Preeclampsia – Clinical Features & Diagnosis

Introduction

• Preeclampsia (PE) = multisystem, progressive disorder beginning ≥20 weeks gestation or postpartum.

• Core diagnostic dyad: new-onset hypertension (HTN) + proteinuria
  OR new-onset HTN + specific end-organ dysfunction (with/without proteinuria).

• Typical onset: $\ge 34$ weeks (≈ 90 % cases) → generally favorable outcomes; early onset <34 weeks (≈ 10 %) ↑ maternal/perinatal risk.

• Always resolves after placental delivery, yet confers ↑ lifelong CV mortality & recurrence risk.

Definitions & Diagnostic Criteria

Blood-pressure cut-offs

• HTN in pregnancy: $\text{SBP}\,\ge 140\,\text{mmHg} \;\text{and/or}\; \text{DBP}\,\ge 90\,\text{mmHg}$.

• Severe HTN: $\text{SBP}\,\ge 160\,\text{mmHg} \;\text{and/or}\; \text{DBP}\,\ge 110\,\text{mmHg}$.

United States (ACOG/SMFM) Criteria

• Preeclampsia = HTN + [one or more] of:
  • Proteinuria ≥$0.3$ g/24 h OR P:Cr ≥$0.3$ (mg/mg) OR dipstick ≥2+.
  • Platelets <100{,}000/\mu L • Creatinine >1.1 mg/dL OR doubling baseline.
  • AST/ALT ≥2× ULN.
  • Pulmonary edema.
  • New persistent headache or visual Sx.

• Preeclampsia with Severe Features (need ≥1):
  • Severe BP (above) ‑ confirmed.
  • Severe neurologic Sx.
  • Thrombocytopenia <100{,}000/\mu L.
  • Creatinine criteria above.
  • Marked LFT elevation / RUQ pain.
  • Pulmonary edema.

• Subtypes: Early- vs late-onset, HELLP, superimposed PE on chronic HTN, eclampsia (tonic–clonic seizure in PE).

ISSHP Differences

Adds uteroplacental dysfunction (FGR, abnormal Doppler, angiogenic imbalance, abruption, IUFD) & uses platelet threshold <150{,}000/\mu L.

Incidence

• Global pooled incidence ≈ 4.6 % (95 % CI 2.7–8.2).

• USA ≈ 5 %; incidence is rising due to ↑ maternal age, obesity, HTN, etc.

• Late-onset (≥34 w): 2.7 %; Early-onset (<34 w): 0.3 %.

Risk Factors (Table 3)

High-risk predictors (RR given):

• Prior PE $RR\,\approx 8.4$ (severity & timing modulate recurrence).

• Chronic HTN $RR\,\approx 5.1$ (dose-response even at pre-stage 1 BPs).

• Pregestational DM $RR\,\approx 3.7$.

• Multifetal gestation $RR\,\approx 2.9$.

• Chronic kidney disease $RR\,1.8$ (↑ with ↓ GFR).

• APS $RR\,2.8$; SLE $RR\,1.8$.

Moderate/Prevalent factors: nulliparity, obesity (risk doubles per $\approx5$–7 kg/m² BMI increment), adolescence, AMA (≥35 y), family history, ART, prior placental-insufficiency events.

Paradox: cigarette smoking ↓ risk (possible artifact).

Pathogenesis (overview)

1. Abnormal spiral-artery remodeling → placental hypoperfusion.

2. Placental hypoxia/ischemia → release of anti-angiogenic factors (sFlt-1↑, PlGF↓) → maternal systemic endothelial dysfunction.

3. Resultant vasoconstriction, capillary leak, coagulation activation → clinical syndrome.

Screening & Risk Reduction

• First visit: identify risk factors → low-dose aspirin (81–150 mg nightly) from 12–28 w (optimally ≤16 w) until delivery.

• Routine BP every visit (pre-20 w establishes baseline).

• Baseline urinalysis for protein; thereafter test only if HTN develops (except in chronic/gestational HTN → every visit).

• No universal lab/imaging screen proven; FMF combined algorithm (MAP + uterine artery PI + PlGF + PAPP-A) not adopted in US.

Clinical Presentation

• 1/3 nulliparous; remainder bear notable risks.

• Onset distribution: ≥34 w 85 %; <34 w 10 %; postpartum 5 % (usually <48 h).

Alarm BP/Symptom Cluster (prompt admission)

• Severe BP.

• Neurologic: persistent headache, visual changes, AMS, clonus, seizure.

• Upper abdominal/epigastric/RUQ pain unrelieved by antacids.

• Dyspnea/orthopnea (pulmonary edema).

Atypical

• <20 w: consider molar pregnancy, APS, TTP/HUS, lupus nephritis.

