Preeclampsia and Eclampsia

Summary

Preeclampsia is a placental disorder (new-onset HTN ≥ 140/90 mm Hg at ≥ 20 weeks with proteinuria or end-organ dysfunction; 3–8% of births). Eclampsia is seizures in preeclampsia; HELLP syndrome is its hemolytic–hepatic variant. Risk factors include previous preeclampsia, chronic hypertension, diabetes, kidney/autoimmune disease, multifetal gestation, and nulliparity. Diagnosis requires repeated BP readings, urine protein/creatinine ratio, platelets, creatinine, and transaminases to stratify severity. Delivery is the only cure: at 37 weeks without severe features, at 34 weeks with severe features, or earlier if eclampsia/HELLP develops.
Magnesium sulfate prevents and treats seizures. Severe-range BP (≥ 160/110 mm Hg) is lowered within 30–60 minutes because intracerebral hemorrhage is the leading cause of maternal death. Low-dose aspirin from 12 weeks reduces risk in high-risk women. Critical: HELLP and eclampsia can occur with minimal hypertension and up to 6 weeks postpartum.

Overview

Definition

• Preeclampsia: new BP ≥ 140/90 mm Hg on 2 readings ≥ 4 hours apart at ≥ 20 weeks (or postpartum) in a previously normotensive woman, plus proteinuria and/or end-organ dysfunction.
• Eclampsia: new generalized tonic-clonic seizures in a woman with preeclampsia, with no other neurologic or metabolic cause.
• HELLP syndrome: hemolysis, elevated liver enzymes and low platelets; usually regarded as a severe variant of preeclampsia.
• Preeclampsia before 20 weeks → suspect a hydatidiform mole.

Epidemiology

• Preeclampsia: about 3–8% of births worldwide; hypertensive disorders as a group complicate about 1 in 7 US delivery hospitalizations.
• Outcome: a leading cause of maternal and perinatal death, mainly through stroke, eclampsia, HELLP, abruption and preterm birth.

Pathophysiology

Preeclampsia starts in the first trimester as a placental disease, long before the BP rises. Normally, cytotrophoblasts invade the spiral arteries and turn them into wide, low-resistance vessels. In preeclampsia this invasion is shallow, the arteries stay narrow and high-resistance, and the placenta becomes chronically ischemic.

• Placental ischemia → release of antiangiogenic factors that bind and lower the proangiogenic VEGF and placental growth factor.
• Maternal endothelial dysfunction → vasospasm (hypertension), leaky capillaries (proteinuria, edema, contracted plasma volume with hemoconcentration) and hypoperfusion of the kidneys, liver, brain and platelets.
• Kidney: afferent arteriole vasospasm → ↓ GFR and creatinine clearance, oliguria, ↑ creatinine and uric acid.
• Brain: failed cerebral autoregulation → vasogenic edema (PRES) and seizures (eclampsia).
• Liver and blood (HELLP): platelets stick to injured endothelium → platelet–fibrin microthrombi → microangiopathic hemolysis, hepatic ischemia and necrosis, thrombocytopenia.
• Fetus: low uteroplacental flow → asymmetric growth restriction and oligohydramnios (blood is shunted away from the fetal kidneys).

Risk Factors

Anything that impairs placentation or maternal vascular health raises the risk. The same lists decide who receives aspirin (see Management & Prevention).

• Nulliparity is a risk factor; multiparity is not.
• Excess trophoblast (multifetal gestation, hydatidiform mole) raises the risk; a mole gives disease before 20 weeks.
• Maternal age: ≥ 35 years is a moderate factor (teenage pregnancy is also often listed); women aged 20–35 are at lowest risk.
• The preeclampsia prevention and risk-factor table summarizes the criteria on one page.

Clinical Features & Complications

Preeclampsia

• Hypertension is the first and essential sign; it is often silent and found at a routine visit.
• Without severe features: BP 140–159/90–109 mm Hg with proteinuria or mild organ involvement; often no symptoms.
• With severe features : severe-range BP or any new end-organ dysfunction (thresholds under Investigations).
• Signs: new edema of the face and hands, hyperreflexia and ankle clonus, crackles of pulmonary edema, oliguria.

HELLP syndrome

• Most common symptom: epigastric or right upper quadrant pain (stretching of the Glisson capsule), with nausea, vomiting and malaise; late 2nd/3rd trimester or soon after delivery.
• Laboratory triad: hemolysis (schistocytes, LDH > 600 IU/L, low haptoglobin), AST/ALT ≥ 2× the upper limit of normal, platelets < 100,000/µL.
• Dangers: DIC, abruption and hepatic subcapsular hematoma, which causes severe RUQ pain radiating to the shoulder and shock if it ruptures.

Eclampsia

• Seizure: generalized tonic-clonic and brief, followed by a postictal phase of drowsiness or confusion; no focal deficit.
• Timing: before, during or after labor; a substantial share occur postpartum, and late cases appear up to 6 weeks after delivery.
• Warning signs usually precede it, but some women seize with mild or no hypertension or proteinuria.
• Imaging (only if atypical): posterior reversible encephalopathy, with parieto-occipital vasogenic edema.

