clinical features, diagnosis, and long-term prognosis of preeclampsia

Official reprint from UpToDate® www.uptodate.com©2011 UpToDate®

AuthorsPhyllis August, MD, MPHBaha Sibai, MD

Section EditorCharles J Lockwood, MD

Deputy EditorVanessa A Barss, MD

Clinical features, diagnosis, and long-term prognosis ofpreeclampsia

Last literature review version 18.3: septiembre 2010 | This topic last updated: septiembre24, 2010

INTRODUCTION — There are four major hypertensive disorders related to pregnancy [1-3]:

Preeclampsia/eclampsia — Preeclampsia refers to a syndrome characterized by the new onset ofhypertension and proteinuria after 20 weeks of gestation in a previously normotensive woman(table 1). It is classified as mild or severe. The classification of severe preeclampsia serves toemphasize the more ominous features of the syndrome; patients with severe disease have oneor more of the findings in the table (table 2). There is no category called moderatepreeclampsia.

Eclampsia refers to the development of grand mal seizures in a woman with gestationalhypertension or preeclampsia. The seizures should not be attributable to another cause. (See"Eclampsia".)

The degree of maternal hypertension, the amount of proteinuria, and the presence/absence oflaboratory abnormalities in preeclampsia are highly variable (ranging from mild to severe), as isthe gestational age at onset [4]. The manifestations of preeclampsia can develop at <34 weeks(early onset), at ≥34 weeks (late onset), during labor, or postpartum. Early and late onsetpreeclampsia may have different pathophysiologies as early onset disease is usually associatedwith fetal growth restriction and evidence of ischemic lesions on placental examination, whereaslate onset disease is not [5]. Maternal hemodynamics also may be different [6].

Chronic hypertension — Chronic hypertension (or preexisting hypertension) is defined assystolic pressure ≥140 mmHg, diastolic pressure ≥90 mmHg, or both, that antedatespregnancy, is present before the 20th week of pregnancy, or persists longer than 12 weekspostpartum. It can be primary (essential hypertension) or secondary to a variety of medicaldisorders.

Preeclampsia superimposed upon chronic hypertension — Superimposed preeclampsia isdiagnosed when a woman with preexisting hypertension develops new onset proteinuria after20 weeks of gestation. Women with both preexisting hypertension and proteinuria areconsidered preeclamptic if there is an exacerbation of blood pressure to the severe range(systolic ≥160 mmHg or diastolic ≥110 mmHg) in the last half of pregnancy, especially ifaccompanied by symptoms or increased liver enzymes or thrombocytopenia. Signs/symptomssuggestive of preeclampsia superimposed upon preexisting hypertension are listed in the table(table 3).

Gestational hypertension — Gestational hypertension refers to hypertension without proteinuria(or other signs of preeclampsia) developing in the latter part of pregnancy (table 4). It should

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resolve by 12 weeks postpartum. If the hypertension persists beyond 12 weeks postpartum,then the diagnosis is chronic hypertension that was masked in early pregnancy by thephysiologic decrease in blood pressure. Women who first present with gestational hypertensionare at greater risk for developing preeclampsia as the pregnancy progresses [7,8]. This is mostlikely when gestational hypertension develops before 30 weeks of gestation [7]. (See"Gestational hypertension".)

The clinical features, diagnosis, differential diagnosis, and maternal prognosis of preeclampsia will bereviewed here. Other issues relating to preeclampsia are discussed separately. (See "Pathogenesis ofpreeclampsia" and "Management of preeclampsia" and "Management of hypertension in pregnant andpostpartum women" and "Prevention of preeclampsia".)

INCIDENCE — Hypertensive disorders complicate 5 to 10 percent of pregnancies, depending on thestudy population.

Preeclampsia occurs in 3 to 14 percent of all pregnancies worldwide, and about 5 to 8 percent ofpregnancies in the United States [1,9-11]. The disease is mild in 75 percent of cases in theUnited States, and severe in 25 percent [12]. Ten percent of preeclampsia occurs in pregnanciesless than 34 weeks of gestation.

Preexisting hypertension complicates about 3 percent of pregnancies [13].

Gestational hypertension occurs in about 6 percent of pregnancies [13].

RISK FACTORS

Clinical — Risk factors for preeclampsia are listed in the table (table 5). The magnitude of riskdepends upon the specific condition and its severity [14]. Selected risk factors for the development ofpreeclampsia are discussed below:

Past obstetrical history of preeclampsia is a strong risk factor for preeclampsia in a futurepregnancy (see 'Recurrence' below). A systematic review of controlled studies reported that therelative risk of preeclampsia in women with a history of the disorder compared to women withno such history was 7.19 (95% CI 5.85-8.83) [15]. Women with early, severe preeclampsia(approximately 2 percent of cases in nulliparas) are at greatest risk of recurrence, rates of 25 to65 percent have been reported [16-19]. In women who had mild preeclampsia during the firstpregnancy, the incidence of preeclampsia in a second pregnancy is 5 to 7 percent, compared toless than 1 percent in women who had a normotensive first pregnancy (does not apply toabortions) [20,21].

First pregnancy increases the risk for developing preeclampsia (RR 2.91, 95% CI 1.28-6.61)[15]. It is unclear why the primigravid state is such an important predisposing factor.

A family history of preeclampsia in a first degree relative is associated with an increase in risk(RR 2.90, 95% CI 1.70-4.93) [15], suggesting a heritable mechanism in some cases [22,23].The father of the baby may contribute to the increased risk, as the paternal contribution to fetalgenes may have a role in defective placentation and subsequent preeclampsia. (See"Pathogenesis of preeclampsia", section on 'Genetic factors'.)

Pregestational diabetes also increases risk of preeclampsia (RR 3.56, 95% CI 2.54-4.99) [15],an effect that is probably related to a variety of factors such as underlying renal or vasculardisease, high plasma insulin levels/insulin resistance, and abnormal lipid metabolism [24]. (See"Pregnancy risks in women with type 1 and type 2 diabetes mellitus" and "Prepregnancyevaluation and management of women with type 1 or type 2 diabetes mellitus".)


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Multiple gestation increases the risk of preeclampsia; for twin pregnancies the relative risk is2.93, 95% 2.04-4.21 [15]. The risk rises with the number of fetuses. (See individual topicreviews on twins, triplets, and high order multiple gestation).

Obesity has been consistently reported to increase the risk of preeclampsia. (See "The impact ofobesity on fertility and pregnancy".)

Preexisting hypertension, renal disease, and collagen vascular disease are well-described riskfactors. (See "Management of hypertension in pregnant and postpartum women", section on'Preexistent hypertension' and "Pregnancy in women with underlying renal disease" and"Pregnancy in women with systemic lupus erythematosus".)

The antiphospholipid syndrome has been associated with multiple pregnancy complicationsincluding preeclampsia, fetal loss, and maternal thrombosis [25]. There is conflicting evidenceregarding an association between hereditary thrombophilias and preeclampsia, but the weight ofevidence suggests no association. (See "Obstetrical manifestations of the antiphospholipidsyndrome" and "Inherited thrombophilias in pregnancy".)

