What this test measures
The Quadruple Marker measures four pregnancy-related proteins / hormones in maternal serum between 15 and 22 weeks: AFP (alpha-fetoprotein), uE3 (unconjugated estriol), β-hCG (total or free), and Inhibin A. Each is expressed as a Multiple of the Median (MoM) for the exact gestational age. The combination is then integrated with maternal age, weight, ethnicity, diabetes status, and IVF history to compute personalised risk for trisomy 21 (Down syndrome), trisomy 18 (Edward), and open neural tube defects (spina bifida, anencephaly).
Detection rate for Down syndrome with the Quad Marker is about 80% at a 5% false-positive rate (vs ~70% for the older Triple Marker — Inhibin A is what improves it). It also detects roughly 80% of open neural tube defects (by AFP elevation) and most trisomy 18 cases.
Why it matters
For many Indian women, the booking visit happens after 13+6 weeks — by then the first-trimester (Dual Marker + NT) window has closed and the Quadruple Marker becomes the next-best option. It is the standard second-trimester screen recommended by FOGSI, ICMR, ACOG and RCOG.
For women who had Dual Marker earlier, the Quadruple Marker provides additional information — specifically the AFP for neural tube defect screening, which the Dual Marker does not cover. Some centres combine first- and second-trimester results into an "integrated" or "sequential" screen with detection rates above 95%.
How to prepare
No fasting required. Schedule between 15+0 and 22+0 weeks (best results at 16–18 weeks). Bring a recent dating ultrasound or LMP date — accurate gestational age is critical because MoM is calculated against the expected level for that day of pregnancy. Disclose IVF/IUI, twins, smoking, ethnicity, weight, and any pre-existing diabetes.
Markers & reference ranges
Reference ranges below are typical adult values. Your lab's reported range may differ slightly based on the assay platform and patient demographics — always read your report against the range printed on it.
| Marker | Normal range | If low | If high |
|---|---|---|---|
| AFP (Alpha-fetoprotein) (IU/mL (or MoM))[1] | Median MoM = 1.0 | Low MoM associated with trisomy 21 and trisomy 18. | High MoM (≥2.5) associated with open neural tube defects, abdominal wall defects, multiple gestation, or wrong gestational dating. |
| uE3 (Unconjugated Estriol) (ng/mL (or MoM)) | Median MoM = 1.0 | Low MoM associated with trisomy 21, trisomy 18, and rare disorders like Smith-Lemli-Opitz syndrome and placental sulfatase deficiency. | High MoM not typically associated with chromosomal abnormality. |
| β-hCG (ng/mL (or MoM)) | Median MoM = 1.0 | Low MoM associated with trisomy 18. | High MoM (>2.5) associated with trisomy 21. |
| Inhibin A (pg/mL (or MoM)) | Median MoM = 1.0 | Low MoM associated with trisomy 18. | High MoM (>2.0) associated with trisomy 21 and with placental dysfunction. |
| Risk for Trisomy 21 | Low risk ≥ 1 in 270 | — | ≥ 1 in 270 = screen positive. Recommend NIPT or amniocentesis. |
Quad Marker pattern by condition
| Condition | AFP | uE3 | β-hCG | Inhibin A |
|---|---|---|---|---|
| Unaffected | Normal | Normal | Normal | Normal |
| Trisomy 21 (Down) | ↓ | ↓ | ↑ | ↑ |
| Trisomy 18 (Edward) | ↓ | ↓ | ↓ | ↓ or normal |
| Open neural tube defect | ↑↑ | Normal | Normal | Normal |
| Wrong gestational age | Often ↑ or ↓ | Often ↑ or ↓ | Often ↑ or ↓ | Often ↑ or ↓ |
Frequently asked questions
When should the Quadruple Marker be done?
Between 15+0 and 22+0 weeks, ideally at 16–18 weeks for best accuracy.
Do I need to fast?
No.
Is the Quadruple Marker better than the Dual Marker?
They cover different things. The Dual Marker (with NT scan) is done at 11–13 weeks and detects ~85–90% of Down syndrome cases. The Quad Marker is done at 15–22 weeks, detects ~80% of Down syndrome, and additionally screens for neural tube defects (which the Dual Marker cannot). If you can choose, first-trimester screening is preferred because it gives more time for follow-up.
I already did the Dual Marker — do I still need a Quad?
Not for chromosomes — your first-trimester result already covers that. However, if your Dual Marker did not include AFP, your doctor may add an AFP (or full Quad) for neural tube defect screening. A detailed anomaly scan at 18–22 weeks is the other key check.
My result says "screen positive" — does that mean my baby has Down syndrome?
No. "Screen positive" means your calculated risk is above the cutoff (typically 1 in 270). It does not confirm anything. About 95% of "screen positive" Quad results turn out to be normal babies. The next step is genetic counselling and either NIPT or amniocentesis.
What does a high AFP mean?
A high AFP can indicate an open neural tube defect (spina bifida, anencephaly), an abdominal wall defect, multiple pregnancy, or simply wrong gestational dating. An anomaly scan at 18–22 weeks is the next step.
Can it be done in twins?
Yes, but accuracy is lower in twins. NIPT is often preferred for twin pregnancies.
How does it compare to NIPT?
NIPT (cell-free foetal DNA) detects >99% of Down syndrome cases vs ~80% for the Quad. NIPT is more expensive (₹8,000–15,000 in India) and does not screen for neural tube defects. Many centres use NIPT as the primary screen and the Quad mainly for AFP / neural tube screening.
Related Pregnancy / Prenatal tests
Tests commonly ordered alongside Quadruple Marker, or that help interpret an unexpected result.
Sources & references
- ACOG — Screening for Fetal Chromosomal Abnormalities · accessed 2026-05-30T00:00:00.000Z
- NIH MedlinePlus — Second Trimester Screening · accessed 2026-05-30T00:00:00.000Z
- RCOG — Antenatal Screening · accessed 2026-05-30T00:00:00.000Z
- FOGSI — Antenatal Care Recommendations · accessed 2026-05-30T00:00:00.000Z
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