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    Preeclampsia and Eclampsia

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    Mar.02.2024

    Preeclampsia and Eclampsia

    Synopsis

    Key Points

    • Preeclampsia is a pregnancy-specific condition defined by new-onset hypertension (greater than 140 mm Hg systolic or 90 mm Hg diastolic) that occurs after 20 weeks of gestation or post partum, accompanied by either proteinuria (greater than 300 mg/24 hours) or other maternal organ dysfunction r1
    • Preeclampsia can progress to the obstetric emergency of eclampsia, which refers to the onset of seizures in patients with preeclampsia
    • Diagnosis of preeclampsia requires evidence of hypertension (greater than 140 mm Hg systolic or 90 mm Hg diastolic) on at least 2 occasions 4 hours apart and either proteinuria (24-hour urine protein level greater than 300 mg) or the presence of maternal organ dysfunction that can be shown with results of blood, renal, and liver function tests r2
    • Management of preeclampsia depends on disease severity and gestational age and may include: r3
      • Frequent observation and fluid management for preeclampsia
      • Administration of antihypertensive drugs in cases of severe preeclampsia to control high blood pressure and administration of corticosteroids to improve fetal growth
    • Management of eclampsia involves immediate delivery after maternal stabilization regardless of gestational age or full benefit from steroids r2
    • Several severe obstetric complications can occur as a result of preeclampsia, including abruptio placentae, acute renal failure, liver dysfunction, pulmonary edema, disseminated intravascular coagulation syndrome, stroke, cardiomyopathy, and heart failure
    • Developing countries have high death rates associated with preeclampsia/eclampsia, whereas maternal mortality associated with preeclampsia/eclampsia is declining in developed countries

    Urgent Action

    • Hypertensive emergency
      • Acute-onset, severe systolic (160 mm Hg or greater) and/or diastolic (110 mm Hg or greater) hypertension during pregnancy or during the postpartum period lasting more than 15 minutes is an obstetric emergency r4
        • Goal of emergent therapy is to achieve a blood pressure range of 140 to 150 mm Hg systolic/90 to 100 mm Hg diastolic (not lower, to avoid hypoperfusion of fetusr5)
        • To reduce risk of stroke, treat with first line agent as soon as identified
      • Treatment
        • Give 20 mg IV labetalol or 5 mg IV hydralazine (first line drugs) r4
        • If blood pressure remains elevated after 10 or 20 minutes, double the dosage r6
        • Give up to a total of 4 doses; if blood pressure remains above 160/110 mm Hg, consult specialists in maternal-fetal medicine, anesthesia, or critical care r6
        • Magnesium sulfate is the drug of choice for seizure prophylaxis in severe preeclampsia and seizures in eclampsia r2
        • Consider intubation for patients whose condition does not respond to therapy
    • Eclamptic seizure
      • Treatment r7
        • Position the patient in a lateral decubitus position to minimize aspiration
        • Give IV magnesium sulfate loading dose (4-6 g) followed by continuous infusion (1-2 g/hour)

    Pitfalls

    • Individual symptoms of preeclampsia have limited predictive value for adverse maternal outcomes, so conduct routine blood pressure monitoring regularly for patients with preeclampsia r1
    • For a pregnant patient with chronic hypertension, do not diagnose preeclampsia with a rise in blood pressure alone. When there is underlying essential hypertension, diagnose preeclampsia by the presence of proteinuria or by documenting the presence of end-organ dysfunction
    • Do not give immediate-release oral nifedipine sublingually (risk of hypotension)

    Terminology

    Clinical Clarification

    • Preeclampsia is a pregnancy-specific condition defined by new-onset hypertension (greater than 140 mm Hg systolic or 90 mm Hg diastolic) that occurs after 20 weeks of gestationr1 or post partum, accompanied by either proteinuria (greater than 300 mg/24 hours) or other maternal organ dysfunction r2
    • Can occur superimposed on chronic or preexisting hypertension (ie, discovered before conception or before 20 weeks of gestation) r5r8
      • In these patients, superimposed preeclampsia is identified by new-onset proteinuria or end-organ dysfunction (usually in conjunction with worsening blood pressure) in the second half of pregnancy
    • Eclampsia is an obstetric emergency defined by onset of seizures, unexplained coma, or both in patients with preeclampsia before, during, or after labor

    Classification

    • Gestational hypertension r9
      • Systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg (or both) documented on 2 separate readings at least 4 hours apart, with no proteinuria or features of severe preeclampsia r2
      • Up to one-half of patients with gestational hypertension will develop proteinuria or organ dysfunction characteristic of preeclampsia; increased likelihood when hypertension is diagnosed before 32 weeks of gestation r2
    • Preeclampsia r2
      • Systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg documented on 2 separate readings at least 4 hours apart; classified as severe hypertension if blood pressure is 160/110 mm Hg or higher (in this case can diagnose based on 2 consecutive blood pressure measures within a short interval to initiate prompt treatment)
        • and
      • Proteinuria greater than 300 mg/24-hour urine collection, protein to creatinine ratio of at least 0.3, or dipstick result of 2+ (if quantitative methods unavailable)
        • or
      • In the absence of proteinuria, the presence of new-onset maternal organ dysfunction
        • Thrombocytopenia (platelet count below 100 × 10⁹ cells/L)
        • Renal insufficiency (serum creatinine level greater than 1.1 mg/dL or doubling of baseline value)
        • Hepatic dysfunction (elevated liver enzyme levels twice the upper reference range)
        • Pulmonary edema
        • New-onset headache or visual symptoms
    • Preeclampsia with severe features
      • Defined by presence of any of the following features: r2r9
        • Systolic blood pressure of 160 mm Hg or higher or diastolic blood pressure of 110 mm Hg or higher (considered a medical emergencyr5) on 2 separate readings that are 4 hours apart or longer
        • Thrombocytopenia (platelet count below 100 × 10⁹ cells/L)
        • Renal insufficiency (serum creatinine level greater than 1.1 mg/dL or doubling of original value)
        • Hepatic dysfunction (elevated liver enzymes twice the upper reference limit or severe right upper quadrant or epigastric pain)
        • Pulmonary edema
        • New-onset headache or visual symptoms
    • HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) r9d1
      • Rare, potentially life-threatening obstetric condition that is a combination of hemolysis, elevated liver enzyme levels, and thrombocytopenia
      • May represent a severe variant of preeclampsia, but the exact relationship between preeclampsia and HELLP syndrome is not fully understood
      • Up to 15% of patients do not have hypertension or proteinuria
    • Eclampsia r2
      • New-onset tonic-clonic, focal, or multifocal seizures (in absence of alternative cause) in association with hypertension in pregnancy
      • May be preceded by preeclampsia or occur abruptly without prior signs and symptoms