• Delayed postpartum (>2 d – 6 wk): headache +/- dyspnea common.

• HELLP or eclampsia may have severe features without overt HTN/proteinuria.

Patient Evaluation

1. Site

   • Severe BP or symptoms → hospital.

   • Mild/asymptomatic → outpatient if reliable follow-up.

2. Accurate BP technique essential (sitting, validated cuff, repeat).

3. Labs (initial): CBC + platelets, creatinine, AST/ALT ± bilirubin, quantitative protein (P:Cr or 24-h).

   • Reflex tests: LDH, coag panel, amylase/lipase, glucose, ADAMTS-13 as indicated.

4. Angiogenic markers (sFlt-1/PlGF)

   • High NPV for ruling out PE within 1–2 wk; routine use: UK (NICE) yes; US (ACOG) no; FDA approved for in-pt hypertensive prediction.

5. Fetal assessment: NST/BPP + U/S est. weight & AFI; Dopplers if FGR.

6. Consults: Neurology for focal deficits/PRES suspicion; others per organ involvement.

Spectrum of Disease – Clinical Findings

• HTN: usually gradual rise; may be abrupt or postpartum.

• Epigastric/RUQ pain: capsule stretch, hepatic ischemia/hematoma.

• Neurologic: Headache, visual disturbances, AMS, PRES, seizures.

• Pulmonary edema: 10 % severe PE (multifactorial – ↑ hydrostatic, ↓ oncotic, capillary leak, iatrogenic fluids, LV dysfunction).

• Renal: oliguria <$500$ mL/24 h; rare DI-induced polyuria.

• Edema & rapid weight gain: capillary leak + Na⁺ retention.

• Abruption incidence: <1 % (non-severe) to 3 % (severe).

Laboratory Manifestations

• Proteinuria thresholds above; may lag behind HTN.

• Creatinine usually mildly ↑; >1.1\,\text{mg/dL} signals severity.

• Platelets ↓ (<$150k$: 20 %; <$100k$ severe).

• Hemolysis: schistocytes, ↑ LDH/indirect bili.

• Hemoconcentration: ↑ Hct (unless offset by hemolysis).

• Coagulation: generally normal unless DIC/abruption.

• LFTs: AST/ALT ≥2× ULN; severe → hemorrhage/rupture.

• Uric acid often ↑ but poor predictor.

• Other: hypocalciuria, dyslipidemia, troponin I elevations (myocardial strain).

Sonographic & Hemodynamic Findings

• Early-onset PE: FGR ± oligohydramnios; late-onset usually normal growth.

• Uterine artery PI ↑, notching; umbilical artery absent/reversed EDF if severe placental disease.

• Maternal echo: ↑ afterload, variable CO; subclinical LV strain; BNP/NT-proBNP 4× normal pregnancy.

Histopathology

• Placenta: acute atherosis, shallow trophoblast invasion, infarcts, villous hypoplasia.

• Kidney: glomerular endotheliosis – endothelial swelling, capillary obliteration; parallels anti-VEGF therapy injury.

Differential Diagnosis (Table 4/6)

• Gestational HTN, chronic HTN.

• HELLP vs acute fatty liver (AFLP), TTP, HUS, SLE flare/APS, pheochromocytoma, lupus nephritis, mirror syndrome.

• Use clinical pattern + labs (e.g., hypoglycemia, ammonia ↑ in AFLP; ADAMTS-13 <10 % in TTP).

Natural History & Outcomes

• 25 % progress rapidly to severe disease (days–weeks) – fatal events can occur without severe BP.

• Post-delivery: diuresis within 48 h; BP may spike 1 wk pp; proteinuria may take months to clear.

• Maternal mortality: 10–15 % of global direct deaths; US ≈1/100 000 live births (higher with heart disease).

• Fetal: ↑ FGR, oligohydramnios, iatrogenic preterm, perinatal mortality (greatest <34 w).

• Long-term: recurrent PE, chronic HTN, CKD, ischemic heart disease; offspring CV & metabolic risks.

Guideline Highlights

• ACOG PB 222 (2020): diagnostic criteria, manage severe BP >$160/110$ immediately.

• ISSHP 2021: includes uteroplacental criteria; sFlt-1/PlGF may support diagnosis.

• NICE (UK): PlGF-based test to aid diagnosis 20–36 + 6 w.

• FDA: sFlt-1:PlGF ratio authorized for hospitalized hypertensive gravidae (predict 2-wk progression).

Key Algorithms & Equations

• See $\text{Algorithm 1}$ for diagnostic work-up (HTN → labs → classify).

• P:Cr spot estimate of 24-h protein: $\text{g/day}\;\approx \frac{\text{mg protein}}{\text{mg creatinine}}$.

