First-trimester and quad screening

First-trimester combined screening

ACOG says first-trimester screening includes a blood test and an ultrasound exam, usually done together between 10 and 13 weeks of pregnancy. The blood test measures the level of two substances. The ultrasound, called nuchal translucency screening, measures the thickness of a space at the back of the fetus's neck. An abnormal measurement means an increased risk of Down syndrome (trisomy 21) or another type of aneuploidy (an abnormal number of chromosomes), and it is also linked to physical defects of the heart, abdominal wall and skeleton. (ACOG FAQ165)

In England, the combined test is a blood test between 10 and 14 weeks and a scan between 11 and 14 weeks that measures the fluid at the back of the baby's neck. This is combined with the pregnant person's age to work out the chance of the baby having Down's, Edwards' (trisomy 18) or Patau's (trisomy 13) syndrome. (NHS screening leaflet, 2026) The NHS programme calls the combined test the test of choice. (NHS FASP)

The second-trimester quad screen

ACOG says the quad (quadruple) blood test measures four substances and screens for Down syndrome, Edwards syndrome and neural tube defects; it is done between 15 and 22 weeks. A separate ultrasound between 18 and 22 weeks checks for major physical defects. (ACOG FAQ165)

MedlinePlus says the test is most accurate between 16 and 18 weeks and measures four pregnancy hormones: alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), unconjugated estriol (uE3) and inhibin A. Without inhibin A it is called the triple screen. The results are factored in with the pregnant person's age, ethnic background and weight and the baby's gestational age. No special preparation is needed. (MedlinePlus, 2026)

In England, the quadruple test is offered to people who are more than 14 weeks pregnant, as a blood test between 14 and 20 weeks, and it screens for Down's syndrome only. Edwards' and Patau's syndromes are screened for at the 20-week scan instead. (NHS screening leaflet, 2026)

ACOG says results from first- and second-trimester tests can be combined in various ways. Combined results are more accurate than a single test result, but final results often are not available until the second trimester. (ACOG FAQ165)

What a result means

ACOG says blood screening results for aneuploidy are reported as a level of risk. A positive (screen-positive) result means the fetus is at higher risk of the disorder than the general population; it does not mean the fetus definitely has it. A negative result means lower risk; it does not rule the disorder out. (ACOG FAQ165)

The NHS leaflet gives each result as a chance, such as 1 in 150. The bigger the second number, the smaller the chance: to understand 1 in 300, imagine a group of 300 women: one of them is pregnant with a baby that has the condition. In England, a higher chance result is 1 in 150 or higher (for example 1 in 100), and a lower chance result is 1 in 151 or lower (for example 1 in 300). Around 3 out of every 100 screening results are higher chance, and most women with a higher chance result have a baby without any of the conditions. (NHS screening leaflet, 2026)

For the quad screen, MedlinePlus says an abnormal result does NOT mean the baby definitely has a birth defect. Results can be abnormal if the baby is older or younger than thought, so an abnormal result usually leads to another ultrasound to check the baby's age. Higher AFP may also mean more than one baby. (MedlinePlus, 2026) Normal ranges vary slightly between labs. (MedlinePlus, 2026)

How accurate they are, in general terms

Every screening test can give false-positive results (showing a problem that is not there) and false-negative results (missing a problem that is there). ACOG says your health care professional can give you the rates for each test. (ACOG FAQ165) MedlinePlus says the quad screen is slightly more accurate than the triple screen. (MedlinePlus, 2026) The ACOG and SMFM Practice Bulletin says no one test is superior in all circumstances. (ACOG/SMFM PB 226, 2020)

An open-access Australian overview gives approximate figures. It puts sensitivity, which it calls the true-positive rate, at about 90% for combined first-trimester screening, about 75% for second-trimester blood screening (trisomy 21 and 18 only) and 98 to 99% for cell-free DNA screening. It puts specificity, where a higher figure means fewer false-positive results, at about 97%, about 93% and 98 to 99%. (Aust Prescr overview, 2025) Figures from other studies and countries may differ. Read more about false positives.

