What level of pregnancy‑associated plasma protein‑A (PAPP‑A) is considered low?

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Last updated: May 11, 2026 • View editorial policy

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What is Considered a Low PAPP-A?

Low PAPP-A is defined as below the 5th centile or below 0.415 Multiples of Median (MoM), though if local reference data is unavailable, a threshold of <0.4 MoM is acceptable. 1

Definition and Thresholds

The 2024 BJOG Green-Top Guideline No. 31 provides the most authoritative definition, establishing that:

  • Primary threshold: Below 5th centile
  • Alternative threshold: Below 0.415 MoM (when local reference data is unavailable)
  • Practical cutoff: <0.4 MoM is widely used and clinically validated 1

This definition is consistent across multiple high-quality guidelines and reflects the threshold at which significant adverse pregnancy outcomes become substantially more likely.

Clinical Significance of Low PAPP-A

Low PAPP-A levels carry serious implications for pregnancy outcomes:

Stillbirth risk: Women with low PAPP-A have a dramatically elevated risk of stillbirth due to placental dysfunction (incidence rate 11.7 vs 0.3 per 10,000 women per week; hazard ratio 46.0,95% CI 11.9-178.0) 1

Small for gestational age (SGA): A meta-analysis of 32 studies involving 175,240 pregnancies demonstrated:

  • SGA <10th centile: OR 2.08 (95% CI 1.8-2.29)
  • SGA <5th centile: OR 2.83 (95% CI 2.52-3.18) 1

Fetal growth restriction (FGR): A UK observational study of 1,079 women with low PAPP-A showed 24.5% developed SGA and 10.3% developed FGR, with most cases occurring after 34 weeks gestation 1

Alternative Thresholds in Research

While the guideline-recommended threshold is <0.4-0.415 MoM, research studies have explored various cutoffs:

  • <0.3 MoM: Associated with higher specificity (98.6%) but lower sensitivity (6.9%) for SGA, resulting in approximately 50% reduction in screening detection compared to 0.4 MoM 2
  • <0.35 MoM: Intermediate threshold with balanced performance 2
  • <10th percentile: Some studies use this broader definition, though it captures more patients and may have lower specificity 3

The <0.4 MoM threshold remains the optimal balance between sensitivity and specificity for clinical screening purposes, as it identifies approximately 23% of women who will develop SGA, hypertensive disorders, or preterm birth 2.

Important Clinical Caveats

Gestational age matters: PAPP-A measurements are most discriminatory at 9 weeks' gestation, with optimal screening timing in the first trimester at 11 completed weeks 4

Risk increases with deviation: The further PAPP-A levels deviate below the median, the greater the risk of adverse outcomes 1

Not a standalone screening tool: While low PAPP-A is strongly associated with adverse outcomes, systematic reviews do not support its use in isolation as a primary detection tool for FGR due to low sensitivity 1

Required Clinical Actions When Low PAPP-A Detected

When PAPP-A is identified as low (<5th centile or <0.415 MoM):

  1. Initiate aspirin therapy as per preeclampsia prevention protocols 1
  2. Perform uterine artery Doppler screening 1
  3. Arrange serial growth scans with frequency dependent on Doppler results 1
  4. Increase surveillance for late-onset FGR (most cases occur after 34 weeks) 1

References

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.