    Diagnosis

    Clinical Presentation

    History

    • Medical history
      • Patients may have a history of hypertension and/or preeclampsia during previous pregnancies c1c2c3c4c5
      • Patients may have coexisting medical conditions that increase risk (eg, diabetes mellitus, lupus, antiphospholipid antibody syndrome)
    • Severity of symptoms ranges from mild to severe c6c7c8
      • Some patients may be asymptomatic at the time they are found to have hypertension and proteinuria, whereas others may present with symptoms of severe preeclampsia r10c9c10
      • Up to 25% of patients who develop eclampsia are asymptomatic before onset of seizures r11
    • Timing of symptoms r10c11c12c13c14c15
      • Onset is gradual in some cases, whereas in others life-threatening complications occur within hours
      • Preeclampsia and eclampsia may develop before, during, or after delivery
      • Approximately 40% of eclamptic seizures occur before delivery, and approximately 16% occur more than 48 hours after delivery
    • Evolving symptoms that develop as preeclampsia progresses include: r12
      • Epigastric pain accompanied by nausea and vomiting (reflects significant liver damage) c16c17
      • Fatigue and malaise c18c19
      • Severe headache with pounding or throbbing quality c20c21
      • Visual disturbances (eg, blurred vision, photophobia, diplopia) c22c23c24
        • May be related to hypertension or cerebral or retinal edema
      • Sudden-onset edema, pronounced in the face c25
      • Chest pain, cough, and dyspnea (with pulmonary edema) c26c27c28
      • Prolonged oliguria (urine output less than 500 mL/24 hours) c29
        • Suggests renal injury outside of pregnancy
    • Symptoms that occur before an eclamptic episode include: r1
      • Persistent headache c30
      • Blurred vision c31
      • Right upper quadrant abdominal pain c32
      • Photophobia c33
      • Altered mental status c34

    Physical examination

    • Prenatal blood pressure measurements r10
      • Elevations range from mild to severe (equal to or greater than 160 mm Hg/90 mm Hg) c35
    • Rapid weight gain and facial edema due to fluid retention r10c36c37
      • Signs are not unique to preeclampsia/eclampsia, but presence prompts assessment for proteinuria and hypertension
    • Measured fundal height may be low for gestational age owing to intrauterine growth retardation r10c38
      • Typically occurs before diagnostic criteria of preeclampsia are met
    • Tachypnea and crackles/rales if pulmonary edema develops r13c39c40
    • Eclamptic seizures are noted by tonic-clonic seizures lasting for approximately 1 minute, followed by postictal coma of short duration r14c41c42c43

    Causes and Risk Factors

    Causes

    • Exact cause of preeclampsia/eclampsia is unknown, but its pathophysiology is linked to immunologic and angiogenic abnormalities in the placenta r2
      • Abnormal trophoblast invasion of decidual spiral arteries and myometrium r15c44c45
      • Diminished uteroplacental circulation, leading to ischemia and oxidative stress in the placenta r15c46c47c48
      • Poor development of the fetoplacental vasculature r15c49
      • Secretion of angiogenic factors into the maternal circulation, resulting in hypertension and proteinuria r16c50c51

    Risk factors and/or associations

    Age
    • Maternal age older than 35 years is a clinical risk factor for development of preeclampsia/eclampsia r17c52
    Sex
    • Male sex of fetus is associated with an increased maternal risk of preeclampsia/eclampsia in all but Asian-ethnicity populations r18c53c54
    Genetics
    • Preeclampsia/eclampsia has a familial association, but no genetic variants have been reproducibly associated with the condition r19c55
    Other risk factors/associations
    • All of the following are associated with increased risk of developing preeclampsia: r17
      • High prepregnancy BMI c56
        • Rate of preeclampsia among pregnant patients with a baseline BMI of 30 or higher is approximately 5.1%
      • Nulliparity c57
      • Multiple gestation c58
      • Prior preeclampsia c59
      • Use of assisted reproductive technology r2c60
      • Coexisting medical problems r2r20
        • Chronic hypertension (pooled adjusted relative risk of 5.1) r17c61
        • Type 1 diabetes mellitus c62
        • Gestational diabetes c63
        • Antiphospholipid antibody syndrome (pooled adjusted relative risk of 2.3) r17c64
        • Systemic lupus erythematosus c65
        • Renal disease c66
        • Obstructive sleep apnea c67

