Quad Screen: What the Second-Trimester Blood Test Checks For and What Results Mean

Written and medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: November 2026 · How we review

Quick Answer

The quad screen (quadruple marker screen) is an optional blood test done in the second trimester of pregnancy, usually between 15 and 22 weeks. It measures four substances in the blood to estimate the chance of Down syndrome, trisomy 18 and neural tube defects such as spina bifida. An abnormal result means a higher chance, not a diagnosis.

What the research says

• Combining markers across trimesters works best: a Cochrane review of 22 studies and 228,615 pregnancies found that a strategy combining first-trimester ultrasound and blood markers with the second-trimester markers (hCG, estriol, AFP and inhibin-A) and maternal age detected about 9 in 10 Down syndrome pregnancies at a 5% false positive rate (Alldred SK et al., Cochrane Database of Systematic Reviews, 2017) [2]

• Cell-free DNA screening is more accurate: in 15,841 pregnant women in routine care, cell-free DNA testing detected 38 of 38 Down syndrome pregnancies (100%) with a 0.06% false positive rate, compared with 78.9% and 5.4% for standard marker-and-ultrasound screening (Norton ME et al., New England Journal of Medicine, 2015) [3]

Key takeaways

• An optional second-trimester screening blood test, offered to all pregnant people.

• Measures AFP, hCG, unconjugated estriol (uE3) and inhibin-A.

• Screens for trisomy 21, trisomy 18 and neural tube defects, and can hint at abdominal wall defects.

• A simple blood draw with no preparation and no risk to the pregnancy; results in about 4–5 days.

• An abnormal result leads to a detailed ultrasound, cell-free DNA testing or amniocentesis.

What is the quad screen?

During pregnancy, the placenta and the baby make substances that pass into the pregnant person's blood. Their levels change with each week of pregnancy, and certain patterns are more common when the baby has a chromosome condition or a defect in the spine or brain. The quad screen measures four of these markers and uses a formula that also includes your age, weight, ethnicity, number of babies and the exact week of pregnancy to calculate a risk estimate. Sources: [1]

The quad screen is a blood test in the second trimester.

Why is the test done?

The quad screen is optional, but providers offer it to everyone because conditions like Down syndrome can occur at any maternal age. It screens for: Sources: [1]

• Trisomy 21 (Down syndrome): an extra copy of chromosome 21.

• Trisomy 18 (Edwards syndrome): an extra copy of chromosome 18.

• Neural tube defects: such as spina bifida and anencephaly.

• Abdominal wall defects: such as gastroschisis or omphalocele, suggested by a high AFP.

The four markers

Each marker is compared with the expected level for your week of pregnancy.

Marker	Made by	Result linked with a higher chance of a condition
AFP (alpha-fetoprotein)	The baby's liver	High: neural tube or abdominal wall defect (or more advanced pregnancy, twins). Low: Down syndrome
hCG (human chorionic gonadotropin)	The placenta	Higher than expected: Down syndrome
uE3 (unconjugated estriol)	The baby and placenta	Lower than expected: Down syndrome
Inhibin-A	The placenta	Higher than expected: Down syndrome

Sources: [1]

How do I prepare?

No special preparation is needed. Because results depend on your exact stage of pregnancy, make sure your provider has an accurate due date, ideally from an early ultrasound. Sources: [1]

What happens during the test?

1. A phlebotomist cleans the skin on your arm.

2. A needle draws a small sample of blood from a vein.

3. The sample is sent to a lab, which measures the four markers and calculates your risk. Sources: [1]

The draw takes about 5–10 minutes. You may feel a brief sting and have a small bruise, but the test has no health risks for you or the baby. Sources: [1]

Understanding your results

Results usually come back in about 4–5 days, depending on the lab. They are reported as a risk estimate, for example "1 in 1,000" or "1 in 50," and labeled screen-negative or screen-positive. Sources: [1]

• Normal (screen-negative): the baby is not at higher risk for these conditions. This is reassuring but doesn't guarantee a healthy pregnancy.

