EBM Consult

Preeclampsia and Eclampsia

    Definition

    Preeclampsia:  Usually 3 elements present, begins in the 3rd trimester (after 20 weeks of gestation), and continues up to 6 weeks post-partum:

    • Hypertension (BP ≥ 140/90 measured on 2 occasions separated by 4-6 hrs)
    • Proteinuria (≥ 0.3 g protein in 24 hr urine in patients without a UTI)
    • With or without edema

    Eclampsia:  Presence of new-onset grand mal seizures in woman with preeclampsia

    • 1/3 of seizures occur in postpartum period, most within 24 hrs and almost all within 48 hrs following delivery
    Pathophysiology

    The exact etiology is unknown, but a common feature in almost all cases include inadequate maternal blood flow to the placenta because of a failure of the spiral arteries to appropriately develop within the uteroplacental bed because the normal musculoelastic walls within the spiral arteries get replaced with fibrinous material which results in their dilation and development of vascular sinusoids.  This process  eventually results in:

    • Placental hypoperfusion
    • Increased risk for placental infarcts
    • Premature aging, villous edema, and development of syncytial epithelial knots of the placental villi
    • Retroplacental hemorrhages (15% of patients)
    • Insufficient trophoblastic influence on vasodilators, prostacyclin, prostaglandin E2, and nitric oxide that would normally counteract the renin-angiotensin system thus leading to increases in blood pressure
    • The production of thrombogenic substances (tissue factor and thromboxane) by the ischemic placenta that likely increase the risk for disseminated intravascular coagulation
    Risk Factors
    • Multifetal gestations

    • Personal or family history of preeclampsia

    • Chronic hypertension (HTN)

    • Advanced maternal age (≥ 35 yrs)

    • Pregestational diabetes

    • Vascular and connective tissue disease

    • Nephropathy

    • Antiphospholipid antibody syndrome

    • Obesity

    • African American, Hispanic, or Native American race

    • Possible genetic link (e.g. thrombophilias)

    Epidemiology
    • Approximately 3%-8% of pregnancies in Western countries

    • 3%-7% for nulliparas

    • 1%-3% for multiparas

    Prognosis
    • Preeclampsia and eclampsia responsible for 14% of maternal deaths per years worldwide
    Clinical Presentation

      Mild to moderate preeclampsia:

      • May be asymptomatic usually starting in the 24-25th week of gestation

        Severe preeclampsia:

          • Headache
          • Visual disturbances (blurred vision, scintillating scotomata (flickering light near or center of visual field)
          • Altered mental status
          • Dyspnea
          • Blindness (cortical or retinal)
          • Edema (sudden increase; facial; pulmonary edema)
          • Epigastric or right upper quadrant (RUQ) pain (due to hepatic subcapsular hemorrhage with significant stretch and/or rupture of the liver capsule)
          • Weakness or malaise (possible evidence of hemolytic anemia)
          Physical Exam Findings
          • Oliguria (urine output < 500ml in 24hrs or serum creatinine > 1.2 mg/dL)

          • Hyperreflexia or clonus (may indicate increased risk for seizures)

          • Retinal hemorrhages on fundoscopic exam (seen more in severe eclampsia)

          Lab Findings
          • Complete Blood Count: Platelets < 100,000/mm3; Decreased fibrinogen
          • Serum alanine aminotransferase & aspartate aminotransferase:  AST of > 70 U/L
          • Serum Creatinine
          • Uric acid (if elevated 33% positive predictive value)
          • 24 hr urine collection or urine dipstick analysis (in patients without an active UTI):  Urine dipstick >1+, Protein/creatinine > 0.3,
          • HELLP syndrome:  Hemolysis (serum lactate dehydrogenase (>600 U/L); indirect bilirubin (>1.2mg/dL); peripheral blood smears); Elevated liver enzymes (AST/ALT); Low platelets (usually < 100,000/mm3)
          Complications
          • Abruptio placentae

          • Preterm delivery

          • Maternal death

          • Fetal death

          • Intrauterine growth restriction

          • Oligohydramnios

          • Nonreassuring fetal heart tones

          • Fetal bradycardia

          • Renal failure

          • Recurrent preeclampsia

          • Temporary blindness (lasting hours up to a week)

          • Subcapsular hepatic hematoma

          • Hepatic hemorrhage

          • Hepatic rupture (rare)

          Differential Diagnosis
          • Chronic HTN or other causes of secondary HTN

          • Chronic renal failure or other causes of proteinuria

          • Primary seizure disorder

          • Thrombotic thrombocytopenic purpura

          • Idiopathic thrombocytopenic purpura

          • Hemolytic uremic syndrome

          • Abdominal pain:  Cholecystitis, Appendicitis, Acute fatty liver of pregnancy

          • Seizures 48-72 hrs postpartum:  Bleeding arteriovenous malformation, Ruptured aneurysm, Idiopathic seizure disorder

          Management

          Delivery is the only cure

          • Mild preeclampsia induced most often after 37 weeks gestation
          • Severe preeclampsia consider induction after 34 weeks gestation; must weigh severity of disease versus infant prematurity

          Continue fetal and maternal observation and evaluation (mild preeclampsia)

