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Summary Table

Category	Details
Risk Factors	High risk: prior preeclampsia, chronic hypertension, chronic kidney disease, diabetes mellitus, autoimmune disease (SLE, antiphospholipid syndrome), multiple gestation. Moderate risk: nulliparity, age >35, BMI >30, pregnancy interval >10 years, new partner, MAP >90 mmHg, family history of preeclampsia, assisted reproductive technology
Etiology	Defective trophoblast invasion of spiral arteries leading to placental ischemia, release of anti-angiogenic factors (sFlt-1), widespread endothelial dysfunction, and systemic vasoconstriction
Patient Presentation	Pregnant woman at ≥20 weeks gestation with new-onset hypertension (≥140/90 mmHg), headache, visual disturbances (blurred vision, scotomata), epigastric or RUQ pain, facial/hand edema, rapid weight gain, dyspnea
Classic Physical Exam	Elevated BP ≥140/90, facial and hand edema, hyperreflexia with clonus, RUQ tenderness, papilledema on fundoscopy
Key Diagnostic Results	Proteinuria (uPCR ≥30 mg/mmol or ≥300 mg/24h), thrombocytopenia (<100,000/uL), elevated AST/ALT (>2x normal), creatinine >1.1 mg/dL, LDH elevated with hemolysis, abnormal uterine artery Doppler (elevated PI, bilateral notching)
Management	Oral antihypertensive: nifedipine GITS (first-line), methyldopa, beta-blockers (metoprolol, bisoprolol). IV emergency: nicardipine (first-line IV), hydralazine, nitroglycerin. Seizure prophylaxis: magnesium sulfate. Definitive treatment: delivery. Prevention: low-dose aspirin 75-150 mg/day from 12-16 weeks in high-risk patients, calcium 1.5-2 g/day
Keywords	"New-onset hypertension after 20 weeks," "headache with visual changes," "epigastric pain," "proteinuria in pregnancy," "HELLP syndrome," "magnesium sulfate," "only cure is delivery"

1. Pathophysiology

Preeclampsia is fundamentally a two-stage disease that begins in the placenta and then manifests as a systemic maternal syndrome.

In the first stage, abnormal trophoblast invasion of the uterine spiral arteries occurs during early placentation. Normally, extravillous trophoblasts remodel these arteries into low-resistance, high-flow conduits to support the growing fetus. In preeclampsia, this remodeling fails, leaving the spiral arteries constricted and unable to deliver adequate blood flow. The result is placental ischemia, which is the central initiating event.

In the second stage, the ischemic placenta releases soluble anti-angiogenic factors, most notably soluble fms-like tyrosine kinase-1 (sFlt-1). sFlt-1 binds and neutralizes pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), creating a state of widespread endothelial dysfunction. This is why preeclampsia is not merely a kidney disease or a blood pressure disease; it is a condition of systemic endothelial injury.

The damaged endothelium shifts the balance of vasoactive mediators: production of vasoconstrictors (endothelin, thromboxane A2) increases, while production of vasodilators (nitric oxide, prostacyclin) decreases. This imbalance explains the hallmark finding of systemic vasoconstriction and hypertension. The endothelial injury also increases vascular permeability, which explains the edema (facial, pulmonary) and proteinuria.

The organ-level consequences follow logically from this mechanism. In the kidney, glomerular endotheliosis (swelling of glomerular endothelial cells) reduces filtration and causes protein leakage (proteinuria) and rising creatinine. In the liver, periportal fibrin deposition and hepatocellular necrosis produce elevated AST/ALT and the subcapsular pain felt in the epigastrium or RUQ. In the brain, vasospasm, endothelial disruption, and loss of cerebrovascular autoregulation lead to headache, scotomata, and seizures (eclampsia). If severe, this can progress to posterior reversible encephalopathy syndrome (PRES) or intracerebral hemorrhage. In the hematologic system, endothelial damage triggers platelet activation and consumption (thrombocytopenia) and mechanical shearing of red blood cells (microangiopathic hemolytic anemia), which together form the basis of HELLP syndrome.

The POGI 2025 guideline emphasizes that the immune system also plays a contributory role. The placenta acts as a trigger for a maternal immune response that worsens endothelial dysfunction. This immunological component explains why nulliparity, new partner pregnancies, and donor gamete pregnancies are risk factors, because immunologic desensitization to paternal antigens has not yet occurred.

