Prenatal Testing Basics

Do you ever feel like it would have been easier to be pregnant a couple of generations ago? How simple things must have been before all of these prenatal testing options. Or you may feel like all of these options are fantastic but struggle knowing which option is the right one for you and your given situation?

Wading through the sea of prenatal testing options can seem daunting, but we are here to help. Depending on your personal beliefs, values, needs and personality, different testing options (or no testing at all) may be better suited for you. Genetic Support Foundation has included some of the most frequently asked questions and detailed information below regarding prenatal testing. For information about specific prenatal testing options, visit our pregnancy and genetics tests page.

One of the most important questions to stop and consider is whether or not you even want any prenatal testing at all.

FAQs


Should I have prenatal testing at all?

This is arguably the most important question of this process and one of the best places to start.

In general, it is important to stop and think about things like:

  • Why do I want this information?
  • What would I do with the results (e.g. would it change the way I manage my pregnancy or the choices I make)?
  • Does more information make me less anxious or more anxious?
  • Other questions to consider include:
    • What conditions are being tested for?
    • How certain is the information?
    • What would I do with the results?


What types of prenatal tests are available and what do they look for?

To the PointThere are a lot of prenatal genetic tests out there and it can be confusing to tell sort through what is what. Generally there are two categories of genetic testing in pregnancy: screening tests and  diagnostic tests. There is no prenatal test that evaluate all conditions that could affect the health and development of your baby. In other words, there is no test that can guarantee a healthy baby. But do keep in mind, most babies (about 95-98%) are born healthy. Most of the prenatal tests only look for a few specific conditions. The pregnancy and genetics tests page provides additional information about genetic tests that are commonly available in pregnancy and what conditions they test for.

Screening Test
Examples of prenatal screening tests include the following: first trimester screening, sequential screening, second trimester maternal serum screening (triple screen, quad screen, msAFP), level II ultrasound, integrated screening, etc. The newest prenatal test available, cell-free DNA (cfDNA), is also a screening test. Prenatal screening tests look for an increased chance of birth defects and chromosome abnormalities, however, they do not typically tell you “yes or no” answers or give you a definitive diagnosis. Screening tests pose no risks to mother or baby apart from the risk of increased anxiety if the screening test comes back abnormal or high risk.

Diagnostic Test
A diagnostic test is considered to be the most accurate test available for a given situation. The diagnostic testing options offered during pregnancy are both invasive and include CVS (chorionic villus sampling) and amniocentesis. Amniocentesis and CVS are considered to be extremely accurate and usually provide “yes or no” answers to questions about age-related chromosome abnormalities (rare lab errors or results that are hard to interpret do occur).  Although it is quite low, there is a risk of miscarriage with CVS and amniocentesis, therefore, the decision to undergo this type of testing warrants careful consideration.



The more traditional prenatal screening tests are usually wrong, right?

To the Point– Most women who have abnormal traditional prenatal screening (first trimester screen, quad screen, etc.) tests have normal healthy babies. This is due to the test design; the tests are not wrong.

This is one of the most common responses from people who have received an abnormal result on one of the more traditional prenatal screening tests.  Traditional screening tests such as first trimester screening, integrated screening, sequential screening, quadruple test, etc. are all intended to identify patients who are at an increased chance of having a baby with a chromosome condition and then give them the option of considering further testing, including diagnostic testing such as CVS or amniocentesis.

So, no, the test results are not necessarily “wrong”, but there is misunderstanding on how they work and what the results mean.

Most women who have abnormal results on traditional prenatal screening tests have health babies with the typical number of chromosomes.  An abnormal result does not mean the baby has the condition, it simply means there is an elevated chance; more testing should be offered to clarify what is going on with the baby.



Will cell-free DNA (cfDNA) testing give me "yes or no" answers?