          • Weekly nonstress tests, biophysical profile (Bi-weekly if suspected intrauterine growth restriction or oligohydraminos)
          • Daily fetal movement assessment
          • Ultrasound for fetal growth and amniotic fluid assessment every 3 weeks

          Other Considerations:

          • Weekly lab work (more frequent in suspected worsening cases)
          • Pulmonary artery catheter (beneficial in severe renal or cardiac disease, refractory hypertension, oliguria, or pulmonary edema)
          • Ultrasound (assess fetal status and evaluate for growth restriction)
          • Cardiotocography (fetal non-stress test and monitoring)
          Drug Therapy

          Magnesium sulfate (recommended for severe preeclampsia and eclampsia)

          • Loading dose: 4-6 g in 100 ml fluid IV administered over 15-20 minutes (min)
          • Maintenance dose: 1 g-2 g/hr continuous IV infusion to maintain therapeutic levels of 4 to 6 mEq/L, then continue infusion for 24 hrs after delivery
          • Magnesium levels (if on infusion): goal to maintain therapeutic levels of 4 to 6 mEq/L
          • Monitoring Parameters:  Urine output hourly, deep tendon reflexes, change in respiratory rate or pulse ox (< 95%)
          • Reversal: consider use of calcium gluconate 1 g IV over 2 minutes

          Labetalol

          • 20 mg IV bolus followed by 40 mg if not effective within 10 min; then 80 mg Q10 min, max 220 mg

          Nifedipine

          • 10 mg PO Q15-30 min, max of 3 doses

          Hydralazine

          • 5-10 mg IV bolus Q15-20 min until desired response achieved, max 30 mg
          • Associated with worse maternal and perinatal outcomes than labetalol and nifedipine

          Sodium nitroprusside

          • Reserved for severe hypertensive emergencies when other BP meds have failed, administer just before delivery of fetus or postpartum

          Anticonvulsants:

          • Since most seizures in eclampsia are self-limiting, treatment should primarily be with Mg sulfate for prevention.   Can consider the below only if this is not working or if the seizure is not resolving as expected.  
          • Phenytoin:  Loading Dose: 10-15 mg/kg IV infused no greater than 50 mg/min; cannot be given IM due to erratic absorption.  Consider fosphenytoin, which can be given IV or IM.  Maintenance Dose: 100 mg IV Q6-8hrs
          • Diazepam:  IV or IM: 5-10 mg Q10-15 min (administer slowly over 2-5 mins), max 30 mg, may be repeated in 2-4 hrs

          Corticosteroids (fetal lung development in premature infants)

          • Betamethasone: 12 mg IM Q24 hrs x2 doses
          • Dexamethasone: 6 mg IM Q12 hrs x4 doses

          Note and caution: 

          • Aggressive volume resuscitation may lead to pulmonary edema especially if on magnesium infusions
          Prevention
          • Low dose aspirin and calcium supplementation (most studies show little to no benefit) 
          • Antioxidant therapy with 1,000 mg/day Vitamin C and 400 mg/day Vitamin E (shows some promise; needs further studies)
          When to Admit
          • Severe preeclampsia or eclampsia

          • Maternal distress:  Severe, unrelenting headache, visual disturbances, and RUQ pain or tenderness

          • Seizure activity

          • Ruptured membranes

          • Nonreassuring fetal status

          • Progressive labor

          • Suspected placental abruption

          • Unstable home or social environment

          When to Discharge
          • Normalizing liver function tests, platelets, and BP

          • Antihypertensive medications are effective

          Counseling Points
          • Bed rest if managed at home with stable environment

          • Stay close to hospital access

          • Reassessment and BP check should be performed no later than 1 weeks after delivery if on BP meds

          • Continue monitoring BP

          References
          • ACOG. Committee on Practice Bulletins-Obstetrics. Diagnosis and management of preeclampsia and eclampsia. Obstet Gynecol. 2001;98:159-67.

          Pathophysiology

          • Ahn H, Park J, Gilman-Sachs A, Kwak-Kim J. Immunologic characteristics of preeclampsia, a comprehensive review. Am J Reprod Immunol. 2011;65:377-394.
          • Cudihy D, Lee RV. The pathophysiology of pre-eclampsia: current clinical concepts. J Obstet Gynaecol. 2009;29:576-582

          Prognosis

          • WHO, 2004. Bethesda, MD. Global Burden of Disease for the Year 2001 by World Bank Region, for Use in Disease Control Priorities in Developing Countries, National Institutes of Health: WHO. Make every mother and child count. World Health Report, 2005, Geneva:World Health Organization, 2005. 2nd ed.

          Risk factors

          • Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am J Obstet Gynecol. Aug 22 2013;[Medline].

          Epidemiology

          • Uzan J, Carbonnel M, et al. Pre-eclampsia: Pathophysiology, diagnosis, and management. Vasc Health Risk Manag. 2011; 7: 467-474.

          Physical exam findings

          • Sibai BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol. May 2004;103(5 Pt 1):981-91.S

          Management and Treatment

          • Antenatal corticosteroid therapy for fetal maturation. Committee Opinion No. 475. American College of Obstetricians and Gynecologists. Obstet Gynecol 2011;117:422-4.

           

        Editors:  Anthony J. Busti, MD, PharmD, MSc, FNLA, FAHA

        Last Reviewed:  10/18/2021