🧪 Introducing the sFLT-1/PLGF Ratio

And Its Role in Managing Patients With Pre-Eclampsia

Dr Muller Rossouw | Ampath Chat No. 98

📌 Introduction

Hypertensive disorders in pregnancy affect ~10% of pregnancies and are the second leading cause of maternal death in South Africa. Complications include:

• Premature delivery
• Intra-uterine growth restriction
• Stillbirths
• Renal/hepatic failure
• Hemorrhage
• Strokes

🧬 Background

Placental dysfunction includes:

• Pre-eclampsia
• Intra-uterine growth restriction
• Abruptio placenta

Causes include:

• Impaired invasion of uterine myometrium
• Poor spiral artery remodeling
• Placental hypoxia

Key biomarkers:

• sFlt-1 (soluble fms-like tyrosine kinase-1)
• PLGF (placental growth factor)

🧪 Screening Strategies

Historically based on symptoms and lab findings. Modern approaches use angiogenic biomarkers.

🧾 ISSHP Definition of Pre-Eclampsia:

• New onset hypertension >140/90
• Plus one of:
  • Proteinuria
  • Maternal organ dysfunction
  • Uteroplacental dysfunction (Doppler evidence)

🧮 First Trimester Screening (Ampath):

• Between 11w0d and 13w6d
• Includes:
  • Blood pressure
  • PLGF, PAPP-A
  • Uterine artery PI

🧬 Second Trimester Tools:

• Use of sFlt-1 to distinguish chronic hypertension vs. pre-eclampsia
• Predict risk of developing pre-eclampsia within 4 weeks

🧫 Angiogenic Biomarkers

PLGF + sFlt-1/PLGF Ratio (Recommended by NICE)

Helps exclude pre-eclampsia between 20–35 weeks gestation.

🧬 Soluble Endoglin

• Marker of endothelial dysfunction
• Elevated in pre-eclamptic patients

❌ sFlt-1

• Anti-angiogenic factor
• Triggered by hypoxia
• Leads to hypertension & systemic vascular issues

✅ PLGF

• Decreased in pre-eclampsia
• Peaks between 26–30 weeks
• Predicts adverse outcomes

⚖️ The sFlt-1/PLGF Ratio

Useful in:

• Diagnosing pre-eclampsia
• Predicting time to delivery
• Stratifying short-term risk

🔬 More predictive than sFlt-1 or PLGF alone

📊 Interpretation

No global consensus on cut-offs, but many international studies support the use of cut-offs around 38.

Selected Study Summary:

StudyNSensitivitySpecificityCut-offThadhani101481%81%≥ 40Xue36298.1%78.2%≥ 58.5Andersen50172%92%≥ 66Zeisler (PROGNOSIS)127366.2%83.1%≥ 38Miller13092.1%88.0%≥ 38Cerdeira (INSPIRE)38195.8%79.6%≥ 38Dröge111778.1%79.2%≥ 38

📝 South African Guideline (Matjila et al., 2018):

• Negative: <38
• Positive: ≥38 (stratify risk accordingly)

🧾 Conclusion

Implementing the sFlt-1/PLGF ratio:

• Enhances diagnosis & monitoring
• Improves care in 2nd trimester hypertensive pregnancies
• Reduces maternal & foetal complications

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