Preeclampsia

Preeclampsia – High-Yield Study Guide for Medical Students

Definition

Preeclampsia is a pregnancy-specific, multi-system hypertensive disorder characterized by new-onset hypertension after 20 weeks of gestation with evidence of maternal organ dysfunction and/or uteroplacental dysfunction (e.g., fetal growth restriction), in a previously normotensive woman.⁷

Classic criteria include systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg on two occasions at least four hours apart after 20 weeks, plus one or more of the following: proteinuria, thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, or new-onset cerebral/visual symptoms.⁷

Epidemiology

Preeclampsia affects approximately 2–8% of pregnancies worldwide and remains a leading cause of maternal and perinatal morbidity and mortality, especially in low- and middle-income countries.⁷

• Global burden: Hypertensive disorders of pregnancy (HDP), including preeclampsia, account for a substantial proportion of maternal deaths, with a particularly high burden in sub-Saharan Africa.⁶
• High-risk groups: Nulliparity, advanced maternal age, multiple gestation, chronic hypertension, diabetes, chronic kidney disease, autoimmune disease, and prior history of preeclampsia are major risk factors.
• Superimposed preeclampsia: Occurs when new preeclampsia develops on top of pre-existing chronic hypertension; this subgroup has particularly high maternal and fetal risk.¹⁰

Pathophysiology

Preeclampsia is best understood as a two-stage disorder involving abnormal placentation and a subsequent systemic maternal response.⁷

• Abnormal placentation (stage 1):
  • During early pregnancy, invasion of extravillous trophoblasts into the maternal spiral arteries is shallow and incomplete.
  • Spiral arteries remain high-resistance, low-capacitance vessels instead of transforming into dilated, low-resistance channels.
  • This leads to placental hypoperfusion, relative ischemia, and oxidative stress.
• Antiangiogenic milieu and endothelial dysfunction (stage 2):
  • Ischemic placenta releases antiangiogenic factors (e.g., sFlt-1) and pro-inflammatory mediators into maternal circulation.
  • These antagonize pro-angiogenic factors such as VEGF and PlGF, causing systemic endothelial dysfunction, vasoconstriction, and increased vascular permeability.
  • The result is hypertension, capillary leak (edema), and multi-organ injury (renal, hepatic, cerebral, hematologic).
• Immunologic and genetic factors: Maternal immune maladaptation to paternal antigens, genetic predisposition, and metabolic factors (obesity, insulin resistance) further modulate risk and severity.⁷

Clinical Presentation

Preeclampsia typically presents after 20 weeks’ gestation and can develop antepartum, intrapartum, or postpartum. Severity ranges from mild, asymptomatic hypertension to fulminant disease with multi-organ failure.

Symptoms

• Often asymptomatic in mild disease; detected on routine antenatal blood pressure and urine screening.
• Headache: persistent, severe, often frontal or occipital; may be refractory to usual analgesics.
• Visual disturbances: scotomata, blurred vision, diplopia, or photopsia, reflecting cerebral/retinal involvement.
• Right upper quadrant / epigastric pain: due to hepatic capsular distension and hepatocellular injury.
• Dyspnea or orthopnea: suggests pulmonary edema.
• Oliguria: indicates renal hypoperfusion or acute kidney injury.
• Edema: generalized or sudden facial/hand swelling; nonspecific but often associated.

Signs

• Hypertension:
  • Systolic ≥140 mmHg or diastolic ≥90 mmHg on two readings at least 4 hours apart.
  • Severe: SBP ≥160 mmHg or DBP ≥110 mmHg, confirmed within minutes to allow urgent treatment.
• Proteinuria: classically ≥300 mg/24 h, protein/creatinine ratio ≥0.3, or dipstick ≥1+ if quantitative testing unavailable.
• Hyperreflexia and clonus: may precede seizures.
• Signs of volume overload: crackles, elevated JVP, oxygen desaturation suggesting pulmonary edema.
• Fetal findings: intrauterine growth restriction (IUGR), oligohydramnios, abnormal Doppler velocimetry, or nonreassuring fetal heart rate patterns.⁹

Diagnostic Criteria

Diagnosis is clinical and laboratory-based, after 20 weeks’ gestation, and requires new-onset hypertension plus proteinuria or end-organ dysfunction.⁷

Hypertension

• Systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg on at least two occasions, at least 4 hours apart, after 20 weeks in a previously normotensive woman.

Plus ANY of the following

• Proteinuria:
  • ≥300 mg in 24-hour urine collection, OR
  • Protein/creatinine ratio ≥0.3, OR
  • Dipstick ≥1+ if quantitative methods unavailable.
• Thrombocytopenia: platelet count <100,000/µL.
• Renal insufficiency: serum creatinine >1.1 mg/dL (97 µmol/L) or doubling of baseline in absence of other renal disease.
• Impaired liver function: elevated transaminases (AST/ALT) to ≥2× upper limit of normal, with or without severe RUQ/epigastric pain.
• Pulmonary edema.
• New-onset cerebral or visual disturbances: severe headache, scotomata, visual changes, altered mental status.
• Uteroplacental dysfunction: fetal growth restriction, abnormal Doppler, or stillbirth related to placental disease.⁹

Severe Features

“Preeclampsia with severe features” indicates higher risk and typically necessitates expedited delivery.

