gradual worsening until delivery, in approximately 25 percent of women,
especially those with early-onset preeclampsia, hypertension becomes severe and/or signs and
symptoms of significant end-organ damage become apparent over a period of days to weeks. It is
important to note that severe sequelae can occur in women without severe hypertension but who
have clinical evidence of significant end-organ dysfunction. Chest pain, dyspnea, and low platelet
count appear to be particularly predictive of fatal or life-threatening complications [158].
Although in some women signs and symptoms of preeclampsia are first recognized postpartum (ie,
postpartum preeclampsia), usually within 48 hours of delivery, complete resolution of the maternal
signs and symptoms of the disease always occurs in the postpartum period, with some symptoms
disappearing in a matter of hours (eg, headache), while others may take weeks or months (eg,
proteinuria). Typically, mobilization of third-space fluid and diuresis begin within 48 hours of delivery.
Hypertension may worsen during the first, and occasionally the second, postpartum week but
normalizes in most women within four weeks postpartum [159]. Rarely, hypertension persists beyond
three months. Proteinuria usually begins to improve within a few days; however, in women with
several grams of protein excretion, complete resolution may take weeks to months [160].
Even though is not clear why signs and symptoms of preeclampsia may be first recognized or worsen
after delivery, postpartum preeclampsia is not caused by large fragments of retained placenta.
Patients with postpartum preeclampsia may represent a subgroup of women who had subclinical
preeclampsia before delivery, delayed clearance of antiangiogenic factors, or activation of the
complement system after delivery [161,162]. In addition, mobilization of extracellular fluid into the
intravascular system can lead to volume load hypertension and cerebrovasoconstriction [152].
Curettage may slightly accelerate the fall of the sFlt-1 concentration by removing residual
cytotrophoblast in the decidua basalis; however, randomized trials have reported conflicting data as to
the value of curettage for hastening recovery from preeclampsia and eclampsia [163-166], and
progression of prepartum preeclampsia to postpartum eclampsia has been reported after cesarean
hysterectomy [167]. Consequently, we do not recommend postpartum curettage in clinical practice.
PROGNOSIS
Women with preeclampsia are at an increased risk for life-threatening obstetric or medical
complications. Worldwide, 10 to 15 percent of direct maternal deaths (ie, resulting from obstetric
complications of pregnancy) are associated with preeclampsia/eclampsia [168]. In the United States,
preeclampsia/eclampsia is one of the four leading causes of maternal death, along with hemorrhage,
cardiovascular conditions, and thromboembolism [169-171]. There is approximately one maternal
death due to preeclampsia/eclampsia per 100,000 live births, with a case-fatality rate of 6.4 deaths
per 10,000 cases [172,173].
For the fetus, preeclampsia can lead to intrauterine growth restriction and oligohydramnios, as well as
medically or obstetrically indicated preterm birth. As a result, perinatal morbidity and mortality are
increased.
Long-term maternal prognosis is reviewed separately. (See "Preeclampsia: Management and

prognosis", section on 'Prognosis'.)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around
the world are provided separately. (See "Society guideline links: Hypertensive disorders of
pregnancy".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The
Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and
they answer the four or five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for patients
who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-
mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Preeclampsia (The Basics)" and "Patient education: High
blood pressure and pregnancy (The Basics)" and "Patient education: HELLP syndrome (The
Basics)")
● Beyond the Basics topics (see "Patient education: Preeclampsia (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● The four major hypertensive disorders related to pregnancy are preeclampsia, chronic
hypertension, preeclampsia superimposed upon chronic hypertension, and gestational
hypertension (algorithm 1). (See 'Definitions of pregnancy-related hypertensive disorders'

