Testing....
Early in pregnancy, it’s not uncommon for a mother’s joy of being pregnant turn to worry about the health of the fetus. Before family and friends are told, it’s not uncommon for prospective parents to wait for 12 weeks or more to make sure the pregnancy is viable.
During that anxious time, non-invasive prenatal testing (NIPT) at the 10-week mark can help arm families with the information they need to determine the course of their pregnancy.
Here’s how NIPT works, what it reveals, its limitations, and why — even if it would not change your decision to carry your baby to term — it could possibly save your life [*].
NIPT, also known as cell-free fetal DNA screening (cfDNA), is the latest and most accurate screening tool designed to detect certain chromosome abnormalities in a developing fetus. Chromosomal abnormalities occur in about 1 in 150 live births and increase with maternal age.
But it’s important to note that NIPT is a screening tool, not a diagnostic test; Parents should never make decisions about their pregnancy on the basis of NIPT results alone.
Unlike the other screening tests that look for the presence of certain proteins or assess hormone levels, cfDNA screening relies on bits of DNA fragments from the placenta circulating in the mother’s blood. NIPT can be conducted as early as 10 weeks’ gestation, while other screening tests may be conducted after 12 weeks.
NIPT results are typically available in a weeks’ time.
Researchers have known for about 50 years that in spite of the presence of the blood-placental barrier, it was possible to detect fetal nucleated cells in maternal blood, but it wasn't until 1997 that cell-free fetal DNA (cfDNA) was first detected in maternal plasma and serum [*]. In the ensuing years, cfDNA screening has gone from obscure research labs to serving more than a third of U.S. pregnant women [*].
With a simple blood draw from the expectant mother, NIPT screens for fetal aneuploidies — a genetic disorder where the fetus has an extra chromosome (trisomy) or a missing one (monosomy) — as well as abnormalities in the number of sex (XY) genes. Some of these fetal aneuploidies can cause devastating intellectual disability, high infant mortality or shortened life span, heart defects, and more.
Available since 2011, NIPT is widely used in Europe, Australia, and the U.S., and in Belgium and the Netherlands, it is the standard of care for all pregnant women to have it. More than 2 million women have had NIPT performed [*].
American College of Obstetrics and Gynecology 2023 guidelines recommend NIPT for all pregnancies regardless of maternal age or risk of chromosomal abnormality. They further state that such testing should be available to all pregnant women without barriers such as prior authorization requirements [*].
Market analysts say the number of women expected to do NIPT will double by 2025, further growing a market expected to reach more than 2.6 billion by 2031 [*].
NIPT screens very effectively for Down syndrome, sex chromosome abnormalities, and the fetus’s Rh factor. It has a very high detection rate for common aneuploidies (98-99%) and low false positives (.1-.2%).
The screening for Trisomy 18 (Edwards syndrome) and Trisomy 13 (Patau syndrome) are somewhat less accurate, according to some experts [*].
Traditional methods of screening for aneuploidies based on maternal age, ultrasound markers, and biochemical factors are not effective in recognizing sex chromosome aneuploidies, except for Turner syndrome. NIPT has been shown to detect about 86% of sex chromosome abnormalities [*].
Where NIPT falls off the rails is in screening for rare conditions caused by microdeletions — small missing snippets of chromosomes. In the interest of bolstering their revenues, many testing companies offer genome-wide NIPT to reveal the presence of extremely rare conditions such as DiGeorge syndrome, an immune disorder that affects only 1 in 4,000 births. A 2022 New York Times expose found that the five major tests performing microdeletion screening give false positives between 81% and 93% of the time [*].
Reasons for test failure can be mundane — not enough fetal DNA in the sample, mistakes during blood collection or transport, or lab failure.
One study showed that conception by assisted reproduction is the most important contributor to NIPT test failure, followed by ethnic origin, BMI (risk increases by 5% with each additional Kg in maternal weight), maternal age, and parity [*].
