Second Trimester Maternal Serum Screening (MSS)

Second Trimester Maternal Serum Screening (MSS)

Alternate names- Quadruple (quad) screen, triple screen, second trimester blood test for Down syndrome

To the Point- Second trimester maternal serum screen (MSS) can evaluate your chances of having a baby with Down syndrome, Trisomy 18 or an open neural tube defect. If results are abnormal or high risk, you need further testing to give you yes or no answers. If your results are normal, it does not completely rule out these conditions either. MSS is a blood draw on mom between 15-20 weeks gestation, and it typically takes less than a week to get results.

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The Basics

Second trimester maternal serum screening (MSS) is a blood test done on mom during the 2nd trimester (15-20 weeks gestation) that evaluates the chance of age-related chromosome abnormalities, including Down syndrome (Trisomy 21) and Trisomy 18. This test also evaluates the chance of a type of birth defect involving the baby’s spine called open neural tube defect(ONTD), such as spina bifida or anencephaly. Results from MSS are not yes or no. Most people who have an “abnormal” or “high risk” MSS result have typically developing, healthy babies. This test is designed to identify individuals who are at increased chance of these conditions and offer them further, more definitive testing. People choose to have screening tests such as MSS for various reasons, however, this is not a mandatory test and it is up to you!

How It Works

There are several proteins produced naturally by baby or placenta during the pregnancy that cross into mom’s blood stream during the second trimester. Research has shown that babies who have Down syndrome, Trisomy 18 or an open neural tube defect, may have levels of these proteins that are higher or lower than usual. So, MSS measures these proteins and looks for certain “patterns” (higher or lower protein levels) and then using a computer algorithm which includes your age, gestational age of the pregnancy (based upon the length of the fetus), number of fetuses, your weight, race and diabetic status, a risk figure is calculated for each of these conditions.

The most common proteins that are measured in MSS include:

AFP, or alpha-fetoprotein, is a protein produced in the fetal liver during the second trimester of pregnancy and increases throughout the pregnancy. AFP tends to be higher in mom’s blood when the baby has an open neural tube defect (ONTD), such as spina bifida. Since there is an opening in the skin when an ONTD is present, AFP has another “escape route” out of the fetus and into the amniotic fluid. The “extra” AFP that has escaped then crosses into mom’s blood stream and makes the AFP level in mom’s blood higher. AFP tends to be lower than average in babies who have Down syndrome or Trisomy 18.

HCG, or human chorionic gonadotropin, which is produced by the placenta and crosses into mom’s blood stream. HCG levels rise in mom’s blood stream until about mid-pregnancy and then they begin to decline. Babies with Down syndrome tend to have higher than average levels of HCG and babies with Trisomy tend to have lower than average levels of HCG.

UE3, or unconjugated estriol, is made by both the fetal liver and the placenta. Levels of this protein rise throughout the pregnancy. Babies with Down syndrome or Trisomy 18 tend to have lower levels of UE3.

DIA, or dimeric inhibin A, comes from the placenta. Levels of this protein in mom’s blood remain relatively constant through the 15th-18th week of gestation in typical pregnancies. Babies with Down syndrome tend to have higher than average levels of DIA.


As discussed earlier, MSS never gives yes or no answers. Results are reported as a chance or risk figure, and based on how high the chance is, the lab will indicate if it is abnormal/high risk or normal/low risk. Your background age-related chances will also be on the report so you can compare “before and after” chances. Each lab may vary a bit, but a typical cut-off for high risk for Down syndrome is 1/270, or <0.5% and 1/100 or 1% for Trisomy 18. In other words, if your chance is greater than 1/270 for Down syndrome, the report would say that your results are abnormal for Down syndrome.

Let’s give an example. Let’s say you had MSS and you got a phone call from your OB office saying, “your results came back indicating an elevated chance or high risk for Down syndrome.” This may not be what you were expecting and often times it is hard to concentrate and listen to what is said beyond that statement, but hopefully the office will also tell you what the actual risk figures are for Down syndrome (if not, you should ask them). In this case, let’s just say it is 1/200 (or 0.5%). What this really means is that if they looked at 200 women who were the same age as you and had the same protein levels, 1 out of those 200 babies would have Down syndrome and the other 199 would not have Down syndrome. Another way of looking at it is that the chance of having a baby without Down syndrome is 99.5%. So, even though the test results are deemed “abnormal”, the odds are the baby does not have Down syndrome.

Here’s one more example that would apply to you if you are over 35 at delivery. The MSS uses maternal age in its calculation, and we have already talked about the fact that the chances of things like Down syndrome increase as mom’s age increases. What this can mean is that the chance of you having a high risk or abnormal MSS increases a bit as you age. For example, if you are 42, your approximate background chance for Down syndrome is 1/64. This chance alone is higher than the abnormal cut-off for the MSS (typically around 1/270 for Down syndrome). If a 42 year old woman with an age-related background chance of Down syndrome of approximately 1/64 has a MSS result of 1/200 (0.5%) for Down syndrome, the result is abnormal. However, this is actually a lower risk than her background age-related risk of 1/64 (1.6%).

Risk figures can be confusing and how they are presented can really make a difference in your perception and understanding. For example, if your chances for Down syndrome came back 1/20, this means that there is a 95% chance that the baby does NOT have the condition. So, make sure you ask your provider or genetic counselor if you have questions about the risk figures or the results in general.

