Prenatal testing once offered only to older expectant mothers or those of certain ancestry is becoming more available to all prospective parents with changes in genetic testing technology and guidelines.
In the past five years, the American College of Medical Genetics and Genomics (ACMG) began recommending carrier screening for gene disorders including cystic fibrosis and sickle cell anemia for all prospective parents, male and female. This screening, done through a blood draw or saliva sample, can help those considering getting pregnant understand their risk of having a child with an inherited genetic condition.
What has Changed?
Previously, individuals were more likely to be screened for diseases linked to their ancestry, such as Tay-Sachs disease for those of Ashkenazi Jewish descent and sickle cell anemia for African Americans.
“It became very clear that the carrier screening programs have been instrumentally impactful to help to decrease diseases,” says Dr. Christina Tise, M.D., Ph.D., a clinical genetics and genomics physician at Stanford Medicine Children’s Health and an assistant professor in the Division of Medical Genetics at Stanford Medicine. “Why should one group be screened for such a condition … if no one necessarily wants their future child to have this condition, or they at least want to be informed of their risk?”
Carrier screening often doesn’t occur until a woman is pregnant but can still provide useful information. But Tise says there are great variations in which genes are screened for by different providers, and even the 113 genes recommended by the ACMG don’t cover all the disorders for which newborns are screened in California.
Still, “I would recommend that anyone who is considering a pregnancy at least discuss carrier screening options with their provider,” Tise says.
Non-Invasive Testing
Another recent change is the use of cell-free DNA screening, also known as non-invasive prenatal testing, in which fetal DNA can be taken from a mother’s blood sample and be analyzed for chromosomal abnormalities including Trisomy 21 (Down syndrome), Trisomy 18 and Trisomy 13.
California is one of only two states that has made this screening standard, Tise says. The state switched to cell-free DNA screening in 2022, following a recommendation by ACMG. Like the state’s newborn screening program, this screening is offered to all pregnant women, regardless of insurance coverage, through a state-run program. It is done through a blood draw after 10 weeks of pregnancy. (To learn more about the California Prenatal Screening Program, visit cdph.ca.gov/Programs/CFH/DGDS/Pages/pns/default.aspx.) (shorten this)
“The use of (cell-free DNA) in a prenatal setting to identify pregnancies with increased risk of a chromosomal abnormality has been around probably for 20 years. It’s just that in its initial rollout, it was very much limited to women of … advanced maternal age,” Tise says. “Similar to carrier screening, just because you’re not over 35 doesn’t mean that you don’t want to be adequately screened for rare diseases so, slowly but surely, most practices started offering it to all individuals, and now it’s recommended to be offered to all pregnant individuals.”
Another Screening Test
Another newer blood-based screening test, single-gene non-invasive prenatal testing, is starting to be introduced for single-gene disorders such as cystic fibrosis. But Tise says it is not yet widely in use. “The sensitivity and specificity of that screen is pretty poor,” she says.
On the other hand, cell-free DNA screening has “sensitivities that are pretty high, meaning that if you screen positive, the chance that your fetus is actually affected is pretty high, and if you screen negative, the chance that your fetus does not have it is pretty low,” Tise says.
Follow-Up Required
But screenings are not 100% accurate. Patients are advised to follow up any positive results through an amniocentesis with a microarray, which is a genetic diagnostic test of the amniotic fluid withdrawn from the mother’s uterus with a needle. The earliest this is generally done is at 16 weeks of pregnancy, and the invasive procedure can pose a small risk to the pregnancy.
“Amniocentesis rates have definitely declined because, I think, of the misconception that cell-free DNA screening replaces it,” Tise says. But “it’s not a test, it’s a screen, and so there are false positives, and there are false negatives.”
When undergoing diagnostic testing, either before or during pregnancy, Tise advises patients to meet with “a certified prenatal genetic counselor so they can understand the possible outcomes of the test – including positive, negative and uncertain results – so that they’re prepared appropriately.” When the results come back, a counselor can discuss the results, the limitations of the test and options moving forward for follow-up testing.
“It’s just not ideal to learn what an amniocentesis is the day that it’s being recommended to you,” she says.
Janine DeFao is an associate editor at Bay Area Parent.
