Quadruple Marker Test: Timing, Normal Values and How to Read Your Risk Result
The quadruple marker test is the preferred second-trimester screening test performed between 15 weeks 0 days and 20 weeks 6 days. It measures AFP, total hCG, unconjugated oestriol (uE3), and Inhibin A to evaluate risk for Down syndrome, trisomy 18, and open neural tube defects.
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The quadruple marker test (Quad Screen) is the gold-standard second-trimester biochemical screen performed between 15 weeks 0 days and 20 weeks 6 days of pregnancy (ideally 16 to 18 weeks).
It measures four markers in maternal serum: Alpha-Fetoprotein (AFP), total hCG (or free beta-hCG), Unconjugated Oestriol (uE3), and Inhibin A. The addition of Inhibin A provides superior sensitivity compared to the triple test.
The test calculates statistical risk figures for Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and open neural tube defects (spina bifida and anencephaly). It is particularly indicated when the first-trimester double marker window was missed.
Clinical Significance
The quadruple marker test adds Inhibin A to the classic triple screen, significantly improving Down syndrome detection rates to 75–81% at a 5% false-positive rate. Inhibin A is produced by the placenta and is typically elevated in Down syndrome pregnancies (often >2.0 MoM).
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Reference Ranges — Quadruple Marker Test: Timing, Normal Values and How to Read Your Risk Result
NABL-validated intervals · Adults · values may vary by age & sex
| Parameter / Group | Range | Unit | Status |
|---|---|---|---|
| AFP (Unaffected Pregnancy) | 0.5 – 2.0 | MoM | Normal |
| AFP (Neural Tube Defect Risk)Elevated; indicates open spina bifida risk | > 2.0 | MoM | Abnormal |
| AFP (Down Syndrome Pattern)Low level associated with trisomy 21 | < 0.5 | MoM | Abnormal |
| Total hCG (Down Syndrome)Elevated level associated with trisomy 21 | > 2.0 | MoM | Abnormal |
| Unconjugated Oestriol (uE3 Low)Decreased in trisomy 21 & trisomy 18 | < 0.5 | MoM | Abnormal |
| Inhibin A (Down Syndrome)Elevated level significantly improves quad screen accuracy | > 2.0 | MoM | Abnormal |
| Trisomy 21 Risk — Screen Negative | < 1 in 250 | Ratio | Normal |
| Trisomy 21 Risk — Screen PositiveHigh risk result — genetic counselling & NIPT recommended | > 1 in 250 | Ratio | Abnormal |
⚕️ Reference ranges are population-based guidelines. Results must be interpreted in clinical context by a qualified physician. Always consult your doctor before making healthcare decisions.
Frequently Asked Questions
Q: When should the quadruple marker test be done?
A: Between 15 weeks 0 days and 20 weeks 6 days of pregnancy, dated by ultrasound. The optimal window is 16 to 18 weeks.
Q: What does the quadruple marker test detect?
A: It estimates the risk of Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and open neural tube defects such as spina bifida and anencephaly.
Q: Why is the quadruple marker test better than the triple marker test?
A: The quadruple marker adds Inhibin A, which increases the Down syndrome detection rate from ~65-70% (triple marker) to ~75-81% at a 5% false-positive rate.
Q: What is a normal quadruple marker test result?
A: A low-risk or screen-negative result, meaning a calculated trisomy 21 risk below 1 in 250 and an AFP MoM below 2.0 or 2.5.
Q: What does a high risk quadruple marker result mean?
A: It means the calculated probability is above the screening threshold. It does not diagnose a condition. Next steps include genetic counselling, NIPT, level-II ultrasound scan, or amniocentesis.
Q: Do I need to fast for a quadruple marker test?
A: No, fasting is not required. What the test needs is accurate gestational age from an ultrasound scan, maternal date of birth, weight, diabetes status, and smoking history.
Q: Can the quadruple marker test replace the 18–22 week anomaly scan?
A: No. The quadruple marker is a biochemical blood screen, whereas the 18–22 week anomaly scan visually evaluates fetal anatomical structures. Both are complementary and essential.
Q: How are quadruple marker results reported?
A: Results are reported as Multiples of the Median (MoM) for each marker, along with calculated numerical risk ratios (e.g., 1 in 1,500) and an overall screen negative or screen positive status.
Q: Is the quadruple marker test suitable for twin pregnancies?
A: Yes, but interpretation requires specialized twin calculation algorithms. Detection rates are slightly lower in twins compared to singletons.
Q: What happens if I miss the 20-week quadruple marker window?
A: After 20 weeks 6 days, biochemical marker screening cannot be performed. NIPT can still be done, and the detailed ultrasound anomaly scan remains essential.
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The quadruple marker test is the preferred second-trimester biochemical screen. By adding Inhibin A, we achieve significantly higher accuracy for Down syndrome detection than the older triple test. I recommend it for any patient who missed the first-trimester double marker window.
Clinically reviewed · October 2026 · QXL Diagnostics NABL Lab
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