By Melissa Damrongvachiraphan, MS, LCGC

“Just tell me that my baby will be completely healthy.”

“Can’t the blood test tell me everything?”

“I want the gender test.”

I hear these kinds of statements and questions every day as a prenatal genetic counselor. The questions have increased over time with the expansion of non-invasive prenatal testing (NIPT), also known as cell-free DNA screening (cfDNA). NIPT is a screening test that analyzes DNA fragments from the pregnancy that are present in the maternal bloodstream to assess the risk for chromosome abnormalities like Down syndrome with high accuracy. The screening test can also assess the risk for less common conditions like microdeletion syndromes, but with a much lower accuracy. A recent New York Times article shed light on these issues with a dramatic claim: that the screening tests are “usually wrong.” 

The report sparked lots of discussion in the obstetric and genetics communities about the promises and pitfalls of prenatal genetic testing – from both the perspective of pregnant individuals and prenatal genetic counselors

To me, the bottom line is that both patients and providers need to work together to ensure that patients understand what genetic tests they consent to, what those tests can and cannot tell them, and what support resources are available.

Let’s set the record straight about prenatal genetic testing.

1. Not all non-invasive prenatal tests (NIPT) are equally accurate.

In general, NIPT from different labs include the core conditions that are routinely screened for in pregnancy: Down syndrome (trisomy 21), Edward syndrome (trisomy 18) and Patau syndrome (trisomy 13).  They screen these more common conditions with high accuracy and also offer the ability to learn the predicted fetal sex.

But many labs also offer screening for rarer conditions using the same blood draw—including sex chromosome aneuploidies where a person can have a missing or extra X or Y chromosome instead of the expected two X chromosomes for females or an X and a Y chromosome for males, and microdeletion/microduplication syndromes where a person has a small missing or extra piece of a chromosome. The detection rate for these additional conditions varies, but accuracy is often lower than with the core conditions.

The bottom line: It is up to your healthcare provider and you to determine which conditions you should include in NIPT.

2. Screening tests and diagnostic tests are not the same.

Screening tests like NIPT do precisely what they are supposed to do: indicate if further testing should be considered. A positive NIPT result does not mean your baby will definitely have the condition, but suggests they have an increased chance.

A screening test doesn’t definitively say whether a pregnancy has a particular condition or not; it lets you know whether there’s a need to investigate further. Screening tests by their nature have false positives, and that is why diagnostic testing is recommended as a follow-up step.

Diagnostic testing is available to anyone in pregnancy. So why not just skip screening tests and go right to the more statistically accurate diagnostic test? Because those procedures have downsides and are not necessary for every pregnancy.

Depending on the stage of pregnancy, diagnostic options called chorionic villus sampling (CVS) or amniocentesis use a small sample of cells from either the placenta or amniotic fluid to confirm or rule out a chromosome condition. They are both invasive procedures with a risk of miscarriage, ranging from 1 in 300 to 1 in 1,000 depending on the provider performing the procedure.

Most pregnant individuals and their healthcare providers choose to take a stepwise approach where they start with a screening test first, and if necessary, consider diagnostic testing after. 

The bottom line: NIPT is just a starting point and one of many tools in prenatal care.

3. NIPT is not the answer to everything.

NIPT has come a long way and continues to improve by being able to screen for more conditions with higher accuracy. But not every condition is discoverable through a blood test. Luckily, healthcare providers have other tools at their disposal.

Prenatal ultrasounds during pregnancy are one such example that allow screening for possible birth defects a blood test wouldn’t identify. And for certain inherited conditions that typically do not show anything on ultrasound, like Tay-Sachs disease, carrier screening is a way to see if parents are carriers for those inherited conditions. Carrier screening can be done during or prior to pregnancy where your DNA as a parent is analyzed to see if you are a carrier of certain autosomal recessive conditions. Like Tay-Sachs disease, autosomal recessive conditions occur when both parents must be carriers of the same condition in order to have a 25% chance of having a child with that condition. Carriers generally do not have any symptoms and there is typically no family history of the condition. Thus, carrier screening is offered to anyone who is planning for a family. 

Testing is not clinically available for conditions that are associated with a multifactorial inheritance, where it’s a mix of genetic, environmental, and other unknown factors that determine risks. 

The bottom line: Each testing option is a personal choice—How much information do you want to have?

4. Pre- and post-counseling allows for better understanding in options and outcomes.

The Times article got it right that more discussion and counseling both before and after testing can prevent the frustration and confusion that patients can have when they do not receive adequate information. It’s okay to ask your healthcare provider why a test is being done, how accurate it is, and if it’s required. Having the discussion beforehand can also help prepare patients for possible outcomes and next steps, as well as set expectations. Part of a healthcare provider’s role, like a genetic counselor, is to help navigate through the different options to determine which route is best for the patient and their family.

The bottom line: Talk to your healthcare provider, like a genetic counselor – or reach out to the Sarnoff Center – to learn more about the advantages and limitations of testing. 

In short, the Times article underscores the need for more truly informed consent in prenatal testing, which includes clearing up any misunderstandings of what NIPT reveals and how that information is used in follow-up care. Having a more detailed discussion with a healthcare provider, like a genetic counselor, before and after testing would address the biggest concerns outlined in the Times article. 

