What are the etiology and signs of pre-eclampsia and eclampsia in pregnant women, particularly those with a history of hypertension, obesity, or previous pregnancy complications?

Etiology and Signs of Pre-eclampsia/Eclampsia

Etiology

Pre-eclampsia results from abnormal placentation leading to placental hypoxia, which triggers release of anti-angiogenic factors (particularly sFlt-1 and soluble endoglin) into maternal circulation, causing widespread endothelial dysfunction and multi-organ involvement. 1, 2

Primary Pathophysiologic Mechanisms

• Defective placentation: Incomplete transformation of maternal spiral arteries occurs due to shallow cytotrophoblast invasion, resulting in high-resistance uteroplacental circulation and reduced placental perfusion 1, 2

• Angiogenic imbalance: The hypoxic placenta releases excessive soluble fms-like tyrosine kinase-1 (sFlt-1), which acts as a decoy receptor antagonizing vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), leading to deficiency of these pro-angiogenic factors 2, 3

• Systemic endothelial dysfunction: The angiogenic imbalance causes widespread endothelial dysfunction affecting kidneys (glomerular endotheliosis), liver (hepatic edema and hemorrhage), brain (cerebral edema), and vascular system 1, 2

• Autoimmune activation: Circulating AT1 receptor autoantibodies are present in >95% of women with pre-eclampsia, inducing vasoconstriction, hypertension, and increased coagulation 2

Risk Factors

• Obstetric factors: First pregnancy, multiple gestation, hydatidiform mole, history of pre-eclampsia in previous pregnancy (25% recurrence risk in women with chronic hypertension) 1

• Medical comorbidities: Pre-existing chronic hypertension, diabetes mellitus, chronic kidney disease, autoimmune disorders (particularly antiphospholipid syndrome), obesity (BMI >35 kg/m²) 1

• Demographic factors: Maternal age >40 years, pregnancy interval >10 years, family history of pre-eclampsia (relative risk 2.9) 1, 2

Signs and Symptoms

Diagnostic Criteria

Pre-eclampsia is defined as new-onset hypertension (BP ≥140/90 mmHg) developing after 20 weeks gestation accompanied by either proteinuria (≥0.3 g/24 hours) or evidence of maternal organ dysfunction. 1

Clinical Manifestations by Severity

Mild to Moderate Pre-eclampsia:

• Blood pressure 140-159/90-109 mmHg measured on two occasions at least 4 hours apart 1
• Proteinuria ≥0.3 g/24 hours or protein:creatinine ratio ≥30 mg/mmol 1
• Edema (present in up to 60% but no longer diagnostic criterion) 1

Severe Pre-eclampsia Features:

• Cardiovascular: Severe hypertension (BP ≥160/110 mmHg) 1

• Hepatic involvement: Right upper quadrant or epigastric pain due to liver capsule distension from edema and subcapsular hemorrhage; elevated liver transaminases (AST/ALT >2x upper limit of normal) 1, 4

• Neurological manifestations: Severe persistent headache unresponsive to analgesics; visual disturbances including scotomata, photophobia, or cortical blindness; hyperreflexia with sustained clonus (≥3 beats) 1, 4

• Renal dysfunction: Serum creatinine >1.1 mg/dL or doubling of baseline creatinine; oliguria (<500 mL/24 hours) 1, 3

• Hematologic abnormalities: Thrombocytopenia (platelet count <100,000/μL); microangiopathic hemolysis with elevated LDH 1

• Pulmonary edema: Dyspnea, oxygen desaturation, rales on auscultation 1

HELLP Syndrome

HELLP syndrome represents the severe end of the pre-eclampsia spectrum, characterized by hemolysis, elevated liver enzymes (AST/ALT >2x normal), and low platelets (<100,000/μL), requiring immediate treatment and delivery. 1

Eclampsia

Eclampsia is defined as new-onset generalized tonic-clonic seizures in a woman with pre-eclampsia that cannot be attributed to other causes, representing a life-threatening emergency. 1, 5

• Seizures can occur antepartum (53%), intrapartum (19%), or postpartum (28%) 5
• May occur without preceding severe features or warning symptoms in up to 20% of cases 4
• Associated findings include loss of consciousness, postictal confusion, aspiration risk 5
• Occipital lobe involvement may cause cortical blindness 1, 4

Fetal Manifestations

• Intrauterine growth restriction due to placental insufficiency 1
• Oligohydramnios from reduced placental perfusion 1
• Abnormal fetal heart rate patterns indicating fetal compromise 4
• Increased risk of preterm birth (pre-eclampsia accounts for 25% of infants with very low birth weight <1500 g) 1

Physical Examination Findings

• Sustained blood pressure elevation on repeated measurements 1
• Brisk deep tendon reflexes with clonus (≥3 beats at ankle) 1, 4
• Right upper quadrant tenderness on palpation 1
• Pulmonary rales if pulmonary edema present 4
• Altered mental status or visual field defects in severe cases 1, 4

Laboratory Abnormalities

• Proteinuria: spot urine protein:creatinine ratio ≥30 mg/mmol or 24-hour urine protein ≥300 mg 1
• Elevated serum creatinine >1.1 mg/dL 1
• Elevated liver transaminases (AST/ALT >2x normal) 1
• Thrombocytopenia (<100,000/μL) 1
• Elevated serum uric acid (though not diagnostic, correlates with worse outcomes) 1
• Elevated LDH indicating hemolysis 1
• Decreased haptoglobin if hemolysis present 3