above.)
● Major risk factors for development of preeclampsia include past history of preeclampsia,
nulliparity, pregestational diabetes, chronic hypertension, obesity, family history of preeclampsia,
and multiple gestation (table 4). (See 'Risk factors' above.)
● The diagnosis of preeclampsia is based on the new onset of hypertension and proteinuria or
significant end-organ dysfunction with or without proteinuria after 20 weeks of gestation in a
previously normotensive woman (table 1). Severe hypertension or signs of significant end-organ
dysfunction characterize the severe end of the disease spectrum (table 2). (See 'Diagnostic
criteria' above.)
● At the first prenatal visit, we evaluate pregnant women for traditional risk factors for preeclampsia
to identify those at high risk for developing the disease. These women are offered low-dose
aspirin therapy in the second and third trimesters to reduce their risk of developing preeclampsia.
(See "Preeclampsia: Prevention", section on 'Candidates'.)
● At all provider visits throughout pregnancy, we recommend routinely measuring blood pressure to
screen for preeclampsia (Grade 1B). The value of any laboratory or imaging test as a screening
tool, including routine assessment of proteinuria at each visit, has not been established. (See
'Screening' above.)
● The gradual development of hypertension and proteinuria in the last half of pregnancy is usually
due to preeclampsia, particularly in a nullipara. These findings typically become apparent after 34
weeks of gestation and progress until delivery, but some women develop symptoms earlier in
gestation, intrapartum, or postpartum. Delivery of the placenta always results in complete
resolution of the maternal signs and symptoms of the disease over a variable period of time.
(See 'Clinical presentation' above and 'Natural history/course of disease' above.)
● Pregnant women with suspected preeclampsia should have a complete blood count, creatinine
level, liver chemistries, and determination of urinary protein excretion. Fetal status is assessed
concurrently or post-diagnosis, depending on the degree of concern when the mother is
evaluated. At a minimum, a nonstress test or biophysical profile is performed. Ultrasound is
indicated to evaluate amniotic fluid volume and estimate fetal weight, given the increased risk for
oligohydramnios and fetal growth restriction. (See 'Patient evaluation' above.)
● Differential diagnosis includes exacerbation of underlying renal disease, acute fatty liver of
pregnancy, thrombotic thrombocytopenic purpura or hemolytic uremic syndrome, and
exacerbation of systemic lupus erythematosus. (See 'Differential diagnosis' above.)
● Atypical presentations of preeclampsia include onset before 20 weeks of gestation or after the
second postpartum day. Some patients initially present with gestational hypertension or
proteinuria alone. Others present with significant end-organ dysfunction and minimal or even
absent hypertension or proteinuria; these patients are typically classified as HELLP syndrome
(hemolysis, elevated liver enzymes, low platelets). (See 'Rare and atypical presentations' above.)
● Women with preeclampsia are at increased risk for life-threatening events, including placental
abruption, acute kidney injury, cerebral hemorrhage, hepatic failure or rupture, pulmonary
edema, stroke, cardiac failure, and progression to eclampsia. The fetus is at increased risk for
growth restriction and medically or obstetrically indicated preterm birth. (See 'Spectrum of
disease' above and 'Prognosis' above.)
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Topic 6814 Version 112.0
GRAPHICS
Criteria for the diagnosis of preeclampsia
Systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg on at least two occasions at
least four hours apart after 20 weeks of gestation in a previously normotensive patient AND the new onset
of one or more of the following*:
Proteinuria ≥0.3 g in a 24-hour urine specimen or protein/creatinine ratio ≥0.3 (mg/mg) (30 mg/mmol) in a
random urine specimen or dipstick ≥2+ if a quantitative measurement is unavailable
Platelet count <100,000/microL
Serum creatinine >1.1 mg/dL (97.2 micromol/L) or doubling of the creatinine concentration in the absence of
other renal disease
Liver transaminases at least twice the upper limit of the normal concentrations for the local laboratory
Pulmonary edema
Cerebral or visual symptoms (eg, new-onset and persistent headaches not accounted for by alternative diagnoses
and not responding to usual doses of analgesics ¶; blurred vision, flashing lights or sparks, scotomata)
In a woman with chronic/preexisting hypertension, criteria for superimposed preeclampsia are new onset of
proteinuria, significant end-organ dysfunction, or both after 20 weeks of gestation. For women with
chronic/preexisting hypertension who have proteinuria prior to or in early pregnancy, superimposed preeclampsia is
defined by worsening or resistant hypertension (especially acutely) in the last half of pregnancy or development of
signs/symptoms of the severe end of the disease spectrum.
* If systolic blood pressure is ≥160 mmHg or diastolic blood pressure is ≥110 mmHg, confirmation within minutes is
sufficient.
¶ Response to analgesia does not exclude the possibility of preeclampsia.
Adapted from: American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 202: Gestational
Hypertension and Preeclampsia. Obstet Gynecol 2019; 133:e1-e25.
Graphic 79977 Version 33.0
In a patient with preeclampsia, the presence of one or more of the following

indicates a diagnosis of "preeclampsia with severe features"
Severe blood pressure elevation:

Systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg on two occasions at least four hours
apart while the patient is on bedrest (antihypertensive therapy may be initiated upon confirmation of severe
hypertension, in which case criteria for severe blood pressure elevation can be satisfied without waiting until four
hours have elapsed)
Symptoms of central nervous system dysfunction:

Photopsia, scotomata, cortical blindness, retinal vasospasm
Severe headache (ie, incapacitating, "the worst headache I've ever had") or headache that persists and
progresses despite analgesic therapy and not accounted for by alternative diagnoses
Hepatic abnormality:
Severe persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by an
alternative diagnosis or serum transaminase concentration ≥2 times the upper limit of the normal range, or both
Thrombocytopenia:
<100,000 platelets/microL
Renal abnormality:
Renal insufficiency (serum creatinine >1.1 mg/dL [97.2 micromol/L] or a doubling of the serum creatinine
concentration in the absence of other renal disease)
Pulmonary edema
In contrast to older criteria, the 2013 criteria do not include proteinuria >5 g/24 hours and fetal growth restriction as
features of severe disease.
Adapted from: American College of Obstetricians and Gynecologists (ACOG Practice Bulletin No. 202: Gestational
Hypertension and Preeclampsia. Obstet Gynecol 2019; 133:e1-e25.
Features of severe disease in a woman with a pregnancy-related hypertensive

disorder
Systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg, or both (on
two separate occasions)
Symptoms of central nervous system dysfunction:

Photopsia, scotomata, cortical blindness, retinal vasospasm
Severe headache (ie, incapacitating, "the worst headache I've ever had") or headache that persists and
progresses despite analgesic therapy
Hepatic abnormality:
Severe persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by an
alternative diagnosis or serum transaminase concentration ≥2 times the upper limit of the normal range, or both
Thrombocytopenia:
<100,000 platelets/microL
Renal abnormality:
Progressive renal insufficiency (serum creatinine >1.1 mg/dL [97.2 micromol/L] or doubling of serum creatinine
concentration in the absence of other renal disease)
Adapted from ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol 2019; 133:e1.
Clinical factors that have been associated with an increased risk of developing
preeclampsia
Nulliparity
Preeclampsia in a previous pregnancy
Age >40 years or <18 years
Family history of preeclampsia
Chronic hypertension
Chronic renal disease
Autoimmune disease (eg, antiphospholipid syndrome, systemic lupus erythematosus)
Vascular disease
Diabetes mellitus (pregestational and gestational)
Multifetal gestation
Obesity
Black race
Hydrops fetalis
Woman herself was small for gestational age
Fetal growth restriction, abruptio placentae, or fetal demise in a previous pregnancy
Prolonged interpregnancy interval if the previous pregnancy was normotensive; if the previous pregnancy was
preeclamptic, a short interpregnancy interval increases the risk of recurrence
Partner-related factors (new partner, limited sperm exposure [eg, previous use of barrier
contraception])
In vitro fertilization
Obstructive sleep apnea
Elevated blood lead level
By comparison, smoking decreases the risk of preeclampsia, and Asian and Hispanic women have a lower risk of
preeclampsia than white women and a much lower risk than black women.
Peripheral smear in microangiopathic hemolytic anemia

showing presence of schistocytes
Peripheral blood smear from a patient with a microangiopathic hemolytic anemia

with marked red cell fragmentation. The smear shows multiple helmet cells
(arrows) and other fragmented red cells (small arrowhead); microspherocytes
are also seen (large arrowheads). The platelet number is reduced; the large
platelet in the center (dashed arrow) suggests that the thrombocytopenia is due
to enhanced destruction.
Courtesy of Carola von Kapff, SH (ASCP).
Normal peripheral blood smear
High-power view of a normal peripheral blood smear. Several platelets

