The implications of non-invasive prenatal testing failures: a review of an under-discussed phenomenon

Non-invasive prenatal testing (NIPT) using cell-free DNA in maternal blood is a relatively new screening modality for the common trisomies of chromosomes 21, 18 and 13 and sex chromosome aneuploidies. For some patients, however, results are not reported because of laboratory technical issues such as low fetal fraction and sequencing failures. In this review, the clinical implications of NIPT test failures are discussed.

A Medline search was performed for all studies on NIPT that include >1000 samples. The failure rates were assessed by technology.

Methods based on massive parallel sequencing have been found to have the lowest failure rate (1.58%), while tests based on single-nucleotide polymorphism analysis have the highest failure rate (6.39%).

Recent publications suggest that patients who receive a 'no call' result are at increased risk of aneuploidy. Some professional societies have therefore recommended that these patients undergo genetic counseling and be offered invasive diagnostic testing. NIPT technology that has a high failure rate may increase the false positive rates, decrease the positive predictive value, and increase the procedure-related pregnancy loss. © 2016 John Wiley & Sons, Ltd.