Can prenatal genetic screening reveal something about miscarriage causes?

Pregnancy loss can be a deeply painful experience, and it often leaves parents with one question: “Why did this happen?”

It’s important to know that most miscarriages aren’t preventable. In fact, around half of early pregnancy losses are due to a chromosomal difference that makes a full-term pregnancy impossible.¹ These random chromosomal differences in early fetal development happen through no fault of the parent.

Many healthcare providers recommend taking an early look at chromosomal development through a prenatal cell-free DNA (cfDNA), also known as NIPT, screen as early as eight weeks into pregnancy. If a pregnancy ends in miscarriage, and NIPT has already been performed, there are times when the results of that screen can offer insight into the loss. (Note that this is not the purpose or indication for the screen.)

Prenatal cfDNA screens are simple blood tests that most often focus on identifying the three most common chromosomal changes, called trisomies²:

• trisomy 21 (Down syndrome)
• trisomy 18 (Edwards syndrome)
• trisomy 13 (Patau syndrome)

While some pregnancy losses can be due to those three trisomies, some are due to other chromosomal changes. This is where an expanded genetic analysis can provide more insight for patients who have miscarried.

How genetic testing can bring clarity to pregnancy loss

Chromosomes typically come in pairs. Aneuploidy is a medical term describing a difference in the number of chromosomes.  Having one fewer (called monosomy) or one more (called trisomy) of a chromosome is what can lead a fetus to have a chromosomal condition.

Doing an expanded aneuploidy analysis that looks at all 23 chromosomes can offer families more insight than screening for only the three most common trisomies—especially after a miscarriage. For example, a fetus with trisomy 7 would not be identified if the patient was only screened for trisomy 21, 18, and 13.

In order to have access to this information, it’s important to note two things:

1. You must have prenatal cfDNA screening performed while you are pregnant, i.e. before the loss.
2. You need to take a prenatal screen with a lab that offers expanded aneuploidy analysis. Not all labs offer this more comprehensive chromosomal analysis.

Remember that even when your screen looks at all the chromosomes, it is still not a diagnostic test. It can’t provide a definitive explanation for why a loss happened. However, it can offer helpful insights, which can be valuable for parents and providers navigating the next steps in care and trying to create a plan for future pregnancies.

Is there a way to find out a definitive miscarriage cause?

While it’s not always possible to discover a definitive cause of pregnancy loss, there are approaches that can offer more context.

One approach to examining what may have caused a pregnancy loss is to analyze the products of conception (POC), which refers to the tissue and blood passed from the uterus during a miscarriage. POC screening can be informative, but many parents also find it logistically complex and emotionally heavy, especially if they’re collecting samples themselves. Some challenges include:

• A collection process that people may find distressing
• Limited access to specialized testing providers
• Risk of collecting tissue samples that aren’t viable for screening

If a pregnancy loss takes place in a healthcare provider’s office, parents may be able to bypass these challenges by requesting POC screening on-site.

However, because of the emotional and logistical toll, some people may prefer a look at all the chromosomes using a screen that they have already taken.

Navigating next steps after miscarriage

It’s natural to want clarity and closure after a pregnancy loss. While genetic screening can’t provide a definitive answer to the question “Why?” it can help parents understand potential contributing factors without having to take extra steps as they process the loss.

During that process of recovery, many people find it helpful to:

• Allow for physical recovery before trying again. Most people physically recover from a miscarriage within about two weeks, barring any complications. Many providers say it’s physically safe to start trying to conceive again at this point, as the risk of infection is lower. ³ But check with your provider to know what timing might be right for you.
• Focus on physical health. Many people find it reassuring to prioritize their overall physical well-being after a loss. This can look like getting better sleep, eating a balanced diet, exercising, and choosing activities that reduce stress.
• Focus on emotional health. Worry, grief, shock, and uncertainty are all common after a miscarriage. From leaning on loved ones to meeting with a counselor trained in reproductive hardship, processing these emotions can take a variety of forms. Regardless of how it’s done, prioritizing emotional health is an important piece of the healing process.
• Explore genetic screening options with their provider. Every person’s situation is unique. If you took a prenatal cell-free DNA/NIPT screen before your loss, your healthcare provider can review prior results with you. They can also discuss other screening options and guide parents on next steps based on their unique health histories.

It’s important to remember that while genetic screening can’t pinpoint a single cause for a pregnancy loss, it can provide a fuller picture of what may have happened, offering parents invaluable insights and the strength to start trying again if and when the time is right.

References

1. LeFevre NM, Sundermeyer RL. Fetal Aneuploidy: Screening and Diagnostic Testing. Am Fam Physician. 2020;101(8):481-488.
2. Cleveland Clinic. Trisomy. https://my.clevelandclinic.org/health/diseases/22912-trisomy
3. Mayo Clinic. Pregnancy after miscarriage: What you need to know. https://www.mayoclinic.org/healthy-lifestyle/getting-pregnant/in-depth/pregnancy-after-miscarriage/art-20044134