• MAP for FMF screen: $\text{MAP}=\frac{\text{SBP}+2\times\text{DBP}}{3}$.

Ethical & Practical Points

• Over-diagnosis risks (lower BP cut-offs) vs missed disease.

• Equity: minority groups & disadvantaged populations bear higher incidence/severity – mandates focused screening & resource allocation.

• Smoking paradox underscores caution interpreting observational risk modifiers.

Study Tips / Mnemonics

PE = "H-T-N":
H – Hypertension / HELLP / Hemolysis / Headache / Hyper-reflexia.
T – Thrombocytopenia / Transaminases / sFT-1 ↑ (anti-angiogenic).
N – Nephropathy (proteinuria, creatinine) / Neurologic (seizure, vision) / "No placenta → No PE" (delivery cures).

Cross-Links to Other Topics

• Pathogenesis details

• Prevention (aspirin, calcium)

• Antepartum, intrapartum, postpartum management

• HELLP, eclampsia, gestational HTN, AFLP, TTP/HUS, Mirror syndrome.

Real-World Relevance

• Leading driver of ICU admissions, maternal stroke, iatrogenic preterm deliveries.

• sFlt-1/PlGF testing poised to refine triage, yet economics & access vary.

• Chronic disease lens: PE history = red flag for future CVD – an early life-course intervention opportunity.

Introduction

• Preeclampsia (PE) = multisystem, progressive disorder, beginning $\ge20$ weeks gestation or postpartum.

• Core diagnosis: new-onset HTN + proteinuria OR new-onset HTN + specific end-organ dysfunction (with/without proteinuria).

• Typical onset: $\ge34$ weeks; early onset <34 weeks ↑ maternal/perinatal risk.

• Resolves after placental delivery, but ↑ lifelong CV mortality & recurrence risk.

Definitions & Diagnostic Criteria

Blood-pressure cut-offs

• HTN in pregnancy: $\text{SBP}\,\ge140\,\text{mmHg} \;\text{and/or}\,\text{DBP}\,\ge90\,\text{mmHg}$.

• Severe HTN: $\text{SBP}\,\ge160\,\text{mmHg} \;\text{and/or}\,\text{DBP}\,\ge110\,\text{mmHg}$.

United States (ACOG/SMFM) Criteria

• Preeclampsia = HTN + [one or more] of:

  • Proteinuria $\ge0.3$ g/24 h OR P:Cr $\ge0.3$ (mg/mg) OR dipstick $\ge2+$.

  • Platelets <100{,}000/\mu L

  • Creatinine >1.1 mg/dL OR doubling baseline.

  • AST/ALT $\ge2$\times ULN.

  • Pulmonary edema.

  • New persistent headache or visual Sx.

• Preeclampsia with Severe Features (need $\ge1$):

  • Severe BP (above) – confirmed.

  • Severe neurologic Sx.

  • Thrombocytopenia <100{,}000/\mu L

  • Creatinine criteria above.

  • Marked LFT elevation / RUQ pain.

  • Pulmonary edema.

• Subtypes: Early- vs late-onset, HELLP, superimposed PE on chronic HTN, eclampsia.

Incidence

• Global ≈ 4.6 %; USA ≈ 5 % (rising).

• Late-onset ($\ge34$ w): 2.7 %; Early-onset (<34 w): 0.3 %.

Risk Factors

• High-risk: Prior PE ($\text{RR}\,\approx8.4$), chronic HTN ($\text{RR}\,\approx5.1$), pregestational DM ($\text{RR}\,\approx3.7$), multifetal gestation ($\text{RR}\,\approx2.9$), chronic kidney disease ($\text{RR}\,1.8$), APS ($\text{RR}\,2.8$), SLE ($\text{RR}\,1.8$).

• Moderate/Prevalent: nulliparity, obesity, adolescence, AMA ($\ge35$ y), family history, ART, prior placental-insufficiency events.

Pathogenesis (overview)

1. Abnormal spiral-artery remodeling $\to$ placental hypoperfusion.

2. Placental hypoxia/ischemia $\to$ anti-angiogenic factors (sFlt-1$\uparrow$, PlGF$\downarrow$) $\to$ maternal systemic endothelial dysfunction.

3. Resultant vasoconstriction, capillary leak, coagulation activation $\to$ clinical syndrome.

Screening & Risk Reduction

• First visit: identify risk factors $\to$ low-dose aspirin (81–150 mg nightly) from 12–28 w (optimally $\le16$ w) until delivery.

• Routine BP every visit.

• Baseline urinalysis for protein; test thereafter only if HTN develops.

• No universal lab/imaging screen proven effective in US.

Clinical Presentation

• Onset distribution: $\ge34$ w (85 %), <34 w (10 %), postpartum (5 %).

