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