    Diagnostic Procedures

    Primary diagnostic tools c68

    • Diagnosis is typically pursued and further investigated when elevated blood pressures are found at prenatal obstetric appointments in pregnant patients after 20 weeks of gestation r5
      • All pregnant patients with new-onset high blood pressure or worsening of preexisting high blood pressure after 20 weeks of gestation should undergo laboratory evaluation r5
    • Diagnosis requires demonstration of elevated blood pressure and proteinuria along with clinical and laboratory assessments to determine presence of end-organ involvement; angiogenic biomarkers may have a role in aiding diagnosis and predicting prognosis
      • Blood pressure measurement r21
        • Systolic blood pressure above 140 mm Hg, diastolic blood pressure above 90 mm Hg, or both meet blood pressure criteria for preeclampsia r2
        • Blood pressure readings above 160/110 mm Hg meet blood pressure criteria for severe preeclampsia r2
        • Manage a pregnant patient who presents with hypertension after 20 weeks of gestation whose prepregnancy or earlier blood pressures are unknown as if they have gestational hypertension or preeclampsia
        • Blood pressure technique c69
          • Must document at least 2 measurements of high blood pressure taken at least 4 hours apart r21
          • Patient must be sitting and should rest for 5 minutes before measurement; cuff must fit properly and be placed on bare upper arm r21
          • Blood pressure can be measured using auscultatory devices or automated methods r21
      • Urine protein measurement r5c70
        • Assess quantitatively by measuring urine protein after either a 12- or 24-hour urine collection or by using a spot measurement of protein to creatinine ratio c71c72
          • Urine protein dipstick test may be administered if other methods of measurement are not available (reading of 2+ meets diagnostic parameter of proteinuria) r2c73c74
      • Laboratory tests to evaluate for maternal end-organ dysfunction r5
        • CBC with peripheral smear c75c76
        • Comprehensive metabolic panel, including renal and liver function tests (include serum creatinine clearance and uric acid level) c77c78c79
      • Angiogenic biomarker testing
        • Commercial assays that measure soluble sFlt1 (fms-like tyrosine kinase 1) and PLGF (placental growth factor) can aid in making diagnosis and determining prognosis of preeclampsia r22r23
        • American College of Obstetricians and Gynecologists does not currently recommend measurement of angiogenic markers for diagnosis or exclusion of preeclampsia r2
        • National Institute for Health and Care Excellence suggests offering PLGF-based tests, along with clinical assessment, to help confirm or exclude suspected preeclampsia in patients between 20+0 and 36+6 weeks of gestation r24
        • International Society for the Study of Hypertension in Pregnancy practice guidelines state that angiogenic markers could be measured if available, but should not be used as a sole criterion for diagnosing preeclampsia r25
        • FDA has approved an sFlt1:PLGF ratio test for use in patients hospitalized with hypertension to predict risk of progression to preeclampsia with severe features within 2 weeks
    • Formal diagnosis of preeclampsia is made when the following criteria are met: r2
      • Hypertension (greater than 140 mm Hg systolic or 90 mm Hg diastolic) and 1 of the following: c80
        • Proteinuria (greater than 300 mg of protein in a 24-hour urine collection or spot protein to creatinine ratio of 0.3) r26c81c82c83
        • 1 or more of the following markers of maternal end-organ dysfunction:
          • Thrombocytopenia (platelet count under 100 × 10⁹ cells/L) c84
          • Impaired liver function (transaminases twice the upper reference limit) c85c86
          • New renal insufficiency (over 1.1 mg/dL or doubling of serum creatinine clearance) c87
          • Pulmonary edema c88
          • New-onset cerebral or visual disturbances c89c90c91c92
    • In a pregnant patient with chronic hypertension, do not diagnose preeclampsia with a rise in blood pressure alone. When there is underlying essential hypertension, diagnose preeclampsia by the presence of proteinuria or by documenting the presence of end-organ dysfunction
    • Formal diagnosis of eclampsia
      • Eclampsia is diagnosed if new-onset seizures occur in setting of hypertensive disorders of pregnancy c93
    • Assess fetal well-being with nonstress test and ultrasonographic evaluation to estimate fetal weight and amniotic fluid index; biophysical profile is indicated if nonstress test findings are nonreactive r27c94c95
      • In potentially unstable situations, fetal monitoring is always performed first using bedside ultrasonography c96
    • Determine whether patient is in labor and evaluate cervix with Bishop score r7c97

    Laboratory

    • Urine protein measurement c98
      • Preeclampsia proteinuria criterion met with 1 of the following: r2r26
        • Quantitative urine protein greater than 300 mg over a 24-hour period
          • Accuracy of a 12-hour urine collection is similar to that of 24-hour collection and can be substituted, as it is less burdensome r28
          • 12-Hour results are doubled
        • Spot urine protein to creatinine ratio of at least 0.3 c99
        • Protein urine dipstick reading of 2+ (only if quantitative measurement is not available) c100
      • Proteinuria is no longer required for the diagnosis of preeclampsia if there are other findings associated with end-organ involvement (thrombocytopenia, elevated liver transaminases, renal insufficiency, pulmonary edema, or new-onset neurologic symptoms) r26
    • Serum chemistry
      • Renal function panel c101
        • Serum creatinine measurement (greater than 1.1 mg/dL or doubling of serum creatinine levelr2) is a diagnostic parameter for maternal organ dysfunction r12c102
        • Uric acid level c103c104
          • Not required, but an increase is associated with renal failure and adverse maternal and perinatal outcomes r12
      • Liver function tests c105
        • ALT or AST level that is twice the upper reference limit is a diagnostic parameter for maternal organ dysfunction r2c106c107
        • Lactate dehydrogenase level c108c109
          • Not required, but elevated levels can be a marker of hemolysis r12
        • Bilirubin level c110c111c112
          • Not required, but increased levels may reflect hemolysis or liver dysfunction r12
        • Albumin level c113c114
          • Not required, but may be decreased in association with liver failure r12
    • CBC panel c115
      • Thrombocytopenia indicated by a platelet count of less than 100 × 10⁹ cells/L is a diagnostic parameter for maternal organ dysfunction r2
      • Hemoglobin level may be increased owing to intravascular volume depletion or decreased owing to microangiopathic process r12
        • Microangiopathic hemolytic anemia on review of peripheral blood smear showing RBC fragmentation is a finding in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)
    • Angiogenic biomarkers
      • PLGF
        • PLGF levels are decreased in females with preeclampsia and may be observed before the onset of clinical symptoms r22
        • National Institute for Health and Care Excellence guidance suggests use of any of 4 specific placental growth factor–based tests, along with standard clinical assessment, for patients with suspected preeclampsia between 20+0 and 36+6 weeks of gestation r24
          • Thresholds for diagnosing and ruling out preeclampsia vary according to the specific test used
        • May be of greater benefit for patients at greater risk for adverse maternal outcome such as people of African, Caribbean, or Asian descent
      • sFlt1
        • Circulating sFlt1 plays an important role in the pathogenesis of preeclampsia, and elevated levels are found in females with established preeclampsia; levels may rise before the onset of clinical symptoms r22
      • sFlt1:PLGF ratio
        • Can be used for pregnant females who have been hospitalized because of hypertensive disorders of pregnancy to assess risk of progression to preeclampsia with severe features within the coming 2 weeks r29
        • Among pregnant women with hypertension who were hospitalized between 23 and 35 weeks of gestation, serum sFlt1:placentalgrowth factor ratio of 40 or higher predicts development of severe preeclampsia, adverse outcomes, and delivery within 2 weeks of testing r30

    Imaging

    • Fetal ultrasonography r31c116
      • All patients diagnosed with preeclampsia should have fetal ultrasonography to assess for suboptimal fetal growth r32
      • Measurements of biparietal diameter, head circumference, abdominal circumference, and femur length are commonly used to identify intrauterine growth restriction that may be associated with preeclampsia r31
        • An abnormal (increased) ratio of head circumference to abdominal circumference is common
      • Other findings include decreased volume of amniotic fluid (index obtained by summing the largest cord-free vertical pocket in each of the 4 quadrants of an equally divided uterus) r31

