12.2 Preeclampsia, Eclampsia & Gestational Hypertension

12.2 Preeclampsia, Eclampsia & Gestational Hypertension

Hypertensive disorders of pregnancy complicate 5–10% of all pregnancies worldwide and represent one of the lethal triad of maternal mortality (alongside hemorrhage and infection). Understanding the diagnostic boundaries, systemic pathophysiology, and emergency pharmacotherapy is essential for clinical practice and competitive examinations.

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1. Classification & Diagnostic Criteria

According to the National High Blood Pressure Education Program (NHBPEP) and American College of Obstetricians and Gynecologists (ACOG) guidelines, hypertensive disorders in pregnancy are classified into 5 distinct categories:

1. Gestational Hypertension

• New-onset blood pressure elevation (Systolic BP $\ge 140\text{ mmHg}$ and/or Diastolic BP $\ge 90\text{ mmHg}$) measured on two occasions at least 4 hours apart after 20 weeks of gestation in a previously normotensive woman.
• Absence of proteinuria or signs of end-organ dysfunction.
• Blood pressure returns to normal by 12 weeks postpartum.

2. Preeclampsia

• New-onset hypertension (SBP $\ge 140$ or DBP $\ge 90\text{ mmHg}$ after 20 weeks) PLUS:
  • Proteinuria: $\ge 300\text{ mg}$ in a 24-hour urine collection, or Protein-to-Creatinine Ratio (PCR) $\ge 0.3\text{ mg/mg}$, or urine dipstick $\ge 1+$ (if quantitative methods unavailable).
• Preeclampsia without Proteinuria: In the absence of proteinuria, preeclampsia is diagnosed if new-onset hypertension is accompanied by any of the following severe end-organ features:
  • Thrombocytopenia: Platelet count $< 100,000/\mu\text{L}$.
  • Renal Insufficiency: Serum creatinine $> 1.1\text{ mg/dL}$ or doubling of serum creatinine in the absence of other renal disease.
  • Impaired Liver Function: Elevated blood transaminases (AST/ALT) to twice the upper limit of normal, or severe persistent right upper quadrant/epigastric pain.
  • Pulmonary Edema.
  • Cerebral / Visual Symptoms: New-onset persistent headache, scotomata, photopsia, or altered mental status.

3. Severe Features of Preeclampsia

Presence of any one of the following criteria upgrades the diagnosis to Preeclampsia with Severe Features:

• SBP $\ge 160\text{ mmHg}$ or DBP $\ge 110\text{ mmHg}$ on two occasions at least 15 minutes apart.
• Platelets $< 100,000/\mu\text{L}$.
• Serum creatinine $> 1.1\text{ mg/dL}$.
• AST or ALT $> 2\times$ upper limit of normal, or severe epigastric/RUQ pain.
• Pulmonary edema.
• New-onset visual or neurological disturbances.

4. Eclampsia

• Development of new-onset generalized tonic-clonic seizures in a woman with preeclampsia that cannot be attributed to other neurological causes (e.g., epilepsy, intracranial hemorrhage, meningitis).

5. Chronic Hypertension & Superimposed Preeclampsia

• Chronic Hypertension: Hypertension present before pregnancy or diagnosed before 20 weeks of gestation, or persisting beyond 12 weeks postpartum.
• Superimposed Preeclampsia: Chronic hypertension with new-onset proteinuria or sudden escalation of BP or development of systemic severe features after 20 weeks.

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2. Pathophysiology & HELLP Syndrome

Two-Stage Model of Pathophysiology

1. Stage 1 (Placental Stage): Abnormal endovascular trophoblastic invasion of the maternal spiral arteries between 16 and 20 weeks of gestation. The spiral arteries fail to transform from narrow, high-resistance muscular vessels into wide, low-resistance non-muscular vascular channels. This results in placental hypoperfusion, ischemia, and hypoxia.
2. Stage 2 (Maternal Systemic Stage): The ischemic placenta releases anti-angiogenic factors into maternal circulation, primarily soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). These factors bind and neutralize vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), precipitating widespread maternal endothelial cell dysfunction, generalized vasospasm, capillary leakage, intravascular volume depletion, and microvascular thrombosis.

[Defective Trophoblastic Invasion] -> [Placental Hypoxia/Ischemia]
                                             |
                                             v
[Anti-Angiogenic Release: sFlt-1, sEng] -> [Systemic Endothelial Dysfunction]
                                             |
       +-------------------+-----------------+-------------------+
       |                   |                 |                   |
       v                   v                 v                   v
[Vasospasm & HTN]  [Capillary Leak]  [Microthrombosis]  [Organ Hypoperfusion]
       |                   |                 |                   |
 (SBP >= 140)         (Proteinuria/     (Thrombocytopenia,   (Headache, HELLP,
                       Edema)            Microangiopathy)     Renal Impairment)

HELLP Syndrome

A severe variant of preeclampsia characterized by:

• H (Hemolysis): Microangiopathic hemolytic anemia with fragmented RBCs (schistocytes) on peripheral blood smear, total bilirubin $\ge 1.2\text{ mg/dL}$, elevated serum Lactate Dehydrogenase (LDH $> 600\text{ U/L}$).
• EL (Elevated Liver Enzymes): AST and ALT $> 70\text{ U/L}$ (twice normal).
• LP (Low Platelets): Platelet count $< 100,000/\mu\text{L}$.

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3. Management of Eclampsia & Magnesium Sulfate Protocols

Magnesium Sulfate ($MgSO_4$) is the anticonvulsant drug of choice for the prevention of eclampsia in preeclampsia with severe features and for treating eclamptic seizures (superior to diazepam, phenytoin, or lytic cocktail in the MAGPIE trial).

Administration Protocols

Mandatory Clinical Monitoring Parameters BEFORE Each Maintenance Dose

$MgSO_4$ is excreted exclusively by the kidneys. To avoid life-threatening toxicity, the following three mandatory clinical criteria must be evaluated prior to administering each maintenance dose:

1. Patellar Reflex (Knee Jerk): Must be PRESENT. (Loss of deep tendon reflexes is the earliest clinical sign of toxicity, occurring at serum levels of 8–12 mEq/L).
2. Respiratory Rate: Must be $> 16\text{ breaths/minute}$. (Respiratory depression occurs at serum levels of 12–16 mEq/L).
3. Urine Output: Must be $> 30\text{ mL/hour}$ (or $> 100\text{ mL}$ over the preceding 4 hours).

MgSO4 Serum Toxicity Levels & Antidote

• Therapeutic Serum Level: 4.0–7.0 mEq/L (4.8–8.4 mg/dL).
• Loss of Patellar Reflex: 8.0–10.0 mEq/L.
• Respiratory Depression: 12.0 mEq/L.
• Cardiac Arrest / Asystole: $> 15.0\text{ mEq/L}$.
• Specific Antidote: Calcium Gluconate 10 mL of 10% solution IV administered slowly over 10 minutes.