Blood tests to screen for chromosomal abnormalities during pregnancy are widely used today. These prenatal screening tests analyze small fragments of DNA from the fetus that are present in the mother’s bloodstream. The tests can screen for common chromosomal abnormalities like Down syndrome, trisomy 18, and trisomy 13. However, the accuracy of these blood tests varies depending on the specific condition being screened for as well as other factors.
What are the main prenatal blood screening tests?
There are two main types of blood tests used for prenatal genetic screening:
- Cell-free DNA (cfDNA) screening, also known as non-invasive prenatal testing (NIPT)
- Quad/triple screenings
Cell-free DNA (cfDNA) tests analyze fragments of DNA from the placenta that are circulating in the mother’s blood. This DNA comes from the fetus and can be used to screen for certain chromosomal abnormalities. cfDNA testing is considered the most accurate prenatal screening test. It is recommended as a primary screening option by the American College of Obstetricians and Gynecologists.
Quad screenings (also called multiple marker screenings) measure 4 pregnancy-related hormones or biomarkers in the mother’s blood. The levels of these markers can indicate an increased risk for certain birth defects. Triple screenings measure 3 markers instead of 4.
How accurate are cfDNA tests?
Cell-free DNA tests are considered highly accurate for screening for common trisomies like Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13). Detection rates are around 99% with false positive rates of less than 1% for these conditions.
Here is the reported accuracy of cfDNA testing for Down syndrome specifically:
| Screening Test | Detection Rate | False Positive Rate |
|---|---|---|
| cfDNA | 99% | 0.1% |
This means that cfDNA testing will correctly identify Down syndrome in 99% of affected pregnancies, while less than 1% of women without an affected pregnancy will receive a false positive result.
cfDNA testing is not quite as accurate for rarer trisomies like trisomy 16 and trisomy 22, with detection rates of around 93% for these conditions. Screening for microdeletions or partial chromosomal deletions is overall less accurate than screening for whole chromosomal abnormalities like trisomies.
What affects the accuracy of cfDNA testing?
There are several factors that can impact the accuracy of cell-free DNA testing:
- Maternal weight: Higher maternal weight is associated with a reduced accuracy. Obese women have lower circulating cfDNA levels, which makes analysis more difficult.
- Multiple gestations: Screening is less accurate with twin or multiple pregnancies.
- Mosaicism: Mosaic fetal chromosomal abnormalities, where some cells are normal and some are abnormal, are challenging to detect.
- Related conditions: Conditions that mimic the screening targets, like placental mosaicism, can lead to false positives.
Low fetal fraction, meaning a low percentage of cfDNA originating from the fetus, can also reduce accuracy. Factors like high maternal weight and early gestational age negatively impact fetal fraction.
How accurate are traditional screenings?
Standard multiple marker screening tests like the quad screen are significantly less accurate than cfDNA testing. Detection rates for Down syndrome are around 80% with false positive rates of 5%, compared to 99% and 0.1% for cfDNA tests.
Here is a comparison of quad screening versus cfDNA testing for Down syndrome:
| Screening Test | Detection Rate | False Positive Rate |
|---|---|---|
| Quad Screen | 81% | 5% |
| cfDNA | 99% | 0.1% |
Standard screenings like the quad or triple test measure different pregnancy biomarkers that are indirectly associated with chromosomal abnormalities. This makes them inherently less accurate than tests like cfDNA that directly analyze fetal DNA.
Traditional screenings have significantly lower detection rates and higher false positive rates for trisomy 18 and 13 as well. Some centers have moved away from standard screenings altogether and now offer cfDNA testing as a first-tier screening option.
Should standard screenings still be used?
Professional groups like the American College of Obstetricians and Gynecologists recommend cfDNA screening as the primary screening choice for all pregnant women. However, standard screenings may still be useful in certain situations:
- As a secondary screening after abnormal cfDNA results to help confirm a diagnosis
- When cfDNA testing is declined or not available
- In lower-risk women when the benefit of cfDNA screening may not outweigh the cost
In some cases, cfDNA screening is followed by a standard quad or triple screening as a secondary test. This dual approach can maximize detection rates while minimizing false positives. This sequential screening strategy identifies the highest risk pregnancies most accurately.
Should women get multiple screening tests?
Getting multiple forms of prenatal screening, like a cfDNA test plus a quad or triple screen, was once a common approach. However, practice guidelines have moved away from recommending multiple sequential screenings.
The disadvantages of multiple screening include:
- Higher cost of multiple tests
- Increased patient anxiety around multiple results
- Diminishing improvements in detection with a second screening
The current recommendation is to offer cfDNA screening as a first-line test whenever possible due to its superior accuracy. Multiple marker screening should not routinely be offered following a cfDNA test unless the cfDNA results are abnormal or unavailable.
Can blood tests detect all chromosomal abnormalities?
Current prenatal blood screening tests cannot detect all types of chromosomal abnormalities. Here are some limitations:
- Balanced translocations and inversions typically cannot be identified from cfDNA testing.
- Low-level fetal mosaicism is challenging to detect.
- Rare and atypical chromosomal abnormalities may not be picked up.
- Certain microdeletions may not be included in the screening panel.
A normal screening result reduces but does not eliminate the chance for chromosomal abnormalities. Definitive diagnosis requires prenatal diagnosis with amniocentesis or chorionic villus sampling (CVS).
What do abnormal blood screening results mean?
An abnormal or positive screening result indicates an increased risk that the fetus may have a chromosomal disorder like Down syndrome. However, it does not diagnose the condition definitively.
Next steps after an abnormal screening result may include:
- Counseling on the limitations of screening tests
- Repeating the blood screening test
- Performing an ultrasound to look for birth defects
- Offering invasive diagnostic testing like amniocentesis or CVS
Only about 5% of women with a positive cfDNA screening result will have an affected pregnancy. Follow-up invasive testing is recommended for confirmation.
How are blood screening tests regulated?
In the United States, the Food and Drug Administration (FDA) regulates cfDNA and other blood screening tests as medical devices. These tests must meet certain validation requirements and performance standards to be approved for clinical use. Ongoing data collection monitors the tests’ real-world performance.
The FDA has an oversight program called the Laboratory Developed Test program which includes many prenatal genetic screening tests. These are tests designed and used within a single laboratory that are not distributed or sold to other labs. This provides a streamlined path for new screening tests to become available clinically while still requiring validation.
Conclusion
Prenatal blood screening provides valuable information about the risk of common chromosomal abnormalities. Cell-free DNA testing offers significantly improved accuracy over standard screening methods like the quad screen. However, both cfDNA and standard screenings have limitations in the range of chromosomal abnormalities they can detect.
Professional groups recommend offering cfDNA screening to all pregnant women given its high performance. Additional screening offers limited benefit after a negative cfDNA test. Women should be informed about the residual risk that exists with even normal prenatal screening results. Definitive diagnosis of chromosomal abnormalities requires invasive testing like amniocentesis or CVS.