Stillbirth Study

Participating in this study may help provide some answers you seek in this difficult time of loss. Stillbirth can have many different causes. Many of the women who experience stillbirth do not have any of the identified risk factors. There may not be an identifiable cause, even if you participate in this study or have stillbirth testing. 

Stillbirth testing, including examination of the fetus, placenta, and umbilical cord, may provide some clues to the possible cause of your loss but does not always. Even after fetal autopsy, placental evaluations, and cytogenetics (the study of genes and chromosomes), the cause of stillbirth often remains undetermined in as many as 20-60 percent of all cases, depending on the degree of the stillbirth evaluation.

Participating in this study gives you access to the most advanced technologies used in stillbirth testing. By looking at the genetic or inherited material (DNA) at a molecular (not seen by the naked eye) level, researchers can look for tiny changes, deletions, or additions in DNA. This microscopic examination of all, or almost all, of the fetal DNA (also called the genome) may help identify problems in the DNA that could have impacted the health of your pregnancy or fetus.

The Fetal Genomics Consortium partners will conduct two types of tests: whole genome sequencing (WGS) and whole exome sequencing (WES). 

Exons are the portion of DNA that contain instructions for making proteins. All of the exons in a person’s DNA are called the exome. The exome is about 1 percent of a person’s genome, so whole exome sequencing is a shorter version of whole genome sequencing that can still provide valuable information.

For several reasons, such information can be very important: 

1. You may find answers for why you experienced stillbirth – information that some families find helpful for their grieving and healing process.
2. You may learn more about how to reduce your risk for future pregnancies.
3. You can help other families and babies by contributing towards learning more about the genetic causes of stillbirth.

Fortunately, stillbirth and the genetic disorders causing stillbirth are rare. But, because they happen so infrequently and not all stillbirths are fully evaluated with genetic testing, they are difficult to study. The more information scientists collect, the better they can accurately predict who might be at risk and prevent future losses.

With the help of families like you, the Fetal Genomics Consortium has already helped expand the medical field’s use of advanced genetic testing techniques to identify new genetic variants responsible for stillbirth and fetal anomalies (birth defects or syndromes). One of the study’s main goals is to develop and evaluate new technologies to transform the standard of care in maternal-fetal medicine (MFM) and improve prenatal diagnosis options.

In the majority of stillbirth cases, even with the full recommended workup, the cause of stillbirth remains unknown. The additional genetic tests offered through the Fetal Genomics Consortium investigate whether genetic variations (changes in genes) may have contributed to a stillbirth. In some cases, a genetic variation may have caused an abnormality in the development of the pregnancy, including with the baby or with the placenta.  

If a genetic variation is found that could have contributed to your loss, it may affect recommendations for future pregnancy care. For example, these genetic variations are sometimes inherited from either or both parents (they are genetic). Knowing this information about the potential for a genetic variation, you may choose in-vitro fertilization (IVF) to avoid the risk of future pregnancies inheriting the same genetic change(s). You may also choose to test future pregnancies for these changes.

If a genetic variation is found that could have contributed to your loss, you may also find out that the genetic variation is not inherited (not genetic). If the identified genetic variation can’t be passed on to future pregnancies, then your risk of future stillbirth may be lower.

Samples for genetic testing after stillbirth may be collected at three possible times once you consent to participate in the study. These are

1. When your healthcare provider diagnoses your pregnancy loss (by amniocentesis).
2. During the time after your stillbirth delivery while you are still in the hospital.
3. At a follow-up visit with your doctor outside the hospital in the outpatient setting.

If it is possible to obtain, an amniocentesis provides the best sample for all necessary genetic testing. Amniocentesis involves introducing a needle through the mom’s belly into the amniotic fluid around the baby in the amniotic sac. This fluid contains skin cells from the baby and provides the best type of sample for fetal genetic testing.

A sample for genetic testing can alternatively be taken from the fetus, placenta, or umbilical cord after birth if an amniocentesis cannot be performed before delivery or you do not want to have an amniocentesis.

