Quad Screen (Maternal Serum Screening)

Quad Screen (Quadruple Marker Test): Complete 2026 Guide

Everything you need to know about the second-trimester maternal serum screening test — the four markers (AFP, hCG, uE3, Inhibin A), real detection rates, how results are interpreted, what an abnormal result really means, and how it compares with NIPT today.

Second Trimester Screening AFP • hCG • uE3 • Inhibin A 15–22 Weeks LabDecoded 2026

Quick summary: The Quad Screen is a blood test performed between 15–22 weeks (ideally 16–18 weeks) that measures four substances in the mother’s blood. It estimates the chance of Down syndrome, Trisomy 18, and open neural tube defects. Detection rate for Down syndrome is approximately 80–85% at a 5% false-positive rate — useful, but significantly less accurate than modern NIPT for chromosomal conditions.

📋 Complete Contents

1. What is the Quad Screen?
2. The four markers explained in detail
3. When is the best time to do the test?
4. Accuracy & detection rates (real numbers)
5. How results are interpreted (patterns & MoM)
6. What happens after an abnormal (high-risk) result?
7. Quad Screen vs NIPT – Which is better in 2026?
8. Important limitations
9. Who should still consider the Quad Screen?
10. Frequently asked questions
11. Bottom line & key takeaways

1. What is the Quad Screen?

The Quad Screen (also called Quadruple Marker Test or AFP4) is a second-trimester maternal blood test that measures four biochemical markers: Alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and Inhibin A.

These levels, combined with maternal age, weight, gestational age, and other factors, are used to calculate a personalized risk for:

• Down syndrome (Trisomy 21)
• Edwards syndrome (Trisomy 18)
• Open neural tube defects (spina bifida, anencephaly)
• Sometimes abdominal wall defects

It is a screening test only — it never diagnoses a condition.

2. The Four Markers Explained

• AFP (Alpha-fetoprotein) – Produced by the fetal liver. High levels raise concern for open neural tube defects or abdominal wall defects. Low levels are seen in many Down syndrome and Trisomy 18 pregnancies.
• hCG (Human chorionic gonadotropin) – Pregnancy hormone. Typically elevated in Down syndrome and low in Trisomy 18.
• uE3 (Unconjugated estriol) – A form of estrogen produced by the placenta and fetus. Often low in both Down syndrome and Trisomy 18.
• Inhibin A – Produced mainly by the placenta. Frequently elevated in Down syndrome pregnancies. Adding this fourth marker is what improved detection over the older Triple Test.

3. When Should the Quad Screen Be Done?

Optimal window: 15 weeks 0 days to 22 weeks 6 days. Best performance is usually between 16–18 weeks.

Accurate ultrasound dating (preferably biparietal diameter) is critical for reliable results. No fasting is required.

4. Accuracy & Detection Rates

Condition	Detection Rate (Sensitivity)	False-Positive Rate	Notes
Down Syndrome (T21)	~80–85%	~5%	Most common use
Trisomy 18	~70–80%	~5%	Slightly lower performance
Open Neural Tube Defects	~80–85% (spina bifida) ~90–95% (anencephaly)	Variable	Main strength of AFP component

These figures assume a 5% screen-positive rate. Positive predictive value is much lower than NIPT, especially in younger women.

5. How Results Are Interpreted

Each marker is reported as a Multiple of the Median (MoM). A MoM of 1.0 is exactly average for that gestational age.

Condition	AFP	hCG	uE3	Inhibin A
Down Syndrome	↓	↑	↓	↑
Trisomy 18	↓	↓	↓	↓ or Normal
Open Neural Tube Defect	↑↑	Normal	Normal	Normal

The laboratory combines the four MoM values with maternal age, weight, ethnicity, diabetes status, and exact gestational age to produce a final risk number (e.g., 1 in 150 or 1 in 2,500).

6. What Happens After an Abnormal Result?

A high-risk Quad Screen is not a diagnosis. Next steps usually include:

1. Genetic counseling
2. Detailed anatomy ultrasound
3. Consideration of NIPT (if not already done)
4. Offer of diagnostic testing (amniocentesis ± chromosomal microarray)

Important: Many high-risk Quad results turn out to be false positives. Never make irreversible decisions based on screening alone.

7. Quad Screen vs NIPT in 2026

Feature	Quad Screen	NIPT (cfDNA)
Timing	15–22 weeks	From 10 weeks
Down syndrome detection	~80–85%	>99%
False-positive rate	~5%	<0.5%
Neural tube defects	Yes (via AFP)	No
Current recommendation	Still useful when NIPT unavailable or for NTD screening	Preferred first-line for aneuploidy screening

NIPT has largely replaced the Quad Screen for chromosomal screening in many settings, but the Quad Screen remains valuable for open neural tube defect screening and for patients who present later or cannot access NIPT.

8. Important Limitations

• Screening test only — not diagnostic
• Misses 15–20% of Down syndrome cases
• 5% false-positive rate means many women receive high-risk results unnecessarily
• Does not screen for most microdeletions or other genetic conditions
• Performance depends heavily on accurate dating

9. Who Should Still Consider the Quad Screen?

• Women who missed first-trimester screening
• Patients who cannot access or afford NIPT
• Those specifically wanting neural tube defect risk assessment via AFP
• Situations where NIPT is not suitable (e.g., certain vanishing twin cases)

10. Frequently Asked Questions

Is the Quad Screen mandatory?

No. It is optional. All prenatal screening should be an informed choice after counseling.

Does it detect all genetic disorders?

No. It mainly screens for Down syndrome, Trisomy 18, and open neural tube defects.

Can it be done in IVF or twin pregnancies?

Yes, but the laboratory needs accurate clinical details. Performance is somewhat reduced in twins.

Is fasting required?

No.

What is better – Quad Screen or NIPT?

For chromosomal conditions (Down syndrome, Trisomy 18), NIPT is far more accurate. The Quad Screen still has value for neural tube defect screening.

11. Bottom Line & Key Takeaways

• The Quad Screen is a useful second-trimester screening tool, especially for neural tube defects.
• Detection rate for Down syndrome is ~80–85% — significantly lower than NIPT (>99%).
• It remains relevant when patients present later or when NIPT is not available.
• Any high-risk result requires careful counseling and usually further testing (ultrasound ± NIPT ± amniocentesis).
• Always discuss options with your obstetrician or genetic counselor.

Medical disclaimer: This article is for educational purposes only and does not replace personalized medical advice. Always discuss screening options and results with your healthcare provider.

About LabDecoded

LabDecoded provides clear, evidence-based explanations of laboratory tests. Content is reviewed for clinical accuracy.

Author: Dr. Pawan Gaba | Updated: 2026