To the PointNo, cfDNA will not give you “yes or no” answers. cfDNA is a very good screening test for Down syndrome, especially, but it is not the same as having a CVS or an amniocentesis. Current recommendations say that you should always confirm abnormal cfDNA results with diagnostic testing if you want more definitive answers.  

cell-free DNA (cfDNA) is also called noninvasive prenatal screening (NIPS) and noninvasive prenatal testing (NIPT), and goes by many brand names (Harmony, Panorama, MaterniT21, Verifi). cfDNA is the newest prenatal screening test available.  It is considered noninvasive because it does not involve going into the amniotic sac or placental tissue in contrast to invasive testing like amniocentesis or CVS.  It involves a blood draw like  more traditional screening tests. However, unlike other screening options available, cfDNA analyzes placental DNA in mom’s blood, which usually has the same genetic make-up as that of the developing baby.  Most professional guidelines currently recommend that cfDNA only be offered to high risk pregnancies (e.g., advanced maternal age, abnormal first trimester screening or second trimester MSS, etc.)  Click here for more detailed information on cfDNA. 



What is the difference between the newer chromosomal microarray and traditional chromosome analysis?

To the point:

  • Both traditional chromosome analysis and chromosomal microarray CMA can evaluate conditions that are increased in risk as mom’s age increases (e.g. Down syndrome). 
  • Both can identify other conditions involving missing chromosomes or major chromosome rearrangements.
  • Unlike traditional chromosome analysis, CMA testing has the capability to detect smaller regions of extra or missing portions of the chromosome, called microduplications or microdeletions which may be associated with intellectual disability and birth defects
  • Both  may identify a change where outcome is uncertain, however, this is arguably more likely with chromosomal microarray.
  • CMA testing has approximately a 1-2% chance of identifying what is called a variant of unknown significance (VUS), meaning, there is not enough data to know whether or not the genetic change will result in abnormalities in the baby; this information may result in substantial anxiety for mom and dad.
  • CMA may detect non-paternity (different father of baby) and consanguinity (parents are closely related to each other, e.g., cousins).
  • Traditional chromosome analysis is still considered standard of care. However, recent guidelines from  American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine have opened the doors for all women to be offered CMA if they are undergoing diagnostic testing, such as CVS or amniocentesis.

“The potential for complex results and detection of clinically uncertain findings identified by prenatal chromosomal microarray testing can result in substantial patient anxiety. This underscores the critical need for comprehensive patient pretest and posttest genetic counseling from qualified personnel about the benefits, limitations, and results of testing so that patients can make informed decisions.” American College of Obstetrics & Gynecology/Society for Maternal Fetal Medicine statement

Traditional chromosome analysis, also known as karyotype analysis or cytogenetic analysis, can evaluate the number of chromosomes and the basic structure of each chromosome (e.g., any extra or missing chromosomes or any major rearrangements of the chromosomes) and can rule out common chromosome conditions like Down syndrome, Trisomy 18, Trisomy 13 and sex chromosome conditions. It can also detect large deletions and duplications of chromosomal material that are visible under the microscope.  Traditional chromosome analysis is still considered the standard of care.  However, recent guidelines from The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine have opened the doors for all women to be offered chromosomal microarray (CMA) if they are undergoing diagnostic testing, such as CVS or amniocentesis.

Besides detecting the vast majority of things that traditional chromosome analysis can detect, CMA has the capability to zoom in on parts of the chromosomes that are too small to visualize using a microscope, allowing detection of smaller regions of extra or missing portions of the chromosome.  Conditions in which several instructions or genes are missing are called microdeletion syndromes. Conditions in which there are several genes duplicated are called microduplication syndromes. Microdeletion and microduplication syndromes are typically associated with mental retardation and birth defects. There are over 150 genetic conditions that can be detected with CMA.  These conditions are not typically increased in risk as mom’s age increases.

In terms of detecting chromosome abnormalities involving an extra chromosome, such as Down syndrome, CMA is just as good as traditional chromosome analysis.  The differences come in when detecting abnormalities involving smaller genetic changes.  Among fetuses with an abnormal ultrasound finding, CMA found clinically relevant chromosomal deletions or duplications in approximately 4% of cases that were not detected with traditional chromosome analysis. In cases sampled for advanced maternal age or positive screening results, microarray analysis picked up an abnormality in 1.7% of pregnancies that had a normal traditional chromosome analysis1.

