How Does NIPT Work?

When you’re pregnant, you share just about everything with your baby, forming an inseparable bond. You share meals (nutrients) and your breath (oxygen) through the placenta via the umbilical cord.

You also share your veins’ real estate.

Within your bloodstream you hold both your own maternal DNA and your baby’s DNA. Your baby’s DNA is cell-free fetal DNA, or cffDNA for short. Little bits of cell free DNA pass through the placenta into your bloodstream. This means a blood sample from you contains maternal plasma which gives insight to the genetic material of your growing child. The percent of cffDNA in your blood is known as the fetal fraction percentage, which increases the further along you are in pregnancy. At the gestational age of around 10-12 weeks, the fetal DNA fraction becomes high enough (above 4%) for an NIPT to accurately screen for chromosomal abnormalities in your baby’s DNA.

What Does NIPT Test For?

The NIPT screens a baby’s DNA to test for fetal aneuploidy or chromosomal abnormality. The two types of chromosomal abnormalities are: duplicated chromosomes called Trisomy (which is more common) and partially missing chromosomes called Monosomy (which is less common).

Of note: This elective NIPT test ordered by your provider is what’s usually referenced when people discuss non-invasive prenatal testing. However, there is another type of NIPT (discussed below) that solely looks at gender and can be taken earlier than 10 weeks.

The more frequent chromosomal abnormalities include:

• Down syndrome – Also known as trisomy 21, Down syndrome affects how both the body and brain develop. It can often result in a flattened face features, poorly developed muscle tone and joints, lower IQ, and various other health problems.
• Edwards syndrome – Also known as trisomy 18, Edwards syndrome is characterized by a low birth weight. Problems continue after birth, resulting in heart defects, small jaw, and overlapping fingers.
• Patau syndrome – Also known as trisomy 13, Patau syndrome is associated with intellectual disabilities and physical defects of the heart, brain, and spinal cord.
• Turner syndrome (Monosomy X) – A female-specific condition, Turner syndrome occurs when one of the fetal sex chromosomes is missing entirely or partially. This results in a shorter stature, undeveloped ovaries, and heart defects.
• Klinefelter syndrome (XXY) – Klinefelter syndrome occurs in males who have more than one X chromosome. This can result in underdeveloped testicles and infertility.
• Triple X Syndrome (XXX) – Also known as Trisonmy X, this is a genetic disorder that occurs in females in which the sex chromosone has an extra X chromosome. Babies with this condition are likely to develop behavioral problems and learning difficulties. Girls with this condition may also grow taller than average for their respective age group.

This isn’t all the genetic abnormality that NIPT can test for. Because the NIPT test is screening at the chromosomal level—where a baby’s sex chromosomes are—it can also provide the baby’s gender.

What Does NIPT Not Test For?

NIPT does not test for all chromosomal disorders. Some chromosome conditions NIPT cannot screen for include:

• Heart defects
• Abdominal wall defects
• Open neural tube defects, such as spina bifida or anencephaly

Maternal serum screening is necessary to test for open neural tube defects. Noninvasive prenatal testing also cannot detect physical birth defects like a cleft palate, certain genetic disorders like sickle cell anemia, and may not be able to screen for cystic fibrosis. Amniocentesis can diagnose nearly every chromosomal abnormality, however, it poses potential physical risks to the mother and child.

Who Receives an NIPT?

As mentioned, not every pregnant women will be recommended for this elective test by their provider. There are a few indicators that will use to determine who should be offered an NIPT.

If the maternal age (the age of mama at the time of delivery) is 35 or higher. As women age, there is a higher chance of various complications with pregnancy. The specific age of 35 came about because it used to be the age in which the risk of having a child with the chromosomal condition trisomy 21 (Down syndrome) was equal to the risk of miscarriage through amniocentesis. Today, the risk of miscarriage during amnio is much lower (around 1 in 500), but the age of 35 has seemed to stick.