Understanding this pathway is critical for exam questions because it directly explains why delivery of the placenta is the only definitive cure. All pharmacologic treatments are temporizing measures aimed at preventing maternal complications (seizures, organ damage) while waiting for the optimal time to deliver.

2. Classification and Clinical Manifestation

Classification	Onset	Key Features
Chronic Hypertension (Primary)	Pre-pregnancy or <20 weeks	Hypertension without identifiable cause, persists >6 months postpartum
Chronic Hypertension (Secondary)	Pre-pregnancy or <20 weeks	Hypertension with known cause (renal disease, endocrine disorder)
White Coat Hypertension	Any	BP ≥140/90 in-clinic but <135/85 on HBPM/ABPM
Masked Hypertension	Any	BP <135/85 in-clinic but ≥140/90 on HBPM/ABPM
Gestational Hypertension	≥20 weeks	New-onset hypertension without proteinuria or features of preeclampsia
Preeclampsia (New-Onset)	≥20 weeks	Gestational hypertension plus one or more: proteinuria, organ dysfunction, uteroplacental dysfunction
Superimposed Preeclampsia	≥20 weeks, on chronic HTN	Chronic hypertension with new proteinuria and/or new organ dysfunction

The clinical manifestations that define preeclampsia beyond hypertension include:

System	Manifestation	Threshold
Renal	Proteinuria	uPCR ≥30 mg/mmol (≥0.3 mg/g) or ≥300 mg/24h
Renal	Acute kidney injury	Creatinine ≥1 mg/dL (≥90 umol/L)
Hepatic	Liver injury	AST or ALT >40 IU/L, with or without RUQ/epigastric pain
Hematologic	Thrombocytopenia	Platelets <150,000/uL (severe: <100,000/uL)
Hematologic	Hemolysis	Fragmented RBCs, elevated LDH, low haptoglobin
Neurologic	Cerebral involvement	Severe persistent headache, scotomata, blurred vision, altered mental status, seizures (eclampsia), hyperreflexia with clonus
Pulmonary	Edema	Acute-onset dyspnea with crackles
Uteroplacental	Fetal compromise	IUGR, abnormal umbilical artery Doppler (absent/reversed end-diastolic flow), placental abruption, intrauterine fetal death

Severe features per ACOG/ISSHP/RCOG include: BP ≥160/110 on two occasions at least 4 hours apart, thrombocytopenia <100,000/uL, liver transaminases >2x upper limit of normal, creatinine >1.1 mg/dL (or doubling of baseline), pulmonary edema, new-onset neurologic symptoms, or HELLP syndrome.

An important exam pearl from the POGI guideline: the term "severe preeclampsia" is no longer recommended in clinical practice because all women with preeclampsia carry the risk of eclampsia. Instead, the guideline distinguishes between preeclampsia with and without severe features (kriteria pemberat).

3. Diagnostic Workup

Test	Purpose	Interpretation
Urine Protein-to-Creatinine Ratio (uPCR)	Best initial test for proteinuria (fast, accurate)	≥30 mg/mmol (≥0.3 mg/g) = significant proteinuria
24-hour urine protein	Confirmatory if uPCR is inconsistent	≥300 mg/24h = significant proteinuria
Urine dipstick	Screening only (low accuracy)	≥1+ requires confirmation with uPCR or 24h collection
CBC with smear	Evaluate for HELLP	Thrombocytopenia <100,000/uL, schistocytes on smear
AST, ALT	Liver involvement	>2x upper limit of normal
LDH, haptoglobin	Hemolysis markers	LDH elevated, haptoglobin decreased
Serum creatinine	Renal function	>1.1 mg/dL or doubling of baseline
Fibrinogen	Coagulopathy/DIC screen	Low fibrinogen suggests consumption
Uterine artery Doppler	Assess uteroplacental flow	PI ≥95th percentile, bilateral notching = abnormal
Umbilical artery Doppler	Fetal perfusion	Absent/reversed end-diastolic flow = severe compromise
sFlt-1/PlGF ratio	Angiogenic biomarker	Elevated ratio helps confirm preeclampsia, distinguishes from CKD exacerbation
EKG, echocardiography	If suspected cardiac involvement	Evaluate for peripartum cardiomyopathy or heart failure
CT/MRI brain	Neurologic emergency	To evaluate for PRES, intracerebral hemorrhage, or RCVS

The diagnostic approach to preeclampsia has evolved considerably. The POGI 2025 guideline emphasizes that proteinuria is no longer a mandatory criterion for diagnosis. A woman with new-onset hypertension after 20 weeks plus any evidence of organ dysfunction (thrombocytopenia, renal insufficiency, liver injury, pulmonary edema, or cerebral/visual symptoms) meets the criteria for preeclampsia, even without proteinuria. This is a critical concept for exam purposes: approximately 10% of women with preeclampsia, and up to 50% of women with eclampsia, will not have proteinuria. So a test question presenting a pregnant woman with headache, visual changes, and elevated liver enzymes but negative dipstick still points to preeclampsia.

