Non-invasive prenatal testing (NIPT) offers a safe and reliable way to screen for certain chromosomal conditions, such as Down syndrome (Trisomy 21), Edwards syndrome (Trisomy 18), and Patau syndrome (Trisomy 13). It can even tell your baby's sex early on.
Still, one key detail plays a significant role in how accurate your results will be — fetal fraction, or the percentage of your baby's DNA circulating in your blood. Understanding the fetal fraction in NIPT can provide helpful insight into your testing experience.
In this guide, we'll explain what fetal fraction is, why it matters, and what factors influence it so you can make empowered choices during your pregnancy.
What is the fetal fraction in NIPT, and why does it matter?
Source: Frontiers
During pregnancy, small fragments of your baby’s DNA, known as cell-free fetal DNA (cfDNA), circulate in your bloodstream. The fetal fraction is the percentage of this fetal DNA compared to the total cell-free DNA in your blood.
A sufficient fetal fraction is important because it affects the sensitivity and specificity of your NIPT results. A higher fetal fraction helps the lab detect chromosomal abnormalities and determine fetal sex more accurately, reducing the chance of false positives or negatives.
This accuracy is key to making confident and informed decisions about your pregnancy and your baby’s health.
What is a good fetal fraction for NIPT?
Labs usually require a minimum fetal fraction of about 2–4% to provide reliable results. Most pregnancies fall within a range of 4% to 15%, though this can vary depending on how far along you are in your pregnancy, your body type, and other factors.
If your fetal fraction is below the minimum, the test might not give reliable results and may need to be repeated.
Here’s a quick look at the average fetal fraction by gestational week:
Gestational week | Average fetal fraction |
|---|---|
Week 10 | Around 4% to 6% |
Week 12 | Around 4% to 10% |
Week 20 | Over 10% |
After the 10th week of pregnancy, the fetal fraction usually levels out and increases gradually as your pregnancy progresses.
Factors that affect fetal fraction levels in NIPT
Several factors affect fetal fraction levels in NIPT testing, most notably:
Your body's characteristics
Factors related to the baby or placenta
Technical aspects of the test
1. Your body's characteristics
Your body has a big influence on how much of your baby’s DNA shows up in your blood, which affects how well the NIPT can read your baby’s genetic info. Here are some key things that can play a role:
Body weight: If you have a higher body weight, there might be more of your own DNA floating around, which can make it harder for the test to pick up your baby’s DNA.
Age: As you get older, changes in your body and placenta might lower the amount of fetal DNA in your bloodstream.
Ethnicity and genetic background: Some studies suggest that women of African American or South Asian descent might naturally have slightly lower fetal DNA levels, which can affect the fetal fraction.
Medications: Certain meds, like blood thinners, could impact fetal DNA levels.
Conceiving through IVF: If you conceived via IVF, it’s common to have a bit less fetal DNA, probably due to how the placenta develops early on.
Exercise: Intense exercise can temporarily raise the amount of your own DNA in the blood, making it harder for the test to detect fetal DNA.
2. Factors related to your baby or the placenta
Sometimes, the amount of your baby's DNA in your bloodstream depends on how far along you are or how well your placenta is functioning. In the early weeks of pregnancy, it's normal for fetal DNA levels to be a little low. They typically rise as your pregnancy progresses, especially after 9 or 10 weeks, which is why many NIPT tests are scheduled around that time.
If you take the test early and get an inconclusive result, don't worry — it may simply mean that there wasn’t enough fetal DNA present yet, and a simple retest a bit later can clear things up.
The health of your placenta also plays a significant role. Because the placenta is the primary source of fetal DNA in your blood, any condition that affects its development or function can impact test results.
3. Technical aspects of the test
While biological factors often get the most attention, technical details behind the scenes can also impact fetal fraction and the accuracy of your NIPT results.
One key factor is how and when your blood sample is collected and processed. If there’s a delay in getting the sample to the lab or it isn’t handled carefully, the delicate DNA fragments can begin to break down, making it harder to obtain an accurate result.
Temperature is another important factor. If your sample is exposed to excessive heat during transport or storage, your white blood cells may break down and release extra maternal DNA. This can dilute the fetal DNA in the sample, reducing fetal fraction and potentially leading to unclear or inconclusive results.
While labs do their best to prevent this, even slight variations can sometimes result in the need to repeat the test.
Potential consequences of low fetal fraction in NIPT
When the fetal fraction is too low, the ability to distinguish between normal (euploid) and abnormal (aneuploid) chromosome patterns decreases, which may lead to inconclusive NIPT results.
Low fetal fraction can also increase the risk of false negative or false positive results, although most labs will avoid reporting results if the fetal DNA isn't high enough to trust. Still, waiting longer or getting unclear information can add unnecessary stress during an already emotional time.