ABNORMAL RESULTS- My second trimester MSS is abnormal or high risk, now what?

People choose prenatal testing for various reasons, some to find out information to simply have a heads-up and be prepared, others because they are uncertain what decisions they would make if their baby did have a genetic condition or birth defect.  As explained above in the MSS results section, most likely your baby does not have the condition at hand. However, if you are like most people, you will be at least a bit worried. It is hard to hear that something “might” be going on with your baby.

So, what happens next? Many obstetricians will refer patients with an abnormal MSS to a high-risk pregnancy doctor (perinatologist or Maternal-Fetal Medicine specialist) for a level II ultrasound and possible amniocentesis. Another option that may be offered is noninvasive prenatal testing (NIPT). Depending on your provider, you may also be referred to a genetic counselor to discuss the test results further. Genetic counselors are trained medical professionals who can explain the test results in detail, answer your questions and discuss all of the further testing options available to help you make decisions that best fit you, your beliefs, values needs and personality.

An important thing to keep in mind is that all further testing options, including level II ultrasound, NIPT and amniocentesis are optional, not mandatory. See specific tests for more information on these other tests.

Normal Results- my MSS was normal/low-risk, now what?

In terms of the conditions screened for on MSS, chances are decreased that your baby has one of these conditions, however, MSS does not detect all cases of Down syndrome, Trisomy 18 or open neural tube defects. Approximately 80% of babies who have one of these conditions will have an abnormal or high-risk MSS, however, approximately 20% will have normal MSS results. Many people do not pursue further screening or diagnostic testing if they have a normal MSS. However, if you want more information, there are other screening tests available including, level II ultrasound, noninvasive prenatal testing (NIPT), and a diagnostic test available called amniocentesis.

How to Decide

The following are some questions and thoughts to consider that may be helpful as you decide whether or not MSS is right for you…

  • How would you feel if results indicated a higher risk for a genetic condition?
    • Would you consider amniocentesis?
    • Do you think this information would help you feel more prepared?
  • If not, would you be ok waiting until the baby is born to know for sure if the condition is present if your MSS result returns high risk?
    • For example, would you consider doing anything differently if you knew the baby had a genetic condition (e.g. prepare, consider placing baby for adoption, consider not continuing the pregnancy)?
  • Does more information with the possibility of uncertainty make you anxious?
  • Some women would prefer definitive answers and since MSS cannot provide that, they may choose to go straight to a more definitive test, such as amniocentesis.
  • On the other hand, some women may feel comfortable with their chance of a genetic condition or are confident that, even if the baby did have a genetic condition, it wouldn’t alter their pregnancy plans.  Or they may prefer not to face the decision of whether or not to have an amniocentesis if the MSS comes back high risk.  In these cases some women may decide not to undergo any prenatal screening.

Ultimately, the decision to have MSS or any other prenatal screening or diagnostic test is yours to make and should reflect your own personal beliefs, values, needs and personality.

What is Down syndrome? READ MORE

What is Trisomy 18? READ MORE

What are Open Neural Tube Defects (ONTDs)? READ MORE

Questions? Get in touch


Everyone says MSS is always wrong, is this true?

MSS is designed to identify people that are at a certain risk level or higher for Down syndrome, Trisomy 18 and ONTDs. In general, approximately 5% (1/20) of women who have second trimester MSS will have an abnormal or positive result. But, in reality most people that have an abnormal result actually have babies that do not have the condition at hand. This does not mean the test is “wrong”, it is just the way it works. This is a screening test, not a diagnostic test. There is no such thing as a “false positive” only a “screen positive.” In order to know with greater certainty if the baby actually has the condition, further testing is required. Diagnostic testing, such as, CVS or amniocentesis is the best way to give you more definitive answers to whether or not your baby has the conditions screened for in MSS.

Another thing to keep in mind with MSS is that it does not pick up all cases of Down syndrome, Trisomy 18 or ONTDs. Detection rates vary depending on the laboratory that is used, but in general, second trimester MSS detects approximately 80% of babies with DS, T18 and ONTD. In other words, you could have a normal MSS and your baby could still have one of these conditions.

Do they ever repeat MSS?

Great question. There are some reasons that MSS either needs to be recalculated or redrawn, but in general, the test is not repeated. Reasons for recalculation or redraw include,

1)Dating of the pregnancy used in the calculation is off

Typically, if the dates are off by 10 days-2 weeks or more (depends on laboratory), the test needs to be recalculated. The reason dating is so important is because the levels of the proteins that are measured change throughout the pregnancy. Make sure the doctor checks your dates and the dates on the MSS results to confirm they agree. If your dating is off and it means that you actually had your MSS drawn too early, you may have to have your blood drawn again. Often, you don’t need another blood draw and your doctor’s office or genetic counselor can call the laboratory and get your new risk figures based on accurate dating of the pregnancy.

2)Twin pregnancy wasn’t taken into account

If for some reason the test was calculated based on you having one baby and you are actually expecting twins or vice versa, this can throw off the results. A simple call to the laboratory will allow for recalculation of your results.

3)Maternal weight used in calculation was way off

This is rarely an issue, but if the maternal weight indicated on the test is significantly different from your actual weight at the time of the test, it can affect the test results. Again, the laboratory would be notified and revised risk figures would be calculated and provided.



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