(arrowheads) and a normal lymphocyte (arrow) can also be seen. The red
cells are of relatively uniform size and shape. The diameter of the normal red
cell should approximate that of the nucleus of the small lymphocyte; central
pallor (dashed arrow) should equal one-third of its diameter.
Helmet cells in microangiopathic hemolytic anemia
Peripheral smears from two patients with microangiopathic hemolytic anemia,

showing a number of red cell fragments (ie, schistocytes), some of which take the
form of combat (arrow), bicycle (arrowhead), or football (short arrow) "helmets."
Microspherocytes are also seen (dashed arrows), along with a nucleated red cell
(thick arrow).
Preeclampsia
Light micrograph in preeclampsia showing glomerular endotheliosis. The primary

changes are swelling of damaged endothelial cells, leading to partial closure of
many of the capillary lumens (arrows). Mitosis within an endothelial cell (short
arrow) is a sign of cellular repair.
Courtesy of Helmut Rennke, MD.
Normal glomerulus
Light micrograph of a normal glomerulus. There are only 1 or 2 cells per

capillary tuft, the capillary lumens are open, the thickness of the glomerular
capillary wall (long arrow) is similar to that of the tubular basement
membranes (short arrow), and the mesangial cells and mesangial matrix are
located in the central or stalk regions of the tuft (arrows).
Courtesy of Helmut G Rennke, MD.
Preeclampsia
Electron micrograph in preeclampsia showing narrowing of the capillary lumen

due to expansion of the mesangium, swelling of the endothelial (Endo) cell
cytoplasm (arrow), and subendothelial deposition of hyaline (Hy) material which
represents large macromolecules such as immunoglobulin M. The damaged
endothelial cell has become partially separated (*) from the glomerular
basement membrane (GBM).
Electron micrograph of a normal glomerulus
Electron micrograph of a normal glomerular capillary loop showing the

fenestrated endothelial cell (Endo), the glomerular basement membrane
(GBM), and the epithelial cells with its interdigitating foot processes (arrow).
The GBM is thin, and no electron-dense deposits are present. Two normal
platelets are seen in the capillary lumen.
Courtesy of Helmut G Rennke, MD.
IgM deposition in preeclampsia
Immunofluorescence microscopy in preeclampsia showing

diffuse immunoglobulin M (IgM) deposition. This represents nonspecific
entrapment of larger proteins in the more permeable glomerular capillary wall,
rather than the formation of discrete immune complexes. There is, for example,
generally no deposition of immunoglobulin G (IgG).
Frequency of various signs and symptoms among imitators of preeclampsia-

eclampsia
Signs and HELLP syndrome, AFLP, TTP, HUS, Exacerbation of

symptoms percent percent percent percent SLE, percent
Hypertension 85 50 20 to 75 80 to 90 80 with APA, nephritis
Proteinuria 90 to 95 30 to 50 With 80 to 90 100 with nephritis

hematuria
Fever Absent 25 to 32 20 to 50 NR Common during flare
Jaundice 5 to 10 40 to 90 Rare Rare Absent
Nausea and 40 50 to 80 Common Common Only with APA

vomiting
Abdominal pain 60 to 80 35 to 50 Common Common Only with APA
Central nervous 40 to 60 30 to 40 60 to 70 NR 50 with APA

system
HELLP: hemolysis, elevated liver enzymes, low platelets; AFLP: acute fatty liver of pregnancy; TTP: thrombotic
thrombocytopenic purpura; HUS: hemolytic uremic syndrome; SLE: systemic lupus erythematosus; APA: antiphospholipid
antibodies with or without catastrophic antiphospholipid syndrome; NR: values not reported; common: reported as the most
common presentation.
Reproduced with permission from: Sibai BM. Imitators of severe preeclampsia. Obstet Gynecol 2007; 109:956. Copyright ©
2007 Lippincott Williams & Wilkins.
Frequency and severity of laboratory findings among imitators of preeclampsia-

eclampsia
HELLP
Laboratory findings AFLP TTP HUS Exacerbation of SLE
syndrome
Thrombocytopenia (less More than More than 20,000 More than More than 50,000
than 100,000/mm 3) 20,000 50,000 or less 20,000
Hemolysis (%) 50 to 100 15 to 20 100 100 14 to 23 in patients with APA
Anemia (%) Less than 50 Absent 100 100 14 to 23 in patients with APA
DIC (%) Less than 20 50 to 100 Rare Rare Rare
Hypoglycemia (%) Absent 50 to 100 Absent Absent Absent
VW factor multimers (%) Absent Absent 80 to 90 80 Less than 10
ADAMTS13 less than 5% Absent Absent 33 to Rare Rare