NIPT tests are designed to assess your risk (positive predictive value, or PPV) of having a baby with Down syndrome, Trisomy 13, Trisomy 18, missing or additional sex chromosomes, the baby’s RH factor, and its sex at birth.
But even when NIPT delivers a false positive or nonreportable result, it can reveal some surprising things.
There are biological reasons for the test failing to produce a result or delivering a false positive which can point to pregnancy complications or health problems in the fetus or mother.
For instance, placental mosaicism, in which the placenta carries an abnormality that the fetus does not, will create a false positive result. A vanishing twin (where a twin pregnancy becomes a singleton pregnancy in the womb) may also deliver a false positive.
When the amount of fetal DNA circulating in the mother’s blood (called fetal fraction, or FF) is higher than expected, researchers have found an association with babies who are small for gestational age [*].
Other studies have shown that when the FF is very low it is associated with an increased risk of preeclampsia, preterm birth, or low birth weight [*].
Perhaps the most surprising outcome of a false positive result is that of an undiagnosed cancer in the mother. In 2013, a woman was found to have multiple aneuploidies in her NIPT results, confirmed by two different labs that each carried out three tests. Diagnostic testing found the fetus to be normal, but after the baby was born, the mother was found to have a neuroendocrine tumor that had been shedding fragments of DNA into her bloodstream that were picked up by NIPT testing.
This led NIH researchers in 2019 to launch a study called IDENTIFY, with the goal of gathering enough evidence to help medical professionals better counsel patients when their results are nonreportable or false-positive [*]. Other research continues to validate the ability of NIPT to reveal maternal cancers [*].
While cfDNA can be detected in maternal blood as early as 5-7 weeks, it grows from about .1% per week in weeks 10-21 to 1% per week beyond 21 weeks. NIPT is typically performed at 10-13 weeks to ensure an accurate analysis, with a single blood draw from the mother [*].
You can expect a screening result for the three main chromosomal abnormalities on average in about a week, or anywhere from 3 to 14 days at most. But the timing issue is a real conundrum because NIPT is a screening tool, not a diagnostic test.
When NIPT was first offered in clinical settings, the wait for results could be long because there were not a lot of labs performing the analysis. This delay would sometimes lead to a diagnosis after further testing in the second trimester, beyond some states’ abortion timelines [*].
The timing problem is exacerbated post-Dobbs, as certain states increasingly seek to restrict the timing and availability of abortion as short as 6 weeks — well before NIPT screening can even be done.
In states where 12 weeks is the cutoff, the end result will be that more women may act to terminate a pregnancy based on NIPT screening alone, perhaps because they haven’t been advised of the possibility of false positive results or simply can’t take the chance.
There’s every reason to believe the timing to get results will continue to improve as the technology moves forward and the marketplace responds to the needs of women. But it may not be enough. A 2014 study found that 6% of women who received NIPT results positive for aneuploidy terminated their pregnancy without getting another test to confirm the result [*].
Currently, only nine states that restrict abortion offer exceptions for fetal anomalies, according to the KFF tracker [*]. Current abortion laws for viable pregnancies are tracked by Axios [*].
Roughly 1%-5% of women will see a positive NIPT result [*]. As previously noted, when cfDNA testing is extended to microdeletions, the number of false positives can be exceptionally high. It may be easier to wrap your head around how common the underlying conditions being screened for are:
Down syndrome - 1 in 700 live births
Trisomy 18 - 1 in 5,000 - 6,000 live births
Trisomy 13 - 1 in 10,000 live births [*]
Turner syndrome - 1 in 2,500 females
XXY (sex chromosome) aneuploidy - 1 in 500 males
Other sex chromosome aneuploidies - 1 in 17,000 - 50,000 live births [*]
According to ACOG, roughly 80% of insured patients in the U.S. are covered for NIPT regardless of risk and nearly all are covered in a high-risk pregnancy [*]. The Coalition for Access to Prenatal Screening has a comprehensive chart of insurer NIPT coverage [*].
