Please create a counseling smartphrase for a pregnant patient with a low cell‑free DNA (cfDNA) fraction on non‑invasive prenatal testing.

Counseling Smartphrase for Low Cell-Free DNA Fraction in Pregnancy

Your cell-free DNA (cfDNA) test did not provide a result due to insufficient fetal fraction, which means there was not enough placental DNA in your blood sample to complete the screening—this finding is associated with a 9.2-fold increased risk of fetal chromosome abnormalities, particularly trisomies 13,18, and triploidy, and we strongly recommend diagnostic testing with amniocentesis or chorionic villus sampling (CVS) to definitively assess your baby's chromosomes. 1, 2

Understanding Your Test Result

What happened with your test:

• Your cfDNA screening could not provide a result because the fetal fraction (the percentage of placental DNA in your blood) was too low for accurate analysis 1
• This occurs in approximately 0.9-8.1% of all cfDNA tests, but the rate doubles to 16% in pregnancies with chromosome abnormalities 1, 2
• The most common reason for test failure is insufficient fetal DNA in the maternal blood sample 3

Why this matters for your pregnancy:

• Women with failed cfDNA tests due to low fetal fraction have a significantly elevated risk of fetal aneuploidy, with an odds ratio of 9.2 compared to women with successful tests 1, 2
• This increased risk applies particularly to trisomies 13,18, and triploidy (a condition where the fetus has three complete sets of chromosomes instead of two) 1, 2
• The association between low fetal fraction and chromosome abnormalities is strong enough that professional guidelines specifically recommend offering diagnostic testing 1, 2

Factors That May Have Contributed

Common reasons for low fetal fraction include:

• Maternal body weight: Testing fails in 20% of women weighing >250 lbs and 50% of women weighing >350 lbs 1, 4
• Early gestational age: Fetal fraction is lower before 10 weeks of gestation 1, 4
• Maternal medical conditions: Autoimmune conditions and use of certain anticoagulants can affect results 4
• Placental factors: Abnormalities in placental development or function may reduce fetal DNA release 4
• Multiple underlying conditions: 58.7% of women with persistent test failure have underlying medical conditions, with 47.7% having two or more coexisting conditions 3

Your Options Moving Forward

Option 1: Diagnostic Testing (Recommended)

Amniocentesis or CVS provides definitive chromosome analysis:

• This is the recommended approach given your 9.2-fold increased risk of aneuploidy 1, 2
• Amniocentesis (performed after 15 weeks) or CVS (performed at 10-13 weeks) directly analyzes fetal cells to provide a definitive diagnosis 4
• These tests can detect all chromosome abnormalities, not just the common trisomies 4
• Results are typically available within 1-2 weeks 4
• The miscarriage risk from amniocentesis is approximately 1 in 300-500 procedures 4

When to choose diagnostic testing immediately:

• If you are at an advanced gestational age and do not want to delay obtaining definitive information 1
• If you have significant anxiety about the increased aneuploidy risk 2
• If you have maternal obesity or other factors that make repeat cfDNA testing less likely to succeed 1, 2

Option 2: Repeat cfDNA Testing

Attempting the test again may provide a result:

• Repeat testing is successful in 50-80% of cases (or 62.9-70.6% depending on the specific circumstances) 1, 2, 5
• Success rates depend heavily on your initial fetal fraction level, maternal weight, and time between blood draws 6, 5
• Waiting 8-14 days between draws optimizes the chance of success 6, 5
• If gestational age was very early (<10 weeks), waiting until after 10 weeks may improve results 1, 4

Important limitations of repeat testing:

• Even if the repeat test is successful, you still had an initial failed test, which carries the 9.2-fold increased aneuploidy risk 1, 2
• 20-50% of repeat attempts will still fail, particularly in women with higher body weight 1, 2, 5
• Delaying may reduce your options if an abnormality is ultimately detected 1

Option 3: Alternative Screening Methods

Traditional serum screening (quad screen) is an option:

• This blood test does not require fetal fraction and can be performed in the second trimester 1
• However, it is less accurate than cfDNA screening and does not address your increased risk from the failed cfDNA test 1
• Given your 9.2-fold increased aneuploidy risk, traditional screening alone may not provide adequate reassurance 1, 2

Additional Pregnancy Monitoring

Beyond chromosome testing, low fetal fraction has been associated with:

• Increased risk of hypertensive disorders of pregnancy (HDP): 5.17% vs 1.91% in women with normal fetal fraction 7
• Placental compromise: Women with low fetal fraction have nearly twice the risk (adjusted odds ratio 1.946) of adverse outcomes related to placental dysfunction 7
• Small for gestational age (SGA) and placental abruption: Though not always statistically significant, these risks may be elevated 7

Recommended additional monitoring:

• Enhanced ultrasound surveillance for fetal growth in the third trimester 7
• Blood pressure monitoring for signs of hypertensive disorders 7
• Discussion with your provider about the timing and frequency of prenatal visits 7

Our Recommendation

We strongly recommend proceeding with diagnostic testing (amniocentesis or CVS) because:

• Your risk of fetal chromosome abnormality is 9.2 times higher than women with successful cfDNA tests 1, 2
• Diagnostic testing provides definitive answers rather than continued screening uncertainty 4
• This approach avoids further delays that could limit your options if an abnormality is detected 1
• Even if you attempt repeat cfDNA testing and it succeeds, the initial failure still confers increased risk 1, 2

If you decline diagnostic testing:

• We recommend at minimum attempting repeat cfDNA testing after an appropriate interval (8-14 days) 6, 5
• Enhanced ultrasound evaluation should be performed to assess for structural abnormalities that might suggest chromosome disorders 1
• Close monitoring for placental complications throughout pregnancy is warranted 7
• Genetic counseling with a qualified genetics professional should be obtained to fully understand your risks and options 4

Important Caveats

Understanding test limitations:

• cfDNA screening analyzes placental DNA, which may not always match the fetal chromosomes due to confined placental mosaicism 4, 8
• Other factors can cause discordant results, including vanishing twin, maternal chromosome abnormalities, or rarely, maternal malignancy 4
• All positive screening results require diagnostic confirmation before making definitive pregnancy decisions 8, 9

Factors affecting your decision:

• Your gestational age and how much time you have for additional testing 1
• Your personal values regarding invasive testing risks versus diagnostic certainty 4
• Your body weight and likelihood of successful repeat cfDNA testing 1, 2, 5
• Your anxiety level and need for definitive information 2

---

Next Steps: Please schedule a follow-up appointment within [timeframe] to discuss your decision and arrange for either diagnostic testing or repeat cfDNA screening. We are available to answer any questions and support you through this process.