Specificity of Low PAPP-A MoM Values
Low PAPP-A values demonstrate high specificity (81.6%) but poor sensitivity (38.7%) for predicting adverse pregnancy outcomes, meaning that while an abnormal result is meaningful, most adverse outcomes occur in women with normal PAPP-A levels. 1
Understanding PAPP-A Specificity in Clinical Context
The specificity of PAPP-A testing varies significantly based on the cutoff value chosen and the population studied:
Standard Cutoff Values and Performance
At the commonly used 0.4 MoM cutoff, PAPP-A demonstrates a specificity of approximately 81.6%, with a positive likelihood ratio of only 2.1, indicating modest discriminatory power 1
At the more stringent 0.2 MoM cutoff, specificity improves substantially with a positive likelihood ratio of 3.7, though this identifies a much smaller proportion of at-risk pregnancies 2
At extremely low levels (≤0.1 MoM), the test becomes highly specific for adverse outcomes, though the absolute number of cases identified remains small 3
Clinical Interpretation of Specificity
The high specificity means that when PAPP-A is abnormally low (<0.4 MoM), there is genuine increased risk - approximately 2-fold for composite adverse outcomes including fetal growth restriction, preeclampsia, preterm delivery, and stillbirth 1. However, the poor sensitivity (38.7%) indicates that most adverse outcomes occur in women with normal PAPP-A levels, limiting its utility as a standalone screening test 1.
Positive and Negative Predictive Values
The positive predictive value is poor - even at very low PAPP-A levels (≤0.23 MoM), only 21.4% of pregnancies will experience adverse outcomes 2
The negative predictive value is high (97.7%), meaning normal PAPP-A levels are reassuring, though not absolute 2
At extremely low levels (≤0.2 MoM), good outcomes still occur in at least 60% of chromosomally normal pregnancies 3
Gestational Age Considerations
The 10-14 week gestational age window is the only period where low PAPP-A shows statistically significant association with adverse outcomes in adjusted models 1
Testing outside this window may have even lower predictive accuracy 1
Population-Specific Variations
Important caveat: The optimal cutoff may vary by ethnicity. Chinese populations demonstrate higher baseline PAPP-A levels, requiring adjustment of cutoff values for optimal performance 2. The standard 0.4 MoM cutoff derived from predominantly Caucasian populations may not perform equivalently across all ethnic groups 2.
Clinical Utility Despite Limited Specificity
Despite modest specificity as a standalone test, PAPP-A <0.4 MoM is recognized by international guidelines as warranting enhanced surveillance throughout pregnancy, including serial growth ultrasounds, uterine artery Doppler assessment, and consideration of low-dose aspirin when identified before 16 weeks 4. The value lies not in ruling in disease, but in identifying a higher-risk population requiring closer monitoring 4.