If there is a history of any of the chromosomal abnormalities within the maternal or paternal family. Because these conditions are genetic, they are hereditary (or passed through family genes). If someone in the family has Down syndrome, for example, the likelihood that a child within the extended family will also have this chromosomal anomaly is higher.

If prior pregnancies have revealed a high chance for fetal aneuploidy. NIPT may be recommended for all future pregnancies. Since the baby’s cell free DNA originates from the placenta, NIPT screening is necessary for each individual pregnancy to screen for chromosomal abnormalities.

Noninvasive prenatal testing has not been shown to give accurate results in multiple pregnancy cases. NIPT is also not recommended for twin pregnancies. Twins have both of their individual cffDNA present in the mother’s bloodstream. If NIPT detects a chromosomal abnormality, there is not a reliable method to differentiate which fetus has the condition.

It is recommended that families undergo genetic counseling prior to NIPT to discuss strategies and options in the event of unexpected or challenging results.

Benefits and Limitations of NIPT Testing

Benefits of NIPT

Early Detection of Genetic Abnormalities

Non-Invasive Prenatal Testing (NIPT) provides expectant parents with early insights into their baby’s genetic health. Performed as early as the first trimester, NIPT screens for specific chromosomal abnormalities such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13). Early detection allows parents and healthcare providers to make informed decisions and prepare for any necessary medical care or interventions. Early awareness through NIPT can significantly impact prenatal planning and management.

Non-Invasive and Safe for Mother and Baby

One of the standout advantages of NIPT is its non-invasive nature. The test requires only a simple blood draw from the mother, posing no physical risk to the baby. This contrasts with invasive procedures like amniocentesis, which carries a small risk of miscarriage. The safety and simplicity of NIPT make it an attractive option for many expectant parents. Studies emphasize that NIPT is safe for both mother and child, providing peace of mind without compromising well-being.

Limitations of NIPT

Screening, Not Diagnostic

While NIPT is highly accurate for certain conditions, it’s important to understand that it is a screening tool, not a diagnostic test. This means that NIPT assesses the risk or likelihood of a genetic condition but does not provide a definitive diagnosis. If NIPT results indicate a high risk for a chromosomal abnormality, additional diagnostic tests like amniocentesis or chorionic villus sampling (CVS) are recommended to confirm the findings. Studies advise that positive NIPT results should be followed up with diagnostic procedures to ensure accurate diagnosis.

Potential for Inconclusive Results

In some cases, NIPT may yield inconclusive or indeterminate results. Factors such as low fetal DNA in the mother’s blood, testing too early in the pregnancy, or maternal obesity can affect the test’s accuracy. An inconclusive result may cause additional anxiety and necessitate repeat testing or alternative screening methods. It is important to counsel patients about the possibility of inconclusive results and discuss potential next steps to ensure they are fully informed.

Results of an NIPT

What does it mean to have a “low” chance vs “high” chance for a chromosomal abnormality?

If the screening test reveals a low chance for the chromosomal abnormality, it is likely your child will not have any of the above conditions. The likelihood of a false negative is incredibly low. According to a scientific literature review of 5,967 high-chance pregnancies, a false negative trisomy happens 0.23% of the time.

What about when the results come back as a high chance for the chromosomal abnormality? According to Catherine Joynson of the Nuffield Council on Bioethics, a high chance doesn’t necessarily mean the child will be born with the condition, either:

“If you receive a high chance result for Down’s syndrome, there is a 1 in 5 (20%) chance that the result is wrong and your fetus does not have the condition. For Patau’s syndrome, there is a 1 in 2 (50%) chance the result is wrong, and for Edwards’ syndrome, it’s a 3 in 5 (60%) chance.”