Advanced maternal age is an independent risk factor for preeclampsia (maternal age ≥40 RR1.96, 95% CI 1.34-2.87 for multiparous women) [15]. Older women tend to have additional riskfactors, such as diabetes mellitus and chronic hypertension. Whether adolescents are at higherrisk of preeclampsia is more controversial [9]; a systematic review did not find an association[15]. (See "Effect of advanced age on fertility and pregnancy in women".)

A prolonged interval between pregnancies appears to increase the risk of developingpreeclampsia. (See "Interpregnancy interval and pregnancy outcome", section on'Preeclampsia'.)

The role of other risk factors is unclear. A systematic review of controlled studies found a consistent,small but statistically significant, association between urinary tract infection during pregnancy anddevelopment of preeclampsia (pooled odds ratio 1.57; 95% CI 1.45-1.70) [26]. This finding may havebeen related to the increased prevalence of underlying renal disease in women with urinary tractinfections. The study also found an association between periodontal disease and preeclampsia (pooledodds ratio 1.76; 95% CI 1.43-2.18), but no association between preeclampsia and other commoninfections (chlamydia, cytomegalovirus, HIV, herpes, malaria, Mycoplasma hominis, bacterialvaginosis, Helicobacter pylori). These relationships require further investigation before drawing anyconclusions about causality.

Of note, women who smoke cigarettes have a lower risk of preeclampsia than nonsmokers. (See"Smoking and pregnancy", section on 'Preeclampsia'.)

Laboratory and imaging markers — A variety of laboratory and imaging tests have beeninvestigated as possible markers for prediction of preeclampsia (eg, AFP, hCG, uE3, inhibin A, uterineartery Doppler). Most have not been shown to be sufficiently sensitive and specific to be clinicallyuseful as a screening test.

Measurement of angiogenic factors (eg, VEGF, sFIt-1, PlGF, sEng) in blood or urine is the mostpromising approach for predicting preeclampsia; however, these tests are investigational and are notavailable for clinical use at present. (See "Prediction of preeclampsia".)

CLINICAL MANIFESTATIONS — Placental pathogenic changes associated with preeclampsia firstoccur weeks to months before clinical manifestations develop. These pathogenic changes and thepathogenesis of the disorder are discussed in detail separately. (See "Pathogenesis of preeclampsia".)

The gradual development of hypertension and proteinuria in pregnancy is usually due to


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preeclampsia, particularly in a primigravida. These findings typically become apparent in the latterpart of the third trimester and progress until delivery [1,27]. In some women, however, symptomsbegin much earlier, in the latter half of the second trimester [1], while others have an onset that isdelayed until delivery or the early postpartum period [27]. The occurrence of signs and symptoms ofpreeclampsia before 20 weeks of gestation is unusual. When present, they are suggestive of anunderlying molar pregnancy or the antiphospholipid antibody syndrome. (See "Gestationaltrophoblastic disease: Epidemiology, clinical manifestations and diagnosis".) The possibility of illicitdrug use or withdrawal [28] or chromosomal aneuploidy in the fetus [29] should also be considered.

All of the clinical features of preeclampsia described below may be explained as maternal responses togeneralized endothelial dysfunction. Disturbed endothelial control of vascular tone causeshypertension, increased vascular permeability results in edema and proteinuria, and abnormalendothelial expression of procoagulants leads to coagulopathy. These changes also cause ischemia oftarget organs, such as the liver, kidney, and placenta, sometimes with life-threatening results.Therefore, preeclampsia is far more complicated than simple hypertension. The complexpathophysiology has led to uncertainty regarding the risks and benefits of treating the hypertensionassociated with this syndrome.

Hypertension — Pregnancy related hypertension is defined as a systolic blood pressure ≥140 mmHgor diastolic blood pressure ≥90 mmHg in a woman who was normotensive prior to 20 weeks ofgestation [3]. The blood pressure should be taken with an appropriately sized cuff (ie, length 1.5times the upper arm circumference or cuff bladder able to encircle 80 percent or more of the arm)placed on the right arm at the same level as the heart with the woman sitting for at least 10 minutes;the disappearance of the fifth Korotkoff sound indicates the diastolic pressure. The pressure should berecorded to the nearest 2 mmHg. Some experts recommend obtaining the blood pressure in each armat the initial visit and, if there is a significant disparity in pressure, then only the arm with the higherpressure is used in subsequent visits [30]. (See "Technique of blood pressure measurement in thediagnosis of hypertension".)

Hypertension is generally the earliest clinical finding of preeclampsia and is the most common clinicalclue to the presence of the disease. The blood pressure (BP) may rise in the second trimester, butusually does not reach the hypertensive range (≥140/90 mmHg) until the third trimester, often afterthe 37th week of gestation [1]. In some cases, however, preeclampsia develops suddenly in apreviously normotensive woman or early in pregnancy.

The typical gradual rise in blood pressure has important implications for management duringpregnancy. As an example, a reading of 130/85 mmHg in the second trimester is abnormal in awoman whose early pregnancy BP was 90/60 mmHg. Such a patient should be seen more frequentlythan the usual monthly visit, if proteinuria is also present [3].

In the past, an elevation of systolic pressure by 30 mmHg or an increase in diastolic pressure by 15mmHg from values recorded in early pregnancy, with or without associated proteinuria, wasconsidered indicative of preeclampsia, even in the absence of hypertension. These blood pressurecriteria have been rejected because of their low sensitivity and predictive values, about 30 percent forboth, and lack of association with adverse pregnancy outcome [31,32].

Before making a diagnosis of hypertension, the possibility of "white coat hypertension" should beconsidered. In one study of 148 pregnant women with the new onset of hypertension in the thirdtrimester, about 30 percent were diagnosed with white coat hypertension after 24-hour ambulatoryblood pressure monitoring [33]. These women had pregnancy outcomes similar to those innormotensive women, except for a significantly higher rate of cesarean delivery (45 versus 12percent). The authors concluded that the higher rate of surgery may be a result of decision-makingprocesses falsely based upon office blood pressures.


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In contrast, another group found that fewer than 5 percent of 121 hypertensive gravida had whitecoat hypertension; the outcome of these pregnancies was not evaluated [34]. A Cochrane reviewconcluded there is insufficient information on which to base a recommendation regarding the routineuse of ambulatory blood pressure monitoring for new onset hypertension in pregnant women [35].(See "Ambulatory blood pressure monitoring and white coat hypertension in adults".)

A systolic blood pressure of ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg on two occasions atleast six hours apart upstages the diagnosis from mild to severe preeclampsia.

