What is offline Placental Growth Factor (PLGF) testing?

Offline PlGF Testing in Pregnancy

Offline PlGF (Placental Growth Factor) testing is a biomarker test used to help rule out preeclampsia in women with suspected disease, where blood samples are collected and analyzed in a laboratory setting rather than at the point of care. This test measures levels of PlGF, an angiogenic factor produced by the placenta whose concentration decreases in preeclampsia due to placental dysfunction 1.

What is PlGF?

PlGF is a pro-angiogenic protein that:

• Supports normal placental development and trophoblast growth
• Promotes angiogenesis in the feto-placental circulation
• Decreases significantly in women with preeclampsia and/or fetal growth restriction
• Can be detected in maternal blood throughout pregnancy

Clinical Applications of PlGF Testing

Rule-Out Testing

• The primary value of PlGF testing is its high negative predictive value
• A normal PlGF level (≥100 pg/mL or above the 5th centile for gestational age) has excellent sensitivity (0.96) and negative predictive value (0.98) for ruling out preeclampsia requiring delivery within 14 days 2
• This is particularly valuable in women presenting with suspected preeclampsia between 20 and 35 weeks' gestation

Diagnostic Performance

• Low PlGF (<5th centile or <100 pg/mL) has better diagnostic accuracy (area under ROC curve 0.87) than all other commonly used tests for predicting preeclampsia within 14 days 2
• The test performs best when using thresholds between 80-120 pg/mL, with a sensitivity of 0.78 and specificity of 0.88 3
• Most effective for predicting early-onset preeclampsia and when performed after 14 weeks' gestation 3

Current Guideline Recommendations

According to the International Society for the Study of Hypertension in Pregnancy (ISSHP):

• The UK National Institute for Health and Care Excellence (NICE) recommends the Triage PlGF test or Elecsys sFlt-1/PlGF ratio to help rule out preeclampsia requiring delivery within 14 days (for Triage PlGF) or 7 days (for sFlt-1/PlGF ratio) 1
• This recommendation applies to women with suspected preeclampsia between 20 and 34+6 weeks' gestation
• However, ISSHP notes that "no test should be used routinely as a rule out test at this stage although PlGF testing may prove useful in selected groups in future studies" 1
• PlGF alone or in combination with sFlt-1 is not recommended to rule-in preeclampsia 1

Interpretation of Results

• A PlGF value ≤100 pg/mL or below the 5th centile for gestational age indicates high risk for developing preeclampsia requiring delivery within 14 days 1
• Very low PlGF (<12 pg/mL) is associated with universal adverse pregnancy outcomes (100% PPV) and shorter test-to-birth intervals, though about half of women with such low levels may continue pregnancy beyond 14 days 4
• PlGF results can alter clinical management (surveillance or timing of birth) in approximately 75% of high-risk cases 4

Limitations and Caveats

• PlGF testing should not trigger iatrogenic delivery in isolation without considering other clinical factors 4
• The test has better prognostic value for predicting fetal/neonatal complications than for maternal outcomes 5
• Cost-effectiveness of routine implementation remains to be established 1
• Further research linking placental pathology, maternal disease, and maternal PlGF levels is needed before widespread implementation in routine clinical practice 4

Practical Considerations

• Offline testing requires blood sample collection and laboratory processing
• Results are not immediately available at the point of care
• Interpretation should be integrated with standard clinical assessment
• The test may be particularly valuable in settings with limited resources for regular antenatal follow-up, though further research in these settings is needed 1