INTRODUCTIONPreeclampsia is a multi-system disorder characterized by the new onset of hypertension and either proteinuria or end-organ dysfunction in the last half of pregnancy (table 1). Although most affected pregnancies deliver at term or near term with good maternal and fetal outcomes, these pregnancies are at increased risk for maternaland/orfetal mortality or serious morbidity [1,2].DEFINITIONS OF PREGNANCY-RELATED HYPERTENSIVE DISORDERSThere are four major hypertensive disorders related to pregnancy [3,4]:Preeclampsia Preeclampsia refers to the new onset of hypertension and either proteinuria or end-organ dysfunction after 20 weeks of gestation in a previously normotensive woman (table 1). Severe hypertension andsigns/symptomsof end-organ injury are considered the severe spectrum of the disease (table 2) [4]. In 2013, the American College of Obstetricians and Gynecologists removed proteinuria as an essential criterion for diagnosis of preeclampsia. They also removed massive proteinuria (5grams/24hours) 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 [4]. Oliguria was also removed as a characteristic of severe disease.

Eclampsiarefers 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".)

HELLPsyndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) probably represents a severe form of preeclampsia, but this relationship remains controversial; HELLP may be an independent disorder. As many as 15 to 20 percent of affected patients do not have concurrent hypertension or proteinuria, leading some experts to believe that HELLP syndrome is a separate disorder from preeclampsia. (See"HELLP syndrome".)Chronic/preexistinghypertensionChronic/preexistinghypertension is defined as systolic pressure 140 mmHgand/ordiastolic pressure 90 mmHg that antedates pregnancy or is present before the 20th week of pregnancy (on at least two occasions) 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".)Preeclampsia superimposed uponchronic/preexistinghypertension Superimposed preeclampsia is defined by the new onset of either proteinuria or end-organ dysfunction after 20 weeks of gestation in a woman withchronic/preexistinghypertension. For women withchronic/preexistinghypertension 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 ofsigns/symptomsof the severe spectrum of the disease (table 2).Gestational hypertension During pregnancy, gestational hypertension refers to hypertension without proteinuria or othersigns/symptomsof preeclampsia that develops after 20 weeks of gestation (table 3). It should resolve by 12 weeks postpartum. If hypertension persists beyond 12 weeks postpartum, the diagnosis is revised tochronic/preexistinghypertension that was masked by the physiologic decrease in blood pressure that occurs in early pregnancy. If hypertension resolves postpartum, the diagnosis is revised to transient hypertension of pregnancy. (See"Gestational hypertension".)PREVALENCEPreeclampsia occurs in up to 7.5 percent of pregnancies worldwide [5,6]. Variations in prevalence reflect, at least in part, differences in the maternal age distribution and proportion of primiparous women among populations [2]. The prevalence of preeclampsia in the United States is about 3.4 percent, but 1.5-fold to 2-fold higher in first pregnancies [7]. Late onset disease (34 weeks) is more prevalent than early onset disease (0.3. Although proteinuria in women with preeclampsia is most often 10g/daymay be seen. [note: the urine protein concentration in a spot sample is measured inmg/dLand is divided by the urine creatinine concentration also measured inmg/dL,yielding a dimensionless number that estimates the 24-hour protein excretion in grams per day (calculator 1) [63-71]. If SI units are desired(mg/mmol),this value is multiplied by 1000 and divided by 8.8] (See"Proteinuria in pregnancy: Evaluation and management".)Urinary protein excretion may be a late finding [72,73], but generally increases as preeclampsia progresses. It is due, in part, to impaired integrity of the glomerular barrier and altered tubular handling of filtered proteins (hypofiltration) leading to increased protein excretion [74]. Both size and charge selectivity of the glomerular barrier are affected [75]. Using special studies, podocyturia (urinary excretion of podocytes) has been observed in patients with preeclampsia [76]. 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 (VEGF) signaling appears to account, at least in part, for these effects. (See"Pathogenesis of preeclampsia", section on 'Pathogenesis of systemic endothelial dysfunction'.)Renal functionGlomerular filtration rate (GFR) decreases by 30 to 40 percent in preeclampsia compared to pregnant normotensive controls; renal plasma flow also decreases, but to a lesser degree. The plasma creatinine concentration is generally normal or only slightly elevated (1.0 to 1.5mg/dL[88 to 133micromol/L]).A creatinine >1.1mg/dLor doubling of the creatinine concentration indicates severe disease and results from renal vasoconstriction and sodium retention due to reduced plasma volume and systemic vasoconstriction. Urine output may decrease to 40 years) nulliparas, although these women are also more likely to have preexisting hypertension, as are older multiparous women (see'Risk factors'above).Superimposed preeclampsiaIn women with known primary (essential) hypertension and increasing blood pressureand/orproteinuria, the presence of systemic manifestations of severe features of preeclampsia, such as thrombocytopenia, increased serum levels of aminotransferases, and visual symptoms strongly suggest development of superimposed preeclampsia (table 2) [117]. Reproductive age women with primary (essential) hypertension typically have no or mild proteinuria so severe proteinuria suggests development of superimposed preeclampsia.Exacerbation of preexisting renal diseaseSuperimposed preeclampsia frequently develops in women with preexisting primary or secondary renal disease [118,119]. 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) [117]. 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 cellsand/orcellular casts]). An active urine sediment is not a feature of preeclampsia. (See"Pregnancy in women with underlying renal disease"and"Pregnancy in women with diabetic nephropathy".)Antiphospholipid syndromeHypertension, proteinuria, and thrombocytopenia, and other signs of end-organ dysfunction can be seen in antiphospholipid syndrome. The absence of laboratory evidence of antiphospholipid antibodies excludes this diagnosis. (See"Clinical manifestations of the antiphospholipid syndrome"and"Diagnosis of the antiphospholipid syndrome"and"Pregnancy in women with antiphospholipid syndrome".)AFLP, TTP, HUS, SLEAlthoughpreeclampsia/HELLPis 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). Low grade fever can be present in AFLP, but does not occur inpreeclampsia/HELLP.AFLP is associated with more serious liver dysfunction: hypoglycemia and disseminated intravascular coagulation are common features, while unusual inpreeclampsia/HELLP.AFLP is also usually associated with more significant renal dysfunction compared topreeclampsia/HELLP.(See"Acute fatty liver of pregnancy".)Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS). Although neurologic abnormalities and acute renal failure are more prominent in TTP-HUS, this disorder may be indistinguishable from severepreeclampsia/HELLPsyndrome. Fever and thrombocytopenia