Noninvasive prenatal testing (NIPT) uses sequencing of fetal DNA in maternal blood plasma to screen for an abnormal number of fetal chromosomes.

Researchers evaluated whether NIPT could also detect DNA duplications or deletions within fetal chromosomes. The authors sequenced maternal plasma collected from 1,476 pregnant women whose ultrasounds indicated fetal structural abnormalities.

DNA duplications and deletions detected by NIPT were compared to the abnormalities detected in fetal DNA collected from the same women using an invasive procedure. The authors detected 78 deletions and duplications in invasively collected fetal DNA, and 56 of these were also detected by sequencing maternal plasma DNA, yielding a sensitivity of 71.8%.

For abnormalities larger than 1 million bp, the sensitivity improved to 94% with increased sequencing depth. The maternal plasma sequencing also produced 58 false positives, 35 of which were found to be caused by duplications or deletions in the maternal DNA, instead of fetal DNA.

Hence, a follow-up test might be necessary to rule out maternal DNA abnormalities before making a diagnosis based on NIPT. These results suggest that NIPT can be extended to detect fetal DNA deletions and duplications, and the authors suggest that a similar method might be used to detect cancer by detection of circulating tumor DNA. 

http://www.pnas.org/content/early/2015/11/04/1518151112