• Abnormal (screen-positive): a higher chance of a condition. Most people with a positive screen have a healthy baby; the result often reflects a wrong due date, twins or normal variation. Sources: [1]

After an abnormal result, your provider may recommend a detailed ultrasound, cell-free DNA testing or amniocentesis, which can diagnose chromosome conditions. Genetic counseling helps you weigh these options. Sources: [1]

Quad screen vs cell-free DNA (NIPT)

Both are screening tests; diagnostic tests confirm a result.

Cell-free DNA screening (NIPT) can be done from about 10 weeks and analyzes fragments of the baby's DNA in your blood. In a large study it detected all Down syndrome pregnancies with far fewer false positives than standard screening. NIPT doesn't screen for neural tube defects, though, so AFP blood testing or a detailed ultrasound is still used for those. Sources: [1, 2, 3]

Conclusion

The quad screen is a safe, simple second-trimester blood test that estimates the chance of Down syndrome, trisomy 18 and neural tube defects. Remember that it's a screen: an abnormal result is a reason for follow-up testing and counseling, not a diagnosis. Ask your provider which screening options fit your pregnancy.

Keep learning: read about the AFP test and prenatal genetic testing.

Frequently asked questions

When is the quad screen done?

Between about 15 and 22 weeks of pregnancy; results are most accurate at 16–18 weeks.

What does the quad screen test for?

Down syndrome (trisomy 21), trisomy 18 and neural tube defects such as spina bifida.

What are the four markers?

AFP, hCG, unconjugated estriol and inhibin-A.

Is the quad screen required?

No. It's optional, though providers offer it to all pregnant people.

Is the test safe for the baby?

Yes. It's a simple blood draw from the pregnant person with no risk to the pregnancy.

How long do results take?

Usually about 4–5 days.

What does a positive quad screen mean?

A higher chance of a condition, not a diagnosis. Most people with a positive screen have a healthy baby.

What happens after an abnormal result?

Usually a detailed ultrasound, cell-free DNA testing or amniocentesis, with genetic counseling.

Is NIPT better than the quad screen?

NIPT is more accurate for Down syndrome, but it doesn't screen for neural tube defects.

Do I need to fast before the test?

No. No special preparation is needed.

Related Reading

Down Syndrome: Symptoms, Causes, Types & Life Expectancy — Complete Guide the main condition the quad screen looks for.

Understanding Neural Tube Defects: Types, Causes, and Prevention birth defects flagged by a high AFP.

Edwards Syndrome (Trisomy 18): Symptoms, Causes, Diagnosis, Treatment, Survival Rates and When to Seek Emergency Care — What You Need to Know trisomy 18, also included in the screen.

NIPT Test (Noninvasive Prenatal Testing): What It Screens For, Accuracy and Results the cell-free DNA screening alternative.

Amniocentesis: Why It's Done, What Happens, Risks and What Your Results Mean the diagnostic test that can follow an abnormal screen.

References

1. Cleveland Clinic. Quad Marker Screen: Purpose, Procedure & Results. Cleveland Clinic. Last updated June 12, 2023. https://my.clevelandclinic.org/health/diagnostics/4698-pregnancy-quad-marker-screen

2. Alldred SK, Takwoingi Y, Guo B, et al. First and second trimester serum tests with and without first trimester ultrasound tests for Down's syndrome screening. Cochrane Database of Systematic Reviews. 2017;3(3):CD012599. PMID 28295159. https://doi.org/10.1002/14651858.CD012599

3. Norton ME, Jacobsson B, Swamy GK, et al. Cell-free DNA analysis for noninvasive examination of trisomy. New England Journal of Medicine. 2015;372(17):1589-1597. PMID 25830321. https://doi.org/10.1056/NEJMoa1407349

Medical disclaimer

This article is for general education only and does not replace advice from a qualified healthcare professional. Talk to your doctor about your own diagnosis and treatment, and seek emergency care right away for severe or sudden symptoms.