What to expect with all the tests offered during pregnancy
There is a lot of blood work and tests done during pregnancy. This post attempts to break down the testing offered and review the benefits and limitations of the following: multiple marker screening, cell-free DNA screening (also known as NIPT), diagnostic testing, and ultrasound scans. This post is not medical advice and will need to be verified with a person’s doctor.
Multiple Marker Screening:
The goal of these tests are to inform if someone’s pregnancy has an increased chance for a chromosomal condition. Common chromosomal conditions include Down syndrome, Trisomy 18, and Trisomy 13. Every person has the chance to have a baby with a chromosomal condition. Some chromosomal conditions result in an early miscarriage. Other times, a baby may be born with a chromosomal condition and can have intellectual disability or a heart defect.
The specific test that is offered may depend on if someone is considered “high risk” or “low risk” for these conditions. Women who are over 35 years of age are more likely to have a baby with a chromosomal condition than a woman who is 20; therefore, she would be considered “high risk”. Really, it should be considered higher risk. The risk for a 35 year old woman to have a baby with a chromosomal condition is about 1 in 178. Some people would not consider that a high risk. Yet, it is higher than if you were planning to conceive a pregnancy at 20 years of age which the chance is about 1 in 525 (3).
For low risk women, the screens offered are generally called multiple marker screens. These screens look at patterns of hormone levels to see if the patterns from the pregnancy resemble patterns from pregnancies in which the baby had Down syndrome or Trisomy 18. The hormones assessed are primarily produced from the placenta. If the test is positive, then it lets someone know there is an increased chance for the baby to have the condition the test was positive for. It does not mean the baby has the condition. These tests can be positive for other reasons that have nothing to do with the condition it was positive for.
The specific multiple marker screen offered depends on gestational age and the preference of the clinic.
First trimester screen: offered in the first trimester around 10-13 weeks and 6 days of pregnancy. The screen assesses the chance for Down syndrome and Trisomy 18. The hormones assessed are Pregnancy Associated Plasma Protein-A (PAPP-A) and human chorionic gonadotropin (hCG). The screen can also use two ultrasound measurements: the absence or presence of the baby’s nasal bone and nuchal translucency (NT). The NT measurement is measuring the amount of fluid that is behind the baby’s neck. There should be less than 3mm of fluid back there.
Quad screen: offered after 15 weeks until 22 weeks and 6 days. The quad screen assesses four hormones called hCG, inhibin-A, estriol, and alpha fetoprotein (AFP). Down syndrome, Trisomy 18, and open neural tube defect risk is assessed with this test.
There are multiple marker screens that combine both the first and second trimester tests. These tests require the person to do two blood draws, one during the first trimester and another in the second trimester, in order to provide risk estimates.
Multiple marker screening for AFP only: this is done when a person only wants to know the chance for open neural tube defects like spina bifida or they had the next type of screen, cell-free DNA screening.
Each multiple marker screen has its own detection rate as well as benefits and limitations. Please talk with your doctor to find out which is most appropriate for you.
Cell-Free DNA Screening (NIPT or NIPS):
The next type of screen, cell-free DNA screening, is usually offered to individuals considered “high risk” for chromosomal conditions; however, “low risk” individuals can also be offered this screen as well and this is becoming more commonplace. This is often clinic dependent. Check out this article for more information on this: https://health.usnews.com/health-care/for-better/articles/2018-07-30/the-fallacy-of-advanced-maternal-age and https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2020/10/screening-for-fetal-chromosomal-abnormalities
Cell-free DNA screening can be called non-invasive prenatal testing (NIPT) or non-invasive prenatal screening (NIPS). There are many labs that offer this type of testing. This test is generally offered when an individuals is considered “advanced maternal age”, had a positive maternal serum screen, previously had a child with a chromosomal condition, a birth defect is detected on ultrasound, or if an individual desires this test.
Cell-free DNA screening is performed after 10 weeks of pregnancy. It assesses the chance for Down syndrome, Trisomy 18, Trisomy 13, and sex chromosomal conditions like Turner syndrome or Klinefelter syndrome. It can also assess the chance for some microdeletions which are small pieces of the chromosome that could be missing. If a small piece of the chromosome is missing, then that means 5-10 genes are missing which can cause a syndrome.
Cell-free DNA screening is performed by a blood draw. The amount of DNA is the bloodstream is analyzed. In the bloodstream during pregnancy, there is DNA from the pregnant person and DNA coming from the placenta (which is a normal process). The lab performing cell-free DNA screening is able to determine which chromosome the DNA is coming from as well as if there is the correct amount of DNA for each chromosome. There should be a certain amount of DNA from each chromosome found in the bloodstream. If there appears to be more or less of the DNA from a certain chromosome, then there may be an extra or missing chromosome. If the lab suspects an extra or missing chromosome, then the result is positive. A positive results means the chance the pregnancy has a chromosomal condition is increased.