For questions and resources, you can also reach out to the Sarnoff Center’s genetic counselor, Melissa Damrongvachiraphan at MelissaDamron@juf.org.

I am thrilled to be joining the Norton & Elaine Sarnoff Center for Jewish Genetics as their Project Coordinator. I started my career with JUF in 2018 with the Professionals Network in the Campaign Division. I’m originally from Evanston but am moving to the Andersonville/Uptown neighborhood! I graduated from Indiana University Bloomington with a major in Sociology and minor in Human Sexuality and Reproductive Health. I’m incredibly passionate about equitable and accessible health education and cannot wait to participate in the wonderful work the Community Outreach and Engagement team does. In my free time I love spending time outside with my pups, eating my way through various Chicago neighborhoods, and finding the best coffee shops! 

By Ariana Roman

Growing up, my family often took an unconventional approach to celebrating Thanksgiving. Whether we were traveling to Puerto Rico to visit extended family or cooking everything except turkey, Thanksgiving was always a favorite holiday of mine. 

Following the passing of my grandfather, my mom and I switched up our typical Turkey Day festivities. We realized that vacationing over the holiday weekend was a great way to fill our travel itch and tap into our roots. One of our most memorable trips was in 2016 when we visited Madrid, Spain. 

As a child, I visited Madrid, Barcelona, and Malaga; I couldn’t turn down an opportunity to travel back to Madrid as an adult. My mom and I went food-market hopping to places like the Mercado de San Miguel; strolled through the Parque del Buen Retiro; attended a fútbol game at Santiago Bernabéu Stadium; and made friends with the owner of Casa Lucio’s, a rustic Spanish restaurant.  

Although I missed being with my family for our typical gathering, it felt refreshing to go off the beaten path. I learned you don’t need to be close to home to give thanks to your family members but can honor their legacy by exploring sites abroad in their absence. Once it is safe to travel abroad again, I look forward to celebrating Thanksgiving in the Basque countryside of Spain, as my mom and I recently learned that most of our Puerto Rican ancestors moved to the island in the early 1700s from the Basque region. 

There’s also an important aspect of family history that tourism won’t help uncover family health.. My family is aware of our history with multiple sclerosis., A discussion about family cultural history lends itself nicely to a new conversation focusing on our shared health history.  

Thanksgiving is all about celebrating family, no matter where you are. This week, take time to reflect on your family health history as well. Discuss your health history, ask questions of other family members, compare anecdotes, and, ultimately, share this information with your healthcare provider and promote your relatives to do the same. Hopefully, these talks will help to keep us grateful for our health in years to come. 

Happy Thanksgiving!

By Carol Guzman

August marks Spinal Muscular Atrophy (SMA) Awareness month, which aims to increase awareness and advocacy efforts for the rare genetic disorder. SMA affects the nerves in the spine that control the muscles for breathing, swallowing, and limb movement. The disorder causes these neurons to degrade, resulting in a child having weak muscles and loss of muscle control. SMA occurs in approximately 1 in 800 live births. The disorder is inherited in the autosomal recessive fashion, meaning if both parents are carriers for SMA, each of their children has a 25% likelihood of having SMA, a 50% chance of carrying the SMA-causing mutation without health effects, and a 25% chance of not carrying the mutation at all. SMA is one of the most common inherited causes of childhood mortality, second only to cystic fibrosis. Fortunately, screening and treatment options for this devastating disorder are available.

In 2017, The American College of Obstetricians and Gynecologists (ACOG) recommended that all women considering pregnancy or currently pregnant be offered screening for SMA, along with cystic fibrosis, and hemoglobin-related disease. While the three recommended diseases are Jewish genetic disorders because of their high carrier frequencies within the Jewish population, the diseases still have relatively high carrier frequencies in the general population. For SMA specifically, the carrier frequency in the Ashkenazi Jewish population is 1 in 62, while in the general population the carrier frequency is 1 in 49. 

There are various SMA types, each with its own characteristics and symptoms:

• Type I is the most severe form of SMA and can cause death from respiratory failure within 2 years.
• Type II is less severe; patients with this type of SMA can lived up to their mid-20s.
• Type III exhibits symptoms after 18 months
• Type IV shows symptoms in adulthood

There are now treatment options for SMA, which was once considered an incurable disease. However, the earlier an infant is diagnosed with SMA, the earlier they can receive treatment to prevent and delay motor neuron degeneration. Carrier screening before pregnancy allows partners to identify whether their future child will inherit an early onset recessive disorder. ACOG recommends that individuals of Ashkenazic ancestry should be screened for additional diseases, including Canavan disease, Familial Dysautonomia, and Tay-Sachs. However, there are many more diseases people of Ashkenazi descent, including those in an interfaith partnership, should consider being screened for even though they are less common in the global population.

Consider talking to your health care provider or a genetic counselor about carrier screening before family planning. In addition, join us on Oct. 6 for Decoding Genetic Tests for Parents to Be, a program that will focus on all the genetic tests offered pre and postnatally.

To learn more about the Sarnoff Center’s affordable, accessible carrier screening program or to speak with a genetic counselor, visit Jewishgenetics.org/cjg/get-screened or contact us at GeneticScreening@juf.org

Additional Resources: 

1. Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG) | Genetics in Medicine (nature.com)