    Functional testing

    • Pulse oximetry r12c117
      • Not required to make a diagnosis, but a measurement of oxygen saturation at the time of diagnostic investigation can indicate likelihood of complications developing owing to preeclampsia
      • Oxygen saturation less than 97% is associated with a risk of severe maternal complications (eg, pulmonary hypertension, peripartum cardiomyopathy, pulmonary embolism)

    Other diagnostic tools

    • Additional laboratory studies and imaging may be needed to determine disease severity and to identify associated components of multisystemic disease r5
      • If oxygen saturation (measured via pulse oximetry) is reduced, or if there are abnormal pulmonary or cardiac findings, order a chest radiograph and ECG and/or echocardiogram c118c119c120
      • MRI or CT scan of the brain is indicated if intracranial hemorrhage, cerebral thrombosis, or posterior reversible encephalopathy syndrome is suspected c121c122
        • Presence of focal neurologic deficits r7c123c124
        • Repeated seizures despite adequate magnesium levels r7c125c126
        • Presence of blindness r7c127c128
        • Onset of eclamptic seizures before 20 weeks of gestation or after 48 hours post partum r7c129c130
      • If abdominal pain is present and liver function test results are abnormal, order abdominal imaging (ultrasonography or CT) to evaluate for liver hematoma c131c132

    Differential Diagnosis

    Most common

    • Gestational hypertension r20c133
      • De novo development of high blood pressure after 20 weeks of gestation without proteinuria or other features of preeclampsia, which also resolves by 12 weeks post partum
      • Similar to preeclampsia in that elevated blood pressure develops in the second half of pregnancy
      • Differentiated from preeclampsia by absence of proteinuria and absence of end-organ dysfunction (ie, no renal or liver dysfunction, thrombocytopenia, pulmonary edema, or cerebral or visual abnormalities)
    • Prepregnancy-onset (chronic) hypertension r20c134d2
      • Elevations in blood pressure (greater than 140 mm Hg systolic and/or 90 mm Hg diastolic) that develop before pregnancy, or before the 20th week of gestation, or that persist beyond 12 weeks postpartum
      • Similar to preeclampsia by virtue of elevated blood pressures
      • Formally differentiated from preeclampsia by time course
        • Identify date of onset or document persistence of hypertension post partum
      • Note: preeclampsia can occur superimposed on chronic or preexisting hypertension
    • HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) c135c136d1
      • A combination of hemolysis, elevated liver enzymes, and thrombocytopenia that occurs in the third trimester of pregnancy or post partum
      • The relationship between preeclampsia and HELLP syndrome is debated; HELLP syndrome may represent a severe form of preeclampsia, and there is significant overlap in clinical and biochemical features
      • Similar to preeclampsia, HELLP syndrome symptoms can include headache, epigastric abdominal pain, and visual disturbances; however, neither hypertension nor proteinuria is required for a diagnosis of HELLP syndrome
      • HELLP syndrome is distinguished from preeclampsia by evidence of a microangiopathic hemolytic anemia (schistocytes) on peripheral blood smear
        • Additional criteria for HELLP syndrome include thrombocytopenia (platelet count of 100 × 10⁹ cells/L or higher), total bilirubin level of 1.2 mg/dL or higher, and serum AST and/or ALT level twice the upper reference limit
    • Systemic lupus erythematosus (exacerbation) r33c137d3
      • Type 3 hypersensitivity reaction in which the body produces autoantibodies, most commonly antinuclear autoantibodies; a high percentage of patients will experience lupus nephritis
      • Similar to preeclampsia, systemic lupus erythematosus with lupus nephritis presents with proteinuria
      • Unlike preeclampsia, systemic lupus erythematosus with lupus nephritis presents with a characteristic rash, joint pain, and fever; whereas blood pressure is often within reference range
      • Systemic lupus erythematosus is distinguished from preeclampsia by blood pressure measurements and laboratory testing for autoantibodies
    • Antiphospholipid antibody disease r34c138
      • Autoimmune condition complicated by multiple episodes of arterial and venous thromboses, which may lead to morbidity in pregnancy (ie, recurrent miscarriages, fetal deaths)
      • Antiphospholipid antibody disease can mimic preeclampsia by virtue of fetal intrauterine growth restriction, which may occur in both
      • Antiphospholipid antibody disease also serves as a risk factor for preeclampsia, or
      • Antiphospholipid antibody disease alone (without meeting criteria for preeclampsia) can cause premature delivery of a fetus owing to placental insufficiency
      • The following laboratory criteria for antiphospholipid antibody disease must be met to make a diagnosis:
        • Presence of antiphospholipid antibodies on 2 or more occasions at least 12 weeks apart and no more than 5 years before clinical manifestations with 1 or more of the following present: r35
          • Lupus anticoagulant
          • Medium- to high-titer (40 or more IgG phospholipid units or IgM antiphospholipid units, or over 99th percentile) anticardiolipin IgG or IgM
          • Anti-β2 glycoprotein-I IgG or IgM over 99th percentile
      • Negative test results for antiphospholipid antibodies exclude this disorder
    • Mirror syndrome r36c139
      • Rare condition characterized by maternal edema in conjunction with fetal hydrops
      • Similar to preeclampsia, mirror syndrome presents with hypertension and proteinuria
      • Mirror syndrome usually occurs during the first 2 trimesters of pregnancy and is identified by fetal ultrasonography r5
      • Distinguishing between preeclampsia and mirror syndrome in the presence of hypertension and proteinuria requires ruling out fetal hydrops or twin-to-twin transfusion syndrome

    Treatment

    Goals

    • Control maternal blood pressure to reduce risk of maternal hemorrhagic stroke r37
    • For eclampsia:
      • Prevent maternal injury and aspiration during seizures
      • Prevent further seizures
    • For preeclampsia
      • Prevent seizures
    • Deliver a mature newborn that does not require prolonged or intensive neonatal care

    Disposition

    Admission criteria

    All patients should be assessed in hospital initially; some may be managed as outpatients providing their condition is stable and the patient can reliably monitor their blood pressure and report problems r9

    Admit patients with severe manifestations (eg, severely elevated blood pressure, unstable neurologic findings) or those who are unable to be monitored adequately as outpatients r2

    Criteria for ICU admission
    • Delivery for patients with preeclampsia should take place in a hospital setting with access to a neonatal ICU