Proteinuria — In addition to hypertension, proteinuria (ie, ≥0.3 g protein in a 24-hour urinespecimen or persistent 1+ (30 mg/dL) on dipstick) must be present to make a diagnosis ofpreeclampsia. Urinary protein excretion increases gradually, may be a late finding, and is of variablemagnitude in preeclampsia. Proteinuria is due, in part, to impaired integrity of the glomerular barrierand altered tubular handling of filtered proteins (hypofiltration) leading to increased protein excretion[36]. Both size and charge selectivity of the glomerular barrier are affected [37]. (See "Evaluation ofproteinuria in pregnancy".)

The approach to women with hypertension but no proteinuria is uncertain, but close follow-up isprudent. This recommendation is supported by the observation that mild gestational hypertension thatoccurs remote from term may subsequently develop into preeclampsia [7,38], 20 percent of womenwho develop eclampsia have no proteinuria [39], and 10 percent of women with other clinical and/orhistological manifestations of preeclampsia have no proteinuria [40].

The presence of ≥5 grams of protein in 24-hour urine collection upstages the diagnosis from mild tosevere preeclampsia.

Other renal findings — The kidney is the organ most likely to manifest endothelial injury related topreeclampsia. Glomerular filtration rate (GFR) decreases by 30 to 40 percent in preeclampticscompared to pregnant normotensive controls; renal plasma flow also decreases, but to a lesserdegree. The plasma creatinine concentration is generally normal or only slightly elevated (1.0 to 1.5mg/dL [88 to 133 micromol/L]). Renal failure is an unusual complication that can occur in patientswho develop severe disease. Rarely, transient diabetes insipidus has been reported in association withpreeclampsia. (See "Renal and urinary tract physiology in normal pregnancy" and "Acute kidneyinjury (acute renal failure) in pregnancy".)

Hyperuricemia and hypocalciuria also occur; the mechanisms for these changes are not clear[36,41,42]. The rise in serum uric acid concentration is thought to reflect increased proximal sodiumand secondarily urate reabsorption induced by renal ischemia. Other possible mechanisms forhyperuricemia in preeclampsia include underlying metabolic syndrome, tissue damage, oxidativestress, and inflammation [43].

The urine sediment is typically benign. Using special studies, podocyturia (urinary excretion ofpodocytes) has been observed in patients with preeclampsia [44]. Urinary shedding of podocytes mayindicate podocyte loss from the glomerulus, which may lead to a disruption of the glomerular filtrationbarrier and consequent proteinuria.

Oliguria, ie. urine output <500 mL/24 hours, upstages the diagnosis from mild to severepreeclampsia.

Pathology — The underlying renal lesion of both preeclampsia and eclampsia is a variant ofthrombotic microangiopathy (TMA) called glomerular endotheliosis. Glomerular endotheliosis sharesthe following histologic features with the nonpreeclamptic TMAs [45]:

Light and electron microscopy demonstrate endothelial cell swelling and loss of fenestrationswith resulting occlusion of capillary lumens.


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Despite marked proteinuria, foot process effacement is not a prominent feature.

Unlike nonpreeclamptic TMAS, thrombi are rare in preeclampsia; however, fibrin deposition may beobserved by immunofluorescence microscopy.

Edema and intravascular volume — Most pregnant women have edema, whether or not they havepreeclampsia. Therefore, the presence of edema is no longer part of the diagnostic criteria. However,sudden and rapid weight gain (eg, >5 pounds/week) and facial edema may occur in women whodevelop preeclampsia, thus, these findings warrant evaluation for other clinical manifestations ofpreeclampsia.

Intravascular volume is lower than in normotensive pregnancy, despite sometimes severe edema.There is no evidence that there is underfilling of the arterial circulation; rather, the reduced volumemay be a consequence of vasoconstriction ("overfill" edema). Nevertheless, this issue has not beenconclusively resolved, thus, diuretics should be avoided in the absence of pulmonary edema.

Hematologic changes — Increased platelet turnover is a consistent feature of preeclampsia [46].The most common coagulation abnormality in preeclampsia is thrombocytopenia due to formation ofmicrothrombi. The prothrombin time, partial thromboplastin time, and fibrinogen concentration arenot affected unless there are additional complications, such as abruptio placentae or severe liverinvolvement.

Microangiopathic hemolysis may also occur and is detected by examination of a blood smear forschistocytes and helmet cells (picture 1A-B) or elevation in the serum lactate dehydrogenaseconcentration. Hemolysis is associated with a low hematocrit, while hemoconcentration is associatedwith a high hematocrit. The presence of both hemolysis and hemoconcentration may negate eachother, resulting in a normal hematocrit value. (See "Thrombocytopenia in pregnancy" and"Abnormalities of coagulation and platelet function in preeclampsia".)

A platelet count less than 100,000 upstages the diagnosis from mild to severe preeclampsia.

Liver — Factors involved in glomerular and hepatic injury may be similar, with vasospasm andprecipitation of fibrin affecting both organs [47]. Periportal hemorrhage, ischemic lesions, andmicrovesicular fat deposition are other histologic findings observed in the livers of preeclampticwomen [48]. The clinical manifestations of liver involvement include right upper quadrant orepigastric pain, elevated transaminases and, in the most severe cases, subcapsular hemorrhage orhepatic rupture, which may represent HELLP syndrome (Hemolysis, Elevated Liver function tests, LowPlatelets). Nausea and vomiting may occur. Hepatitic changes upstage the diagnosis from mild tosevere preeclampsia. (See "HELLP syndrome".)

Central nervous system and eye — Central nervous system manifestations of preeclampsia includeheadache, blurred vision, scotomata, and, rarely, cortical blindness; their presence upstage thediagnosis from mild to severe preeclampsia. Generalized hyperreflexia and sustained ankle clonusmay also be present. The cerebrovascular manifestations of severe preeclampsia are poorlyunderstood, but may represent a form of reversible posterior leukoencephalopathy syndrome (RPLS),with loss of cerebrovascular autoregulation, and cerebral edema. (See "Reversible posteriorleukoencephalopathy syndrome".)

Most women who develop eclampsia describe headache prior to developing a seizure. The headachecan be temporal, frontal, occipital, or diffuse [49,50]. It is usually a throbbing/pounding pain, butpiercing pain can occur. Although not pathognomonic, a feature that suggests preeclampsia-relatedheadache rather than another type of headache is that it persists despite administration of over-the-counter analgesics and it can progress to become severe (ie, incapacitating, "the worst headache ofmy life").


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Most women with headaches attributed to preeclampsia are treated with antihypertensive medicationto maintain blood pressure in a safe range, magnesium sulfate to prevent seizures, analgesia, anddelivery. If, despite this approach, severe headache persists or a focal neurological deficit is present,neuroimaging studies are indicated. The choice of neuroimaging study should be based on the clinicalpresentation, the physical examination (eg, presence of focal findings, visual defects), and availability.Neuroradiographic abnormalities of RPLS are often apparent on computed tomography (CT) scans, butare best depicted by magnetic resonance imaging (MRI).