Besides the possibility of detecting conditions like Down syndrome and other genetic conditions, microarray testing may also detect what are called variants of unknown significance (VUS).  These are changes in the baby’s DNA that may or may not affect the baby’s development but there is not enough data to know for sure.  Recent studies have shown that approximately 1-2% of patients receive a result that is a VUS (this is the chance after all testing has been done on parents and literature has been searched to try and identify the meaning of the variant). Many labs request samples of mom and dad’s blood to look at their DNA to help interpret the meaning of a VUS; in some cases this can be helpful but not always.  When a VUS is found in the baby during the pregnancy, it may cause a lot of anxiety in mom and dad as the outcome for baby may be very uncertain.  The issue of VUS’s is one of the main reasons that genetic counseling and informed consent prior to having prenatal chromosomal microarray is critical.

Prenatal chromosomal microarray results take approximately 7-10 days to receive, compared to 10-14 days for traditional karyotype analysis.  CMA may be offered to all women undergoing invasive testing, such as amniocentesis or CVS, but this is an optional test and is always your choice.

There are certain situations where microarray will be offered or recommended based on abnormalities on ultrasound.  However, if you are being offered microarray for no specific indication here are some thoughts to consider…

Prenatal CMA is an exciting technology that is relatively new within the arena of prenatal testing.  You may want to consider if you want to know all of this information in the first place and would it change your decisions about how you would proceed with the pregnancy, etc. Additionally, and often understated, there is a real chance, 1/50 or greater1, that you may get results that indicate there is a difference or change found in the baby’s DNA, but doctors and researchers don’t know exactly what it means because technology is ahead of us.  This type of result may cause a lot of anxiety.

CMA during pregnancy cannot necessarily be equated with microarray testing after the baby is born, when you can actually see the baby, know what he/she looks like, etc.  Finding out uncertain information about the prognosis of the baby during the pregnancy can be especially challenging and make decision-making extremely difficult. CMA may also reveal information about the future health of the parents and also may detect things like non-paternity (if the father is someone other than previously thought) and consanguinity (if parents are closely related to each other).   CMA does not rule out all birth defects or genetic conditions.

 

1.  Hillman et al. Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta-analysis. Ultrasound Obstet Gynecol 2013; 41: 610–620.

 

 

 



There are so many prenatal testing options, how do I decide what is right for me?

The following are some questions and thoughts to consider that may be helpful as you decide whether or not prenatal testing is right for you, and if so, which type of testing (traditional screening, noninvasive prenatal testing or diagnostic testing such as amniocentesis).

  • If you decided to have a screening test, 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 screening 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 screening tests (first trimester screening, quad screen, noninvasive prenatal testing) 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 a screening test comes back high risk.  In these cases some women may decide not to undergo any prenatal testing.

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

 



I have received abnormal test results/ultrasound indicating that my baby has genetic condition or birth defect, now what?

If you are reading this and you have received an abnormal result, it may be that you are finding out that your baby has Down syndrome or it may be something more severe, such as Trisomy 13 or Trisomy 18, or something potentially more mild, such as Turner syndrome (45, X) or Klinefelter syndrome (47,XXY). No matter what condition has been diagnosed, we know that this is not necessarily an easy time or what you expected.

If your results indicate a chromosome condition or birth defect, it is often very helpful to take time to talk to your provider, a genetic counselor, friends and family, and possibly get a second opinion if you feel like that may be helpful. Taking time and consulting with others is especially important if your results are confusing, unclear, or if you don’t know much about the condition that has been diagnosed.

Even if you know some information about the condition, it’s often helpful to get up-to-date information as things have changed dramatically for some conditions. For example, in the case of individuals with Down syndrome, quality of life and life expectancy is quite different than it was two generations ago. Also, depending on what resources you find and who you talk to, you will find differing opinions on what life may be like for a child with the condition that has been diagnosed, what it is like to parent a child with the condition, etc. Some people benefit from finding someone who has a child with the same diagnosis and speaking with them directly. Your provider or genetic counselor should be able to help facilitate this.

Ultimately, you have 3 options if you find out through amniocentesis that your baby has a chromosome abnormality, genetic condition or birth defect….

  1. Continue the pregnancy and prepare – READ MORE
  2. Continue the pregnancy and place the baby for adoption – READ MORE
  3. Choose to not continue the pregnancy – READ MORE



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