    Recommendations for specialist referral

    • Patients diagnosed with preeclampsia should have an integrative care plan managed by obstetricians and perinatologists
    • Refer to specialists in maternal fetal medicine, hypertension, anesthesiology, or critical care if blood pressure is resistant to first line pharmacotherapy r33r38
    • Refer to anesthesiologist to plan neuraxial analgesia or anesthesia during labor for patients undergoing cesarean delivery r1

    Treatment Options

    Management of preeclampsia depends on disease severity and gestational age r3

    • Preeclampsia without severe features r2
      • At less than 37 weeks of gestation (and no other indication for delivery), expectant management with fetal and maternal monitoring is generally recommended r2
        • Planned delivery from 34 weeks of gestation onward has been shown to significantly reduce risk of maternal morbidity and infants being born small for gestational age compared with expectant management r39r40
          • Balance against increased risk of short-term neonatal respiratory morbidity associated with late preterm planned delivery
      • At or beyond 37 weeks of gestation, planned delivery rather than observation is suggested r2
      • Threshold for initiating antihypertensive medication varies; the American College of Obstetricians and Gynecologists does not recommend treating blood pressure less than 160/110 mm Hg unless associated with comorbidities or end-organ damage r2r8
        • Canadian and British guidelines recommend treatment of blood pressure greater than 140/90 mm Hg r24r41
        • Treatment may reduce risk of developing severe hypertension but must be balanced against potential risk of adverse effects to fetus r42r43
      • Magnesium sulfate for universal prevention of eclampsia is not generally recommended for patients with blood pressure that is persistently lower than 160/110 mm Hg in the absence of maternal symptoms of severe disease r2
      • All commonly prescribed antihypertensives reduce the risk of severe hypertension pregnancy; however, labetalol may also reduce risk of proteinuria/preeclampsia r44
    • Preeclampsia with severe features r2
      • Initiate immediate antihypertensive therapy promptly for patients with persistent, severe hypertension (blood pressure of at least 160 mm Hg systolic or 110 mm Hg diastolic) r2
        • First line therapy for immediate urgent control of hypertension includes labetalol (IV), hydralazine (IV), and nifedipine (oral) r24
          • Second line therapy includes esmolol or nicardipine by infusion pump r5
          • Use sodium nitroprusside only in the short term and as a last resort because it can worsen maternal cerebral edema r5
          • Do not give immediate-release oral nifedipine sublingually (risk of hypotension)
        • For longer-term blood pressure control during expectant management, options include methyldopa (oral), labetalol (oral), and nifedipine (oral) r5
          • Second line therapy for long-term control of hypertension includes use of diuretics (thiazide diuretics) r5
      • Administer magnesium sulfate for seizure prophylaxis r2
      • Timing of delivery depends on gestational age and maternal and fetal condition
        • Initiate delivery after maternal stabilization for patients with severe preeclampsia at or beyond 34 weeks of gestation and for those with unstable maternal or fetal conditions irrespective of gestational age r2
        • If less than 34 weeks of gestation but stable maternal and fetal conditions: r2
          • Continue pregnancy at facility with maternal and neonatal intensive care resources
          • Administer corticosteroids for benefit of fetal lung maturity r2
      • Route of delivery is selected based on gestational age, fetal presentation, cervical status, obstetric history, and maternal and fetal condition
        • Vaginal delivery is preferred for patients with preeclampsia without severe features r2
        • Cesarean delivery is recommended for standard obstetric indications (eg, unfavorable cervix, oligohydramnios) and should be individualized r2
        • Spinal or epidural anesthesia is recommended if analgesia or anesthesia is required for delivery; risk of epidural hematoma is low for patients with platelet counts higher than 70 × 10⁹ cells/L r2
        • General anesthesia for delivery may increase risk of eclampsia in postpartum period r2
      • Therapy decisions related to preeclampsia are not based on amount of proteinuria r2
    • HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) r2
      • At 34 weeks or more of gestation, delivery is recommended shortly after maternal stabilization
      • From gestational age of fetal viability to 33 weeks of gestation, delay delivery (24-48 hours) only if fetal and maternal conditions remain stable for completion of course of corticosteroids to assist fetal lung maturation r2
        • Role of high-dose corticosteroids in reducing maternal mortality and morbidity is uncertain r2
          • May improve maternal platelet counts, but no overall evidence of benefit exists r45
      • Before gestational age of fetal viability, delivery is recommended shortly after maternal stabilization r2

    Therapy for eclampsia

    • For immediate management of seizures: r7
      • Position patient in lateral decubitus position to minimize aspiration of oral secretions and vomitus
      • Provide supplemental oxygen via face mask with or without reservoir at 8 to 10 L/minute to treat hypoxemia
    • Administer parenteral magnesium sulfate to treat eclampsia-related seizures and for seizure prophylaxis r37r46r47
    • Use antihypertensives to control blood pressure (same manner as for preeclampsia) r2
    • Proceed to prompt delivery after maternal stabilization irrespective of gestational age r2
      • A trial of vaginal labor is acceptable under selected circumstances r48
      • Decision on whether to proceed with cesarean delivery after maternal stabilization depends on gestational age of fetus, fetal condition, presence of labor, and cervical Bishop score r7

    Postpartum management

    • Administer parenteral magnesium sulfate for postpartum patients who present with new-onset hypertension and headaches or blurred vision or preeclampsia with severe hypertension
    • For patients with eclampsia, continue magnesium sulfate for at least 24 hours after delivery, or after the last seizure, or both