(%) 100
Impaired renal function 50 90 to 100 30 100 40 to 80

(%)
LDH (international units/L) 600 or more Variable More More than May be elevated in patients with
than 1000 APA and liver involvement
1000
Elevated ammonia (%) Rare 50 Absent Absent Absent
Elevated bilirubin (%) 50 to 60 100 100 NA Less than 10
Elevated transaminases 100 100 Usually Usually In patients with APA and liver
(%) mild* mild* involvement
HELLP: hemolysis, elevated liver enzymes, low platelets; AFLP: acute fatty liver of pregnancy; TTP: thrombotic
thrombocytopenic purpura; HUS: hemolytic uremic syndrome; SLE: systemic lupus erythematosus; APA: antiphospholipid
antibodies with or without catastrophic antiphospholipid syndrome; DIC: disseminated intravascular coagulopathy; VW: von
Willebrand; ADAMTS13: von Willebrand factor-cleaving metalloprotease; LDH: lactic dehydrogenase; NR: values not reported.
* Levels less than 100 international units/L.
Reproduced with permission from: Sibai BM. Imitators of severe preeclampsia. Obstet Gynecol 2007; 109:956. Copyright ©
2007 Lippincott Williams & Wilkins.
Causes of epigastric abdominal pain
Epigastric Clinical features Comments
Acute myocardial infarction May be associated with shortness of Consider particularly in patients with
breath and exertional symptoms. risk factors for coronary artery
disease.
Acute pancreatitis Acute-onset, persistent upper

abdominal pain radiating to the back.
Chronic pancreatitis Epigastric pain radiating to the back. Associated with pancreatic
insufficiency.
Peptic ulcer disease Epigastric pain or discomfort is the Occasionally, discomfort localizes to
most prominent symptom. one side.
Gastroesophageal reflux disease Associated with heartburn,

regurgitation, and dysphagia.
Gastritis/gastropathy Abdominal discomfort/pain, Variety of etiologies including alcohol

heartburn, nausea, vomiting, and and nonsteroidal antiinflammatory
hematemesis. drugs (NSAIDs).
Functional dyspepsia The presence of one or more of the Patients have no evidence of
following: postprandial fullness, early structural disease.
satiation, epigastric pain, or burning.
Gastroparesis Nausea, vomiting, abdominal pain, Most causes are idiopathic, diabetic,
early satiety, postprandial fullness, or postsurgical.
and bloating.
Causes of right upper quadrant (RUQ) abdominal pain
RUQ Clinical features Comments
Biliary
Biliary colic Intense, dull discomfort located in the Patients are generally well-appearing.
RUQ or epigastrium. Associated with
nausea, vomiting, and diaphoresis.
Generally lasts at least 30 minutes,
plateauing within one hour. Benign
abdominal examination.
Acute cholecystitis Prolonged (>4 to 6 hours) RUQ or

epigastric pain, fever. Patients will
have abdominal guarding and
Murphy's sign.
Acute cholangitis Fever, jaundice, RUQ pain. May have atypical presentation in
older adults or immunosuppressed
patients.
Sphincter of Oddi dysfunction RUQ pain similar to other biliary pain. Biliary type pain without other
apparent causes.
Hepatic
Acute hepatitis RUQ pain with fatigue, malaise, Variety of etiologies include hepatitis
nausea, vomiting, and anorexia. A, alcohol, and drug-induced.
Patients may also have jaundice, dark
urine, and light-colored stools.
Perihepatitis (Fitz-Hugh-Curtis RUQ pain with a pleuritic component, Aminotransferases are usually normal
syndrome) pain is sometimes referred to the or only slightly elevated.
right shoulder.
Liver abscess Fever and abdominal pain are the Risk factors include diabetes,
most common symptoms. underlying hepatobiliary or pancreatic
disease, or liver transplant.
Budd-Chiari syndrome Symptoms include fever, abdominal Variety of causes.

pain, abdominal distention (from
ascites), lower extremity edema,
jaundice, gastrointestinal bleeding,
and/or hepatic encephalopathy.
Portal vein thrombosis Symptoms include abdominal pain, Clinical manifestations depend on
dyspepsia, or gastrointestinal extent of obstruction and speed of
bleeding. development. Most commonly
associated with cirrhosis.
Causes of left upper quadrant (LUQ) abdominal pain
LUQ Clinical features Comments
Splenomegaly Pain or discomfort in LUQ, left Multiple etiologies.

shoulder pain, and/or early satiety.
Splenic infarct Severe LUQ pain. Atypical presentations common.

