A double marker test is a type of blood screening that measures two substances to help estimate the risk of certain chromosomal abnormalities in a pregnancy. It is one version of several “multiple marker screening” tests used during pregnancy.
Double marker blood tests measure two substances, or markers, in the mother’s blood:
- Pregnancy-associated plasma protein A (PAPP-A)
- Human chorionic gonadotropin (hCG)
Abnormal levels of these markers may indicate an increased risk for certain genetic disorders in the fetus such as Down syndrome. While not diagnostic, double marker tests help assess whether further diagnostic testing may be warranted.
How Do Double Marker Tests Work?
Double marker screening tests are typically performed between weeks 15-20 of pregnancy. During this timeframe, levels of both PAPP-A and hCG can be measured in the mother’s bloodstream.
PAPP-A is produced by the placenta during pregnancy while hCG is made by the placenta and fetus. Both markers normally increase throughout a healthy pregnancy.
Too much or too little of these markers in the blood may signify chromosomal or genetic issues with the fetus. Abnormal levels are associated with:
- Down syndrome
- Trisomy 18
- Neural tube defects
However, levels can be impacted by factors unrelated to genetics, such as inaccurate pregnancy dating, multiple fetuses, or maternal weight. Elevated marker levels alone are not enough to diagnose a disorder. But significant variations outside the normal range warrant additional testing.
Double marker screens are not diagnostic tests. They simply provide a risk score that indicates the chances of a fetus having certain genetic abnormalities. This allows doctors to determine if more definitive diagnostic testing, such as amniocentesis or chorionic villus sampling (CVS), may be needed.
Detection Rates of Double Marker Testing
Double and multiple marker screening tests gained popularity in the 1990s as a standard non-invasive method to estimate risk for certain fetal disorders.
However, detection rates for Down syndrome with just a double marker test are modest compared to newer methods:
- Double marker testing only detects **60-70%** of Down syndrome cases
- In comparison, the “quad screen” (four markers) detects around **80%** of Down syndrome
- Current cell-free DNA blood tests have a Down syndrome detection rate of **99%**
Still, in cases where women did not get first trimester screening, double marker testing in the second trimester is better than no screening at all. It offers a preliminary snapshot of potential genetic risks.
Below is a breakdown of the detection rates for common disorders with a double marker test:
- **Down syndrome** – 69%
- **Trisomy 18** – 77%
- **Neural tube defects** – 80%
While double marker testing leaves much room for improvement compared to newer techniques, it can indicate high-risk pregnancies that warrant follow-up testing. It also provides some level of risk assessment for women who did not get first trimester screening.
Interpreting Double Marker Test Results
Double marker test results provide a numerical risk score for genetic disorders. This is calculated based on the levels of the markers combined with physical factors like maternal age, weight, race, and number of fetuses.
The risk score indicates the probability that a pregnancy is positive for a condition like Down syndrome. It is expressed as a ratio, like 1 in 100.
- A risk score of 1 in 100 means a 1% chance the fetus has the disorder
- 1 in 30 indicates a 3.3% chance
- 1 in 1000 is a 0.1% chance
So a lower risk score is more ideal, while higher risk scores warrant further testing.
A result is considered screen-positive or high-risk if the probability exceeds a predetermined cut-off:
- Down syndrome: typically a risk score of 1 in 270 or greater
- Trisomy 18: risk score of 1 in 150 or higher
- Neural tube defect: risk score of 1 in 250 or greater
If the risk score exceeds the defined cut-off, the patient is offered diagnostic testing like amniocentesis to confirm if the fetus is truly positive. Screen-positive results occur in only about 5% of pregnancies.
The majority of pregnancies (around 95%) will receive a low-risk result from double marker screening. This indicates the fetus most likely does not have major chromosomal abnormalities. However, false negatives are possible. Low-risk women may still choose additional prenatal testing for extra peace of mind.
Proper interpretation of marker screening tests requires counseling from medical professionals. Make sure to discuss results thoroughly with your doctor.
Pros and Cons of Double Marker Screening
There are both advantages and disadvantages of double marker screening for expectant mothers to consider:
Pros:
- Non-invasive blood draw with no risk of miscarriage
- Assesses risk for genetic issues and neural tube defects
- Allows for risk-appropriate care during pregnancy
- Determines need for more invasive diagnostic testing
- Low false positive rate compared to single marker tests
- Detects many, but not all, cases of Down syndrome
Cons:
- Does not definitively diagnose genetic disorders
- Lower sensitivity than newer screening methods
- Higher false positive rates than current options like cfDNA screening
- 5% or less of women receive a positive result, causing unnecessary concern
- Does not detect 30-40% of Down syndrome cases
- Limited detection of other trisomies and microdeletions
While double marker screening provides useful preliminary information about potential fetal abnormalities, current recommendations favor more sensitive techniques like cell-free DNA testing as a first-line screen.
Marker testing is not wholly obsolete yet, but its limitations leave much to be desired compared to cutting-edge noninvasive prenatal screening technology. However, for women getting late prenatal care, it offers a bare minimum level of risk assessment.
Who Should Have Double Marker Screening?
Professional groups like the American College of Obstetricians and Gynecologists (ACOG) have updated their guidelines to recommend newer methods of prenatal genetic screening over traditional marker tests.
