A clinician-friendly comparison of Dual (first-trimester) vs Triple and Quad (second-trimester) maternal serum screening tests — markers measured, expected detection ranges, timing, and practical limitations.
Quick summary
In brief: Dual marker (first trimester) is an early screen combining biochemical markers (free β-hCG + PAPP-A) with nuchal translucency (NT) ultrasound and offers good early detection. Triple and Quad marker tests are second-trimester screens — Quad adds inhibin-A to the triple panel and modestly increases detection of Down syndrome. All are screening tests (not diagnostic); positive screens need follow-up with NIPT or invasive testing (CVS/amniocentesis).
Side-by-side comparison
| Feature | Dual Marker (1st Trimester) | Triple Marker (2nd Trimester) | Quad Marker (2nd Trimester) |
|---|---|---|---|
| Timing | 11–14 weeks (combined with NT ultrasound) | 15–20 weeks | 15–20 weeks |
| Markers measured | Free β-hCG, PAPP-A (+ NT) | AFP, total hCG, unconjugated estriol (uE3) | AFP, total hCG, uE3, Inhibin-A |
| Primary conditions screened | Trisomy 21 (Down), Trisomy 18 (less often), general risk | Trisomy 21, Trisomy 18, Neural tube defects (AFP) | Trisomy 21, Trisomy 18, Neural tube defects (AFP) — better Down detection than triple |
| Typical detection range (approx.) | ~60–85% for Down syndrome depending on whether NT is included (combined screening higher). Early detection advantage. | ~65–75% for Down syndrome (varies by population & protocol). | ~70–80% for Down syndrome — modest improvement over triple (due to Inhibin-A). |
| False positive rate | Typically set around 5% in many screening programs (varies). | Often calibrated around 5% (depends on lab cutoffs). | Often calibrated around 5% (may give slightly higher PPV than triple). |
| Strengths | Early timing; allows earlier decision-making and follow-up; combined screening (NT + markers) increases detection. | Includes AFP — screens for neural tube defects; widely available. | Improved sensitivity for Down syndrome vs triple; retains AFP for NTD screening. |
| Limitations | Depends on accurate NT measurement and correct gestational dating; biochemical markers alone are less accurate than when combined with NT. | Later timing (can't detect as early); lower Down detection than combined first-trimester screening in many settings. | Still a screening test — positive result requires diagnostic confirmation; limited specificity. |
Note: Detection ranges are approximate and depend on protocol, population, gestational dating, and whether ultrasound parameters (like NT) are included. These numbers are intended to give an overview rather than absolute guarantees.
The science behind detection differences
Detection rate differences arise because each test measures different biologic signals and because timing matters. The first trimester combined approach (biochemistry + NT) captures early placental and fetal changes — this often increases detection for chromosomal anomalies earlier in pregnancy. In the second trimester, the triple panel adds AFP (useful for neural tube defects), while the quad panel adds inhibin-A to refine Down syndrome risk estimates.
Why adding Inhibin-A helps
Inhibin-A, a placental glycoprotein, tends to be elevated in pregnancies affected by Down syndrome. When added to the triple screen it modestly increases sensitivity (detection) for trisomy 21 — hence the quad panel is generally more sensitive than the triple.
Role of MoM and maternal factors
Laboratories report marker values as MoM (Multiples of the Median), which normalizes for gestational age. Risk calculations adjust for maternal age, weight, ethnicity, insulin use, and gestational dating. Proper dating (via ultrasound) is critical — misdating can change MoM values and alter risk classification.
What to do after a positive screen
- Don't panic — a positive (high-risk) screen indicates increased probability, not diagnosis.
- Offer a non-invasive cell-free DNA test (NIPT) for higher sensitivity and specificity for common trisomies.
- If NIPT is positive (or if clinical decisions require it), discuss diagnostic testing (CVS in 1st trimester or amniocentesis in 2nd trimester).
- Consider repeat ultrasound for structural markers and ensure correct gestational dating.
Frequently asked questions (FAQ)
Is the quad screen better than the triple screen?
Generally yes — adding Inhibin-A in the quad panel modestly improves detection for Down syndrome compared to the triple screen while keeping AFP (useful for neural tube defect screening).
Should I do the first-trimester dual marker or wait for quad?
If you want earlier risk assessment, first-trimester combined screening (NT + dual markers) is recommended. Many programs prefer first-trimester combined screening followed by targeted second-trimester tests if needed.
Are these tests diagnostic?
No — Dual, Triple and Quad are screening tests. Positive results require confirmatory diagnostic testing such as CVS or amniocentesis.
0 Comments