• Systolic BP ≥160 mmHg or diastolic BP ≥110 mmHg, on two occasions at least minutes apart.
• Thrombocytopenia (<100,000/µL).
• Progressive renal insufficiency.
• Elevated liver enzymes with severe RUQ/epigastric pain.
• Pulmonary edema.
• New-onset cerebral or visual symptoms.
• Evidence of severe fetal compromise (e.g., severe IUGR, abnormal Dopplers).

Laboratory Evaluation

• Complete blood count: assess hemoglobin/hematocrit, platelets (thrombocytopenia suggests severity; hemolysis suggests HELLP).
• Liver function tests: AST, ALT, bilirubin, LDH.
• Renal function: serum creatinine, BUN, electrolytes, uric acid.
• Urine protein assessment: 24-hour urine protein or protein/creatinine ratio.
• Coagulation profile: indicated if HELLP or DIC suspected.
• Fetal assessment: ultrasound for growth, amniotic fluid, Doppler studies; non-stress testing or biophysical profile.⁹

Classification

• Gestational hypertension: new-onset hypertension after 20 weeks without proteinuria or severe features.
• Preeclampsia without severe features: hypertension plus proteinuria and/or minimal end-organ findings.
• Preeclampsia with severe features: hypertension plus severe end-organ dysfunction as above.
• Eclampsia: new-onset, generalized tonic-clonic seizures in a woman with preeclampsia (or gestational hypertension) not attributable to other neurologic conditions.⁷
• Superimposed preeclampsia: new-onset proteinuria or sudden worsening of hypertension in a woman with chronic hypertension.¹⁰

Maternal and Fetal Complications

Preeclampsia is associated with substantial maternal and perinatal morbidity and mortality, particularly when severe features or HELLP syndrome develop.⁸

Maternal Complications

• Progression to eclampsia: seizures, status epilepticus, and risk of aspiration, hypoxia, and brain injury.
• HELLP syndrome: hemolysis, elevated liver enzymes, and low platelet count; associated with liver hematoma/rupture, DIC, and multi-organ failure.⁸
• Cerebral complications: stroke, intracerebral hemorrhage, posterior reversible encephalopathy syndrome (PRES), and postpartum headaches with neurologic red flags.⁴
• Renal injury: acute kidney injury, oliguria, and, rarely, cortical necrosis.
• Pulmonary edema: due to capillary leak, decreased oncotic pressure, and LV dysfunction.
• Placental abruption: painful vaginal bleeding, uterine tenderness, fetal distress or demise.
• Postpartum hypertension and readmissions: persistent or new-onset hypertension postpartum can drive urgent care and hospital utilization.³

Fetal/Neonatal Complications

• Fetal growth restriction: due to chronic placental insufficiency.⁹
• Preterm birth: iatrogenic (for maternal/fetal indications) or spontaneous.
• Perinatal mortality: stillbirth, neonatal death, especially in severe early-onset disease.
• Placental complications: abruption, infarction, and oligohydramnios.

Management Principles

The only definitive cure for preeclampsia is delivery of the placenta. Management aims to balance maternal risk from ongoing disease against risks of prematurity, with close maternal and fetal surveillance.⁷

General Approach

• Determine gestational age: key in deciding expectant vs. delivery management (cutoffs often <34, 34–37, ≥37 weeks).
• Assess severity: presence of severe features, maternal stability, and fetal status.
• Hospitalize: usually recommended for preeclampsia with severe features or early-onset disease for close monitoring.
• Multidisciplinary care: obstetrics, anesthesia, neonatology, critical care as needed, especially in resource-limited settings where HDP is a major contributor to maternal deaths.⁶

Blood Pressure Control

Goal is to prevent maternal cerebrovascular events while maintaining adequate uteroplacental perfusion.

• Indications for acute treatment: severe hypertension (SBP ≥160 mmHg or DBP ≥110 mmHg, persistent for ≥15 minutes).
• First-line agents (parenteral):
  • Labetalol (IV) – common initial agent, titratable, avoid in asthma or heart block.
  • Hydralazine (IV) – arterial vasodilator; watch for reflex tachycardia.
  • Nifedipine (oral immediate-release) – used where IV access or agents are limited; avoid sublingual route.
• Maintenance therapy: oral labetalol, nifedipine ER, or methyldopa are commonly used for ongoing BP control.