You and your birth partner may also choose to provide a blood sample obtained through a standard blood draw to be analyzed as part of the stillbirth testing. Alternatively, parents can provide a saliva sample, which they would collect and mail directly to the researchers.

FGC staff will offer you and your partner pre-stillbirth test counseling in person or via a telehealth appointment. This counseling session will include a discussion of the potential benefits of the study, which include the possibility of determining an cause or a likely cause of the stillbirth, which could provide additional information about future pregnancies.

Pre-test counseling also includes a discussion of risks, which include:

1. Detection of variants of uncertain clinical significance (VUS)
2. A normal result or failure to detect information to explain the stillbirth
3. No results due to technical reasons (the test didn’t work).

This counseling process is designed to follow best practices as detailed by the American College of Medical Genetics and Genomics (ACMG).

There are several possible results from testing after stillbirth. They are

1. A positive result. This would mean that the stillbirth testing identified a possible cause for your stillbirth.

• A positive result may or may not change your future plans for pregnancy or your prenatal care for future pregnancies.
• A positive result may or may not be able to predict your risk for future stillbirths.

2. A negative result. The stillbirth testing did not identify a cause for your stillbirth. A negative result does not mean genetic variations did not cause your stillbirth. A negative result means none of the genetic variations tested for were positive.

An inconclusive result. This is also known as a variant of unknown significance (VUS). This type of result means that a change exists, but it is not known if this is a “normal” change or a change that could have contributed to the stillbirth. All humans have changes in their DNA. This is what makes us unique. It can sometimes be hard to know which changes are “normal” and which are harmful. In order to understand these uncertain results, researchers have to obtain more data from other families and babies in the future.

1. It may take a long time (up to a year) to get results.
2. Not all of the genetic causes of stillbirth are known. WES/WGS are not perfect tests. They can miss a possible genetic variation that you or your fetus have.
3. Because these tests are still experimental, it is not known how accurately they can predict your risk of stillbirth in future pregnancies is not known.
4. WES may reveal information that is unexpected or unwanted. This information might upset some people, especially if related to an inherited health condition or genetic disorder that may be related or unrelated to the stillbirth. You can choose to receive these types of results if they are found, or you can opt out as part of the initial consent process

Talk with your healthcare provider, a genetic counselor, or one of the Fetal Genetics Consortium Support Staff about the potential benefits and risks of having these tests so that you can make an informed decision about what feels best for your family.

Most insurance plans will cover the cost of clinical tests for stillbirth (blood draws, amniocentesis, fetal autopsy or X-ray and MRI, examination of the placenta, umbilical cord, and amniotic membranes). Each insurance coverage plan is different, so check with your insurance plan or ask your healthcare team to help determine what will be covered.

Currently, the genetic testing of the whole genome and exome (WGS/EGS) is not covered by insurance. If you choose to participate in this research study, the testing will be free as part of the study, and you will have no additional charges, regardless of your insurance status.

This study only includes families with a fetal loss at 13 completed weeks and older. If you have experienced a miscarriage or earlier pregnancy loss, you can still speak with your healthcare provider about what types of testing are available to you.

Results of recommended blood work, pathology, and autopsy studies will be available to you through your primary OB/GYN or maternity care provider. Standard genetic testing such as karyotype or chromosomal microarray will also be available to you through your primary OB/GYN or maternity care provider. 

The additional genetic testing performed through the Fetal Genomic Consortium will be analyzed by the study’s staff. Your usual doctors, hospitals, or laboratories will not handle this part of the stillbirth testing.

At this time, we cannot provide a firm timeline for the return of results. Once your results are available, which could take months or years, a clinician (a physician or genetic counselor) will review them via phone or in person with you.

You are always welcome to contact the study staff at info@fetalgenomics.com to inquire about the timeline for when you might receive genetic testing results.

We would love to hear from you and answer your questions. You can reach us by completing the Contact Us form. Medical staff, researchers, and trained genetic counselors can speak one-on-one with providers and families.