Prenatal Genetic Testing Options, Explained

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So, you’re pregnant? Congratulations! Or, you’re thinking about family planning? Still, congratulations. Either way, you may be wondering, “What tests will I be offered?” “What are they testing for anyway?” Or, “Why are they taking so much blood?!” For the patient that wants to know what testing is available, and what these tests can do for them BEFORE they’re ever stuck with a needle, here are your prenatal genetic screening and testing options, explained.

First, we need to make an important distinction. Screening tests provide a patient with information on the chance a pregnancy will be affected with certain conditions, not an actual diagnosis. Diagnostic testing is able to offer a definitive answer as to whether or not a condition truly affects a baby.

Let’s also clarify what types of conditions screening tests specifically can give you information about. Screening tests can look at 2 different types of genetic disease: sporadic conditions, such as chromosome abnormalities (like Down syndrome) and inheritable genetic diseases; ones that can be passed down through a family (such as Fragile X syndrome). Beyond genetic disease, some types of screening can also detect birth defects that may or not be due to an underlying genetic issue.

Now let’s get down to the nitty gritty. In this post, we will discuss the screening options available to you. They are presented in the order in which they can be done, starting before pregnancy through the second trimester. Think of this as your roadmap to reproductive genetic testing. Ready for a crash course? Here we go!

Before and during pregnancy:

Carrier Screening   

Carrier screening analyzes a person’s DNA for hundreds or thousands of mutations, or genetic changes. This can be done for either a single condition or multiple inheritable genetic conditions at the same time. Examples of conditions that carrier screening is available for include Cystic Fibrosis, Tay-Sachs Disease, and Sickle-Cell Disease. Depending upon a person’s ethnicity, medical guidelines state that they should be screened for different sets of conditions.

Carrier screening assess a person’s DNA for mutations that cause autosomal recessive genetic diseases. For conditions that follow autosomal recessive inheritance, if a person is found to carry a mutation, partner testing would be necessary to provide further risk assessment. If both parts of a couple are carriers for the same condition, they would have a 25% risk to have an affected child with each pregnancy. For X-linked recessive conditions, only a woman’s carrier status is important in determining the risk to a pregnancy. Expanded carrier screening panels, or ECS, can screen a person for over 300 recessive conditions with one blood sample, saving both time and money.  

First Trimester:

First Trimester Screening (FTS)
FTS assesses the risk for a pregnancy to be affected with Down syndrome, trisomy 13, and trisomy 18. These are all chromosome abnormalities which are sporadic, and therefore not inherited like the conditions discussed when talking about carrier screening. FTS involves (1) an ultrasound to measure fluid at the back of the baby’s neck and (2) a maternal blood sample to measure certain hormones between 11 and 14 weeks of pregnancy. An increased amount of fluid at the back of the baby’s neck can be a sign of heart issues and/ or chromosome abnormalities, while different patterns of the hormones analyzed have been associated with different conditions.

Both parts of this combined screen are expected to identify 85-90% of Down syndrome and a large proportion of trisomies 13 and 18. As this is a screening test, false positive or false negative results can occur. First trimester screening has a false positive rate of 5%.

Non-invasive prenatal screening (NIPS)

NIPS is a screen that assesses cell-free fetal DNA in mom’s blood. It can provide a risk assessment for the same chromosome abnormalities as FTS, but with higher accuracy, and can be performed at any time during a pregnancy from 10 weeks on. NIPS has been validated to detect ~99% of Down syndrome pregnancies and a high proportion of pregnancies with trisomy 13 and 18 with a ~0.1% false positive rate.

In addition, testing for the sex chromosomes (X and Y) is possible with NIPS. Presence or absence of Y can predict fetal sex with a very high certainty. Testing for the X chromosome may predict risk for an incorrect number of fetal sex chromosomes, which causes conditions like Turner syndrome.

Second Trimester:

Level II Ultrasound/ Fetal Anatomy Survey

Level II ultrasound, typically performed between 18-20 weeks of gestation, looks at the baby’s anatomy from head to toe. At this time in pregnancy, the baby is large enough that many of the details of the anatomy can be visualized. The purpose of this ultrasound is to evaluate the baby for large, significant structural malformations.

In addition, the baby is evaluated for more subtle physical changes that have been reported more often in fetuses with Down syndrome or other sporadic chromosome abnormalities. Over 90% of fetuses with trisomy 13 or 18 are expected to have findings at the time of this ultrasound. A fetus with Down syndrome would have findings 50-80% of the time. Specific inheritable conditions, such as Smith-Lemli-Optiz, may also have characteristic findings that are seen at this  time. While not all pregnancies with a genetic disease will be detected by ultrasound, any suspicious or concerning findings would be a good reason to consider pursuing a diagnostic test.

Maternal Serum AFP (MSAFP)

MSAFP is performed less in today’s day and age due to the advancements made in the field of ultrasound. This blood test is still available to assess a baby’s risk for birth defects along the back (like spina bifida) or abdomen (like gastroschisis). When either of these are present, the amount of alpha-fetoprotein, a protein produced by a fetus, is higher in the mother’s blood.  An abnormal MSAFP result warrants a repeat ultrasound of the baby’s spine and abdomen. Depending upon the results, diagnostic testing may be pursued to measure the levels of AFP in the amniotic fluid or to rule out a specific genetic diagnosis.

We’ve come to the end of your screening options. It cannot be stressed enough that any high risk screening result should not be used to make decisions regarding the continuation of a pregnancy. A diagnostic prenatal test should be performed first to confirm or rule out a high risk screening result.  

Our next post will discuss the diagnostic testing options available during pregnancy.  

I sure do hope this was helpful. Pregnancy can be a very exciting time for a couple, but inevitably can be very stressful as well. I would like to think that this little crash course will help alleviate some of the stress of pregnancy testing. Want more information on the tests discussed here? I recommend talking to your OB/GYN or a genetic counselor in your area. More information regarding the conditions discussed in this post can be found here. Take this road map I have gifted you, go forth, and family plan. Signing off for now, your friendly neighborhood genetic counselor, Nicholas.

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About Author

Nicholas Paolino

Nicholas Paolino is a board-certified genetic counselor at Recombine. In addition to providing genetic counseling services to Recombine’s patients, Nicholas is also responsible for overseeing the quality control and internal operations of Recombine’s ChromoMap test, a non-invasive prenatal screening technology. Nicholas has a background in high-risk perinatal and reproductive genetic counseling, previously working at Rutgers Robert Wood Johnson Medical School in the Division of Maternal Fetal Medicine. Nicholas received his B.S. in pre-med biology from the University of Scranton and his M.S. in human genetics and genetic counseling from Sarah Lawrence College. He is a licensed genetic counselor in the states of New Jersey and California.