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. MSS is a blood draw done on mom between 15-22 weeks gestation, and it typically takes less than a week to get results.

The Basics
How to Decide



The Basics

Second trimester maternal serum screening (MSS) is a blood test done on mom during the 2nd trimester (15-22 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), like spina bifida or anencephaly. Results from MSS are not yes or no, and 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 the 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 ONTD, may have levels of these proteins that are higher or lower than usual. MSS measures these proteins and looks for certain patterns of higher or lower protein levels. A computer calculates a risk number, or chance, for each of these conditions based on:

  • protein levels measured in mom’s blood
  • mom’s age
  • how far along in the pregnancy (gestational age)
  • number of babies (single versus twins)
  • mom’s weight
  • mom’s race
  • if mom has diabetes

The most common proteins that are measured in MSS include AFP, hCG, uE3, and inhibin-A.

AFP, or alpha-fetoprotein, is a protein produced in the baby’s liver during the second trimester of pregnancy. The levels of AFP generally increase the further along in the pregnancy a woman is. AFP tends to be higher in mom’s blood when the baby has an 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 baby and into the amniotic fluid. The extra AFP in the amniotic fluid then crosses into mom’s blood stream and makes the AFP level in mom’s blood higher. AFP levels tend to be lower than average in babies who have Down syndrome or trisomy 18.

HCG, or human chorionic gonadotropin, 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 18 tend to have lower than average levels of hCG.

UE3, or unconjugated estriol, is made by both the baby’s 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.

Inhibin-A, 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 pregnancy. Babies with Down syndrome tend to have higher than average levels of inhibin-A and babies with trisomy 18 tend to have lower than average levels of inhibin-A.


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 age-related chances will also be on the report so you can compare “before and after” chances; before is your chance just based on age alone, and the after is taking into account age as well as all of the information from MSS. Each lab may vary a bit, but a typical cut-off for high-risk for Down syndrome is 1/270 (<0.5%), and 1/100 (1%) for trisomy 18. For example, if your chance is greater than 1/270 for Down syndrome, the report would say that your results are high-risk.

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, 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. 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 most likely thing is that 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 as a starting point, and we have already talked about the fact that the chances of things like Down syndrome increase as mom’s age increases. This means that the chance of you having a high-risk or abnormal MSS increases as you age. If you are 42, your approximate age-related chance to have a baby with Down syndrome is 1 in 64. This chance alone is higher than the cutoff for what is considered ‘abnormal’ with MSS (typically around 1 in 270 for Down syndrome). If a 42-year-old woman starts with an age-related risk of 1 in 64 and has a MSS result of 1 in 200 for Down syndrome, the result is flagged as abnormal, even though the blood test said her risk is lower than what she started with. So, even though the blood test took her risk from 1 in 64 (almost 2%) down to 1 in 200 (0.5%), the results will still be called abnormal because her 1 in 200 results is above the lab’s 1 in 270 cutoff.

Risk figures can be confusing and how they are presented can really make a difference in your perception and understanding. 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 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 any of these conditions. 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 OB-GYNs 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 to discuss other testing options, such as cell-free DNA (cfDNA) or amniocentesis. 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 your beliefs, values, needs, and personality.

An important thing to keep in mind is that all further testing options, including level II ultrasound, cfDNA, and amniocentesis are optional, not mandatory.

Normal Results: My MSS was normal, or low-risk. Now what?

Chances are decreased that your baby has one of these conditions; however, MSS does not detect all cases of Down syndrome, trisomy 18, or ONTDs. Approximately 80% of babies who have one of these conditions will have an abnormal or high-risk MSS, which means approximately 20% will have normal MSS results. Many people do not pursue further screening or diagnostic testing if they have a normal MSS. If you want more information, there are other screening tests available including, level II ultrasound, cell-free DNA (cfDNA), 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?
    • 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.
  • Other women may choose not to undergo any prenatal screening because they:
    • Feel comfortable with their chances for a genetic condition
    • Are confident that even if the baby did have a genetic condition, it wouldn’t alter their pregnancy plans
    • May prefer not to face the decision of whether or not to have an amniocentesis if the MSS comes back high risk

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.

[make_anchors name=”FAQs”]

What is Down syndrome? READ MORE

What is trisomy 18? READ MORE

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