Associated with a variety of
underlying conditions (eg,
hypercoagulable state, atrial
fibrillation, and splenomegaly).
Splenic abscess Associated with fever and LUQ Uncommon. May also be associated
tenderness. with splenic infarction.
Splenic rupture May complain of LUQ, left chest wall, Most often associated with trauma.
or left shoulder pain that is worse with
inspiration.
Causes of lower abdominal pain
Lower abdomen Localization Clinical features Comments
Appendicitis Generally right lower Periumbilical pain initially Occasional patients present
quadrant that radiates to the right with epigastric or
lower quadrant. Associated generalized abdominal pain.
with anorexia, nausea, and
vomiting.
Diverticulitis Generally left lower Pain usually constant and Clinical presentation
quadrant; right lower present for several days depends on severity of
quadrant more common in prior to presentation. May underlying inflammatory
Asian patients have associated nausea and process and whether or not
vomiting. complications are present.
Nephrolithiasis Either Pain most common Cause symptoms as stone

symptom, varies from mild passes from renal pelvis to
to severe. Generally flank ureter.
pain, but may have back or
abdominal pain.
Pyelonephritis Either Associated with dysuria,

frequency, urgency,
hematuria, fever, chills,
flank pain, and
costovertebral angle
tenderness.
Acute urinary retention Suprapubic Present with lower

abdominal pain and
discomfort; inability to
urinate.
Cystitis Suprapubic Associated with dysuria,

frequency, urgency, and
hematuria.
Infectious colitis Either Diarrhea as the Patients with Clostridioides

predominant symptom, but (formerly Clostridium)
may also have associated difficile infection can
abdominal pain, which may present with an acute
be severe. abdomen and peritoneal
signs in the setting of
perforation and fulminant
colitis.
Pelvic causes of abdominal pain in women
Pelvic causes
of abdominal
Lateralization Clinical features Comments
pain in
women
Ectopic Either side or Vaginal bleeding with abdominal pain, typically six to eight Patients can
pregnancy diffuse abdominal weeks after last menstrual period. present with
pain life-threatening
hemorrhage if
ruptured.
Pelvic Lateralization Characterized by the acute onset of lower abdominal or Wide spectrum
inflammatory uncommon pelvic pain, pelvic organ tenderness, and evidence of of clinical
disease inflammation of the genital tract. Often associated with presentations.
cervical discharge.
Ovarian torsion Localized to one Acute onset of moderate-to-severe pelvic pain, often with Generally not
side nausea and possibly vomiting, in a woman with an associated with
adnexal mass. vaginal
discharge.
Ruptured Localized to one Sudden-onset unilateral lower abdominal pain. The classic Generally not
ovarian cyst side presentation is sudden onset of severe focal lower associated with
quadrant pain following sexual intercourse. vaginal
discharge.
Endometriosis Associated with dysmenorrhea, pelvic pain, dyspareunia, Patients may

and/or infertility, but other symptoms may also be present present with
(eg, bowel or bladder symptoms). one symptom
or a
combination of
symptoms.
Acute Most often preceded by pelvic inflammatory disease. Diagnostic

endometritis criteria the
same as pelvic
inflammatory
disease.
Chronic Present with abnormal uterine bleeding, which may

endometritis consist of intermenstrual bleeding, spotting, postcoital
bleeding, menorrhagia, or amenorrhea. Vague, crampy
lower abdominal pain accompanies the bleeding or may
occur alone.
Leiomyomas Symptoms related to bulk or infrequently acute pain from