• Alarm BP/Symptom Cluster (prompt admission): Severe BP, neurologic (headache, visual changes, AMS, clonus, seizure), upper abdominal/epigastric/RUQ pain, dyspnea/orthopnea.

• Atypical: $\le20$ w, delayed postpartum (>2 d – 6 wk), HELLP/eclampsia without overt HTN/proteinuria.

Patient Evaluation

1. Site: Severe BP/symptoms $\to$ hospital; mild/asymptomatic $\to$ outpatient.

2. Accurate BP technique essential.

3. Labs (initial): CBC + platelets, creatinine, AST/ALT $\pm$ bilirubin, quantitative protein.

4. Angiogenic markers (sFlt-1/PlGF): High NPV for ruling out PE (UK uses, US FDA approved for in-pt prediction).

5. Fetal assessment: NST/BPP + U/S est. weight & AFI; Dopplers if FGR.

6. Consults: Neurology for PRES suspicion; others per organ involvement.

Spectrum of Disease – Clinical Findings

• HTN: gradual or abrupt rise.

• Epigastric/RUQ pain: hepatic capsule stretch/ischemia.

• Neurologic: Headache, visual disturbances, AMS, PRES, seizures.

• Pulmonary edema: 10 % severe PE.

• Renal: oliguria <500 mL/24 h.

• Edema & rapid weight gain: capillary leak + Na$^{+}$ retention.

• Abruption: incidence <1 % (non-severe) to 3 % (severe).

Laboratory Manifestations

• Proteinuria thresholds above; may lag HTN.

• Creatinine: usually mildly $\uparrow$; >1.1\,\text{mg/dL} signals severity.

• Platelets: $\downarrow$ (<150k: 20 %; <100k severe).

• Hemolysis: schistocytes, $\uparrow$ LDH/indirect bili.

• Hemoconcentration: $\uparrow$ Hct.

• Coagulation: generally normal unless DIC/abruption.

• LFTs: AST/ALT $\ge2$\times ULN.

• Uric acid: often $\uparrow$.

Sonographic & Hemodynamic Findings

• Early-onset PE: FGR $\pm$ oligohydramnios.

• Uterine artery PI $\uparrow$, notching; umbilical artery absent/reversed EDF if severe placental disease.

• Maternal echo: $\uparrow$ afterload, variable CO.

Histopathology

• Placenta: acute atherosis, shallow trophoblast invasion, infarcts, villous hypoplasia.

• Kidney: glomerular endotheliosis.

Differential Diagnosis

• Gestational HTN, chronic HTN, HELLP vs acute fatty liver (AFLP), TTP, HUS, SLE flare/APS, pheochromocytoma, lupus nephritis, mirror syndrome.

Natural History & Outcomes

• 25 % progress rapidly to severe disease (days–weeks); fatal events can occur without severe BP.

• Post-delivery: diuresis within 48 h; BP may spike 1 wk pp; proteinuria may take months to clear.

• Maternal mortality: 10–15 % of global direct deaths; US $\approx1/100\,000$ live births.

• Fetal: $\uparrow$ FGR, oligohydramnios, iatrogenic preterm, perinatal mortality.

• Long-term: recurrent PE, chronic HTN, CKD, ischemic heart disease; offspring CV & metabolic risks.

Guideline Highlights

• ACOG PB 222 (2020): manage severe BP >160/110 immediately.

• ISSHP 2021: includes uteroplacental criteria; sFlt-1/PlGF may support diagnosis.

• NICE (UK): PlGF-based test aids diagnosis.

• FDA: sFlt-1:PlGF ratio authorized for hospitalized hypertensive gravidae.

Key Algorithms & Equations

• Algorithm 1 for diagnostic work-up.

• P:Cr spot estimate of 24-h protein: $\text{g/day}\;\approx \frac{\text{mg protein}}{\text{mg creatinine}}$.

• MAP for FMF screen: $\text{MAP}=\frac{\text{SBP}+2\times\text{DBP}}{3}$.

Ethical & Practical Points

• Over-diagnosis risks vs missed disease.

• Equity for minority/disadvantaged groups.

• Smoking paradox.

Study Tips / Mnemonics

PE = "H-T-N":

• H – Hypertension / HELLP / Hemolysis / Headache / Hyper-reflexia.

• T – Thrombocytopenia / Transaminases / sFT-1 $\uparrow$ (anti-angiogenic).

• N – Nephropathy (proteinuria, creatinine) / Neurologic (seizure, vision) / "No placenta $\to$ No PE" (delivery cures).

Real-World Relevance

• Leading cause of ICU admissions, maternal stroke, iatrogenic preterm deliveries.

• sFlt-1/PlGF testing can refine triage.

• PE history = red flag for future CVD.