What is cell free (cf) DNA?
As a name suggests, cell free DNA (cfDNA) freely circulates in blood and is not contained within the cells. cfDNA is a normal by-product of biological cells turnaround (called apoptosis).
During pregnancy the placenta leaks fetal DNA which circulates in the maternal bloodstream. As a result, a maternal plasma sample contains a mixture of fetal and maternal cfDNA. This circulating free fetal (cffDNA) constitutes from 3% to 13% (10% on average) of all maternal cfDNA (so called “fetal fraction”); it increases throughout pregnancy. Cell free fetal DNA was firstly discovered back in 1997, but only recent advances in the next generation sequencing technology (NGS) allowed its wide adoption in clinics from 2011. cffDNA already has made huge impact in prenatal care thanks to high efficacy to detect chromosomal anomalies (see “aneuploides” or “trisomy”), which reduces the need for invasive screening for normal pregnancies. Non-invasive prenatal screening of cffDNA from the plasma of pregnant women can be performed starting as early as 9 weeks and until delivery. cffDNA is rapidly cleared from the maternal circulation after the delivery, meaning that during subsequent pregnancy it will come from a new fetus.
What you should know about cfDNA fraction considering NIPT:
- The fetal DNA fraction is essential for accurate NIPT results – most laboratories report results only when fetal DNA percentage is at least 4-5%.
- The fraction of cffDNA is increasing during pregnancy and can be reliably analyzed from 9-10 weeks of pregnancy (gestation).
- Increased maternal weight is associated with lower fetal DNA percentage, so obesity can lead to higher rates of inconclusive results.
- There is a small (0-5%) chance of NIPT failure (a “no call” test result), which varies depending on the laboratory and the methodology used. This can happen due to low cffDNA fraction or obesity.
- If you fail to receive reportable cfDNA NIPT screening results, your healthcare provider should recommend genetic counseling, because some studies have shown that women who have a no-call result may have an increased an increased risk of aneuploidy in their pregnancy.
- Only around half of repeated NIPT screens will provide results again. Therefore you maybe offered the option of having comprehensive ultrasound evaluation and invasive diagnostic testing after receiving a no-call result rather than repeating the NIPT or after a repeat if it is still a no-call.