Seizures in a preeclamptic woman signify a change in diagnosis to eclampsia. One in 400 mildlypreeclamptic and 2 percent of severely preeclamptic women will develop eclamptic seizures. Strokeleading to death or disability is the most serious complication of severe preeclampsia/eclampsia, but isalso rare. (See "Management of preeclampsia", section on 'Anticonvulsant therapy'.)

Histopathologic correlates include hemorrhage, petechiae, vasculopathy, ischemic brain damage,microinfarcts, and fibrinoid necrosis [51,52]. Cerebral edema and ischemic/hemorrhagic changes inthe posterior hemispheres observed on computed tomography and magnetic resonance imaging helpto explain, but do not fully account for, the clinicopathological findings [53,54]. (See "Eclampsia".)

Visual symptoms are common and caused, at least in part, by constriction of retinal arteries.Symptoms include blurred vision, flashing lights, and scotomata (dark areas or gaps in the visualfield) [55,56]. Cortical blindness is typically transient [57]. Blindness related to retinal pathology,such as retinal artery or venous thrombosis, retinal detachment, optic nerve damage, retinal arteryspasm, and retinal ischemia, may be permanent [58].

Heart — Preeclampsia does not directly affect the myocardium. However, decrements in leftventricular performance can occur and reflect a physiologically appropriate response to increasedafterload [59]. For example, the high afterload can cause cardiac strain, which is reflected by four-foldhigher concentrations of natriuretic peptides in women with preeclampsia compared to pregnantwomen who are normotensive or have chronic hypertension [60].

Some women who develop preeclampsia have elevated cardiac outputs before clinical diagnosis, withnormal (low) total peripheral resistance during the latent phase [61,62]. After clinical manifestationsbecome apparent, there is a marked reduction in cardiac output and increase in peripheral resistance[59,61,63]. However, severe preeclampsia can be associated with a highly variable hemodynamicprofile [64-68].

Women with severe disease are at risk of coronary events. Troponin I levels should be obtained whenclinically indicated, such as when the patient complains of chest pain suggestive of myocardialischemia and new electrocardiogram changes are observed [69,70]. Preeclampsia is not associatedwith elevated troponin levels in the absence of cardiac disease [71].

Pulmonary edema — The presence of pulmonary edema upstages the diagnosis from mild to severepreeclampsia.

The etiology of pulmonary edema in preeclampsia is multifactorial. Excessive elevations in pulmonaryvascular hydrostatic pressure compared to plasma oncotic pressure may produce pulmonary edema insome women, particularly in the postpartum period. However, not all preeclamptic patients withpulmonary edema demonstrate this phenomenon [72]. Other causes of pulmonary edema arecapillary leak, left heart failure, and iatrogenic volume overload.

Fetus and placenta — The fetal consequences of chronic placental hypoperfusion are fetal growthrestriction and oligohydramnios. Fetal growth restriction upstages the diagnosis from mild to severepreeclampsia.

Severe and early onset preeclampsia result in the greatest decrements in birth weight compared to


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normotensive pregnancies, 12 and 23 percent, respectively [73]. By comparison, late onsetpreeclampsia can be associated with higher than average birth weight, possibly related to greaterplacental perfusion due to elevated cardiac output and blood pressure [74-76].

Abruptio placenta is infrequent (less than 1 percent) in women with mild preeclampsia, but has beenreported in 3 percent of those with severe disease [77]. (See "Clinical features and diagnosis ofplacental abruption".)

Indicated preterm delivery is a secondary result of fetal or maternal complications. Preeclampsia doesnot appear to accelerate fetal maturation, as once believed. The frequency of neonatal morbiditiessuch as respiratory distress, intraventricular hemorrhage, and necrotizing enterocolitis are similar ininfants of preeclamptic women and age-matched nonhypertensive controls [78]. (See "Management ofpreeclampsia", section on 'Outcome'.)

Histology of placental vasculopathy is described separately. (See "Histopathology of placentaldisorders".)

DIAGNOSIS — The diagnosis of preeclampsia is largely based upon the characteristic clinical featuresdescribed above developing after 20 weeks of gestation in a woman who was previously normotensive(table 1) [11,79]. Preeclampsia is usually diagnosed antepartum or intrapartum, but may first presentclinically in the postpartum period [80-82].

The elevated blood pressure should be documented on two occasions at least six hours, but nomore than seven days, apart [3].

Screening urine for proteinuria is an integral part of antepartum care strategy to detectpreeclampsia. Testing is commonly performed by dipping a paper test strip into a fresh cleanvoided midstream urine specimen. The specimen should be obtained before pelvic examinationto minimize the chance of contamination from vaginal secretions. Women with proteinuria ondipstick should undergo quantitative measurement of protein excretion as urinary proteindipstick values do not correlate well with 24-hour urinary protein excretion values.Protein/creatinine ratios have not been found to accurately reflect 24-hour urine excretion inpregnant women. (See "Evaluation of proteinuria in pregnancy".)

The presence of any of the findings listed in the table (table 6) increase the certainty of the diagnosisand also suggests more severe disease. However, severe disease is defined by the criteria in the table(table 2). Preeclampsia should be suspected in any pregnant woman with hypertension andcharacteristic signs/symptoms, even if proteinuria is absent.

Mild glomerular endotheliosis on renal biopsy specimens (picture 2A-C) has been observed in womenwith normal pregnancy, as well as in both nonproteinuric and proteinuric hypertension [83]. Theclinical significance of mild glomerular endotheliosis in otherwise normal pregnant women is notknown, and raises some questions regarding the sensitivity and specificity of this finding forpreeclampsia [40].

Differential diagnosis — Clinical and laboratory findings are used to distinguish preeclampsia fromgestational hypertension and preexisting hypertension, but signs and symptoms of these disordersmay overlap. Measurement of circulating angiogenic peptides (soluble fms-like tyrosine kinase,soluble endoglin) is under investigation as an approach to differential diagnosis [84]. (See"Pathogenesis of preeclampsia".)

Mild preeclampsia versus preexisting hypertension — In the absence of documentedprepregnancy blood pressure measurements, distinguishing between mild preeclampsia andpreexisting hypertension may be difficult due to the reduction in blood pressure that typically occursduring the first two trimesters. Thus, a patient with preexistent hypertension may be normotensive


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when first seen by the obstetrical provider early in pregnancy.

In this setting, a variety of factors may be helpful in establishing the likely diagnosis:

Onset — Hypertension occurring before the 20th week is usually due to preexistinghypertension rather than to preeclampsia.

Proteinuria — Proteinuria is present and increases with time in preeclampsia, occasionallyreaching the nephrotic range; by comparison, protein excretion is usually absent or less than 1g/day in hypertensive nephrosclerosis [20]. (See "Clinical features and treatment ofhypertensive nephrosclerosis".)

Parity — Preeclampsia is far more common in primiparas than in multiparas (see 'Riskfactors' above).

Age — Preeclampsia is somewhat more common in older (>40 years) primigravidas, althoughthese women are also more likely to have preexisting hypertension, as are older multiparouswomen (see 'Risk factors' above).

