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Preeclampsia

Definition & Epidemiology

• Affects 5–7% of all pregnancies globally
• A leading cause of maternal and perinatal morbidity/mortality worldwide
• In the absence of treatment, ~1 in 100 cases progresses to eclampsia (generalized tonic-clonic seizures)

Harrison's Principles of Internal Medicine 22E, p. 3942; Creasy & Resnik's Maternal-Fetal Medicine, pp. 1055–1140

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Diagnostic Criteria

Hypertension

• Systolic BP ≥140 mmHg OR diastolic BP ≥90 mmHg on two readings ≥4 hours apart
• An incremental rise of 30 mmHg systolic / 15 mmHg diastolic is no longer part of the diagnostic criteria (no increased adverse outcome risk in this group)

Proteinuria (any one of):

• ≥300 mg protein in 24-hour urine collection
• Protein:creatinine ratio ≥0.3
• Dipstick 2+ (only if quantitative methods unavailable — false positives/negatives common)

Without proteinuria, preeclampsia is diagnosed if hypertension co-exists with:

Creasy & Resnik's Maternal-Fetal Medicine, p. 1055

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Severe Features

• BP ≥160/110 mmHg on two occasions ≥4 hours apart (unless antihypertensives already initiated)
• New-onset cerebral or visual disturbances
• Pulmonary edema
• Persistent epigastric or RUQ pain unresponsive to medication
• Liver enzymes >2× normal
• Thrombocytopenia (platelets <100,000/μL)
• Progressive renal insufficiency (creatinine >1.1 mg/dL)

⚠️ ACOG recommends abandoning the term "mild" preeclampsia — even without severe features, significant morbidity and mortality risk remain.

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Pathophysiology

1. Abnormal Placentation & Uteroplacental Ischemia

• Defective trophoblastic invasion of spiral arteries → failure of normal vascular remodeling → high-resistance, low-flow uteroplacental circulation
• Placental ischemia is the primary driver

2. Angiogenic Imbalance

• Excess production of sFlt-1 (soluble fms-like tyrosine kinase 1) — an anti-angiogenic factor
• Decreased PlGF (placental growth factor) — a pro-angiogenic factor
• sFlt-1/PlGF ratio ≥40 is associated with increased risk of developing severe features within 2 weeks
• sFlt-1 acts by binding and neutralizing VEGF and PlGF → endothelial dysfunction

3. Endothelial Dysfunction & Systemic Inflammation

• Endothelial activation → increased vascular permeability, vasospasm
• Leukocyte activation (neutrophils, monocytes) and platelet activation
• Exaggerated maternal inflammatory response with pro-inflammatory cytokines

4. Oxidative Stress

• Reactive oxygen species (ROS) from NADPH oxidase, eNOS uncoupling, mitochondrial dysfunction
• Lipid peroxidation and large VWF multimer formation → prothrombotic state

5. Immunological Mechanisms

• Impaired HLA-G/HLA-C interactions between extravillous trophoblasts and maternal NK cells/macrophages → deficient spiral artery remodeling
• Early-onset preeclampsia (before 34 weeks): dominated by defective placentation
• Late-onset preeclampsia (≥34 weeks): normal initial remodeling, but placental demands exceed uterine perfusion capacity over time

Barash, Cullen & Stoelting's Clinical Anesthesia 9e, p. 3508; Creasy & Resnik's Maternal-Fetal Medicine, p. 1060; Harrison's 22E, p. 3942

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Organ-System Pathology

Neurological

• Loss of cerebral vascular autoregulation → focal hypoperfusion despite elevated MAP
• Posterior Reversible Encephalopathy Syndrome (PRES): vasogenic, parietooccipital edema — typically reversible
• Petechial hemorrhage after convulsions
• White matter lesions and cognitive dysfunction in long-term follow-up
• Symptoms: headache, blurred vision, scotomata, diplopia, hyperreflexia, cortical blindness, convulsions
• Cerebral hemorrhage is a leading cause of death

Liver

• Gross lesions visible in 60% of eclamptic women
• Periportal hemorrhage (early) → hepatic infarction (late, from intense vasospasm)
• HELLP syndrome: Hemolysis, Elevated Liver enzymes, Low Platelets — a severe subtype with high morbidity

Kidney

• Glomerular endotheliosis (pathognomonic lesion): enlarged endothelial cells occlude capillary lumens, reduced GFR
• Glomerular changes include decreased size, reduced capillary diameter, increased cytoplasmic endothelial-mesangial volume
• Results in proteinuria, oliguria, anuria, and rising creatinine

Cardiovascular

• Hypovolemia paradoxically (fluid shifts from intravascular to extravascular space)
• Mean plasma volume up to 30–40% below normal in severe disease
• Pulmonary edema in ~2% of severe cases (from fluid overload, cardiac failure, aspiration, or magnesium sulfate)
• Airway edema — important for anesthetic management (risk of difficult intubation)

Hematologic

• Thrombocytopenia (platelets 100–150 × 10⁹/L typically)
• Elevated fibrin degradation products; fibrinogen usually normal (unless abruption)
• PT/PTT prolongation indicates consumption of procoagulant factors

Metabolic

• Exaggerated insulin resistance → elevated triglycerides, LDL, fatty acids; reduced HDL
• These changes may predate clinical disease and resolve postpartum

Fetal

• Reduced placental intervillous blood flow → chronic fetal hypoxia
• IUGR, preterm birth, increased perinatal mortality — risks correlate with severity

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Risk Factors

Creasy & Resnik's Maternal-Fetal Medicine, pp. 1056–1058

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HELLP Syndrome

• Hemolysis (microangiopathic hemolytic anemia)
• Elevated liver enzymes (transaminases >2× normal)
• Low platelets (<100,000/μL)

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Eclampsia

• Preeclampsia + new-onset generalized tonic-clonic seizures with no other identified cause
• Occurs in ~1% of untreated preeclampsia cases
• Risk of seizures correlates poorly with BP level
• Managed with magnesium sulfate (first-line anticonvulsant and seizure prophylaxis)

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Management

Definitive Treatment

Delivery Timing by Severity

Antihypertensive Therapy

• Goal: prevent cerebral hemorrhage, myocardial ischemia, renal injury while maintaining uteroplacental flow
• ACOG: treat BP ≥160/110 mmHg within 30–60 minutes

• ACE inhibitors / ARBs are contraindicated (stillbirth, fetal anomalies)

Seizure Prophylaxis & Treatment

• Magnesium sulfate (MgSO₄) — standard of care for seizure prevention in severe preeclampsia and treatment of eclampsia
• Loading dose 4–6 g IV, then maintenance 1–2 g/hr

Expectant Management Components

• Frequent BP monitoring and lab surveillance
• Serial fetal surveillance (biophysical profile, umbilical artery Doppler)
• Limited physical activity
• Corticosteroids (betamethasone 12 mg IM × 2 doses) if delivery anticipated before 34 weeks

Aspirin Prophylaxis

• Low-dose aspirin 81 mg/day initiated between 12–16 weeks (by 28 weeks at the latest)
• Recommended for high-risk women
• Reduces preeclampsia incidence by ~50% in diabetic women; reduces IUGR by ~20%
• Endorsed by ACOG, SMFM, and ADA

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Long-Term Consequences

• Chronic hypertension
• Cardiovascular disease (2–4× increased risk)
• Chronic kidney disease
• Diabetes mellitus
• White matter lesions and cognitive dysfunction

Harrison's 22E, p. 3942; Barash, Cullen & Stoelting's Clinical Anesthesia 9e, pp. 3508–3512

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Summary Table: Preeclampsia vs Severe Features

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