(fibroids) degeneration or torsion of pedunculate tumor. Pain may
be associated with a low-grade fever, uterine tenderness
on palpation, elevated white blood cell count, or peritoneal
signs.
Ovarian Abdominal distention/discomfort, nausea/vomiting, and Women

hyperstimulation diarrhea. More severe cases can have severe abdominal undergoing
pain, ascites, intractable nausea, and vomiting. fertility
treatment.
Ovarian cancer Abdominal or pelvic pain. May have associated symptoms

of bloating, urinary urgency or frequency, or difficulty
eating/feeling full quickly.
Ovulatory pain Occurs mid-cycle, coinciding with timing of ovulation. May be right-
(Mittelsmerz) or left-sided,
depending on
site of
ovulation
during that
cycle.
Pregnancy and related complications*
* Refer to the UpToDate topics on abdominal pain.
Diagnostic evaluation of a pregnant or postpartum woman with persistent

systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90
mmHg*
A reduction in blood pressure early in pregnancy is a normal physiologic occurrence. For this reason,
women with primary (essential) hypertension may be normotensive at their first few prenatal visits. Later
in pregnancy, when their blood pressure returns to its prepregnancy baseline, they may appear to be
developing preeclampsia or gestational hypertension if there are no documented prepregnancy blood
pressure measurements.
BP: blood pressure.

* Blood pressure should be elevated on at least two occasions at least four hours apart. However, if systolic
pressure is ≥160 mmHg or diastolic pressure is ≥110 mmHg, confirmation after a short interval, even within a
few minutes, is acceptable to facilitate timely initiation of antihypertensive therapy.
¶ The onset of preeclampsia and gestational hypertension is almost always after 20 weeks of gestation.
Preeclampsia before 20 weeks of gestation may be associated with a complete or partial molar pregnancy or fetal
hydrops. Postpartum preeclampsia usually presents within two days of delivery. The term "delayed postpartum
preeclampsia" is used for signs and symptoms of the disease leading to readmission more than two days but less
than six weeks after delivery.
Δ Significant proteinuria is defined as ≥0.3 g in a 24-hour urine specimen or protein/creatinine ratio ≥0.3
(mg/mg) (30 mg/mmol) in a random urine specimen or dipstick ≥1+ if a quantitative measurement is
unavailable.
◊ Almost all women with the new onset of hypertension and proteinuria at this gestational age or postpartum
have preeclampsia, but a rare patient may have occult renal disease exacerbated by the physiologic changes of
pregnancy. An active urine sediment (red and white cells and/or cellular casts) is consistent with a proliferative
glomerular disorder but not a feature of preeclampsia. Women with primary (essential) hypertension who had
proteinuria prior to or in early pregnancy may develop superimposed preeclampsia. This can be difficult to
diagnose definitively, but should be suspected when blood pressure increases significantly (especially acutely) in
the last half of pregnancy/postpartum or signs/symptoms associated with the severe end of the disease spectrum
develop.
§ Photopsia (flashes of light), scotomata (dark areas or gaps in the visual field), blurred vision, or temporary
blindness (rare); severe headache (ie, incapacitating, "the worst headache I've ever had") or headache that
persists and progresses despite analgesic therapy; altered mental status. Seizure occurrence upgrades the
diagnosis to eclampsia.
¥ The differential diagnosis of preeclampsia with severe features includes but is not limited to:
Antiphospholipid syndrome
Acute fatty liver of pregnancy
Thrombotic thrombocytopenic purpura (TTP)
Hemolytic uremic syndrome (HUS)
The laboratory findings in these disorders overlap with those in preeclampsia with severe features. (Refer to
table in UpToDate topic "Preeclampsia: Clinical manifestations and diagnosis.") The prepregnancy history,
magnitude and spectrum of laboratory abnormalities, and additional presence of signs and symptoms not
typically associated with preeclampsia help in making the correct diagnosis, which is not always possible during
pregnancy.
In addition, a variety of medical disorders may be associated with hypertension and one or more of the signs and
symptoms that occur in women with preeclampsia with severe features. These patients can usually be
distinguished from patients with preeclampsia by taking a detailed history, performing a thorough physical
examination, and obtaining relevant laboratory studies.
‡ In contrast to preeclampsia, gestational hypertension is not associated with end-organ involvement, so neither
proteinuria nor the symptoms or laboratory findings of preeclampsia are present. Refer to UpToDate topic on
gestational hypertension.
Contributor Disclosures
Phyllis August, MD, MPH Consultant/Advisory Boards: Bayer [Diabetic kidney disease progression
(Finerenone)]; Janssen [Diabetic kidney disease progression (Invokana)]. Baha M Sibai, MD Nothing to
disclose Charles J Lockwood, MD, MHCM Nothing to disclose Vanessa A Barss, MD, FACOG Nothing to
disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy

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Official reprint from UpToDate®

Preeclampsia: Clinical features and diagnosis

Preeclampsia is a multisystem progressive disorder characterized by the new onset of hypertension

● (See "Preeclampsia: Pathogenesis".)