ACOG currently recommends:
- All pregnant women should be offered screening or diagnostic testing for aneuploidies and neural tube defects
- Cell-free DNA screening as first-line for Down syndrome and other common trisomies
- Ultrasound as first-line screening for neural tube defects
So while double marker testing is still sometimes performed, it is no longer the primary screening method in most developed countries. The detection rates are simply too low compared to highly accurate cfDNA and early ultrasound options now available.
However, double marker testing may still be useful in certain situations such as:
- As backup screening if a patient misses the opportunity for first trimester screening
- For low-resource areas without access to cfDNA or early ultrasounds
- When invasive diagnostic testing cannot be offered due to risks
- If a patient declines more accurate cfDNA screening due to cost
- To provide some level of risk assessment, even if minimal, for late-presenting women
- When ultrasound is not definitive enough by itself
- Along with first trimester screening for an integrated risk assessment
Talk to your doctor about whether double marker testing is recommended in your individual case based on timing, preferences, and availability of preferred screening methods. It should not necessarily be the front-line or only method but can fill gaps when warranted.
What Happens After a High-Risk Result?
If double marker screening shows a high probability or positive result for a condition like Down syndrome, next steps include:
- Further counseling about the meaning of screen positive results. A positive screen does not diagnose a disorder but indicates increased risk.
- Offering definitive diagnostic testing, preferably via CVS or amniocentesis. These directly analyze fetal cells to confirm or rule out chromosomal abnormalities with 99% accuracy.
- Reviewing further options after diagnostic testing confirms a diagnosis:
- Continuing with pregnancy and planning care for delivery and baby
- Meeting with specialists like genetic counselors
- Considering pregnancy termination options and laws in your state
- Repeating multiple marker screening for ongoing risk assessment later in pregnancy. Levels and risk scores can change over time.
- Following up on other concerns such as neural tube defects with detailed ultrasound.
The decision about how to proceed with a high-risk pregnancy is a very personal one. Take time to consider all options and get professional medical advice.
Current Recommendations for Prenatal Screening
Professional groups like ACOG now advise different approaches over traditional double marker screening for prenatal risk assessment:
Cell-Free DNA Screening
Cell-free DNA (cfDNA) testing is the top recommended choice for first-line prenatal screening today. Also called non-invasive prenatal testing (NIPT), it involves a simple blood draw from the mother. Cell-free fetal DNA circulates in maternal blood and is screened for chromosomal abnormalities.
Advantages of cfDNA screening:
- Safe – no miscarriage risk like amniocentesis
- Highly accurate – detects over 99% of Down syndrome cases
- Detects trisomies 21, 18 and 13 along with sex chromosomes
- Available from 10 weeks gestation
- Low false positive rate of <1% compared to 5% for marker screening
ACOG recommends offering cfDNA screening to all women, regardless of age or risk factors. It replaces the need for double marker testing for most patients.
First Trimester Screening
This screening is done between weeks 11-14 and combines:
- Nuchal translucency ultrasound to measure the fluid at the back of the fetus’s neck
- Blood tests for free beta-hCG and PAPP-A
It provides an 85% Down syndrome detection rate. This is lower than cfDNA testing but still much higher than double screening alone. It remains an option for women who desire screening earlier in pregnancy but wish to avoid the cost of cfDNA testing.
Integrated Screening
This combines first and second trimester screening for a more accurate assessment. It involves:
- First trimester screening via the NT ultrasound and blood work
- Second trimester quadruple marker blood testing
- The values are used together to calculate overall risk scores
Integrated screening has a 95% detection rate for Down syndrome. It is more costly than double screening alone but compensates for the limitations of single testing timeframes. This approach is primarily used in practices without access to cfDNA screening.
Discuss all options with your provider and the availability of preferred tests in your region to decide on appropriate screening.
Should I Have Double Marker Testing?
The decision about prenatal genetic screening is a very personal one. Here are some key points to help determine if double marker testing may be suitable for your situation:
- Double screening is most useful if first trimester screening was missed
- It may be the only available screening for low-resource regions
- It provides preliminary risk information, even if minimal
- Marker levels can change later in pregnancy, so later screening has value
- It may supplement ultrasound or cfDNA for an integrated risk assessment
- It does not definitively diagnose disorders
- The detection rate for common trisomies is only around 60-70%
- More sensitive options like cfDNA and early ultrasound are recommended first-line
- Discuss your specific preferences and availability of tests with your provider
- Any high-risk result needs to be followed with a diagnostic test like amniocentesis or CVS
- Make sure you understand the meaning of any screen positive result before proceeding
While limited compared to today’s options, double marker screening still offers some level of risk assessment for genetic abnormalities in pregnancy. Have an open discussion with your doctor about the best screening approach for your individual healthcare needs and values.
Conclusion
Double marker screening provides a non-invasive way to assess risk for certain genetic disorders in pregnancy by analyzing two substances in the mother’s blood. It screens for conditions like Down syndrome, trisomy 18, and neural tube defects. While not diagnostic, it helps determine if further testing may be warranted.
However, detection rates for double marker testing are modest compared to highly accurate cfDNA screening and early ultrasound. It is no longer the primary screening method recommended. But it can fill gaps for women with limited testing access or late prenatal care.
Make sure to discuss all prenatal screening options with your provider based on availability, timing, and your preferences. Though imperfect, double marker testing delivers valuable risk information to guide discussions about further diagnostic testing and pregnancy management when used appropriately.
