PAPP-A (Pregnancy Associated Plasma Protein-A)

Pregnancy

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Marker of certain chromosomal abnormalities such as Down syndrome (Trisomy 21) and Trisomy 18

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PAPP-A (Pregnancy Associated Plasma Protein-A) Test Information Guide

Why is it done?
- Test Description: PAPP-A is a protein produced by the placenta during pregnancy. This blood test measures the levels of PAPP-A in maternal serum to assess fetal development and pregnancy-related risks.
- Primary Indications: First trimester screening (11-14 weeks gestation) for chromosomal abnormalities (Down syndrome/Trisomy 21, Edwards syndrome/Trisomy 18, Patau syndrome/Trisomy 13)
- Risk Assessment: Identifies increased risk for intrauterine growth restriction (IUGR) and preeclampsia during pregnancy
- Timing: Typically performed between 11-14 weeks of gestation as part of first trimester combined screening; may also be used in second trimester screening (15-20 weeks)
- Clinical Context: Used in combination with nuchal translucency ultrasound and beta-hCG measurements for comprehensive prenatal screening
Normal Range
- Reference Values: PAPP-A levels are typically expressed as Multiples of the Median (MoM). Normal range: 0.5-2.5 MoM for first trimester (11-14 weeks gestation)
- Units of Measurement: mIU/mL (milli-international units per milliliter) or ng/mL (nanograms per milliliter); most commonly reported as MoM relative to gestational-age-specific medians
- Normal Result: PAPP-A levels between 0.5-2.5 MoM indicate a normal, age-appropriate protein level with low risk for chromosomal abnormalities
- Low Values: PAPP-A < 0.5 MoM (below 0.5 multiples of median) is considered low and associated with increased risk for Down syndrome (Trisomy 21) and other chromosomal abnormalities
- High Values: PAPP-A > 2.5 MoM (above 2.5 multiples of median) is generally considered elevated; typical interpretation focuses on low values rather than high values
- Critical Cut-off: Values below 0.5 MoM are considered abnormal and warrant further investigation with additional screening tests
Interpretation
- Low PAPP-A (< 0.5 MoM): Indicates increased risk for Down syndrome (Trisomy 21), Edwards syndrome (Trisomy 18), and other chromosomal abnormalities. Combined with elevated beta-hCG and increased nuchal translucency, risk is further elevated. Risk assessment is individualized based on maternal age and other screening markers.
- Normal PAPP-A (0.5-2.5 MoM): Reassuring result suggesting low risk for chromosomal abnormalities when combined with other normal screening markers. However, does not completely exclude risk, and interpretation must consider overall screening profile.
- Risk Stratification: PAPP-A results are interpreted as part of combined screening that includes maternal age, nuchal translucency (NT) measurement, and beta-hCG. Low PAPP-A with normal or high beta-hCG and increased NT increases risk significantly.
- Detection Rates: First trimester combined screening (including PAPP-A) detects approximately 85-95% of Down syndrome cases and 80-85% of Edwards syndrome cases at 5% false positive rate.
- Second Trimester Context: In second trimester screening, low PAPP-A is also associated with increased risk for preeclampsia, intrauterine growth restriction, and adverse pregnancy outcomes.
- Factors Affecting Results: Gestational age accuracy is critical; dating errors significantly impact interpretation. Maternal weight, insulin-dependent diabetes, and multiple gestations can affect values. PAPP-A tends to increase with gestational age throughout pregnancy.
- Clinical Significance Patterns: Very low PAPP-A (< 0.3 MoM) combined with abnormal ultrasound findings warrants highest risk classification. Mildly low PAPP-A (0.3-0.5 MoM) with reassuring ultrasound findings may result in moderate risk assessment.
Associated Organs
- Primary Organ System: Placenta (source of PAPP-A production) and fetal development (specifically fetal aneuploidy detection)
- Associated Chromosomal Disorders: Down syndrome (Trisomy 21) - most commonly associated with low PAPP-A; Edwards syndrome (Trisomy 18); Patau syndrome (Trisomy 13)
- Pregnancy Complications: Low PAPP-A associated with intrauterine growth restriction (IUGR), preeclampsia, placental insufficiency, miscarriage risk, and preterm delivery
- Fetal Development Effects: Abnormal PAPP-A may indicate compromised placental function and reduced nutrient delivery to developing fetus, affecting fetal growth and development
- Maternal Health Implications: Low PAPP-A increases maternal risk for preeclampsia, gestational hypertension, and cardiovascular complications during and after pregnancy
- Potential Perinatal Complications: Stillbirth, neonatal complications, need for neonatal intensive care, congenital anomalies if chromosomal abnormality confirmed
Follow-up Tests
- Immediate Follow-up (Abnormal Results): Detailed ultrasound evaluation of nuchal translucency, nasal bone, cardiac structures, and other fetal anatomy; confirmatory serum markers (beta-hCG, uE3, AFP) if not previously obtained
- Diagnostic Testing: Cell-free DNA testing (non-invasive prenatal testing/NIPT) for high-risk pregnancies; amniocentesis or chorionic villus sampling (CVS) if diagnostic confirmation needed; karyotyping and microarray analysis of fetal cells
- Second Trimester Screening: Repeat PAPP-A measurement in second trimester (15-20 weeks); combined interpretation with triple or quadruple marker screening (AFP, hCG, uE3, inhibin A)
- Surveillance Testing: Serial ultrasound examinations to monitor fetal growth, amniotic fluid volume, umbilical artery Doppler studies if IUGR suspected; increased monitoring frequency in third trimester
- Blood Pressure Monitoring: Regular maternal blood pressure monitoring if low PAPP-A identified; urinalysis to screen for preeclampsia; consideration of prophylactic aspirin therapy in high-risk cases
- Complementary Screening Markers: Beta-hCG (human chorionic gonadotropin) measurement; pregnancy-associated placental protein A retesting; placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) for preeclampsia risk assessment in some cases
- Genetic Counseling: Referral to genetic counselor to discuss results, implications, and options for further testing and management; prenatal consultation with maternal-fetal medicine specialist
- Monitoring Frequency: High-risk pregnancies require more frequent monitoring (biweekly to monthly ultrasounds); routine pregnancies continue with standard prenatal care; individualized follow-up based on specific risk profile and test results
Fasting Required?
- Fasting Requirement: No - Fasting is NOT required for PAPP-A testing. The test can be performed on non-fasting blood samples, and meal intake does not significantly affect PAPP-A measurement.
- Timing Flexibility: Blood sample can be collected at any time of day; no specific fasting window requirement; can be drawn before or after meals without affecting results
- Medications: No medications need to be avoided prior to PAPP-A testing; continue all routine prenatal medications as prescribed, including prenatal vitamins, iron supplements, or thyroid medications
- Patient Preparation: Wear loose-fitting clothing with accessible sleeves for venipuncture; stay well-hydrated to facilitate blood draw; inform healthcare provider of any bleeding disorders or anticoagulant medications
- Gestational Age Documentation: Ensure accurate dating of pregnancy by last menstrual period or prior ultrasound; critical for proper PAPP-A result interpretation, as values are normalized to gestational age-specific medians
- Special Considerations: No need to fast if other tests requiring fasting are also planned; PAPP-A is typically drawn simultaneously with other prenatal screening serum markers; inform laboratory staff of exact gestational age for proper interpretation

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