That said, proteinuria evaluation remains important because it helps stratify severity and prognosis. The recommended method is the urine protein-to-creatinine ratio (uPCR) on a morning spot urine sample. The POGI guideline notes that uPCR ≥30 mg/mmol correlates well with the 24-hour collection threshold of ≥300 mg and is faster and more practical. The dipstick test (urine carik celup) has poor accuracy and should only be used as a preliminary screen in resource-limited settings; a result of ≥1+ must be confirmed.

The workup should include baseline labs for organ injury: CBC with platelet count, liver transaminases (AST/ALT), serum creatinine, LDH, and haptoglobin. These serve the dual purpose of confirming the diagnosis and detecting HELLP syndrome. When neurologic symptoms are present (severe headache unresponsive to analgesics, visual changes, altered mental status, or seizures), brain imaging with CT or MRI is indicated to evaluate for PRES, hemorrhage, or RCVS.

For fetal surveillance, the guideline recommends uterine artery Doppler (ideally at 11-14 weeks as part of first-trimester screening), serial ultrasound for estimated fetal weight, umbilical artery Doppler, middle cerebral artery PI (to detect brain-sparing), and the biophysical profile (BPP). The cerebroplacental ratio (CPR), defined as the ratio of MCA PI to umbilical artery PI, is a key integrative parameter: a CPR <1 indicates pathologic redistribution of blood flow to the brain and correlates with increased perinatal risk.

In women with pre-existing chronic hypertension, diabetes, or autoimmune disease, baseline proteinuria should be assessed before or at the first prenatal visit. This is essential because without a baseline, it becomes impossible to determine whether worsening proteinuria represents superimposed preeclampsia or progression of the underlying disease.

4. Management and Treatment

Setting	Intervention	Details
Prevention (high-risk)	Low-dose aspirin	75-150 mg/day, start at 12-16 weeks, continue to ~36 weeks
Prevention	Calcium supplementation	1.5-2 g/day if dietary intake <600 mg/day, from first antenatal visit
BP target (all pregnancy HTN)	Antihypertensive therapy	Target <140/90 mmHg; diastolic should not fall below 80 mmHg; BP <120/70 not recommended
First-line oral	Nifedipine GITS	20-60 mg/day
Alternative oral	Methyldopa	250-500 mg PO 2-3 times daily (max 2 g/day); caution: associated with postpartum depression
Alternative oral	Beta-blockers (metoprolol, bisoprolol)	Standard doses; avoid atenolol (linked to fetal growth restriction)
IV emergency (first-line)	Nicardipine	Start 5 mg/h IV, titrate 2.5 mg/h every 5-15 min, max 15 mg/h
IV emergency	Hydralazine	5 mg IV bolus every 20-40 min, max 30 mg
IV emergency	Nitroglycerin	5 ug/min IV, titrate 5 ug/min every 5 min, max 200 ug/min (preferred if pulmonary edema)
Seizure prophylaxis	Magnesium sulfate (MgSO4)	Loading dose 4-6 g IV over 15-20 min, then 1-2 g/h continuous infusion; monitor patellar reflexes, respiratory rate, and urine output
Fetal lung maturity	Betamethasone or dexamethasone	Given if delivery anticipated at <34 weeks
Definitive treatment	Delivery	Timing depends on severity (see below)
Postpartum diuresis	Furosemide	20 mg/day for 5 days; shown to reduce persistent postpartum hypertension by 60% at day 7
Contraindicated	ACE inhibitors, ARBs	Teratogenic (fetal renal dysgenesis, oligohydramnios, pulmonary hypoplasia); contraindicated throughout pregnancy

