Prenatal cell-free DNA (cfDNA) screens, also called NIPTs, are prenatal screenings that look for fragments of fetal DNA in a pregnant person’s bloodstream. By looking at these DNA fragments, prenatal cfDNA screens tell us whether a developing fetus is at risk of having certain chromosomal conditions.

It’s important to understand that cfDNA screens can’t diagnose a medical condition. Instead, they offer insight into the likelihood of a chromosomal condition when they work as intended. Sometimes, a screen is returned with an inconclusive or “no-call” result. This can happen for a variety of reasons, one of the more common being that the lab wasn’t able to retrieve enough fetal DNA to make an interpretation.

Getting an inconclusive result on an NIPT screen can be frustrating. However, by understanding why it happens—and by learning about screens that can provide more reliable results the first time—you can navigate your prenatal care with greater clarity and confidence.1,2

Three common reasons for an inconclusive NIPT result

Getting an inconclusive, or “no-call,” result on a cfDNA screen is often due to a lab’s inability to extract enough fetal DNA from a blood sample.3 This is known as low fetal fraction. When the fetal fraction is too low, the lab can’t reliably offer insights and must label the screen as inconclusive.

What causes low fetal DNA? Here are three common reasons:4

  1. High body mass index – Weight can affect NIPT results and having a high BMI is one of the most common reasons for prenatal cfDNA screening failures.5 When more blood is in circulation, it can dilute the fetal DNA in a sample, causing it to have a low fetal fraction. This makes it harder for some screens to look at the necessary DNA fragments.
  2. Advanced maternal age (AMA) –  Pregnant individuals are considered AMA when they are 35 years or older. Increasing maternal age is associated with decreasing fetal fractions, and lower fetal fractions increase the risk for inconclusive screening results.6,7
  3. Early gestational age – If a screen is performed before eight weeks and/or before enough fetal DNA has entered the maternal bloodstream, it can lead to an inconclusive screening.

How to get better results on an NIPT

Some prenatal cfDNA screens aren’t typically equipped to catch low levels of fetal DNA in the bloodstream. However, some screens have “signal boosting” technology for fetal DNA, improving the lab’s ability to deliver conclusive results.

For example, the Prequel® Prenatal Screen uses AMPLIFY® technology designed to better distinguish fetal DNA from the maternal DNA. This can be especially useful for a parent-to-be with a higher BMI or who is starting a family later in life. Prequel is also the only NIPT available at eight weeks into pregnancy, regardless of BMI. AMPLIFY makes it possible to screen for chromosomal differences like trisomy 21, trisomy 18, or trisomy 13, and many others, while reducing the likelihood of an inconclusive result.

What to do after an inconclusive NIPT result

Receiving an inconclusive result can feel discouraging, but it’s not necessarily a cause for concern. Many pregnancies with an initial inconclusive result progress healthily.

If your cfDNA screen is inconclusive, consider taking the following steps:

  • Talk to your healthcare provider – Your healthcare provider can explain potential reasons for a no-call result, review your health history, and determine whether additional screenings and tests are necessary.
  • Undergo another screen – Many labs recommend retaking the cfDNA screen a few weeks later, as fetal DNA levels may increase. This can often lead to a reportable result.

It’s important to remember that an inconclusive cfDNA screen does not necessarily indicate something is wrong with your pregnancy. Rather, it shows the technical limitations of some screenings and points the way to trying other, more reliable options.

With proper guidance, timing, and screening methods, many people can obtain reliable results the first time and plan their prenatal journey with greater clarity.

References

  1. Muzzey D, Goldberg JD, Haverty C. Noninvasive prenatal screening for patients with high body mass index: Evaluating the impact of a customized whole genome sequencing workflow on sensitivity and residual risk. Prenat Diagn. 2020;40(3):333-341. doi:10.1002/pd.5603
  2. Hancock S, Ben-Shachar R, Adusei C, et al. Clinical experience across the fetal-fraction spectrum of a non-invasive prenatal screening approach with low test-failure rate. Ultrasound Obstet Gynecol. 2020;56(3):422-430. doi:10.1002/uog.21904
  3. Hui L, Bianchi DW. Fetal fraction and noninvasive prenatal testing: What clinicians need to know. Prenat Diagn. 2020 Jan;40(2):155-163. doi: 10.1002/pd.5620. Epub 2019 Dec 10. PMID: 31821597; PMCID: PMC10040212.
  4. Kong X, Zhang L, Yang R, et al. Reasons for failure of noninvasive prenatal test for cell-free fetal DNA in maternal peripheral blood. Mol Genet Genomic Med. 2024;12(1):e2351. doi:10.1002/mgg3.2351
  5. Maines J, Langaker MD. Prenatal Genetic Screening. [Updated 2025 Apr 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557702/
  6. Galeva, S., Gil, M. ., Konstantinidou, L., Akolekar, R. and Nicolaides, K. . (2019), First-trimester screening for trisomies by cfDNA testing of maternal blood in singleton and twin pregnancies: factors affecting test failure. Ultrasound Obstet Gynecol, 53: 804-809. https://doi.org/10.1002/uog.20290
  7. Rolnik, D.L., da Silva Costa, F., Lee, T.J., Schmid, M. and McLennan, A.C. (2018), Association between fetal fraction on cell-free DNA testing and first-trimester markers for pre-eclampsia. Ultrasound Obstet Gynecol, 52: 722-727. https://doi.org/10.1002/uog.18993

Reviewed by Lauren Siems Watson, MS, CGC

Lauren is a Medical Science Liaison (MSL) Manager at Myriad Genetics who leads a team of genetic counselor and scientist MSLs providing education, clinical support, and technical expertise to health care providers interested in reproductive genetic screening and hereditary cancer risk assessment. She is a licensed and certified genetic counselor in the greater Los Angeles area, currently serving as President on the Board of Directors for the Southern California Genetic Counselors (SCGC). Prior to joining Myriad, Lauren trained at Northwestern University Graduate Program in Genetic Counseling. She is also a member of NSGC and an alumna of the City of Hope Intensive Course in GCRA.

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NIPT vs. cfDNA screen: What’s the difference?

NIPT, or non-invasive prenatal testing, is a common term for a non-invasive prenatal blood screening that checks for certain chromosomal conditions in a developing baby. However, the name can be misleading, as NIPT isn’t an actual test and it is not meant to diagnose conditions. Instead, it estimates the likelihood of genetic changes in a developing fetus. A cfDNA screen is a more precise, updated term for the same type of assessment. In other words, cfDNA screens and NIPTs are functionally the same. The only difference is the name, which highlights that the technique is a screening, not a diagnostic test.