    Drug therapy

    • First line antihypertensive agents for severe hypertension r5c140
      • Most labor units have standard protocols in place for labetalol, hydralazine, or nitroprusside drip, if needed c141
      • Labetalol (immediate or emergent therapy for acute-onset hypertension) c142
        • Bolus dosing
          • Labetalol Hydrochloride Solution for injection; Adults: 10 to 20 mg IV, then 20 to 80 mg IV every 10 to 30 minutes until goal blood pressure is attained. Max cumulative dose: 300 mg.
        • Infusion dosing
          • Labetalol Hydrochloride Solution for injection; Adults: 0.5 to 2 mg/minute continuous IV infusion, initially. Titrate dose every 15 minutes until goal blood pressure is attained. Max: 10 mg/minute. Max cumulative dose: 300 mg.
      • Hydralazine (immediate or emergent therapy for acute-onset hypertension) c143
        • Hydralazine Hydrochloride Solution for injection; Adults: 5 mg IV, then 5 to 10 mg IV every 20 to 40 minutes until goal blood pressure is attained. Max cumulative dose: 20 mg.
      • Nifedipine c144
        • Immediate-release oral nifedipine may be considered as a first line therapy when IV access is not available. r2r49
          • Initiate fetal heart rate monitoring before first dose.
          • Nifedipine Oral capsule; Adults: 10 to 20 mg PO every 15 to 30 minutes, then 10 to 20 mg PO every 2 to 6 hours until blood pressure control is attained. Max: 180 mg/day.
        • Use with caution (if at all) if patient is concurrently receiving magnesium sulfate owing to risk of hypotension and neuromuscular blockade when combined r5
      • Sodium nitroprusside c145
        • Reserve for extreme emergencies (last resort), and use for the shortest time possible owing to risk of maternal/fetal cyanide toxicity and other possible adverse effects r6
        • Sodium Nitroprusside Solution for injection; Adults: 0.3 to 0.5 mcg/kg/minute continuous IV infusion, initially. Titrate by 0.5 mcg/kg/minute every 5 minutes until desired effect or blood pressure cannot be further reduced without compromising organ perfusion. Max: 10 mcg/kg/minute for 10 minutes.
    • Second line agents for severe hypertension
      • Esmolol c146
        • Esmolol Hydrochloride Solution for injection; Adults: 500 to 1,000 mcg/kg IV over 1 minute, then 50 mcg/kg/minute continuous IV infusion, initially. Repeat bolus and titrate by 50 mcg/kg/minute until goal blood pressure is attained. Max: 200 mcg/kg/minute.
      • Nicardipine c147
        • Nicardipine Hydrochloride Solution for injection; Adults: 5 mg/hour continuous IV infusion, initially. Titrate by 2.5 mg/hour every 5 to 15 minutes until goal blood pressure is attained. Max: 15 mg/hour. Reduce to 3 mg/hour after response achieved.
    • First line agents for long-term control of blood pressure
      • Labetalol c148
        • Avoid in asthma, heart disease, congestive heart failure, or if maternal heart rate is less than 60 beats per minute. r5
        • Labetalol Hydrochloride Oral tablet; Adults: 100 mg PO twice daily, initially. Titrate dosage by 100 to 200 mg twice daily every 2 to 3 days until goal blood pressure is attained. Usual dose: 200 to 400 mg twice daily. Max: 2,400 mg/day.
      • Nifedipine c149c150
        • Nifedipine Oral tablet, extended-release; Adults: 30 or 60 mg PO once daily, initially. May increase dose over 7 to 14 days if further control is needed. Usual dose range: 30 to 90 mg/day. Max: 120 mg/day.
      • Methyldopa r5c151
        • May be less effective in controlling higher blood pressures than other commonly used medications
        • Methyldopa Oral tablet; Adults: 250 mg PO 2 to 3 times daily, initially. May increase dose every 2 days if further control is needed. Usual dosage: 250 to 2,000 mg/day in 2 to 4 divided doses. Max: 3,000 mg/day.
    • Second line agent for long-term control of blood pressure
      • Thiazide diuretics r5c152
        • Use with caution owing to potential for intravascular volume depletion and hypokalemia
        • Hydrochlorothiazide Oral tablet; Adults: 25 mg PO once daily, initially. May increase dose to 50 mg/day in 1 to 2 divided doses.
    • Corticosteroids c153c154
      • Betamethasone c155
        • Antenatally, to induce fetal lung maturation in preparation for premature delivery
        • Betamethasone is the most well-studied and preferred corticosteroid for fetal lung maturation
          • Betamethasone Acetate, Betamethasone Sodium Phosphate Suspension for injection; Adults: 12 mg IM every 24 hours for 2 doses. Consider a repeat or rescue course when at risk of preterm delivery within the next 7 days and prior course administered more than 14 days previously. Rescue course could be provided as early as 7 days from the prior dose if indicated by clinical situation.
      • Dexamethasone c156c157
        • For HELLP syndrome:
          • Dexamethasone Solution for injection; Adults: 10 mg IV every 12 hours for 48 hours has been reported. r45
        • For preeclampsia:
          • Antenatally, to promote fetal pulmonary maturity when delivery is anticipated within the next 7 days and gestational age is less than 34 weeks r45
          • Acceptable alternative to betamethasone for fetal lung maturation
    • Anticonvulsant (for both treatment and prophylaxis) c158
      • Magnesium sulfate r50c159
        • Dosage schedule for severe preeclampsia is the same as for eclampsia r48
        • Continue magnesium sulfate for at least 24 hours after delivery, after the last seizure, or both r7
        • Has been associated with an increased risk of postpartum hemorrhage and uterine atony in observational studies; however, this has not been confirmed in randomized trials r51
        • Magnesium Sulfate Solution for injection; Adults: 4 to 6 g IV loading dose, followed by 1 to 2 g/hour continuous IV infusion for at least 24 hours. A 2 g IV bolus may be administered for recurrent seizures. Alternately, 4 to 5 g IV with simultaneous 10 g IM loading dose, followed by 1 to 2 g/hour continuous IV infusion or 4 to 5 g IM every 4 hours until seizures cease. Max: 30 to 40 g/day.
    • Low-dose aspirin prophylaxis for prevention of preeclampsia r52
      • Indicated for patients at high risk and should be initiated between 12 and 28 weeks of gestation (optimally before 16 weeks)
        • High-risk status includes any of the following: history of preeclampsia, multifetal gestation, chronic hypertension, type 1 or 2 diabetes, renal disease, or autoimmune disease (systemic lupus erythematosus, antiphospholipid syndrome)
      • Can be considered for patients at moderate risk if more than 1 of the following risk factors are present:
        • Nulliparity, BMI greater than 30, family history of preeclampsia (mother or sister), sociodemographic characteristics (African American race, low socioeconomic status), age 35 years or older, or personal history factors (eg, low birth weight or small for gestational age, previous adverse pregnancy outcome, more than 10-year pregnancy interval)
      • Aspirin
        • American Diabetes Association recommends dose of 100 to 150 mg/day; however, a dose of 162 mg/day (ie, 2 81-mg tablets, which is the low-dose aspirin available in the United States) may be acceptable r53
        • Aspirin Oral tablet; Adults: 81 mg PO once daily starting at 12 weeks gestation. Consider 162 mg PO once daily with pre-existing diabetes mellitus.