Prevention

In women identified as high risk (one high-risk factor or two or more moderate-risk factors), low-dose aspirin 75-150 mg/day should be initiated between 12 and 16 weeks of gestation and continued until approximately 36 weeks. The mechanism involves selective COX-1 inhibition, which restores the thromboxane-prostacyclin balance, and COX-2 acetylation, which triggers production of aspirin-triggered lipoxins (ATL-4) with anti-inflammatory and pro-resolution properties. Aspirin also indirectly enhances endothelial NO synthase (eNOS) activity, improving vasodilation. Meta-analysis data (Roberge et al., 2017) showed a 90% reduction in early-onset preeclampsia when aspirin was started before 16 weeks. Calcium supplementation at 1.5-2 g/day is recommended for women with dietary calcium intake <600 mg/day.

Blood pressure control

The POGI 2025 guideline (aligned with ESC 2024) recommends initiating antihypertensive therapy when BP exceeds 140/90 mmHg, with a treatment target of <140/90 mmHg and diastolic not below 80 mmHg. BP below 120/70 mmHg is not recommended because of insufficient safety data. The first-line oral agent is nifedipine GITS (a dihydropyridine calcium channel blocker). Methyldopa and beta-blockers (metoprolol, bisoprolol) are alternatives. Atenolol must be avoided because of its association with impaired uteroplacental circulation and fetal growth restriction. RAAS inhibitors (ACEi and ARBs) are absolutely contraindicated in pregnancy due to fetal and neonatal toxicity.

Hypertensive emergency is defined as BP >160/100 mmHg with signs of end-organ damage. The immediate goal is to reduce MAP by 15-25% within 30 minutes, targeting systolic 140-150 and diastolic 90-100 mmHg. The first-line IV agent per the POGI guideline is nicardipine (start 5 mg/h, titrate up to 15 mg/h). Hydralazine 5 mg IV boluses and oral nifedipine 10-20 mg (repeated in 30 min if needed, max 30 mg) are alternatives. When pulmonary edema is present, nitroglycerin IV is preferred.

Seizure prophylaxis

Magnesium sulfate is the drug of choice for preventing and treating eclamptic seizures. Its mechanism involves calcium antagonism and NMDA receptor blockade. The standard regimen (Zuspan protocol) is a loading dose of 4-6 g IV over 15-20 minutes, followed by a maintenance infusion of 1-2 g/h. Monitoring during magnesium infusion is essential: check patellar reflexes (loss of reflexes is the earliest sign of toxicity), respiratory rate (must remain >12/min), and urine output (must remain >25-30 mL/h). The antidote for magnesium toxicity is calcium gluconate 1 g IV. This is a frequently tested concept.

Delivery Timing

Condition	Recommended Delivery
Chronic HTN, well-controlled, no complications	38-39 weeks
Chronic HTN with superimposed preeclampsia or uncontrolled BP	36-37 weeks (or earlier if unstable)
Gestational HTN without severe features	37 weeks
Gestational HTN with severe features	34 weeks or earlier if deteriorating
Preeclampsia without severe features	37 weeks (expectant management before 37 weeks if stable)
Preeclampsia with severe features, ≥34 weeks	Deliver regardless of stability
Preeclampsia with severe features, <34 weeks	Deliver if maternal or fetal instability; give corticosteroids for lung maturity if time allows
Eclampsia	Immediate delivery after maternal stabilization (seizure control, BP management)

The POGI guideline is very clear: delivery is the only way to halt and reverse the pathologic process of preeclampsia. On preterm cases with severe features, the decision to deliver balances the risk to the mother against fetal prematurity, but maternal safety always takes priority.