DEFINITIONS OF PREGNANCY-RELATED HYPERTENSIVE DISORDERS

There are four major hypertensive disorders related to pregnancy [1,2]:

● Preeclampsia – Preeclampsia refers to the new onset of hypertension and proteinuria or

hypertension or signs/symptoms of significant end-organ injury, as listed in the table, represent

In 2013, the American College of Obstetricians and Gynecologists removed proteinuria as an

● Chronic/preexisting hypertension – Chronic/preexisting hypertension is defined as

● Preeclampsia superimposed upon chronic/preexisting hypertension – Superimposed

● Gestational hypertension – Gestational hypertension refers to hypertension (systolic ≥140 and

of preeclampsia-related end-organ dysfunction that develops after 20 weeks of gestation.

New-onset cerebral or visual disturbance, such as:

● A past history of preeclampsia increases the risk of developing preeclampsia in a subsequent

● Preexisting medical conditions:

• Systemic lupus erythematosus (RR 1.8, 95% CI 1.5-2.1) [12].

• Antiphospholipid syndrome (RR 2.8, 95% CI 1.8-4.3) [12].

hypertension. In some studies, as many as 40 to 60 percent of women with advanced CKD

● Prior pregnancy complications associated with placental insufficiency – Fetal growth

● Persistent and/or severe headache

Routine laboratory evaluation — Pregnant women with suspected preeclampsia due to

Measurement of angiogenic factors — In the future, measurement of urinary or plasma

What remains to be determined is whether, and in what circumstances, measurement of these

A prospective, multicenter, international observational study (PROGNOSIS) attempted to derive and

Potential clinical findings

Pheochromocytoma is a rare cause of hypertension during pregnancy and may be difficult to

Stroke — Stroke leading to death or disability is the most serious complication of

Generalized hyperreflexia — Hyperreflexia is a common finding. Sustained ankle clonus may

Seizure — Seizure in a preeclamptic woman upstages the diagnosis to eclampsia. Eclamptic

The etiology of pulmonary edema in preeclampsia is multifactorial [79-82]. Excessive elevation in

Oliguria — Contraction of the intravascular space secondary to vasospasm leads to worsening

Potential laboratory findings

● Proteinuria – Proteinuria in preeclampsia can be defined as any of the following [2]:

Proteinuria generally increases as preeclampsia progresses, but increased urinary protein

Thrombocytopenia is the most common coagulation abnormality in preeclampsia.

● Hemoconcentration – Hemoconcentration may result from contraction of the intravascular

Elevation in the serum indirect bilirubin level suggests hemolysis.

• Urine sediment – The urine sediment is typically benign.

• Hypocalciuria – Hypocalciuria in women with preeclampsia has been attributed to increased

Potential sonographic findings

Fetal hydrops of any etiology is an uncommon cause of preeclampsia-like symptoms. (See

● Maternal hemodynamic imaging studies – Preeclampsia can be associated with a highly

Potential histologic findings

The parenchymal finding most characteristically associated with preeclampsia on routine

Glomerular endotheliosis shares some histologic features with nonpreeclamptic thrombotic

Preexisting hypertension versus preeclampsia — In a prospective study, maternal blood pressure

hypertensive nephrosclerosis [17]. (See "Clinical features, diagnosis, and treatment of

● Preeclampsia is more common in nulliparas than in multiparas.

Superimposed preeclampsia — Reproductive age women with primary (essential) hypertension

Exacerbation of preexisting renal disease — Superimposed preeclampsia frequently develops in

Antiphospholipid syndrome — Hypertension, proteinuria, thrombocytopenia, and other signs of

● Thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS) – Although

Pheochromocytoma — Pheochromocytoma is a rare cause of hypertension during pregnancy and

RARE AND ATYPICAL PRESENTATIONS

Isolated proteinuria — Isolated gestational proteinuria may be an early manifestation of

Onset or exacerbation of symptoms >2 days postpartum — Delayed postpartum preeclampsia

NATURAL HISTORY/COURSE OF DISEASE

Long-term maternal prognosis is reviewed separately. (See "Preeclampsia: Management and

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

hypertension (algorithm 1). (See 'Definitions of pregnancy-related hypertensive disorders'