Hypertensive Disorders of Pregnancy (HDP)

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1. Classifications and Definitions

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A. Gestational Hypertension

• New-onset BP ≥140/90 mmHg after 20 weeks' gestation in a previously normotensive woman
• No proteinuria and no end-organ damage
• Severe range: SBP ≥160 or DBP ≥110 mmHg (confirmed within minutes)
• Resolves by 12 weeks postpartum; if it persists, reclassified as chronic hypertension
• Occurs in 6-17% of nulliparous and 2-4% of parous patients

B. Preeclampsia

• Gestational hypertension (BP ≥140/90 mmHg after 20 weeks) PLUS:
  • Proteinuria: >300 mg/24h, protein:creatinine ratio ≥0.3, or dipstick 2+; OR
  • New-onset end-organ damage, any one of the following:
    • Thrombocytopenia: platelets <100 × 10⁹/L
    • Renal insufficiency: creatinine >1.1 mg/dL or doubling from baseline
    • Impaired liver function: transaminases ≥2× upper limit of normal
    • Pulmonary edema
    • New-onset headache unresponsive to analgesics
    • Visual disturbances

• Without severe features - BP 140-159/90-109 mmHg, no end-organ criteria above
• With severe features - any of the criteria listed in the table below
• Early-onset (<34 weeks) vs. Late-onset (≥34 weeks) - early-onset carries the highest morbidity

C. Eclampsia

• Preeclampsia PLUS new-onset generalized tonic-clonic, focal, or multifocal seizures not attributable to another condition (epilepsy, intracranial hemorrhage, drug use)
• Incidence in high-resource settings: 1 in 2,000-3,000 deliveries
• Often preceded by headache, visual disturbances, or epigastric pain

D. Chronic Hypertension

• Hypertension present before 20 weeks' gestation, or diagnosed before pregnancy, or failing to resolve by 12 weeks postpartum
• May be primary (essential) or secondary

E. Chronic Hypertension with Superimposed Preeclampsia

• New-onset proteinuria or new/worsening end-organ damage in a woman with known chronic hypertension
• Carries higher morbidity than either condition alone

F. White Coat Hypertension

• Elevated BP in clinical settings only (typically before 20 weeks)
• Requires ambulatory BP monitoring to confirm
• May progress to gestational hypertension

G. HELLP Syndrome

• A severe subtype/variant of preeclampsia characterized by:
  • Hemolysis (microangiopathic hemolytic anemia)
  • Elevated Liver enzymes
  • Low Platelet count
• Occurs in 10-20% of women with severe preeclampsia and 0.2-0.9% of all pregnancies
• Mortality rate: 7.4-34%
• 20% of cases occur before 28 weeks; 30% occur postpartum

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2. Etiology and Pathophysiology

Stage 1 - Abnormal Placentation (Silent Phase)

• In normal pregnancy, extravillous trophoblasts invade the spiral arteries, transforming them from narrow, high-resistance vessels into wide, low-resistance channels - maximizing uteroplacental perfusion
• In preeclampsia, this endovascular trophoblastic remodeling is deficient, resulting in:
  • Shallow trophoblast invasion
  • Persistence of high-resistance spiral arteries
  • Chronic uteroplacental ischemia and hypoxia
• Genetic, immunologic (inadequate maternal tolerance of paternal antigens), and inflammatory mechanisms contribute

Stage 2 - Systemic Endothelial Dysfunction (Clinical Phase)

• The ischemic placenta releases factors into maternal circulation:

• sFlt-1 (soluble fms-like tyrosine kinase 1) - a decoy receptor that sequesters VEGF and PlGF, causing widespread endothelial dysfunction
• Soluble endoglin (sEng) - antagonizes TGF-β signaling, further impairing endothelial function
• Decreased PlGF (placental growth factor) - an angiogenic factor

A ratio of sFlt-1/PlGF ≥40 is associated with increased risk of developing preeclampsia with severe features within 2 weeks of measurement.