Plasma uric acid concentration — Normally, plasma uric acid concentration decreases in earlypregnancy and then increases [85,86]. Preeclampsia is typically associated with a rise in theplasma urate level to above 5.5 to 6 mg/dL (327 micromol/L) [87]. The plasma urateconcentration tends to remain below this level in preexisting hypertension, unless the patient istaking diuretics or has superimposed preeclampsia. Although hyperuricemia is associated withpreeclampsia, serum uric acid level is a poor predictor of development of the disease ormaternal and fetal complications in women with preeclampsia [88,89].

Severe preeclampsia versus preexisting hypertension — Severe preeclampsia can usually bedistinguished from preexisting hypertension with more certainty because the former is oftenaccompanied by a variety of laboratory abnormalities including proteinuria, hyperuricemia, abnormalliver function tests, thrombocytopenia, and hemoconcentration or hemolysis (table 2) (see 'Clinicalmanifestations' above).

Hypertension related to preeclampsia tends to resolve within two to six weeks postpartum. Womenwith persistent hypertension beyond 12 weeks postpartum are likely to have preexisting, chronichypertension. Although there is generally no indication to perform a renal biopsy, the renal lesions ofpreeclampsia also resolve after delivery. The fibrin-like deposits clear within a few weeks, but theglomerular endotheliosis takes somewhat longer, as long as to eight weeks [90].

Mild preeclampsia versus gestational hypertension — Hypertension without proteinuria maydevelop any time after mid pregnancy. This is referred to as gestational hypertension, and has littleadverse effect on the mother or fetus (table 7) [1], unless hypertension is severe (≥160/110 mmHg)[38,91]. The hypertension typically resolves within three months of delivery [3], but may recur insubsequent pregnancies. (See "Gestational hypertension".)

There are two situations in which gestational hypertension may not be benign:

Remote from term — Gestational hypertension that occurs remote from term is a risk factor forthe development of preeclampsia and adverse neonatal outcome [7]. As many as 50 percent ofwomen with gestational hypertension go on to develop preeclampsia, with the highest risk inwomen who develop gestational hypertension before 30 weeks [7,8].

Development of severe hypertension with signs of preeclampsia — If severe hypertension,persistent headache, visual changes, growth restriction, oligohydramnios, epigastric or rightupper abdominal pain, thrombocytopenia, or liver function abnormalities, occur in a woman


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diagnosed with gestational hypertension.

In these two situations, women with gestational hypertension should be treated as though they havepreeclampsia (or HELLP syndrome), even in the absence of proteinuria. These women are at high riskof maternal and/or fetal morbidity [38,91,92].

Preeclampsia versus exacerbation of renal disease — Preeclampsia frequently develops inwomen with preexisting primary or secondary renal disease; in this setting, it may occur earlier ingestation and may be particularly severe [93,94]. Alternatively, worsening hypertension andproteinuria in a woman with primary or secondary renal disease may merely represent anexacerbation of the underlying disease or the physiological effects of pregnancy at advancedgestational ages. Although this differential diagnosis can be difficult, the ability to accuratelydistinguish between these two possibilities is extremely important. The institution of incorrect therapymay have serious consequences for both the mother and baby, such as maternal convulsions orunnecessary preterm delivery [95].

In such cases, significant clues to the diagnosis of severe preeclampsia are the presence of systemicmanifestations of the disorder, such as thrombocytopenia, increased serum levels ofaminotransferases, and evidence of fetal compromise (growth restriction, oligohydramnios) (table 2)[96]. Onset of disease in the first half of pregnancy suggests exacerbation of underlying disease,rather than preeclampsia. Whether measurement of urinary angiogenic factors (soluble fms-liketyrosine kinase, placental growth factor) will be useful in distinguishing severe preeclampsia fromother hypertensive-proteinuric disorders is under investigation [97]. (See "Pathogenesis ofpreeclampsia".)

By comparison, evidence suggestive of exacerbation of renal disease include the presence of specificsystemic findings of disease activity (eg, low complement levels in a patient with systemic lupuserythematosus) or a urinalysis consistent with a proliferative glomerular disorder (eg, red and whitecells and/or cellular casts), findings which are inconsistent with preeclampsia. (See "Pregnancy inwomen with systemic lupus erythematosus" and "Differential diagnosis of glomerular disease".)

Focal segmental glomerulosclerosis, a disorder that can simulate preeclampsia, may first becomeclinically apparent during pregnancy and also may be exacerbated by pregnancy [98]. (See"Pathogenesis and diagnosis of focal segmental glomerulosclerosis", section on 'Pregnancy'.)

Other disorders — A variety of conditions can present with signs or symptoms similar topreeclampsia, eclampsia, and HELLP syndrome. Although preeclamptic syndromes are the mostcommon causes of hypertension, coagulation abnormalities, liver abnormalities, and renalabnormalities in pregnant women, the following conditions should be considered and excluded asindicated (table 8A-B):

Acute fatty liver (see "Acute fatty liver of pregnancy")

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (see "Diagnosis ofthrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults")

Exacerbation of systemic lupus erythematosus (see "Pregnancy in women with systemic lupuserythematosus")

Gestational thrombocytopenia and autoimmune thrombocytopenia (see "Thrombocytopenia inpregnancy")

Cerebral hemorrhage (see "Spontaneous intracerebral hemorrhage: Pathogenesis, clinicalfeatures, and diagnosis")


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Migraine (see "Headache in pregnancy")

Hepatitis (see "Clinical manifestations and natural history of hepatitis B virus infection")

Cholestasis (see "Intrahepatic cholestasis of pregnancy")

Pancreatitis (see "Clinical manifestations and diagnosis of acute pancreatitis")

PROGNOSIS — Prognostic issues include the risk of recurrent preeclampsia in subsequentpregnancies and long-term maternal health risks. The short-term outcome of preeclampticpregnancies is discussed separately. (See "Management of preeclampsia", section on 'Outcome'.)

In addition, uteroplacental insufficiency may manifest in different ways in different pregnancies.Preeclampsia, growth restriction, preterm delivery, abruption, and stillbirth can all be sequelae ofimpaired placental function. Early onset preeclampsia is more likely to be associated with adverseevents in a subsequent pregnancy, even if normotensive, than late onset preeclampsia [99].

Recurrence — The recurrence risk varies with the severity and time of onset of the acute episode[14]. As discussed above (see 'Risk factors' above), women with early, severe preeclampsia are atgreatest risk of recurrence (as high as 25 to 65 percent), the incidence is much lower (5 to 7 percent)in women who had mild preeclampsia during the first pregnancy, versus less than 1 percent in womenwho had a normotensive first pregnancy (does not apply to abortions) [16,18,20,21,100-102].