    Nondrug and supportive care

    Fluid management r1c160

    • Resuscitation r54
      • Restrict fluid to a maximum of 80 mL/hour when IV administration is initiated r1
      • Titrate to systolic blood pressure above 90 mm Hg r54
    • Maintenance r54
      • NPO status (60-80 mL/hour crystalloid) r54
    • Preloading r54
      • Fluid challenge before vasodilation or regional anesthesia: administer volume expanders (300 mL crystalloid) r54

    Bed rest is not indicated as a form of management r2r8

    Procedures
    Induction of labor r10c161
    General explanation
    • Procedure to stimulate uterine contractions before development of spontaneous labor; may be preceded by measures to facilitate cervical ripening r55
      • Oxytocin is the most common medication used to induce labor
      • Other methods to induce labor include prostaglandin E analogues, mechanical cervix dilation, membrane stripping, and amniotomy
    • Vaginal delivery is preferred to avoid added physiologic stressors r10
    Indication
    • Fetal indications in cases of preeclampsia include severe intrauterine growth restriction, nonreassuring fetal surveillance, and oligohydramnios r10
    • Maternal indications in cases of preeclampsia include deterioration of hepatic and/or renal function, suspected placental abruption, neurologic signs, severe epigastric pain, nausea or vomiting, gestational age of 38 weeks or greater, and eclampsia r10
    Contraindications
    • Maternal hemodynamic instability
    • General contraindications for induction of labor
      • Active genital HSV infection
      • Vasa previa or complete placenta previa
      • Transverse fetal lie
      • Umbilical cord prolapse
      • Previous classic cesarean delivery
      • Previous myomectomy
    Complications
    • Same as those associated with induction of labor for any cause
      • Uterine hyperstimulation
      • Uterine rupture
      • Fetal distress and fetal acidosis
      • Failed labor induction requiring cesarean delivery
      • Complications associated with prematurity
    Cesarean delivery c162
    General explanation
    • Fetus is delivered through abdominal wall (laparotomy) and uterine wall (hysterotomy) incisions r56
    Indication r57
    • Demonstrable fetal hypoxia or imminent fetal demise
    • Unequivocal cephalopelvic disproportion, soft-tissue obstruction, or fetal malpresentation not caused by gross fetal malformations incompatible with life
    Contraindications
    • No absolute contraindications and very few relative contraindications
      • Severe congenital abnormalities of the fetus predicting probable proximate fetal death
      • Compromise of maternal cardiovascular status (severe pulmonary disease)
    • Severe thrombocytopenia; platelet transfusions are required before procedure
    Complications
    • Same as those with cesarean delivery for any cause
      • Uterine lacerations
      • Bladder lacerations
      • Ureter injury
      • Bowel injury
      • Uterine atony
      • Hemorrhage
      • Postoperative infection

    Special populations

    • Patients with preeclampsia superimposed on chronic or prepartum hypertension
      • Preeclampsia can occur superimposed on chronic or preexisting hypertension that is often identified owing to worsening control of blood pressure
      • In these patients, superimposed preeclampsia is identified by de novo proteinuria and/or end-organ dysfunction in the second half of pregnancy
    • Patients with HELLP syndrome r2
      • If gestational age is before fetal viability, proceed to delivery shortly after maternal stabilization
      • At 34 weeks of gestation and beyond, proceed to delivery soon after maternal stabilization
      • From gestational age of fetal viability up until 34 weeks of gestation, delay delivery for 24 to 48 hours to complete a course of corticosteroids for fetal benefit, if possible
    • Postpartum preeclampsia r58
      • New-onset hypertension developing 48 hours to 6 weeks after delivery; usually within the first 7 to 10 days
      • Most patients present with headache or other neurologic symptoms; other symptoms include shortness of breath, chest pain, and peripheral edema
        • Consider neuroimaging to exclude other causes of postpartum headache such as stroke or posterior reversible cerebral encephalopathy, or subarachnoid hemorrhage
      • Less frequently detected based on routine home or in-office blood pressure monitoring
      • Treatment consists of antihypertensive agents and magnesium as for preeclampsia of antenatal onset; diuresis is indicated for volume overload if present
      • May be associated with a higher risk of maternal morbidity than preeclampsia with antepartum onset

    Monitoring

    • Closely monitor patients with preeclampsia without severe features for progression of disease r2
      • Measure blood pressure twice weekly c163
      • Measure platelet counts and serum creatinine and liver enzyme levels weekly r2c164
        • Reassessement for proteinuria is no longer considered necessary r2r26c165
      • Serially assess maternal symptoms and fetal movement daily c166c167c168c169c170
      • Use ultrasonography to assess fetal growth every 3 to 4 weeks r2c171c172
        • If fetal growth restriction is found, fetoplacental assessment by umbilical artery Doppler velocimetry is recommended c173
      • Use ultrasonography to assess amniotic fluid volume at least once weekly r2c174c175
      • Obtain weekly amniotic fluid measurement r37c176
      • Invasive hemodynamic monitoring is not routinely necessary c177
    • Postpartum monitoring of patients with preeclampsia or superimposed preeclampsia r2
      • Monitor blood pressure in the hospital for at least 72 hours post partum and again 7 to 10 days after delivery c178
      • Monitor for symptoms of headache or blurred vision and treat with IV magnesium sulfate; continue for at least 24 hours or until symptoms resolve and blood pressure normalizes r37c179c180c181
    • Monitoring for patients with eclampsia r37
      • Monitor for magnesium toxicity r48c182
        • Assess deep tendon reflexes periodically c183
        • Measure serum magnesium level at 4 to 6 hours and adjust infusion to maintain levels between 4 and 7 mEq/L (4.8-8.4 mg/dL) c184
        • Measure serum magnesium levels if serum creatinine level is equal to or greater than 1 mg/mL c185
      • Excessive magnesium can lead to respiratory and cardiac depression c186
    • Later-life monitoring of patients with prior preeclampsia
      • For patients with history of preeclampsia who gave birth before term (less than 37 weeks of gestation) or who had recurrent preeclampsia, assess cardiovascular status yearly owing to elevated risk for cardiovascular disease in later life r1c187
      • Screen for and control cardiovascular risk factors such as obesity, hypertension, and dyslipidemia r59