If you receive a negative result and there is other evidence of aneuploidy in ultrasound or other biochemical testing, your care provider may ask you to repeat the screening. If the screening is positive, your care provider will counsel you on the diagnostic tests needed to confirm the diagnosis. These include:
Amniocentesis, in which a needle is used to draw a sample of the amniotic fluid. Amnio can test for neural tube (what will become the baby’s brain and spinal cord) defects, such as spina bifida.
Chorionic Villus Sampling (CVS), in which a needle draws a sample from the placenta. Alternately, the test can be performed with a thin tube inserted through the vagina. CVS tests for Down syndrome, Trisomy 18, Cystic fibrosis, sickle cell disease, and Tay-Sachs disease. CVS does not detect neural tube defects.
Both of these procedures carry a minute risk of miscarriage — roughly 1 in 300-500 [*].
Note that CVS is usually performed at 10-13 weeks’ gestation, while amniocentesis is performed after 15 weeks. If timing is a concern, CVS may be advisable. If you have had vaginal bleeding during your pregnancy or have an infection, your care provider may counsel against having CVS.
The other caveat with CVS is that, in cases of placental mosaicism, where the placenta and the fetus do not share the same DNA, CVS testing is still going to reflect the DNA of the placenta, the same as the NIPT test, so there is still a chance it could be wrong. Confined placental mosaicism occurs in 2-3% of pregnancies [*].
As always, it’s best to discuss your results and your diagnostic options with your care provider.
Yes. Remember that NIPT tests the DNA in the placenta. In cases where the DNA in the placenta differs from that of the fetus, Down syndrome can be missed or conversely, reported as a false positive. There have also been reported incidences of false negatives in cases where mosaicism was not present [*]. Still, the rate of detection is higher than the combined traditional standard tests which assess the risk of Down syndrome with first-trimester ultrasound and blood tests [*].
NIPT involves a simple blood draw. There is no miscarriage risk associated with NIPT.
Very! NIPT can determine fetal sex accurately about 99% of the time [*].
No. Care providers routinely use noninvasive prenatal screening but none of the tests have yet been authorized, cleared, or approved by the FDA, and none are subject to FDA regulation. The FDA is concerned about marketing that over-promises on accuracy in tandem with cases where the screening has delivered a false positive and women have acted on that information alone, going so far as to issue a Safety Communication in 2022 urging patients and care providers not to make decisions based on screening alone [*].
While cord blood stem cell treatments cannot reverse chromosome aneuploidies, babies born with aneuploidies may also have congenital heart defects or other problems that might benefit from stem cell treatment. There are FDA-approved stem cell treatments for more than 80 diseases, including cancers such as lymphoma and leukemia, blood diseases like sickle cell anemia, immune system disorders such as DiGeorge syndrome, and metabolic disorders like Krabbe Disease and Hunter Syndrome.
MiracleCord offers the industry’s most advanced and comprehensive technologies, accommodating service, and affordable pricing. Learn more about the life-saving potential of cord blood and cord tissue stem cells by downloading our Free Info Kit, or call 888.743.2673 to speak to a representative now.
The ACOG recommends all pregnant women get noninvasive prenatal testing regardless of their risk factors, and insurers are increasingly covering the cost. While NIPT has been available since 2011, this technology continues to evolve in response to market competition and advances in science.
Today, it is the most sensitive tool care providers have to screen for Down syndrome and other trisomies, and it may be used in the near future to predict preeclampsia and other complications of pregnancy, including maternal cancer. It’s not a substitute for ultrasound or diagnostic testing, but a powerful complement that can help families be better prepared.
DISCLAIMER: THE INFORMATION ON THIS WEBSITE IS NOT INTENDED TO BE USED AS MEDICAL ADVICE.The materials and information contained on the MiracleCord website is provided for educational and informational purposes only, and is not intended to, and does not constitute, medical or other health advice or diagnosis, and should not be used as such. You should not use this information to diagnose or treat a health problem or disease. If you are seeking personal medical advice, you should consult with a licensed physician. Always consult with a qualified health care provider regarding a medical condition.
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