In one series of 125 women with severe second trimester preeclampsia followed for five years,35 percent were normotensive during subsequent pregnancy and 65 percent developedrecurrent preeclampsia [18]. Of the latter group, approximately one-third developedpreeclampsia at ≤27 weeks, one-third at 28 to 36 weeks, and one-third at ≥37 weeks. Thus, 21percent of subsequent pregnancies were complicated by severe preeclampsia in the secondtrimester. By comparison, only 2 percent of nulliparous women develop severe preeclampsia[103].

In another series of 120 women with a history of preeclampsia resulting in delivery before 34weeks of gestation, preeclampsia developed in the second pregnancy in 30 women (25 percent)[17]. Of the latter group, six women again delivered before 34 weeks of gestation, representinga recurrence risk of 5 percent for need for delivery before 34 weeks. In this series, recurrencerates for preeclampsia or preterm delivery were not related to severity of first pregnancycomplications, such as delivery before 28 weeks of gestation, HELLP syndrome, or small-for-gestational age infants.

Recurrent preeclampsia is more likely following a singleton preeclamptic pregnancy than a twinpreeclamptic pregnancy [104].

Prevention — Preventive therapy and the recurrence risk in women with HELLP syndrome (whomay develop either HELLP or preeclampsia in a subsequent pregnancy) are discussed separately. (See"Prevention of preeclampsia" and "HELLP syndrome".)

Long-term maternal risks

Cardiovascular risks — Case-control and cohort studies consistently report that preeclampsia ispredictive of future cardiovascular and cerebrovascular disease. This risk was summarized in twosystematic reviews of controlled studies that evaluated the risk of late cardiovascular events inwomen with and without a history of preeclampsia [105,106]:

Compared with women with no history of the disease, women with preeclampsia were atincreased risk of developing hypertension (RR 3.70, 95% CI 2.70-5.05 at mean follow-up of 14


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years), ischemic heart disease (RR 2.16, 95% CI 1.86-2.52 at mean follow-up of 11.7 years),stroke (RR 1.81, 95% CI 1.45-2.27 at mean follow-up of 10.4 years), and venousthromboembolism (RR 1.79, 95% CI 1.37-2.33 at mean follow-up of 4.7 years) [105]. Theabsolute risk that a woman with or without a history of preeclampsia would develop one ofthese cardiovascular events at age 50 to 59 years was estimated to be 17.8 and 8.3 percent,respectively.

In addition, a graded relationship was observed between severity of preeclampsia and risk offuture cardiac disease (mild preeclampsia RR 2.00, 95% CI 1.83-2.19; moderate preeclampsiaRR 2.99, 95% CI 2.51-3.58; severe preeclampsia RR 5.36, 95% CI 3.96-7.27), as well as acorrelation between preeclampsia and future peripheral arterial disease (RR 1.87, 95% CI0/94-3.73) [106]. The authors defined preeclampsia as 'mild' if the pregnancy had anuncomplicated course, 'moderate' if preeclampsia was complicated by fetal growth restriction ormaternal seizures, and 'severe' if preeclampsia was complicated by preterm delivery or fetaldemise.

Further review of these data shows that women with early onset/severe preeclampsia, recurrentpreeclampsia, gestational hypertension, or preeclampsia with onset as a multipara appear to be athighest risk of cardiovascular disease later in life, including during the premenopausal period [105].These women may have unrecognized latent hypertension, thrombophilic disorders, or other geneticor environmental factors predisposing them to hypertension during and subsequent to pregnancy. Incontrast, mild preeclampsia occurring late in gestation in primigravid women and followed by anormotensive pregnancy does not appear to be associated with increased remote cardiovascular risk[107].

The prognostic importance of early onset preeclampsia was illustrated in a review of over 626,000first deliveries in Norway that was included in the meta-analysis [108]. Primiparous women withpreeclampsia and preterm delivery were at increased risk of death from cardiovascular disease duringa median follow-up of 13 years (range 0 to 25 years) compared to preeclamptics andnonpreeclamptics who delivered at term and nonpreeclamptics who delivered preterm (table 9). Theassociation between cardiovascular disease and preterm, but not term, preeclampsia suggests that thepathogenesis as well as the prognosis of early versus late preeclampsia are different.

Several studies have demonstrated that women with a history of preeclampsia exhibit impairedendothelial function and vasodilatation remote from pregnancy [109-111]. Data from someepidemiologic studies suggest the increased risk of late cardiovascular morbidity in previouslypreeclamptic women reflects an underlying predisposition in these women for both disorders, but it isalso possible that preeclampsia results in permanent arterial changes leading to late cardiovasculardisease [112-114]. Some investigators have hypothesized that increased insulin resistance,sympathetic overactivity, proinflammatory activity, endothelial dysfunction, and the abnormal lipidprofile in preeclamptic women constitute an early manifestation of metabolic syndrome and that thesechanges persist after pregnancy, thereby putting affected woman at increased risk of cardiovasculardisease [115-118].

End-stage renal disease — Women with preeclampsia appear to be at increased risk ofdeveloping end-stage renal disease (ESRD) later in life, but the absolute risk is small. A study thatlinked four decades of data from the Norwegian national birth and ESRD registries found that womenwith preeclampsia in their first pregnancy had a four-fold increase in risk of ESRD compared withwomen without preeclampsia (RR 4.7, 95% CI 3.6-6.1), but the absolute risk of ESRD was low (lessthan 1 percent within 20 years) [119]. The significant increase in risk persisted after adjusting forknown confounders, such as diabetes, essential hypertension, preexisting renal disease, andrheumatological disorders. Although women who went on to develop ESRD may have had subclinical


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renal disease during pregnancy, it is also possible that as yet undefined risk factors predisposed thesewomen to both preeclampsia and ESRD. It is less likely that preeclampsia damages the kidney,thereby initiating a process of chronic deterioration.

Cancer — A systematic review did not find a significant association between preeclampsia andlater development of cancer [105]. Observational studies from the United States, Sweden, andNorway reported that women with preeclampsia were at reduced risk or had no excess risk of cancerwhen followed 13 to 19 years postpartum [108,120-125]. In contrast, a study from Israel reported anincreased risk of cancer in such women (hazard ratio 1.27, 95% CI 1.03-1.57) with a medianfollow-up of 29 years [126,127]. Site-specific increases were noted for cancer of the stomach, lung orlarynx, breast, and ovary. The discordant results may be explained by a number of factors, includingdifferences in patient populations, absence of or insufficient adjustment for confounders, differencesin length of follow-up, and incomplete ascertainment.

Reduced thyroid function — A nested case-control study found that nulliparous women whodeveloped preeclampsia were more likely to develop subclinical hypothyroidism during pregnancythan matched normotensive controls [128]. In addition, women with a history of preeclampsia weremore likely to have an elevated TSH 20 years postpartum than women with no such history. The riskwas strongest in women with recurrent preeclampsia and without thyroid peroxidase antibodies,suggesting the absence of the usual autoimmune mediated mechanism. The authors hypothesizedthat the anti-angiogenic protein s-Flt-1, which appears responsible for the clinical phenotype ofpreeclampsia, may also affect the thyroid gland. (See "Pathogenesis of preeclampsia" and "Subclinicalhypothyroidism".)

INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients.(See "Patient information: Preeclampsia".) We encourage you to print or e-mail this topic review, orto refer patients to our public web site, www.uptodate.com/patients, which includes this and othertopics.

SUMMARY AND RECOMMENDATIONS

The four major hypertensive disorder related to pregnancy are preeclampsia (table 1), chronichypertension, preeclampsia superimposed upon chronic hypertension, and gestationalhypertension (table 4). (See 'Introduction' above.)

Some of the major risk factors for development of preeclampsia include past history ofpreeclampsia, nulliparity, pregestational diabetes, family history of preeclampsia, and multiplegestation. (See 'Risk factors' above.)

The gradual development of hypertension and proteinuria in pregnancy is usually due topreeclampsia, particularly in a primigravida. These findings typically become apparent in thelatter part of the third trimester and progress until delivery, but some women developsymptoms in the latter half of the second trimester or intrapartum or the early postpartumperiod. (See 'Clinical manifestations' above.)

The diagnosis of preeclampsia is clinical, based on the new onset of hypertension andproteinuria after 20 weeks of gestation in a previously normotensive woman. (See'Diagnosis' above.)

Preeclampsia is characterized as mild or severe. Criteria for severe disease are listed in thetable (table 2). Severe hypertension, coagulopathy, thrombocytopenia, liver functionabnormalities, and fetal growth restriction are features of severe disease. Symptoms can includeheadache, visual disturbance (blurring, flashing lights, defects), epigastric pain,nausea/vomiting, or decreased fetal movement. (See 'Clinical manifestations' above and


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'Diagnosis' above.)

Differential diagnosis includes preexisting hypertension, gestational hypertension, exacerbationof underlying renal disease, acute fatty liver of pregnancy, thrombotic thrombocytopenicpurpura-hemolytic uremic syndrome, exacerbation of systemic lupus erythematosus, andgestational thrombocytopenia and autoimmune thrombocytopenia. (See 'Differentialdiagnosis' above.)

Prognostic issues include an increased risk of recurrence in subsequent pregnancies and possiblelong-term risks of cardiovascular disease and cancer. (See 'Prognosis' above.)

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McDonald, SD, Malinowski, A, Zhou, Q, et al. Cardiovascular sequelae ofpreeclampsia/eclampsia: a systematic review and meta-analyses. Am Heart J 2008; 156:918.

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Chesley, SC, Annitto, JE, Cosgrove, RA. The remote prognosis of eclamptic women. Sixth periodicreport. Am J Obstet Gynecol 1976; 124:446.

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Irgens, HU, Reisaeter, L, Irgens, LM, Lie, RT. Long term mortality of mothers and fathers afterpre-eclampsia: population based cohort study. BMJ 2001; 323:1213.

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Agatisa, PK, Ness, RB, Roberts, JM, et al. Impairment of endothelial function in women with ahistory of preeclampsia: an indicator of cardiovascular risk. Am J Physiol Heart Circ Physiol2004; 286:H1389.

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128.


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GRAPHICS

Criteria for the diagnosis of preeclampsia

Systolic blood pressure ≥140 mmHg

or

Diastolic blood pressure ≥90 mmHg*

and

Proteinuria of 0.3 grams or greater in a 24-hour urine specimen•

The elevation in blood pressure should be sustained, which is generally regarded as twomeasurements at least six hours, but no more than seven days, apart. * Diastolic blood pressure isdetermined based upon the fifth Korotkoff sound (disappearance) with patient sitting.• A random urine protein determination of 30 mg/dL or 1+ on dipstick is suggestive, but not diagnostic, of thepresence of this criterion.


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Criteria for severe preeclampsia

New onset proteinuric hypertension and at least one of the following:

Symptoms of central nervous system dysfunction:

Blurred vision, scotomata, altered mental status, severe headache (ie, incapacitating, "the worst headacheI've ever had") or headache that persists and progresses despite analgesic therapy

Symptoms of liver capsule distention:

Right upper quadrant or epigastric pain

Nausea, vomiting

Hepatocellular injury:

Serum transaminase concentration at least twice normal

Severe blood pressure elevation:

Systolic blood pressure ≥160 mm Hg or diastolic ≥110 mm Hg on two occasions at least six hours apart

Thrombocytopenia:

Less than 100,000 platelets per cubic millimeter

Proteinuria:

5 or more grams in 24 hours

Oliguria <500 mL in 24 hours

Severe fetal growth restriction

Pulmonary edema or cyanosis

Cerebrovascular accident

Based on Diagnosis and Management of Preeclampsia and Eclampsia. American College of Obstetricians andGynecologists. ACOG Practice Bulletin #33, January 2002 and Working Group Report on High Blood Pressure inPregnancy. National Instititutes of Health, Washington, DC 2000


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Signs suggestive of preeclampsia superimposed on chronic hypertension

New onset proteinuria

Hypertension and proteinuria beginning prior to 20 weeks of gestation

A sudden increase in blood pressure

Thrombocytopenia

Elevated aminotransferases

Working Group on High Blood Pressure in Pregnancy. National Institutes of Health Washington, DC 2000.


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Criteria for gestational hypertension

Systolic blood pressure ≥140 mmHg

OR

Diastolic blood pressure ≥ 90 mmHg

AND no proteinuria

Developing AFTER the 20th week of gestation in women known to be normotensive beforepregnancy. Blood pressure should be elevated on at least two occasions at least six hours apart.


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Factors 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

Antiphospholipid antibody syndrome or inherited thrombophilia

Vascular or connective tissue disease

Diabetes mellitus (pregestational and gestational)

Multifetal gestation

High body mass index

Male partner whose mother or previous partner had preeclampsia

Hydrops fetalis

Unexplained fetal growth restriction

Woman herself was small for gestational age

Fetal growth restriction, abruptio placentae, or fetal demise in a previous pregnancy

Prolonged interpregnancy interval

By comparison, smoking decreases the risk of preeclampsia


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Microangiopathic smear

Peripheral blood smear from a patient with a microangiopathichemolytic anemia with marked red cell fragmentation. The smearshows multiple helmet cells (small black arrows), otherfragmented red cells (large black arrow); microspherocytes arealso seen (blue arrows). The platelet number is reduced; thelarge platelet in the center (red arrow) suggests that thethrombocytopenia is due to enhanced destruction. Courtesy ofCarola von Kapff, SH (ASCP).


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Normal peripheral blood smear

High power view of a normal peripheral blood smear. Severalplatelets (black arrows) and a normal lymphocyte (blue arrow)can also be seen. The red cells are of relatively uniform size andshape. The diameter of the normal red cell should approximatethat of the nucleus of the small lymphocyte; central pallor (redarrow) should equal one-third of its diameter. Courtesy of Carola vonKapff, SH (ASCP).