Seizure Prophylaxis and Treatment

• Magnesium sulfate is the drug of choice for both prophylaxis in preeclampsia with severe features and treatment of eclamptic seizures.
• It reduces the risk of eclampsia in women with preeclampsia with severe features and improves maternal outcomes.⁷
• Standard regimen (conceptually): loading dose followed by maintenance infusion, with monitoring of reflexes, respiratory rate, and urine output to avoid toxicity.

Timing of Delivery

Delivery is the definitive management and should be individualized based on severity and gestational age.

• ≥37 weeks: delivery is generally recommended for all women with preeclampsia.
• 34–36+6 weeks with severe features: delivery is usually recommended after maternal stabilization.
• <34 weeks with severe features:
  • Consider short-term expectant management in carefully selected stable patients at tertiary centers with intensive monitoring.
  • Administer antenatal corticosteroids for fetal lung maturity when preterm delivery is anticipated.
• Maternal or fetal decompensation: nonreassuring fetal status, uncontrolled severe hypertension, eclampsia, HELLP, pulmonary edema, or abruption warrant prompt delivery regardless of gestational age.

Intrapartum Management

• Mode of delivery: based on obstetric indications; vaginal birth is often possible with careful monitoring.
• Continuous maternal monitoring: BP, urine output, neurologic status, oxygen saturation.
• Continuous fetal monitoring: cardiotocography for signs of compromise.
• Anesthesia: early involvement of anesthesia; neuraxial techniques are preferred if platelet count and coagulation are adequate.

Postpartum Management

Hypertensive disorders and their complications may worsen or newly present postpartum, and careful follow-up is essential.³

• Continue magnesium sulfate infusion for 24 hours postpartum in women with preeclampsia with severe features or eclampsia.
• Monitor blood pressure frequently; many patients will have persistent or worsening hypertension in the first postpartum week.
• Oral antihypertensives: adjust and taper based on BP; agents compatible with breastfeeding (e.g., labetalol, nifedipine) are typically preferred.
• Postpartum headaches:
  • Consider differential beyond post-dural puncture headache, including preeclampsia/eclampsia, cerebral venous thrombosis, and intracranial hemorrhage.⁴
  • Red-flag features (focal deficits, altered mental status, thunderclap onset) warrant urgent evaluation.
• Long-term cardiovascular risk counseling: history of preeclampsia increases lifetime risk of chronic hypertension, ischemic heart disease, and stroke.⁷

Risk Stratification and Prevention

Early identification of high-risk women can guide preventive strategies and closer surveillance.

• Risk prediction models: Increasing use of machine-learning tools and combined clinical, biochemical, and biophysical markers to predict HDP and preeclampsia, especially in resource-rich settings.⁵
• Low-dose aspirin: In high-risk women (e.g., prior preeclampsia, multifetal gestation, chronic hypertension, diabetes, CKD, autoimmune disease), low-dose aspirin started in early pregnancy reduces the risk of preeclampsia and severe outcomes.⁷
• Optimization of chronic disease: Tight control of pre-existing hypertension, diabetes, and renal disease before conception and early in pregnancy.
• Close antenatal surveillance: more frequent BP checks, urine protein testing, and fetal surveillance in at-risk populations, particularly in regions with high maternal mortality from HDP.⁶

Key Clinical Pearls for Exams and Practice

• Preeclampsia definition: new-onset hypertension after 20 weeks with proteinuria or end-organ dysfunction in a previously normotensive woman.
• 20-week cutoff: onset before 20 weeks suggests alternative diagnoses (e.g., molar pregnancy, chronic hypertension with superimposed preeclampsia, renal disease).
• “Severe features” matter: presence of severe features dictates need for magnesium sulfate, acute BP control, and usually earlier delivery.
• Eclampsia management triad: airway/breathing/circulation stabilization, magnesium sulfate to control seizures, and timely delivery once the mother is stabilized.
• HELLP syndrome: variant of severe preeclampsia with higher maternal morbidity (hemolysis, elevated liver enzymes, low platelets); requires prompt delivery and intensive supportive care.⁸
• Postpartum risk: new or worsening hypertension and preeclampsia can occur postpartum; persistent headaches or neurologic symptoms should not be dismissed as benign.^{4, 3}
• Definitive cure is delivery: antihypertensives and magnesium control maternal complications, but placental delivery is the only curative step.
• Long-term implications: history of preeclampsia is a red flag for future cardiovascular disease; emphasize long-term follow-up and risk factor modification.⁷

Summary

Preeclampsia is a common, potentially life-threatening hypertensive disorder of pregnancy resulting from abnormal placentation and systemic endothelial dysfunction. Early recognition, accurate risk stratification, and appropriate timing of delivery are critical to reducing maternal and perinatal complications. For examinations, focus on diagnostic criteria, severe features, eclampsia management, and the implications of HELLP syndrome and postpartum disease; for clinical practice, emphasize multidisciplinary care, postpartum follow-up, and the broader cardiovascular risk profile of affected women.