    Complications and Prognosis

    Complications

    • Maternal complications of preeclampsia
      • Neurologic complications r1
        • Stroke (ischemic cerebral edema) c188
        • Cortical blindness (often a result of ocular edema) c189
        • Retinal detachment c190
        • Posterior reversible encephalopathy c191
      • Hepatic complications include liver dysfunction, hematoma, and hepatic rupture r1c192c193c194
    • Obstetric and fetal complications of preeclampsia r1
      • Abruptio placentae c195
      • Preterm birth c196
      • Intrauterine growth restriction c197
      • Stillbirth and neonatal death c198c199
      • Possible late adverse effects on neurodevelopmental outcomes r60
    • Eclampsia and severe preeclampsia are associated with additional maternal complications r61
      • Disseminated intravascular coagulation syndrome c200
      • Need for mechanical ventilation c201
      • Acute renal failure c202
      • Acute respiratory distress syndrome c203
      • Puerperal cerebrovascular disorder c204
      • Pulmonary edema c205
      • Increased risk of mortality c206

    Prognosis

    • Outcomes depend on disease severity, coexisting medical conditions, and gestational age at which condition develops
      • Maternal and perinatal outcomes are favorable for patients with mild preeclampsia who develop disease after 33 weeks of gestation
      • Maternal and perinatal morbidity and mortality rates are higher among patients who develop preeclampsia before 33 weeks of gestation, patients with preexisting medical conditions, and patients in developing countries
    • Preeclampsia and eclampsia account for approximately 50,000 maternal deaths worldwide each year r62
      • Eclampsia is associated with an increased risk of maternal death in developed countries (0%-1.8%) and a mortality rate as high as 15% in developing countries
    • There is evidence that preeclampsia is associated with long-term increased risk of cerebrovascular and cardiovascular disease r63r64r65

    Screening and Prevention

    Screening

    At-risk populations r66

    • Patients with previous pregnancies complicated by preeclampsia, and especially those who had adverse outcomes
    • Patients with:
      • Type 1 or type 2 diabetes
      • Chronic hypertension
      • Chronic kidney disease
      • Multifetal gestation
      • Autoimmune disease

    Screening tests

    • Screen all pregnant patients with routine measurement of blood pressure and obtain medical history to identify relevant risk factors r2r67c207c208
    • Screening tests to predict development of preeclampsia, including use of biomarkers and Doppler ultrasonographic characteristics, are not currently recommended outside of investigational settings in the United States r2r27r68
    • In the first trimester, the Fetal Medicine Foundation prediction model, which consists of a combination of maternal risk factors, blood pressure, uterine artery pulsatility index on Doppler, and serum placental growth factor is more accurate at predicting preterm preeclampsia than screening based on maternal risk factors alone, with a 10% false-positive rate r69
      • May be used to identify patients who may benefit from treatment with low-dose aspirin to prevent preeclampsia developing before 37 weeks of gestation; the International Society for the Study of Hypertension in Pregnancy supports this approach, although cost-effectiveness is unclear r9c209c210c211

    Prevention

    • Low-dose aspirin c212
      • Low-dose aspirin significantly reduces the incidence of preterm preeclampsia when daily doses of 100 mg or more are initiated before 16 weeks of gestation r70r71r72r73
        • Aspirin doses of less than 100 mg are not effective in reducing risk of preeclampsia
      • US Preventive Services Task Force and American College of Obstetricians and Gynecologists recommend the use of low-dose aspirin (81 mg/day) for prevention of preeclampsia in patients at high risk r2r52r66r74
        • The World Health Organization makes similar recommendations r74
        • American Diabetes Association recommends dose of 100 to 150 mg/day; however, a dose of 162 mg/day (ie, 2 81-mg tablets, which is the low-dose aspirin available in the United States) may be acceptable r75
        • Begin between 12 weeks and 28 weeks of gestation (ideally before 16 weeks) r52
        • The optimal duration of aspirin use for preventing preeclampsia is unclear, and aspirin use up to the time of delivery may be associated with increased risk of peripartum bleeding r76
          • American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine recommend continuing aspirin until delivery r52
          • Other guidelines recommend to discontinue aspirin at term and before onset of labor r77
      • The following pregnant patients are at high risk for preeclampsia and should be offered low-dose aspirin: r2
        • Those with history of preeclampsia in prior pregnancies, and especially those who had adverse outcomes (eg, delivery at an early gestational age)
        • Those with:
          • Multifetal gestation
          • Chronic kidney disease
          • Diabetes mellitus
          • Autoimmune disease
          • Chronic hypertension
        • Those with a combination (more than one) of the following moderate risk factors r52
          • Obesity
          • Nulliparity
          • Age 35 years or older
          • History of earlier adverse pregnancy outcomes, low birth weight, or long interval between pregnancies (more than 10 years)
          • Adverse socioeconomic circumstances
          • Family history of preeclampsia (mother or sister)
          • In vitro fertilization
          • Black race (as a proxy for underlying racism)
          • Lower income
      • May also consider use of low-dose aspirin for patients with 1 or more of the following factors that are associated with increased risk due to environmental, social, structural, and historical inequities affecting access to health care r52
        • Black race (as a proxy for underlying racism)
        • Lower income
    • Lifestyle interventions c213
      • Physical activity r59
        • All patients without contraindications should be physically active during pregnancy
        • Exercise may reduce risk of preeclampsia by 40%
      • Calcium supplementation if dietary calcium intake is inadequate
        • International Society for the Study of Hypertension in Pregnancy recommends supplemental calcium (1.2-2.5 g/day) for pregnant patients at increased risk for preeclampsia if their intake is low r9
        • Patients should aim to achieve the recommended daily allowance of calcium (1000 mg daily) through diet or calcium supplementation r78
    • Treatment of nonsevere hypertension in pregnancy
      • Optimal blood pressure goals vary among the professional organizations
      • Antihypertensive therapy treatment is known to prevent development of severe hypertension; however, until recently, it had not been shown to reduce rates of preeclampsia r43r59
      • More recent studies suggest tight blood pressure control during pregnancy is associated with a reduced risk of preeclampsia; in addition, it may permit prolongation of pregnancy and avoidance of premature delivery and its complications r59
    • Strategies that have been investigated but are not currently recommended by the American College of Obstetricians and Gynecologists include: r2
      • Vitamin C or vitamin E supplementation c214c215
      • Dietary salt restriction c216
      • Bed rest, restriction of physical activity, or both c217c218
      • Calcium supplementation (unless dietary calcium intake is inadequate) c219
      • Treatment with metformin r79c220
      • Treatment with pravastatin r80
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