5. Differential Diagnosis and Distractors

Differential Diagnosis	Why It Is Similar	Key Discriminator
Gestational hypertension	New-onset HTN after 20 weeks, same timeline as preeclampsia	No proteinuria and no evidence of organ dysfunction (normal platelets, normal liver enzymes, no neurologic symptoms). However, ~50% eventually progress to preeclampsia.
Chronic hypertension	Elevated BP in pregnancy	BP elevated before 20 weeks or before conception; no new proteinuria or organ dysfunction (unless superimposed preeclampsia develops)
HELLP syndrome	Shares features with preeclampsia (liver pain, thrombocytopenia)	HELLP is a variant/complication of preeclampsia characterized by the triad of hemolysis (elevated LDH, schistocytes, low haptoglobin), elevated liver enzymes, and low platelets. BP may be only mildly elevated or even normal in up to 15% of cases.
Thrombotic thrombocytopenic purpura (TTP)	Thrombocytopenia + hemolytic anemia in pregnancy	TTP presents with fever, severe thrombocytopenia (often <20,000), neurologic changes, and renal dysfunction but liver enzymes are typically normal and proteinuria is less prominent. ADAMTS13 activity is severely reduced (<10%).
Hemolytic uremic syndrome (HUS)	Microangiopathic hemolytic anemia + renal failure	Predominant renal failure with severe hemolysis; associated with complement dysregulation; less hepatic involvement than HELLP
Acute fatty liver of pregnancy (AFLP)	RUQ pain, liver dysfunction, third trimester	AFLP presents with hypoglycemia, markedly elevated bilirubin, and often coagulopathy with low fibrinogen; hypertension and proteinuria may be absent or mild; liver imaging may show fatty infiltration
Lupus nephritis flare	Proteinuria, hypertension, edema, low platelets in a pregnant woman	History of SLE, low complement levels (C3/C4), elevated anti-dsDNA; proteinuria may predate 20 weeks; differentiated by serology and baseline renal function
Pheochromocytoma	Paroxysmal hypertension in pregnancy, headaches	Episodic rather than sustained hypertension, accompanied by tachycardia, diaphoresis, pallor; diagnosed by elevated plasma/urine fractionated metanephrines

The most common exam trap in this differential is distinguishing preeclampsia from gestational hypertension. Both present with new-onset hypertension after 20 weeks. The key is looking for end-organ damage (even in the absence of proteinuria): elevated liver enzymes, low platelets, creatinine rise, neurologic symptoms, or pulmonary edema. The other high-yield distractor is HELLP syndrome presenting without significant hypertension, which can fool students into searching for another cause of thrombocytopenia and hemolysis.

6. Traps and High-Yield Pearls

The single most common way students lose points on preeclampsia questions is by requiring proteinuria to make the diagnosis. This is outdated. Per current ACOG, ISSHP, and POGI 2025 guidelines, preeclampsia can be diagnosed based on new-onset hypertension after 20 weeks plus any evidence of end-organ dysfunction, even with completely negative urine studies. About 10% of women with systemic features of preeclampsia (thrombocytopenia, liver injury, neurologic symptoms) will have no proteinuria. Furthermore, up to 50% of eclampsia cases present without proteinuria. If the vignette gives you a pregnant woman with headache, blurred vision, and platelets of 80,000 but a normal urine dipstick, the answer is still preeclampsia.

Another major trap involves drug contraindications. Exam writers love testing whether students reflexively prescribe ACE inhibitors or ARBs for hypertension without checking for pregnancy. These agents are absolutely contraindicated throughout pregnancy because of fetal renal toxicity (oligohydramnios, renal dysgenesis, pulmonary hypoplasia, neonatal anuria). Similarly, atenolol should not be used because of its association with fetal growth restriction from reduced uteroplacental perfusion. The safe choices are nifedipine, methyldopa, and other beta-blockers like metoprolol.

A third frequently tested trap is magnesium sulfate toxicity. Students are expected to know the monitoring sequence: loss of patellar reflexes (first sign, occurs at serum Mg 8-12 mg/dL) precedes respiratory depression (Mg >12 mg/dL), which precedes cardiac arrest (Mg >15-20 mg/dL). If the question describes a patient on MgSO4 who has lost her deep tendon reflexes, the immediate next step is to stop the infusion, not to increase the dose. The antidote is IV calcium gluconate.

Regarding delivery timing, the core principle is that preeclampsia with severe features at or beyond 34 weeks mandates delivery. Expectant management is only considered before 34 weeks, and only if the mother and fetus are stable. If the vignette describes worsening labs, uncontrollable BP, or signs of fetal distress at any gestational age, the answer is delivery. The "only cure is delivery" concept is the single most tested pearl for this diagnosis.

Finally, watch for the vignette that presents a woman with chronic hypertension whose BP worsens with new proteinuria or new organ dysfunction after 20 weeks. This is superimposed preeclampsia, not simply worsening chronic hypertension. The distinction matters because superimposed preeclampsia carries the same risk of eclampsia and requires magnesium sulfate prophylaxis and earlier delivery planning. The POGI guideline recommends that all women with chronic hypertension, diabetes, or autoimmune disease have baseline proteinuria measured before or at the first prenatal visit, precisely to enable this distinction later in pregnancy.

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