• Increased systemic vascular resistance → hypertension
• Increased capillary permeability → proteinuria, edema
• Hemoconcentration (hallmark - NOT hypervolemia; volume expansion is hazardous)
• Increased afterload → cardiac compromise
• Platelet activation and consumption → thrombocytopenia
• Microangiopathic hemolysis → HELLP
• Cerebral dysautoregulation → seizure risk (eclampsia can occur at even modestly elevated BP)
• Hepatocellular ischemia → elevated liver enzymes, subcapsular hematoma

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3. Risk Factors

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4. Diagnostic Workup

Blood Pressure Measurement

• Use validated device; patient seated, arm at heart level, after 5 minutes rest
• Two readings ≥4 hours apart for non-severe range; can confirm within minutes for severe range (≥160/110)

Urinalysis and Proteinuria

• 24-hour urine protein: ≥300 mg diagnostic; quantification after initial diagnosis is not required to follow severity
• Spot protein:creatinine ratio: ≥0.3 is equivalent to 24h urine >300 mg
• Urine dipstick 2+ is acceptable if other methods unavailable

Laboratory Panel (Preeclampsia Workup)

Fetal Assessment

• Ultrasound - fetal growth (for IUGR), amniotic fluid index
• Non-stress test (NST) - fetal well-being
• Biophysical profile (BPP) - twice weekly in severe disease
• Umbilical artery Doppler - reversed end-diastolic flow = urgent delivery consideration

Neuroimaging (Eclampsia)

• CT head - urgently if intracranial hemorrhage suspected
• MRI - posterior reversible encephalopathy syndrome (PRES): classically shows T2/FLAIR hyperintensities in occipital and parietal regions

Angiogenic Biomarkers (Emerging)

• sFlt-1/PlGF ratio ≥40 predicts preeclampsia with severe features within 2 weeks; being integrated into clinical protocols in many centers

HELLP Diagnosis (Tennessee Classification by Sibai)

• Class 1: platelets ≤50,000/µL
• Class 2: platelets 50,000-100,000/µL
• Class 3: platelets 100,000-150,000/µL (partial HELLP)
• LDH >600 IU/L, AST ≥70 IU/L, platelets <100,000/µL

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5. Management and Action Plan

General Principles

1. Delivery is the only definitive cure - timing balances maternal safety vs. fetal maturity
2. Prevent seizures with magnesium sulfate
3. Control severe hypertension within 30-60 minutes of sustained severe-range values
4. Careful fluid management (hemoconcentration is the rule; over-hydration causes pulmonary edema)

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A. Preeclampsia WITHOUT Severe Features

• Inpatient or close outpatient monitoring
• BP checks twice weekly
• CBC, liver enzymes, creatinine weekly
• Daily fetal kick counts; NST twice weekly
• BPP as clinically indicated
• Restrict physical activity

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B. Preeclampsia WITH Severe Features

• ≥37 weeks: Deliver with magnesium sulfate prophylaxis
• 34-37 weeks: Consider antenatal corticosteroids for fetal lung maturity, then deliver
• <34 weeks: Admit to tertiary center with ICU/NICU resources; antenatal corticosteroids; expectant management unless indications for delivery arise

• Unrelenting symptoms (persistent severe headache, visual changes, epigastric pain)
• Laboratory deterioration (HELLP, worsening renal/liver function)
• Severe-range BP refractory to therapy
• Placental abruption
• Reversed end-diastolic flow on umbilical Doppler
• Non-reassuring fetal status

• BP, urine output, symptoms assessed every 8 hours
• Daily CBC, AST, creatinine (can space to every other day if stable)
• Daily NST, twice-weekly BPP with AFI
• Fetal growth assessment every 2 weeks

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C. Acute Severe Hypertension (BP ≥160/110 mmHg) - Urgent Treatment

Note: ACE inhibitors and ARBs are contraindicated in pregnancy (stillbirth, fetal renal anomalies, oligohydramnios).

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D. Chronic Hypertension in Pregnancy

• Labetalol (combined alpha/beta blocker) - most commonly used
• Extended-release Nifedipine (calcium channel blocker) - safe, no effect on uterine blood flow
• Methyldopa (centrally acting alpha-2 agonist) - the only agent with long-term infant safety data; limited by side effects (fatigue, orthostatic hypotension); iron supplementation interferes with absorption

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E. Magnesium Sulfate (Seizure Prophylaxis and Treatment)

• Loading dose: 4-6 g IV over 15-20 minutes
• Maintenance: 2 g/hour continuous infusion
• Continue for 24-48 hours postpartum

• Give MgSO₄ empirically even while evaluation is underway
• If seizures persist: additional 2 g loading dose
• Avoid respiratory depressants

• Loss of deep tendon reflexes (first sign; at ~7-10 mEq/L)
• Respiratory depression (at ~10-13 mEq/L)
• Cardiac arrest (at >15 mEq/L)
• MgSO₄ is renally cleared - women with renal impairment require close monitoring

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F. Postpartum Management

• Preeclampsia/eclampsia can present or worsen up to 6 weeks postpartum - most common in the first 48-72 hours after delivery
• Continue MgSO₄ for 24-48 hours after delivery
• Monitor BP closely; treat postpartum hypertension ≥150/100 mmHg
• Nifedipine, labetalol, and furosemide (if pulmonary edema) are compatible with breastfeeding
• Ambulatory BP monitoring and home BP checks recommended