On MRI, the edema of eclampsia sits in the posterior white matter and resolves after delivery.

Complications

Fetal growth falls away once maternal hypertension starts, so serial growth scans are part of monitoring.

Differential Diagnosis

• Hypertension:
  • Chronic hypertension: present before pregnancy or before 20 weeks; persists beyond 12 weeks postpartum.
  • Gestational hypertension: new BP ≥ 140/90 mm Hg at ≥ 20 weeks with no proteinuria and no organ dysfunction; up to half progress to preeclampsia.
  • Superimposed preeclampsia: chronic hypertension plus new or worse proteinuria, a sudden BP rise, or organ dysfunction.
  • Hydatidiform mole: preeclampsia before 20 weeks, uterus large for dates, very high β-hCG.
• Seizures:
  • Epilepsy, hypoglycemia, intracranial hemorrhage, meningitis, brain tumor, other metabolic disorders.
  • Oxytocin-induced hyponatremia: seizure after a long oxytocin infusion, with normal BP and very low sodium (oxytocin acts like ADH).
  • A seizure 2–3 days postpartum or with focal signs → image the brain to look for another cause.
• HELLP-like pictures:
  • Acute fatty liver of pregnancy: liver failure with hypoglycemia, prolonged PT and high ammonia.
  • Intrahepatic cholestasis: itching of palms and soles, high bile acids, no hemolysis or thrombocytopenia.
  • TTP/HUS: TTP with severe ADAMTS13 deficiency, often earlier in pregnancy and normotensive; HUS mostly postpartum with marked renal failure; little liver injury.
  • SLE flare (RBC casts), viral hepatitis, gallstone disease.

The classification of hypertensive disorders of pregnancy and the comparison of HELLP, cholestasis and acute fatty liver set the look-alikes side by side; the Hypertension in Pregnancy lesson covers the hypertensive categories in full.

Investigations

Every woman with new hypertension after 20 weeks is worked up for preeclampsia; the same tests grade its severity.

1. Step 1: Confirm hypertension: ≥ 140/90 mm Hg twice, ≥ 4 hours apart. A severe-range reading (≥ 160/110 mm Hg) is confirmed within minutes and treated without waiting 4 hours.
2. Step 2: Quantify proteinuria
   • Spot urine protein/creatinine ratio ≥ 0.3 mg/mg: best initial quantitative test and an accepted alternative to the 24-hour collection.
   • 24-hour urine protein ≥ 300 mg: traditional gold standard.
   • Dipstick ≥ 2+: counts only when quantitative testing is unavailable.
3. Step 3: Look for end-organ dysfunction (severe-feature criteria)
   • CBC: platelets < 100,000/µL; hemoglobin often ↑ from hemoconcentration unless hemolysis is present.
   • Renal: creatinine > 1.1 mg/dL or doubled; uric acid ↑; creatinine clearance ↓.
   • Liver: AST/ALT ≥ 2× the upper limit of normal.
   • Hemolysis screen (low platelets or RUQ pain): LDH, haptoglobin, bilirubin, peripheral smear.
   • Coagulation (PT, aPTT, fibrinogen): normal unless DIC complicates HELLP or abruption.
4. Step 4: Assess the fetus: ultrasound for growth, amniotic fluid and umbilical artery Doppler; nonstress test or biophysical profile; continuous CTG in labor.
5. Step 5: Image only when indicated: brain CT/MRI for atypical, focal or late postpartum seizures; liver CT/MRI (or FAST) for severe RUQ pain in HELLP.

The preeclampsia definition, severe features and management are summarized in one table.

Management

Delivery of the placenta is the definitive treatment, and its timing weighs maternal risk against prematurity. Magnesium and antihypertensives protect the mother but do not treat the placental disease.

