MFM Clinical Protocol
sFlt-1 / PlGF
Ratio Evaluation
Suspected Preeclampsia with Mild Hypertension
PROGNOSIS Validated
ISSHP 2021
NICE Guidance
Roche Elecsys Platform
Indication
When to Order
Indicated when preeclampsia is suspected — new or worsening hypertension,
proteinuria, or other signs — at ≥20 weeks. Optimally validated from
24+0 to 36+6 weeks.
20 wks
24 wks
28 wks
32 wks
36 wks
40 wks
▲ Validated
Window Begins
▲ Validated
Window Ends
Normal reference range (23–34+6 wks, healthy US cohort): 0.9–13.5
Pathophysiology
Angiogenic Imbalance
🫀
Trigger
Placental Ischemia
→
⬆
Anti-Angiogenic
sFlt-1 ↑
⊣
→
🩸
Outcome
Vasoconstriction & Hypertension
Elevated sFlt-1/PlGF ratio is detectable in maternal serum before clinical onset of preeclampsia.
Clinical Decision Thresholds
Three Ratio Zones
Rule-Out Zone
≤ 38
Low Risk
NPV 99.3% — reliably excludes preeclampsia within 1 week; NPV 94.3% at 4 weeks.
Outpatient management
Intermediate Zone
39–85
Equivocal
Cannot rule in or rule out. Increased risk of progression. Serial monitoring required.
Enhanced surveillance
Rule-In Zone
> 85
High Risk (<34 wks)
High probability of preeclampsia. Severe angiogenic imbalance. Adverse outcomes likely.
Consider admission
Late-onset (≥34 wks) rule-in threshold: >110 | PROGNOSIS single cutoff: 38
Management Protocol
Clinical Action by Zone
| sFlt-1/PlGF Ratio |
Interpretation |
Recommended Action |
| ≤ 38 |
Rule-out — low short-term risk of preeclampsia (NPV 99.3%) |
Outpatient management; repeat assessment in 1–4 weeks if symptoms persist |
| 39 – 85 |
Intermediate — cannot exclude or confirm preeclampsia |
Close surveillance; serial BP, labs, fetal assessment; consider repeat testing in 1–2 weeks |
| > 85 (<34 wks) |
Rule-in — high probability of preeclampsia with severe features |
Strongly consider admission; intensive maternal/fetal surveillance; corticosteroids if preterm; plan delivery |
| > 110 (≥34 wks) |
Rule-in — late-onset threshold |
Same as above; expedited delivery planning per clinical context |
Zone Detail — Rule-Out
Ratio ≤ 38
Clinical Benefit
Safely excludes imminent preeclampsia, eclampsia, and HELLP syndrome within 1 week.
Prevents unnecessary hospital admissions and premature iatrogenic delivery.
Performance
NPV 99.3% at 1 week | NPV 94.3% at 4 weeks
Negative likelihood ratio ≤ 0.16 for progression to severe features
Outpatient Plan
Reduced surveillance intensity appropriate. Repeat clinical assessment or biomarker testing
in 1–4 weeks if symptoms persist.
Zone Detail — Rule-In
Ratio > 85 (<34 weeks)
Associated Risks
Placental abruption · IUGR · Pulmonary edema · Renal failure · DIC
Inpatient Monitoring
Serial labs · BP management · Uterine, umbilical & cerebral Doppler ultrasound
Fetal Considerations
Antenatal corticosteroids if delivery anticipated <34 weeks. Prepare for potential preterm delivery.
Predictive Performance
Positive LR 6.0–8.2 for severe features. AUC 0.92 vs. <0.70 for conventional labs (PRECISE study).
Clinical Integration
Ratio + Clinical Context
📊
Blood Pressure Trends
Serial BP measurements over time, not single readings
🔬
Laboratory Panel
CBC, LFTs, creatinine, urine protein/creatinine ratio
👶
Fetal Status
Biophysical profile, growth, Doppler indices
📋
Symptoms
Headache, visual changes, RUQ pain, edema
📅
Gestational Age
Guides delivery timing and corticosteroid decisions
⚠️
Key Caveat
Abnormal ratio alone is not an indication for delivery
Repeat Testing Strategy
When to Retest
Initial sFlt-1/PlGF Result
↓
≤ 38 (Normal)
↓
Retest in ≥2 weeks if symptoms return or worsen
PARROT-2: Routine repeat testing confers no additional benefit beyond initial test
39–85 (Intermediate)
↓
Repeat in 1–2 weeks; monitor ratio trajectory
Rising ratio (Δ >30 at 2 wks) predicts progression to preeclampsia
> 85 (Elevated)
↓
Repeat testing adds limited value; manage clinically
Immediate clinical action is the priority
Retest immediately if clinical situation changes, regardless of initial result.
Clinical Caveats
Important Considerations
-
⚠
An abnormal ratio alone is not an indication for delivery — integrate with BP trends, labs, and fetal status.
-
🧪
Platform matters: Cutoffs above apply to the Roche Elecsys platform. QuidelOrtho PlGF-alone uses different thresholds (rule-out: PlGF >100 pg/mL; rule-in: PlGF <12 pg/mL).
-
📅
Best validated for preterm suspected preeclampsia (24–36+6 wks). Evidence beyond 37 weeks is more limited.
-
📈
Even in confirmed preeclampsia, the ratio adds independent prognostic value for progression to severe features.
Summary
Protocol at a Glance
| Step |
Action |
| 1. Identify |
Suspected preeclampsia ≥20 wks; optimally 24+0–36+6 wks |
| 2. Measure |
sFlt-1/PlGF ratio via Roche Elecsys immunoassay |
| 3. Interpret |
≤38 rule-out · 39–85 intermediate · >85 rule-in (<34 wks) |
| 4. Integrate |
Combine with BP, labs, symptoms, fetal status, gestational age |
| 5. Retest |
In 1–2 weeks if intermediate; immediately if clinical change |
Sources: PROGNOSIS (NEJM 2016) · PARROT-2 (Lancet 2024) · PRECISE (AJOG 2026) · ISSHP 2021 · NICE Guidance