The false positive, high-chance result could be due to:

• The trisomy being in the placenta, not the baby – The cell-free fetal DNA transfers from the placenta into mom’s bloodstream. So, when the trisomy is found in the cff DNA, this usually corresponds with a trisomy in the baby’s DNA. However, sometimes this chromosomal abnormality is confined to the placental tissue DNA—not the baby’s. This is known as placental mosaicism, and it causes about 1% of false positives.
• A vanishing twin – A vanishing twin is a type of miscarriage where one twin is lost early in pregnancy. If this twin had a chromosomal abnormality, there is a chance that the fetus’s cffDNA is still present in the placenta. This means the positive result is not applicable to the remaining, growing baby. A vanishing twin causes about 0.11% of false positives.

The Third NIPT Result: Inconclusive

As previously mentioned, the fetal DNA fraction needs to be above 4% for an NIPT to be accurate and increases with gestational age. This usually occurs around 10-12 weeks but could occur later for some mothers. If low fetal fraction is below 4%, the NIPT will likely fail to provide a result at all. This is because both mom’s and baby’s chromosomes are being included in the analysis; the test cannot separate them. If there’s not enough of the baby’s cffDNA in the maternal plasma, the screening doesn’t have enough data to identify them via statistical analysis.

The 4% marker is the cut-off for when this test result becomes unreliable. Below this, the NIPT returns the result “inconclusive.”

Weight is one factor that influences low fetal fraction. Studies show that on average a pregnant woman with higher maternal BMI will have lower cell free fetal DNA present in her maternal blood. Additionally, unusually low fetal fraction is at higher risk for preterm birth.

After the NIPT Results: Next Steps

Because the chromosomal abnormality analysis requires DNA sequencing, it typically takes between 1-2 weeks to return results. Depending on these results, your doctor may have different recommendations:

Low-chance result – With a low-chance result, doctors typically won’t recommend a secondary screening or diagnostic test.

Inconclusive result – When this occurs, your doctor might recommend a follow-up test. It’s possible low fetal fraction ( low ff ) was the cause and during the 1-2 weeks you were waiting for the result, the fetal fraction percentage in your blood increased.

High-chance result – Should the result be a high chance of a chromosomal abnormality, your doctor might offer a follow-up diagnostic test called an amniocentesis. Because this poses risks to the baby, however, the test isn’t mandatory.

Amniocentesis: Confirming the Screening Result

Screenings and diagnostic tests are different in one fundamental way. A screening test offers a probability, not a 100% yes or no answer. A diagnostic test can confirm for sure.

An amniocentesis is an invasive prenatal diagnostic test. The procedure uses a needle to remove amniotic fluid from the uterus, while an ultrasound device monitors the positioning of both the needle and the baby to reduce the risk of injury. The amniotic fluid that surrounds a baby throughout pregnancy contains fetal cells that are shed during development. These cells are isolated and analyzed, offering direct insight into the baby’s chromosomes.

So while an NIPT screens for abnormalities using cffDNA and statistical analysis to create probabilities, amniocentesis goes “straight to the source” of that DNA and provides a diagnosis.

While an amniocentesis does provide an accurate result, the reason it’s not done first is that it is an invasive procedure, meaning there are physical risks to both mom and baby. These risks include:

• Leaking amniotic fluid
• Needle injury to the baby
• Infection to mom, baby, or both
• Miscarriage (low risk, 0.1% to 0.3%)

Only about 5-10% of pregnant women opt for an amniocentesis test. This number is low, thanks to the development and accuracy of non-invasive screenings. Even when NIPT screening does come back with a high probability of chromosomal abnormality, parents weigh the risks of the procedure to determine whether it’s worth an invasive test to confirm with a diagnostic.

It’s one more reason why non-invasive prenatal diagnosis is so necessary today.

Other Types of NIPT Testing

If you want to know the gender of your baby and you aren’t included in the three indicators that prompt a physician-ordered NIPT, then this is not your go-to test. Not only would this be an expensive option, but if your doctor doesn’t think you need one, then insurance isn’t likely to cover it. This can result in thousands of dollars in lab bills.