How they compare with cell-free DNA (NIPT)

Cell-free DNA screening is a different blood test with its own page: Prenatal cell-free DNA screening (NIPT). The NHS leaflet says NIPT is more accurate than the combined or quadruple test. (NHS screening leaflet, 2026) ACOG lists neural tube defects among what the quad test screens for, and links an abnormal nuchal translucency measurement to physical defects of the heart, abdominal wall and skeleton; the conditions it lists for cell-free DNA are Down, Edwards and Patau syndromes and problems with the number of sex chromosomes. (ACOG FAQ165) In England, NIPT is offered as a second screening test after a higher chance combined or quadruple result (between 1 in 2 and 1 in 150). (NHS FASP)

Next steps after a higher-risk result

ACOG says diagnostic testing with chorionic villus sampling (CVS) or amniocentesis, which gives a more definite result, is an option for all pregnant women, and that it is your choice whether to have prenatal testing. An obstetrician or genetic counselor will discuss what the results mean. (ACOG FAQ165) After a higher chance result in England, the options offered are no further testing, a second screening test (NIPT), or a diagnostic test. (NHS screening leaflet, 2026) CVS is usually done from 11 to 14 weeks and amniocentesis after 15 weeks; about 1 in 200 women (0.5%) who have a diagnostic test miscarry because of the test. (NHS screening leaflet, 2026) After a quad screen, MedlinePlus lists more ultrasound, genetic counseling, cell-free DNA screening and amniocentesis as possible next steps, and notes that some people choose not to have more tests. (MedlinePlus, 2026)

This page does not give advice about decisions in pregnancy. The MedlinePlus quad screen page has no "When to contact" section; ask your obstetric care team about your result.

Where they differ:

• Who is offered what. ACOG and SMFM say all patients should be offered both screening and diagnostic tests, and their 2020 bulletin expanded the use of cell-free DNA in all patients regardless of maternal age or baseline risk. (ACOG/SMFM PB 226, 2020) In England, the combined or quadruple test comes first, and NIPT is offered only after a higher chance result. (NHS FASP) (NHS screening leaflet, 2026) The UK NSC recommends screening for Down's syndrome and recommended evaluating NIPT within the programme for results of 1 in 150 or higher. (UK NSC)
• What the quad screen covers. ACOG lists Down syndrome, Edwards syndrome and neural tube defects. (ACOG FAQ165) The English programme uses it for Down's syndrome only, with Edwards' and Patau's screened at the 20-week scan. (NHS screening leaflet, 2026)
• Timing. ACOG gives 10 to 13 weeks for first-trimester screening and 15 to 22 weeks for the quad test. (ACOG FAQ165) The NHS leaflet gives 10 to 14 weeks for the combined blood test and 14 to 20 weeks for the quadruple test. (NHS screening leaflet, 2026)
• How results are reported. ACOG describes positive or negative results as higher or lower risk than the general population. (ACOG FAQ165) The English programme reports a chance with a fixed cutoff of 1 in 150. (NHS screening leaflet, 2026)

Your doctor decides what your result means for you.

Questions people ask

Is a screen-positive result a diagnosis?

No. ACOG says a positive screening result means the fetus is at higher risk of the disorder than the general population, not that it definitely has it. The NHS leaflet says most women with higher chance results will have a baby without any of the conditions. (ACOG FAQ165) (NHS screening leaflet, 2026)

What does 1 in 150 mean?

It is the chance from the screening test. The NHS leaflet explains that the bigger the second number, the smaller the chance, so 1 in 200 is smaller than 1 in 100. In England, 1 in 150 or higher (for example 1 in 100) is a higher chance result, and 1 in 151 or lower (for example 1 in 300) is a lower chance result. (NHS screening leaflet, 2026)

Who is offered this screening?

ACOG and SMFM say each patient should be counseled in each pregnancy about testing for fetal chromosomal abnormalities, and all patients should be offered both screening and diagnostic tests, with the right to accept or decline. In England, screening is offered to people having one baby or twins. (ACOG/SMFM PB 226, 2020) (NHS screening leaflet, 2026)

Why can a quad screen come back abnormal when the baby is fine?

MedlinePlus says an abnormal result does not mean the baby definitely has a birth defect, and results are often abnormal if the baby is older or younger than thought. An abnormal result usually leads to another ultrasound to check the baby's age. (MedlinePlus, 2026)

Is first-trimester screening more accurate than the quad screen?

The NHS leaflet says the quadruple test is not as accurate as the combined test, and that NIPT is more accurate than either. ACOG says results from first- and second-trimester tests can be combined, and combined results are more accurate than a single test. (NHS screening leaflet, 2026) (ACOG FAQ165)

Can the screening test harm the baby?

The NHS leaflet says the screening test cannot harm the pregnant person or the baby. The diagnostic tests that may follow are different: about 1 in 200 women (0.5%) who have one miscarry because of the test. (NHS screening leaflet, 2026)

Related

• Prenatal cell-free DNA screening (NIPT)
• Pregnancy screenings by week
• Genetic carrier screening
• Rh blood type and antibody screen in pregnancy
• False positives and overdiagnosis