Testing for Down syndrome happens in two stages during pregnancy: screening tests that estimate risk, and diagnostic tests that give a definitive answer. Every pregnant person is now recommended access to screening regardless of age, and the most accurate screening option, cell-free DNA testing, can be done as early as 10 weeks into pregnancy.
Screening vs. Diagnostic Tests
The distinction matters. Screening tests tell you the likelihood that a baby has Down syndrome, but they can’t confirm it. They carry no physical risk to the pregnancy. Diagnostic tests analyze actual fetal chromosomes and provide a yes-or-no answer, but they require collecting a small tissue or fluid sample from inside the uterus, which carries a slight risk of miscarriage.
Most people start with screening. If a screening test comes back high-risk, the next step is a diagnostic test to confirm or rule out the result. Some people skip screening entirely and go straight to diagnostic testing, which is a valid choice at any age.
First Trimester Combined Screening (Weeks 11 to 13)
This is one of the earliest screening options. It combines two things: an ultrasound measurement of the fluid at the back of the baby’s neck (called nuchal translucency) and a blood draw from the mother measuring two proteins produced by the placenta.
In a typical pregnancy, the fluid pocket behind the baby’s neck measures between 1.0 and 1.65 mm depending on gestational age. The 95th percentile ranges from 1.8 to 2.35 mm. Measurements above 3.5 mm are associated with the highest risk of chromosomal abnormalities. The ultrasound alone isn’t enough to assess risk, which is why it’s paired with the blood markers.
When the ultrasound and blood results are combined with maternal age, this screening detects about 85 to 90 percent of Down syndrome cases, with a false positive rate around 5 percent. That means roughly 1 in 20 women screened will get a high-risk result even though their baby doesn’t have Down syndrome. A high-risk result from this screen is not a diagnosis. It’s a signal that further testing is worth considering.
Cell-Free DNA Screening, or NIPT (Week 10 Onward)
Cell-free DNA screening, commonly called NIPT (noninvasive prenatal testing), is the most accurate screening test available. It’s a simple blood draw from the mother’s arm. Small fragments of the baby’s DNA circulate in the mother’s bloodstream, and the test analyzes these fragments to detect extra copies of chromosome 21.
NIPT detects Down syndrome with about 99 percent sensitivity and 99.5 percent specificity. Its false positive rate is remarkably low at 0.06 percent, compared to 5.4 percent for first trimester combined screening. When NIPT flags a high-risk result, the chance that the baby actually has Down syndrome (the positive predictive value) is around 81 percent. That’s a dramatic improvement over the 3.4 percent positive predictive value of traditional first trimester screening, but it still means roughly 1 in 5 high-risk NIPT results are false positives.
The American College of Obstetricians and Gynecologists now recommends that cell-free DNA screening be routinely available to all pregnant patients, not just those over 35 or those considered high-risk. It’s also recommended as a first-line screening option for twin pregnancies. Despite its accuracy, NIPT remains a screening test. A positive result still needs confirmation through diagnostic testing.
Second Trimester Blood Screening (Weeks 15 to 20)
The quad screen is a blood test that measures four substances: alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), a form of estrogen called estriol, and a hormone called inhibin-A. In pregnancies affected by Down syndrome, AFP levels tend to be lower than expected. The results are combined with maternal age to calculate a risk estimate.
Some providers use the quad screen alone. Others combine first and second trimester blood results into what’s called integrated or sequential screening to improve accuracy. The quad screen is typically offered if you missed the window for first trimester screening or if NIPT isn’t available.
Chorionic Villus Sampling (Weeks 11 to 14)
CVS is a diagnostic test, meaning it provides a definitive answer. It involves collecting a tiny sample of tissue from the placenta, which shares the baby’s genetic makeup. There are two approaches. In the transabdominal method, a thin needle is guided through the abdomen into the placenta using ultrasound for guidance. In the transcervical method, a thin tube is passed through the cervix to reach the placenta. Both take only a few minutes.
The main advantage of CVS is timing. It can be done earlier than amniocentesis, giving families more time to process results and make decisions. The procedure-related pregnancy loss rate is low. One large cohort study found pregnancy loss occurred in about 1 percent of CVS procedures, a rate that was not statistically different from the matched control group of women who didn’t have the procedure. Current estimates place the added risk attributable to the procedure itself at under 0.5 percent.
Amniocentesis (Week 16 Onward)
Amniocentesis is the other diagnostic option. A thin needle is inserted through the abdomen into the amniotic sac, and a small amount of amniotic fluid is withdrawn. The fluid contains fetal cells that can be analyzed for chromosomal abnormalities. Like CVS, the needle is guided by ultrasound throughout the procedure.
The pregnancy loss rate after amniocentesis is approximately 0.8 percent, and recent studies suggest the procedure-related risk is also below 0.5 percent. Recovery is straightforward for most women: mild cramping and soreness at the needle site for a day or two. Results from the full chromosome analysis (karyotype) typically take one to two weeks. A rapid preliminary result using a technique that targets specific chromosomes can sometimes be available within a couple of days.
How the Lab Confirms a Diagnosis
Whether tissue comes from CVS or amniocentesis, the lab runs a karyotype, which is a visual map of all 46 chromosomes arranged in pairs. In Down syndrome, there are three copies of chromosome 21 instead of two. A rapid test can flag common chromosome abnormalities within days, but the full karyotype remains the gold standard because it can also detect structural rearrangements and mosaic patterns, where only some cells carry the extra chromosome.
Testing After Birth
Some families don’t pursue prenatal testing, or results are inconclusive. Down syndrome can also be identified after a baby is born based on physical features that are often apparent right away: a flat nasal bridge, upward-slanting eyes, a short neck, small ears and hands, a single crease across the palm, and low muscle tone. These features vary from baby to baby, so a clinical suspicion is always confirmed with a blood karyotype test. A small blood sample is drawn and the chromosomes are examined under a microscope to check for the extra copy of chromosome 21. This test provides a definitive diagnosis, usually within one to two weeks.
Choosing a Testing Path
There’s no single correct sequence. Some people start with NIPT because of its accuracy and low false positive rate. Others begin with first trimester combined screening because it also evaluates the baby’s anatomy via ultrasound. Some skip screening entirely and opt for CVS or amniocentesis from the start, especially if they know they want a definitive answer regardless of screening results.
Your choices may also depend on timing. If you’re already past 14 weeks, CVS is no longer an option, and the quad screen or amniocentesis become the relevant tests. If you’re past 20 weeks, amniocentesis is the primary diagnostic route. The key point is that screening and diagnostic testing are available to everyone, not limited by age or risk category, and you can pursue or decline any of them at any stage.