Thankfully, there’s another type of NIPT used specifically for the gender that’s more affordable and accessible.

Early Gender DNA Test

An NIPT is merely taking a sample of mom’s blood to look for answers within the cffDNA. While a 4% fetal fraction is needed to determine genetic abnormalities, a significantly lower fetal fraction is needed to predict gender. This is why the SneakPeek Early Gender DNA Test can be taken as early as 6 weeks into pregnancy, instead of 10-12 weeks.

How Does the SneakPeek Test Identify your Baby’s Gender?

With SneakPeek, our early gender test uses maternal blood from a blood draw or small prick of the finger (if you choose an at-home kit). Back at SneakPeek Labs, the blood sample is analyzed for male DNA or Y chromosomes. Since mom wouldn’t have any Y chromosomes in her blood unless she’s carrying a boy, the test only has to detect their presence, rather than run a statistical analysis like other NIPTs. Because of this, less fetal fraction is needed to return a boy or girl result, and the test can be run in 1 day rather than 1 to 2 weeks. That means results are returned quickly!

In sum, the test simply asks: is there, or is there not any Y chromosomes in the blood sample?

• If the test detects even a tiny amount of Y chromosomes, the baby is a boy !
• If no male chromosomes are detected in the blood sample, the baby is a girl !

Using cutting-edge technology, these gender reveal tests are over 99% accurate1as early as 6 weeks 7 weeks pregnant—weeks earlier than a provider-ordered NIPT test. The best part? You can do this from the comfort of your home and find out baby gender without an ultrasound.

Ethical Considerations Around NIPT

NIPT provides parents with unprecedented access to early insights about their baby’s genetic health, but with this knowledge comes complex ethical considerations. While early screening allows families to prepare for potential medical challenges, it also raises questions about how this information should influence decision-making. The National Institutes of Health (NIH) stresses the importance of informed consent and counseling to ensure that parents fully understand the implications of NIPT results, both emotionally and practically.

For some, NIPT results may lead to difficult decisions about further diagnostic testing or pregnancy management. It’s crucial to approach these scenarios with sensitivity, focusing on providing clear, unbiased information and support to help parents make choices aligned with their values and circumstances.

The Future of NIPT Testing

Advances in Genetic Screening Technology

As technology continues to evolve, NIPT is becoming more sophisticated, offering even greater accuracy and expanded testing capabilities. Current advancements in genetic sequencing are allowing scientists to detect more nuanced genetic variations, such as microdeletions and rare chromosomal conditions. These innovations promise to make NIPT an even more comprehensive tool for prenatal care.

Potential to Screen for Additional Conditions in the Future

The future of NIPT testing may include screening for a broader range of conditions, including single-gene disorders and hereditary diseases. This could provide expectant parents with a deeper understanding of their baby’s health while still maintaining the test’s non-invasive and low-risk nature. However, as capabilities expand, so do ethical and societal questions about how this information should be used. Ensuring that these advancements are applied responsibly will be critical to preserving trust in genetic testing technologies.

As NIPT continues to advance, it holds the potential to revolutionize prenatal care, offering parents more options to ensure the health and well-being of their growing families.

How to Take a SneakPeek Early Gender DNA Test

If you want to discover your baby’s gender and start planning for his or her arrival, SneakPeek offers two ways to perform this test:

• At-home test – You can collect your blood sample from the comfort of your home with the SneakPeek At-Home Early Gender DNA Test. The gender blood test kit comes with everything you need to take the test and a prepaid return label to send your sample back to SneakPeek Labs. With this method, you’ll learn your baby’s gender within days.
• Clinical test – If you prefer to have a phlebotomist draw your blood, you can visit a participating SneakPeek Clinical Early Gender DNA Test location and get a gender blood test at doctors offices near you to learn your baby’s gender, also within days.

If you’re ready, you can order your test today and learn whether your little world is a boy or girl sooner than ever before.