Testing for Down syndrome happens in two stages: screening tests that estimate risk, and diagnostic tests that give a definitive answer. Screening is now recommended for all pregnant people regardless of age, and most testing begins as early as 10 weeks into pregnancy. Here’s how each test works, when it’s done, and what the results actually tell you.
Screening vs. Diagnostic Tests
The distinction matters. Screening tests tell you the probability that a pregnancy is affected by Down syndrome. They carry no risk to the pregnancy but can produce false positives and false negatives. A screening result is never a diagnosis.
Diagnostic tests analyze the actual chromosomes of the fetus and give a yes-or-no answer. They require collecting fetal cells, which involves a needle procedure and a small risk of complications. A positive screening result is always followed up with a diagnostic test before any diagnosis is confirmed.
Cell-Free DNA Screening (NIPT)
The most accurate screening option is cell-free DNA testing, often called NIPT (non-invasive prenatal testing). It’s a simple blood draw from your arm, available from around 10 weeks of pregnancy onward. The test picks up tiny fragments of fetal DNA circulating in your bloodstream and checks whether there’s extra material from chromosome 21.
A large meta-analysis of 40 studies found NIPT detects Down syndrome with 99.3% sensitivity and 99.9% specificity. That means it catches nearly every affected pregnancy and almost never flags an unaffected one. The American College of Obstetricians and Gynecologists now recommends cell-free DNA screening be routinely available to all obstetric patients as the most sensitive and specific screening option for Down syndrome.
Despite those impressive numbers, NIPT is still a screening test. A positive result needs confirmation through amniocentesis or chorionic villus sampling. Occasionally, the lab can’t return a result at all, which itself raises the statistical risk and warrants further evaluation.
First Trimester Combined Screening
Before NIPT became widely available, combined first trimester screening was the standard early option, and it’s still used when NIPT isn’t accessible or isn’t appropriate (for example, in certain twin pregnancies or when insurance doesn’t cover cell-free DNA testing). It’s performed between weeks 11 and 13.
This screening has two parts. The first is a specialized ultrasound called a nuchal translucency scan, which measures the pocket of fluid at the back of the fetus’s neck. All fetuses have some fluid there, but a measurement above 3 millimeters at 12 weeks raises concern. The second part is a blood test measuring two pregnancy-related hormones. Your age, the ultrasound measurement, and the blood results are combined into a single risk estimate.
Second Trimester Blood Screening
Between weeks 15 and 22, a blood test called the quad screen can assess risk by measuring four substances in your blood. In pregnancies affected by Down syndrome, these markers shift in a characteristic pattern: two of the four (a protein called AFP and a hormone called unconjugated estriol) tend to be lower than expected, while the other two (hCG and inhibin-A) tend to be higher. The lab combines all four levels with your age and gestational timing to calculate a risk number.
The quad screen is less accurate than NIPT, but it remains relevant for patients who missed first trimester screening or who prefer it after counseling. Some providers offer an “integrated” approach that combines first and second trimester blood results for better accuracy than either test alone.
Diagnostic Testing: CVS and Amniocentesis
When screening suggests an increased risk, or when you want a definitive answer regardless of screening results, the next step is diagnostic testing. Two procedures are available, and the main difference is timing.
Chorionic villus sampling (CVS) can be done earlier, typically between weeks 10 and 13. It collects a tiny sample of tissue from the placenta, which shares the fetus’s genetic makeup. A needle is guided by ultrasound either through the abdomen or through the cervix.
Amniocentesis is performed later, usually between weeks 15 and 20. During the procedure, an ultrasound guides a thin needle through the abdominal wall and into the uterus, where a small amount of amniotic fluid is drawn into a syringe. That fluid contains fetal cells that can be analyzed in the lab.
Both procedures give a definitive chromosome-level diagnosis. The commonly quoted risk of procedure-related miscarriage is lower than many people expect. A pooled analysis found the additional miscarriage risk from amniocentesis is about 0.3% at most (roughly 1 in 300), and for CVS the data showed no statistically significant increase in risk compared to pregnancies where no procedure was performed.
What Happens in the Lab
Once fetal cells are collected, the lab can run several types of analysis. The most common is a karyotype: technicians stain the chromosomes so they’re visible under a microscope, then arrange them into pairs and count them. A typical human cell has 46 chromosomes in 23 pairs. In Down syndrome, there are three copies of chromosome 21 instead of two, making 47 total. The stained chromosomes show a distinct banding pattern that also reveals whether the extra chromosome is a full extra copy, part of a translocation (where it’s attached to another chromosome), or present in only some cells.
For faster preliminary results, labs sometimes use a technique called FISH, which tags chromosome 21 with a fluorescent marker and can confirm an extra copy within a day or two rather than the one to two weeks a full karyotype takes. FISH results are always confirmed with a complete karyotype because only the full analysis reveals the specific type of trisomy 21, which matters for genetic counseling about recurrence risk in future pregnancies.
Chromosomal microarray analysis offers even more detail than a standard karyotype, detecting smaller missing or extra segments of DNA. It’s not always necessary for a straightforward Down syndrome diagnosis but may be used when results are ambiguous or when doctors want to check for additional chromosomal differences.
Diagnosis After Birth
Sometimes Down syndrome is first identified at delivery. Doctors may notice physical features such as low muscle tone, a flat facial profile, upward-slanting eyes, a single deep crease across the palm, or short hands with a curved fifth finger. These features vary widely, and no single sign is enough to make a diagnosis on its own.
A clinical suspicion at birth is always confirmed with a blood test for chromosomal analysis. A sample of the newborn’s blood is sent for karyotyping, which provides the definitive diagnosis and identifies the genetic type. FISH testing may be used for a rapid preliminary result within 24 to 48 hours while the full karyotype is processed.
Choosing Which Tests to Have
Every patient has the right to pursue or decline any prenatal genetic screening and diagnostic testing. There’s no single “right” path. Some people want every piece of information as early as possible. Others prefer to skip screening entirely. Your decision may depend on what you would do with the results, how you feel about the small procedural risk of diagnostic testing, and how much uncertainty you’re comfortable with.
If you opt for screening, NIPT is now considered the first-line option for Down syndrome detection. A low-risk NIPT result is highly reassuring. A high-risk result is not a diagnosis, and you’ll be offered genetic counseling and a diagnostic procedure to confirm or rule it out before any conclusions are drawn.