1. Step 1: Stabilize the mother: ABCDE, left lateral position, oxygen; an eclamptic seizure follows the sequence below.
2. Step 2: Magnesium sulfate, first-line for eclampsia, HELLP and preeclampsia with severe features (not routine without severe features): 4–6 g IV over 20–30 min, then 1–2 g/h, continued for 24 hours after delivery or after the last seizure.
   • It raises the seizure threshold (central calcium antagonism) and is not an antihypertensive.
   • Monitor: patellar reflexes, respiratory rate and urine output; check serum levels when creatinine is raised or toxicity is suspected (therapeutic about 5–9 mg/dL, ie, 4–7 mEq/L).
   • Contraindicated in myasthenia gravis (risk of myasthenic crisis); another anticonvulsant is used.
3. Step 3: Treat severe-range BP (≥ 160/110 mm Hg) within 30–60 min with IV labetalol, IV hydralazine or oral immediate-release nifedipine; aim for about 130–150/80–100 mm Hg and avoid abrupt falls that cut placental flow.
   • Labetalol 20 mg IV, escalating every 10 min (avoid in asthma or bradycardia); hydralazine 5–10 mg IV; nifedipine 10–20 mg PO. Full drug details are in the Hypertension in Pregnancy lesson.
   • Nifedipine causes reflex tachycardia (not bradycardia), flushing, headache and ankle edema.
   • Diuretics are not used, except for pulmonary edema.
4. Step 4: Deliver at the right time
   • Without severe features: at 37 weeks (at diagnosis if later); before that, outpatient BP twice weekly, weekly labs and fetal testing.
   • With severe features: at ≥ 34 weeks after stabilization; before 34 weeks and stable, inpatient expectant management with antenatal corticosteroids.
   • At any gestational age, after stabilization: eclampsia, HELLP, uncontrollable severe BP, pulmonary edema, abruption, DIC, worsening renal function, nonreassuring fetal status or fetal death. If HELLP occurs before 34 weeks with mother and fetus stable, delivery may wait 48 hours for steroids.
   • Route: vaginal delivery (usually induction) is preferred; cesarean only for the usual obstetric indications. Neuraxial anesthesia is avoided when platelets are < 50,000/µL.
   • Third stage: oxytocin; ergometrine and methylergonovine are contraindicated (vasoconstriction, hypertensive crisis, stroke).
5. Step 5: Postpartum care: continue magnesium for 24 hours; labs and BP may worsen in the first 48 hours, and BP rises again around days 3–5, so recheck it within 3–10 days. Hypertension beyond 12 weeks is chronic hypertension. Counsel about recurrence and lifelong cardiovascular risk.

Eclamptic seizure

During and after the fit, the patient lies on her side in a protected bed with suction and oxygen ready.

Magnesium toxicity

• Sequence: loss of patellar reflexes (> 9 mg/dL) → respiratory depression (> 12 mg/dL) → cardiac arrest (> 30 mg/dL).
• Main risk factor: renal insufficiency or oliguria, because magnesium is excreted by the kidneys.
• Treatment: stop the infusion; give calcium gluconate 1 g IV (10 mL of 10%) slowly over about 3 min; support ventilation. The magnesium toxicity levels and treatment are tabulated.

Prevention

Prevention

• Low-dose aspirin 81 mg daily: start between 12 and 28 weeks (ideally before 16) and continue until delivery, for ≥ 1 high-risk or ≥ 2 moderate-risk factors (see Risk Factors). It is the only proven preventive drug.
• Calcium supplementation where dietary calcium intake is low.
• Preconception: optimize BP on pregnancy-safe drugs, weight and diabetes; measure BP and test for proteinuria at every antenatal visit.
• In later pregnancies, counsel about recurrence and restart aspirin.

Key Points for Exams – نقاط مهمة للامتحانات

• Definition: BP ≥ 140/90 mm Hg twice ≥ 4 h apart at ≥ 20 weeks plus proteinuria (protein/creatinine ≥ 0.3 or ≥ 300 mg/24 h) or end-organ dysfunction; hypertension is the first sign.
• Severe features: BP ≥ 160/110, platelets < 100,000/µL, transaminases ≥ 2× normal, creatinine > 1.1 mg/dL or doubled, pulmonary edema, new cerebral or visual symptoms. The amount of proteinuria is not one of them.
• Mechanism: failed spiral artery remodeling → placental ischemia → ↑ antiangiogenic, ↓ VEGF → maternal endothelial dysfunction.
• Labs: ↑ uric acid, ↑ creatinine, ↓ creatinine clearance, ↑ hemoglobin (hemoconcentration), ↓ platelets; PT/aPTT normal unless DIC.
• Risk: previous preeclampsia is the strongest factor; nulliparity (not multiparity) is the most common; disease before 20 weeks suggests a mole.
• HELLP: RUQ/epigastric pain is the most common symptom, and about 20% of patients are normotensive.
• Impending eclampsia: headache, epigastric pain, hyperreflexia, visual change; edema is not a warning sign.
• Leading cause of maternal death: intracerebral hemorrhage, so treat BP ≥ 160/110 within 30–60 min (labetalol, hydralazine, nifedipine); no diuretics.
• Magnesium: 4–6 g IV then 1–2 g/h until 24 h postpartum; the first sign of toxicity is loss of the patellar reflex; antidote calcium gluconate; renal failure raises toxicity risk; avoid in myasthenia gravis.
• Delivery: 37 weeks without severe features, 34 weeks with them, any gestational age for eclampsia, HELLP and other complications after stabilization; vaginal route preferred.
• Eclamptic seizure: airway and left lateral position first, then magnesium; oxytocin for the third stage, never ergometrine.
• Postpartum seizure with normal BP and very low sodium after prolonged oxytocin → water intoxication, not eclampsia.
• Fetal effects: growth restriction, oligohydramnios, abruption, preterm birth; not macrosomia, polyhydramnios or placenta previa.
• Prevention: aspirin 81 mg daily from 12–28 weeks (ideally before 16) for ≥ 1 high-risk or ≥ 2 moderate-risk factors.