Cell-free DNA testing usually has a higher detection rate for certain chromosomal conditions given DNA is assessed and not just hormone levels. Chromosomal conditions are caused by having too much or too little DNA. However, while cell-free DNA screening can suggest a chromosomal condition, it cannot diagnose a chromosomal condition.
If cell-free DNA screening comes back positive for a chromosomal condition, then a certain value needs to be considered. This value is called the positive predictive value or PPV. The PPV is the lab’s confidence that the positive result is truly a positive result. For example, if the test is positive for Down syndrome and has a PPV of 60%, then the chance this result is a true positive result is 60%. A screening test can be a false positive, so diagnostic testing is offered to provide a conclusive result.
Diagnostic Testing:
The above screens provide the chance the baby could have select chromosomal conditions. The following tests are how the conditions can be diagnosed during the pregnancy period. Testing after birth is also an option.
Chorionic Villus Sampling (CVS)
CVS is a procedure performed after the 10th week of pregnancy until 13 weeks and 6 days. A biopsy of the placenta, specifically the chorionic villi, is sent to a lab to be tested for chromosomal conditions or molecular conditions (like sickle cell disease or cystic fibrosis). The placental biopsy can be obtained either through the cervix or through the abdomen. Ultrasound guidance is used throughout the procedure. There is risk for miscarriage, bleeding, infection, etc. Some studies quote a 1 in 100 risk for a complication, yet it is important to ask the physician performing this procedure what he or she personally quotes.
Amniocentesis
Amniocentesis is a procedure performed after the 16th week of pregnancy. Amniotic fluid is obtained with a long, thin needle entering through the abdomen into the amniotic sac. Ultrasound guidance is used throughout the procedure to get a pocket of fluid away from the baby. The fluid is sent to a lab to be tested for chromosomal conditions or molecular conditions (like sickle cell disease or cystic fibrosis). There is risk for miscarriage, bleeding, infection, etc. Some studies quote a 1 in 500 to 1 in 1000 risk for a complication, yet again, ask the physician performing this procedure what he or she personally quotes.
Given diagnostic testing has a risk for complication, not everyone decides to do this testing. It would be suggested to test the baby after birth if testing during pregnancy is not completed and there was suspicion for a chromosomal condition.
Ultrasound:
Ultrasound is helpful to diagnose or suggest birth defects like a heart defect or clubfoot. Ultrasound uses sound waves to create images of the baby within the womb. There is a 3-5% chance for a birth defect (check out https://www.cdc.gov/ncbddd/birthdefects/types.html to learn more about the types of birth defects) for any pregnancy; therefore, ultrasound is typically performed in both the first and second trimester to assess for any defects.
The first trimester is not going to be a comprehensive assessment of the baby. The main points of interest are the amount of amniotic fluid, the growth of the baby, the absence or presence of a nasal bone, and nuchal translucency (NT). The NT measurement is measuring the amount of fluid that is behind the baby’s neck. There should be less than 3mm of fluid back there.
The second trimester is historically the time in which the family finds out the predicted sex of the baby. If someone has had cell-free DNA screening, then this ultrasound confirms the predicted sex (most of the time). This ultrasound can usually help to identify if there are any birth defects. Generally, this ultrasound is performed 18-22 weeks of pregnancy.
Ultrasound can also provide additional context to screening results. For example, if someone had a positive blood test for Trisomy 18 and their ultrasound revealed a heart defect, then there is even more suspicion for the condition. However, still, ultrasound cannot diagnosis chromosomal conditions and it can have limitations.
Carrier Screening:
This article has additional details on carrier screening: Navigating Carrier Screening. These are additional blood tests that are usually offered during pregnancy. However, they can be most helpful before conceiving a pregnancy.
This is not a comprehensive list of all the possible tests that can be offered during pregnancy. As always, please consult your doctor, physician, care providers, or genetic counselors of what tests makes the most sense for you. This article is for informational purposes only.
Resources:
American College of Ob/Gyns Practice Bulletins 162
American College of Ob/Gyns Practice Bulletins 226
Hook and Chambers (1977) and Hook (1981)
* This blog constitutes general information about genetic testing and medical screening. This blog does not offer or provide medical advice or diagnosis, and nothing in this blog/webinar should be construed as medical advice or diagnosis. Do not rely on the information in this blog/webinar to make medical management decisions. Please consult with a medical professional before making those decisions. Do not delay in seeking professional medical advice if you think you have a medical concern. Do not disregard professional medical advice based on any information received in this blog.