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G. Prevention - Low-Dose Aspirin

• Chronic hypertension
• Prior preeclampsia
• Multifetal gestation
• Pregestational diabetes
• Renal disease
• Autoimmune conditions
• Prior preterm birth <34 weeks

• Nulliparity
• BMI >30
• Family history of preeclampsia
• Age ≥35 years
• Personal/socioeconomic factors

A 2025 Cochrane review (PMID 41330480) further confirms calcium supplementation (especially in low-calcium-intake populations) reduces hypertensive disorders.

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6. Complications

Maternal Complications

• Eclampsia - generalized tonic-clonic seizures; post-ictal state with hypoxia, hypercapnia, lactic acidemia
• Cerebrovascular accidents (ischemic or hemorrhagic stroke) - cerebral dysautoregulation allows hypertensive injury at modest BP elevations
• PRES (posterior reversible encephalopathy syndrome) - occipital/parietal cortical edema; usually reversible with BP control
• Cortical blindness

• HELLP syndrome (see below)
• Subcapsular hepatic hematoma - life-threatening; can rupture spontaneously
• Acute liver failure

• Acute kidney injury (renal failure in ~50% of HELLP cases)
• Glomerular endotheliosis (pathognomonic histologic lesion - endothelial cell swelling causing near-occlusion of capillary lumens)
• Cortical necrosis in severe cases

• Pulmonary edema - majority develop postpartum; worsened by aggressive fluid administration
• Cardiomyopathy (increased afterload, LV diastolic dysfunction)

• DIC
• Microangiopathic hemolytic anemia

• Placental abruption
• Retinal detachment or Purtscher-like retinopathy

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HELLP Syndrome - Detailed

• Occurs in 10-20% of severe preeclampsia; ~20% have no prior recognized preeclampsia
• Complications: renal failure, hepatic rupture, placental abruption, DIC, pulmonary edema, cerebrovascular events, permanent vision loss, fetal demise
• LDH:AST ratio in HELLP with preeclampsia is ~13:1 vs ~29:1 without preeclampsia (diagnostic aid)
• ADAMTS13 activity is reduced 30-60% in HELLP (but not <10% as in TTP)
• Management: Delivery is key; MgSO₄ seizure prophylaxis; antihypertensives; plasma exchange has no proven benefit; antenatal corticosteroids may accelerate recovery; screen for TTP/aHUS
• Usually resolves spontaneously after delivery

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Fetal/Neonatal Complications

• Intrauterine growth restriction (IUGR) - from placental insufficiency
• Preterm birth - from iatrogenic delivery for maternal/fetal indications
• Placental abruption - abrupt placental separation
• Intrauterine fetal demise (stillbirth)
• Neonatal respiratory distress syndrome - from prematurity
• Low Apgar scores, hypoxic-ischemic encephalopathy

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Long-Term Complications for the Mother

The American Heart Association recognizes a history of hypertension in pregnancy as an established cardiovascular risk factor. Relative risk for CVD diminishes post-menopause but absolute burden remains high.

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7. Additional Important Components

Postpartum Surveillance (Long-Term)

• Annual BP checks for all women with prior HDP
• Cardiovascular risk factor modification (lifestyle, statins if indicated)
• Renal function monitoring
• Referral to cardiology or internist if high-risk

Differential Diagnosis of Hypertension in Pregnancy

• Chronic essential hypertension unmasked
• Secondary hypertension: renal artery stenosis, pheochromocytoma, Cushing syndrome, primary hyperaldosteronism, coarctation of aorta
• TTP vs. aHUS vs. HELLP (all can present with thrombocytopenia + renal failure in pregnancy)
• Antiphospholipid syndrome

Key Drug Contraindications in Pregnancy

Anesthetic Considerations (for Delivery)

• Epidural/spinal anesthesia preferred over general anesthesia in preeclampsia - reduces BP response to intubation, avoids airway risks of edema
• Risk of spinal hematoma if platelets <70,000-100,000/µL (assess case-by-case)
• Aggressive fluid preloading with spinal should be avoided (risk of pulmonary edema)

ACOG vs. ESC/ESH Differences in Management

• US (ACOG): Target <140-150/90-100 mmHg for non-severe disease
• European (ESH/ESC): Target <140/90 mmHg
• Canadian guidelines: Target DBP <85 mmHg
• All agree on immediate treatment of BP ≥160/110 mmHg

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