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Helmet cells

Peripheral smears from two patients with microangiopathichemolytic anemia, showing a number of red cell fragments (i.e.,schistocytes), some of which take the form of combat (red arrow),bicycle (thick black arrow), or football (blue arrow) "helmets."Microspherocytes are also seen (thin black arrows), along with anucleated red cell (green arrow). Courtesy of Carola von Kapff, SH(ASCP).


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Findings which increase the certainty of the diagnosis of preeclampsia

Systolic blood pressure of 160 mm Hg or more

Diastolic blood pressure of 110 mm Hg or more

Proteinuria occurring for the first time during pregnancy, especially if 2.0 g or more in 24 hours. Aqualitative result of 2+ or 3+ is also suggestive.

Serum creatinine greater than 1.2 mg/dL (106 mmol/L)

Platelet count less than 100,000 cells per cubic millimeter

Evidence of microangiopathic hemolytic anemia (eg, elevated lactic acid dehydrogenase)

Elevated liver enzymes (eg, alanine aminotransferase or aspartate aminotransferase)

Persistent headache or other cerebral or visual disturbances

Persistent epigastric pain

Working group report on high blood pressure in pregnancy. National Instititutes of Health, Washington, DC2000.


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Preeclampsia

Light micrograph in preeclampsia showing glomerularendotheliosis. The primary changes are swelling of damagedendothelial cells, leading to partial closure of many of thecapillary lumens (large arrows). Mitosis within an endothelial cell(small arrow) is a sign of cellular repair. Courtesy of Helmut Rennke,MD.


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Normal glomerulus

Light micrograph of a normal glomerulus. There are only 1 or 2cells per capillary tuft, the capillary lumens are open, thethickness of the glomerular capillary wall (long arrow) is similarto that of the tubular basement membranes (short arrow), andthe mesangial cells and mesangial matrix are located in thecentral or stalk regions of the tuft (arrows). Courtesy of Helmut GRennke.


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Preeclampsia

Electron micrograph in preeclampsia showing narrowing of thecapillary lumen due to expansion of the mesangium, swelling ofthe endothelial (Endo) cell cytoplasm (arrow), and subendothelialdeposition of hyaline (Hy) material which represents largemacromolecules such as IgM. The damaged endothelial cell hasbecome partially separated (*) from the glomerular basementmembrane (GBM). Courtesy of Helmut Rennke, MD.


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Normal glomerulus

Electron micrograph of a normal glomerular capillary loopshowing the fenestrated endothelial cell (Endo), the glomerularbasement membrane (GBM), and the epithelial cells with itsinterdigitating foot processes (arrow). The GBM is thin and noelectron dense deposits are present. Two normal platelets areseen in the capillary lumen. Courtesy of Helmut Rennke, MD.


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IgM deposition in preeclampsia

Immunofluorescence microscopy in preeclampsia showing diffuseIgM deposition. This represents nonspecific entrapment of largerproteins in the more permeable glomerular capillary wall, ratherthan the formation of discrete immune complexes. There is, forexample, generally no deposition of IgG. Courtesy of Helmut Rennke,MD.


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Pregnancy outcome with gestational hypertension

Parameter Mean values, percent

Preterm birth <37 weeks 5 to 17

Preterm birth <34 weeks 1 to 5

Fetal growth restriction 2 to 14

Abruptio placentae 0.3 to 0.5

Perinatal death 0 to 0.8

Adapted from: Sibai, SM. Obstet Gynecol 2003; 102:181.


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Frequency of various signs and symptoms among imitators ofpreeclampsia-eclampsia

Signs andsymptoms

HELLPsyndrome,

percent

AFLP,percent

TTP,percent

HUS,percent

Exacerbationof SLE,percent

Hypertension 85 50 20-75 80-90 80 with APA,nephritis

Proteinuria 90-95 30-50 Withhematuria

80-90 100 with nephritis

Fever Absent 25-32 20-50 NR Common duringflare

Jaundice 5-10 40-90 Rare Rare Absent

Nausea andvomiting

40 50-80 Common Common Only with APA

Abdominal pain 60-80 35-50 Common Common Only with APA

Central nervoussystem

40-60 30-40 60-70 NR 50 with APA

HELLP: hemolysis, elevated liver enzymes, low platelets; AFLP: acute fatty liver of pregnancy; TTP: thromboticthrombocytopenic 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. Imitatorsof Severe Preeclampsia. Obstet Gynecol 2007; 109:956. Copyright ©2007 Lippincott Williams and Wilkins.


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Frequency and severity of laboratory findings among imitators ofpreeclampsia-eclampsia

Laboratoryfindings

HELLPsyndrome AFLP TTP HUS Exacerbation

of SLE

Thrombocytopenia (lessthan 100,000/mm3)

More than20,000

More than50,000

20,000or less

Morethan20,000

More than 20,000

Hemolysis (percent) 50-100 15-20 100 100 14-23 with APA

Anemia (percent) Less than 50 Absent 100 100 14-23 with APA

DIC (percent) Less than 20 50-100 Rare Rare Rare

Hypoglycemia (percent) Absent 50-100 Absent Absent Absent

VW factor multimers(percent)

Absent Absent 80-90 80 Less than 10

ADAMTS13 less than 5percent (percent)

Absent Absent 33-100 Rare Rare

Impaired renal function(percent)

50 90-100 30 100 40-80

LDH (IU/L) 600 or more Variable Morethan1000

Morethan1000

With APA

Elevated ammonia(percent)

Rare 50 Absent Absent Absent

Elevated bilirubin(percent)

50-60 100 100 NA Less than 10

Elevated transaminases(percent)

100 100 Usuallymild*

Usuallymild*

With APA

HELLP: hemolysis, elevated liver enzymes, low platelets; AFLP: acute fatty liver of pregnancy; TTP: thromboticthrombocytopenic purpura; HUS: hemolytic uremic syndrome; SLE: systemic lupus erythematosus; APA:antiphospholipid antibodies with or without catastrophic antiphospholipid syndrome; DIC; disseminatedintravascular coagulopathy: VW: von Willebrand; ADAMTS: von Willebrand factor-cleaving metalloprotease;LDH: lactic dehydrogenase; NR: values are not available.* Levels less than 100 IU/L. Reproduced with permission from: Sibai, BM. Imitators of Severe Preeclampsia.Obstet Gynecol 2007; 109:956. Copyright ©2007 Lippincott Williams and Wilkins.


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Deaths from cardiovascular causes

Population Relative hazard rate (95 percent confidenceinterval)

Nonpreeclamptic, term delivery 1

Nonpreeclamptic, pretermdelivery

2.95 (2.12 to 4.11)

Preeclamptic, term delivery 1.65 (1.01 to 2.70)

Preeclamptic, preterm delivery 8.12 (4.31 to 15.33)

Data from: Irgens, HU, Reisaeter, L, Irgens, LM, Lie, RT. BMJ 2001; 323:1213.


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clinical features, diagnosis, and long-term prognosis of preeclampsia

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