Cell-Free Fetal DNA Test: Very Accurate, Low Risk

What is the cell-free fetal DNA test? How can it help you detect Down Syndrome and other disorders, at minimal risk to the baby?

Learn more about this modern advance in fetal genetic testing.

Background to Cell-Free Fetal DNA Testing

The primary purpose of prenatal screening is to detect chromosomal abnormalities, the most common being Down Syndrome, or trisomy 21. Tests also screen for the rarer Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13), both more severe than Down Syndrome with babies rarely surviving their first year. Families at high risk for genetic disorders may also screen.

The risk of Down Syndrome increases with maternal age, from 1 in 1488 from ages 20-24, to 1 in 746 in ages 30-34, to 1 in 30 for age 45 (a fuller chart is shown later). For some comparison, the risk of a car accident in the next year is 1 in 50, and the risk of being audited in the next year is 1 in 200.

There are largely two types of screening: non-invasive (cell-free fetal DNA, ultrasound), and invasive (amniocentesis, chorionic villus sampling). Non-invasive tests pose no risk to the fetus but are more prone to false positives and false negatives. In contrast, invasive tests have higher accuracy, but pose a risk of miscarriage (according to Oster, 1 in 800).

Spoiling the punchline: cell-free fetal DNA tests have advanced non-invasive screening considerably from the ultrasound days.

Noninvasive Test: Cell-free Fetal DNA

Cell-free fetal DNA tests use fetal DNA that is circulating in the mother’s bloodstream. 

The mother’s bloodstream contains not just fetal cells but also fetal DNA outside of cells. In fact, 10-20% of DNA isolated from maternal plasma is from the fetus. 

Theoretically, if the fetal DNA could be isolated fully from the mother’s DNA, then full genomic sequencing could occur. We’re not quite there yet, but bulk defects can still be detected – for instance, if a higher than expected proportion of chromosome 21 is in the mix, there’s a good chance it indicates trisomy 21.

The sensitivity (true positive rate, or accurate detection of a disorder) of the cell-free DNA test is remarkably high – in one large-scale study, 99.1% of trisomies are detected with this procedure. The false negative rate is also low, at 0.05% (of 146,000 women without Down Syndrome, 61 were given a false positive).

Given your age and test result from the cell-free DNA test, then, what is the likelihood of your child having Down Syndrome? Here’s a helpful chart:

AgeRisk of Down SyndromeWIth negative test result, chance of Down SyndromeWith positive test result, chance of Down Syndrome
20-241 in 14881 in 179,8301 in 1.8 (55.6%)
25-291 in 11181 in 135,0851 in 1.6 (62.5%)
30-341 in 7461 in 90,0971 in 1.4 (71.4%)
351 in 3741 in 45,1091 in 1.2 (83.3%)
361in 2891 in 34,8301 in 1.15 (87.0%)
371 in 2241 in 26,9691 in 1.12
381 in 1731 in 20,8011 in 1.09
391 in 1361 in 16,3271 in 1.07 (93.5%)
401 in 1061 in 12,6991 in 1.06
411 in 821 in 9,7961 in 1.04
421 in 631 in 7,4981 in 1.03 (97.1%)
431 in 491 in 5,8051 in 1.03
441 in 381 in 4,4751 in 1.02
451 in 301 in 3,5081 in 1.01 (99.0%)

In essence, if you get a positive result, it’s very likely the child has Down Syndrome; and if it’s negative, it’s very unlikely the test is wrong.

If you get a positive result when you’re younger, the chances that the child actually has Down Syndrome are lower as well.

(Shortform note: the true positive rate increases with age because the risk increases a lot with age. When the baseline rate is high and the test is positive, chances are better that the test is correct, compared to younger mothers.)

Cell-Free Fetal DNA Test: Very Accurate, Low Risk
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Allen Cheng

Allen Cheng is the founder of Shortform. He has a passion for non-fiction books (having read 200+ and counting) and is on a mission to make the world's best ideas more accessible to everyone. He reads broadly, covering a wide range of subjects including finance, management, health, and society.Allen graduated from Harvard University summa cum laude and attended medical training at the MD/PhD program at Harvard and MIT. Before Shortform, he co-founded PrepScholar, an online education company.

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