Unit Converter
Pregnancy-associated plasma protein A (PAPP-A)
(First-Trimester Marker for Chromosomal Abnormalities & Placental Function)
Synonyms
- PAPP-A
- Pregnancy-associated plasma protein A
- PAPPA
- Metalloproteinase PAPP-A
- First-trimester Down syndrome marker
- Placental protein A
Units of Measurement
- mIU/L
- µIU/mL
- IU/L
- mIU/mL
Unit Relationships
1 mIU/mL=1000 mIU/L1\ \text{mIU/mL} = 1000\ \text{mIU/L}1 mIU/mL=1000 mIU/L 1 µIU/mL=0.001 mIU/mL1\ \text{µIU/mL} = 0.001\ \text{mIU/mL}1 µIU/mL=0.001 mIU/mL 1 IU/L=1000 mIU/L1\ \text{IU/L} = 1000\ \text{mIU/L}1 IU/L=1000 mIU/L
Most laboratories report PAPP-A in mIU/L or mIU/mL.
Description
Pregnancy-Associated Plasma Protein A (PAPP-A) is a large zinc-binding metalloproteinase produced mainly by:
- Syncytiotrophoblasts of the placenta
- Decidual cells
- Granulosa cells
PAPP-A plays a key role in placental development through cleavage of insulin-like growth factor–binding proteins (IGFBPs), especially IGFBP-4 → increasing free IGF, promoting:
- Trophoblast invasion
- Placental perfusion
- Fetal growth
PAPP-A is a first-trimester maternal serum marker used in aneuploidy screening.
Physiological Role
- Enhances IGF bioavailability
- Regulates trophoblast proliferation
- Supports placental and fetal development
- Influences vascular remodeling of uteroplacental circulation
Low PAPP-A reflects early placental dysfunction.
Clinical Significance
LOW PAPP-A (Most Important Finding)
Strongly associated with:
1. Trisomy Risk
Used in first-trimester aneuploidy screening:
- Down syndrome (Trisomy 21) → low PAPP-A
- Trisomy 18
- Trisomy 13
Typically:
- PAPP-A < 0.4 MoM → elevated aneuploidy risk
- PAPP-A < 0.2 MoM → high risk
2. Placental Dysfunction
Low PAPP-A in 1st trimester is linked with:
- Preeclampsia
- Fetal growth restriction (FGR/IUGR)
- Preterm birth
- Stillbirth
- Placental abruption
3. Adverse Pregnancy Outcomes
Lower PAPP-A = higher risk.
4. First-Trimester Screening Panels
Part of FMF algorithm with:
- Nuchal translucency (NT)
- Free β-hCG
- Maternal age
- Doppler resistance indices
HIGH PAPP-A
Usually benign and not clinically problematic.
Mild increase seen in:
- Multiple gestation
- Diabetic pregnancies
- High placental volume
Not used clinically to diagnose disease.
Reference Intervals (Gestation-Dependent)
(Values vary widely by gestational age; interpreted as MoM - Multiples of Median)
Absolute PAPP-A Values (General Ranges)
| Gestational Age | Typical PAPP-A (mIU/mL) |
| 8–9 weeks | 0.5 – 2.0 mIU/mL |
| 10–11 weeks | 1.0 – 4.0 mIU/mL |
| 11–12 weeks | 2.0 – 6.0 mIU/mL |
| 12–13 weeks | 3.0 – 10.0 mIU/mL |
(Exact values vary by assay → MoM is used.)
MoM Interpretation
- 1.0 MoM → expected median
- <0.4 MoM → high risk (aneuploidy, placental disease)
- >1.5 MoM → usually normal/benign
Diagnostic Uses
1. First-Trimester Combined Screening (Primary Use)
PAPP-A + NT + free β-hCG for detecting:
- Down syndrome (T21)
- Edwards syndrome (T18)
- Patau syndrome (T13)
2. Predicting Placental Insufficiency
Low PAPP-A strongly linked with:
- Early-onset preeclampsia
- IUGR
- Preterm birth
- Stillbirth
- Abnormal uterine artery Dopplers
3. Maternal-Fetal Risk Stratification
Women with PAPP-A <0.3 MoM often undergo:
- Serial growth scans
- Additional Doppler studies
- Closer surveillance in 2nd–3rd trimester
4. First-Trimester Fetal Health Indicator
Reflects overall placental health early in pregnancy.
Analytical Notes
- Sample: maternal serum
- Best measured between 8–13+6 weeks
- Strong gestational-age dependency → MUST convert to MoM
- Hemolysis and lipemia may interfere with assays
- Automated immunoassays used (chemiluminescence, ELISA)
Clinical Pearls
- Low PAPP-A = placental dysfunction until proven otherwise.
- When PAPP-A is low, always check uterine artery Doppler at 20–24 weeks.
- Extreme low (<0.2 MoM) strongly predicts early severe preeclampsia.
- PAPP-A is not a stand-alone test — used only as part of combined screening.
- High PAPP-A values generally have no adverse clinical meaning.
Interesting Fact
PAPP-A was originally discovered as a protein elevated in pregnancy serum - later found to be a protease regulating IGF, crucial to placental development. Its molecular role explains why low levels indicate poor placental growth.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Maternal Serum Screening
- Fetal Medicine Foundation (FMF) - PAPP-A Screening
- ACOG - First-Trimester Screening Guidelines
- ISUOG - Early Pregnancy Biomarkers
- Mayo Clinic Laboratories - PAPP-A
- ARUP Consult - Maternal Serum Screening
- NIH / MedlinePlus - PAPP-A Test