Some labs may try to improve accuracy by testing more DNA fragments — a method called deep sequencing. While it’s helpful in some cases, this method is not always practical, plus it’s costly and often not covered by insurance. If your fetal fraction is very low (below 3%), even this advanced testing might not make a difference.
Is a high fetal fraction in NIPT a cause for concern?
Source: 3billion
A higher fetal fraction improves test accuracy by providing a clearer signal, making results more reliable. Still, it isn’t always ideal.
Elevated fetal fraction levels, particularly in the first trimester, have been linked to certain pregnancy complications. For example, an unusually high fetal fraction (around 35.3%) may be an indicator of conditions like abnormally invasive placenta. Additionally, significantly increased fetal fraction may be associated with risks such as spontaneous preterm birth.
Some studies have also shown that fetal fraction levels above 16.5% may be linked to a higher risk of having a baby with low birth weight (under the fifth percentile for gestational age).
In some cases, a fetal fraction that's too high may even lead to a "no call" result, where the lab is unable to report a finding. This is uncommon, but it's something your provider may consider if your fetal fraction is unusually elevated.
Still, it’s important to remember that a high fetal fraction result doesn’t automatically mean something is wrong. It often prompts your provider to monitor fetal growth more closely through additional screenings later in pregnancy.
What happens if you receive an inconclusive NIPT result?
Getting an inconclusive result can be upsetting, but it doesn't mean there's a problem with your baby. It simply means the test couldn't get enough fetal DNA to provide a clear answer. Your healthcare provider will guide you on the next steps to get more reliable information.
You'll often be advised to repeat the NIPT after a few weeks, which gives your body time to increase the fetal fraction, improving the chances of a clear result the second time.
In some cases, your provider might suggest other screening options, such as sequential screening. They may also recommend diagnostic tests such as amniocentesis or chorionic villus sampling (CVS), which provide more definitive answers but are more invasive.
How does fetal fraction affect gender accuracy in NIPT?
Fetal fraction plays a role in determining your baby's sex.
Since the mother’s blood doesn't naturally contain any Y chromosomes, the test only needs to detect whether Y chromosome material is present. If it is, you're likely carrying a boy. If not, it's most likely a girl.
Most labs can accurately determine fetal sex with a fetal fraction as low as 2–4%, but confidence increases as the fetal fraction rises. Once it reaches 10% or more, gender accuracy can exceed 99%. And with the latest technology, some early gender tests (not always provider-ordered) can offer results with over 99% accuracy as early as 6 or 7 weeks into pregnancy.
What’s next? Consider carrier screening for more insights
While NIPT focuses on identifying chromosomal conditions in your baby, another type of genetic screening looks at something just as important — you. Carrier screening analyzes the parents’ DNA to identify whether they carry genetic changes that could be passed on to their children.
Even if you and your partner are healthy, you could be carriers for certain inherited conditions without knowing it. Carrier screening helps uncover those hidden risks early, offering peace of mind or the opportunity to plan ahead.
Nucleus offers advanced carrier screening using whole-genome sequencing (WGS) technology. This approach provides a more accurate view of your genetic makeup, giving you and your partner the most reliable insights possible.
Nucleus: Advanced genetic screening for informed family planning
Unlike tests that only scan for a few conditions, Nucleus gives you a wider lens. It helps uncover silent genetic risks that might go unnoticed, especially conditions you and your partner could unknowingly pass to your child.
Using whole-genome sequencing, Nucleus offers one of the most comprehensive and accurate DNA analyses today. Through its carrier screening test, you’ll gain valuable insights into your genetic predisposition to over 900 hereditary health conditions, including:
Common diseases like ADHD, Alzheimer’s, breast cancer, celiac disease, and dozens more.
Rare diseases often ignored by commercial tests, like immunodeficiency, sickle cell disease, and Tay-Sachs disease
9+ traits, such as BMI, height, intelligence (IQ), longevity, etc.
Your results are presented in clear, easy-to-understand reports with helpful visuals. And if you have questions, Nucleus connects you to a licensed genetic counselor through its partnership with SteadyMD, so you’re never left to navigate complex information alone.
Unlock your genetic insights with Nucleus
The Nucleus WGS test kit costs $499 and is eligible for payment through HSA or FSA accounts. The price includes the collection kit, return shipping, comprehensive reports, and future updates as genetic science advances. Couples can save $200 when purchasing two kits together by paying $798.
Getting started is simple:
Sign up for Nucleus
Provide your personal information
Order the test kit
Once your kit arrives, collect your cheek swabs and return the sample to the lab. Your results will be available in 6–8 weeks through Nucleus's secure, user-friendly online portal. The platform also uses AI-driven insights to deliver personalized health recommendations, helping you interpret your genetic data.
You may also like…
Read our insights on popular genetic testing options available today:
Featured image source: Valeriia Svietlova
