Factors associated with test failure in pregnant women undergoing cell-free DNA-based testing for fetal trisomy

Abstract

Objective To investigate the factors associated with cell-free DNA test failure, and the optimal subsequent management of these pregnancies. Methods This was a retrospective study of 27,363 singleton pregnancies undergoing cell-free DNA testing. Women with cell-free DNA test failure were divided into a high-risk group and a low-risk group according to their indications. The subsequent management and pregnancy outcomes of these women were followed up. Results The rate of cell-free DNA test failure at the first sampling was 1.49%, and 78.4% of failures were due to a low fetal fraction. Of the 66 women who refused any subsequent management, an adverse pregnancy outcome was seen in 5 cases, all belonging to the high-risk group. Of the 13 low-risk women who chose second-trimester maternal serum screening, all obtained a low-risk maternal serum screening result and an unaffected pregnancy outcome. A redraw was chosen by 171 women, which yielded a result in 75.4% and their pregnancy outcomes were unaffected; 42 women had an uninformative result again and received an amniocentesis. As 158 women had an amniocentesis after the first sampling, this procedure was offered in 200 cases altogether. Abnormal genetic testing results were shown in six (3%, 6/200) cases, all in the high-risk group. Conclusions High-risk pregnant women with cell-free DNA test failure are at increased risk of adverse pregnancy outcomes. A second sampling for cell-free DNA test or maternal serum screening might be suggested to low-risk women. Invasive prenatal diagnosis should be offered to the high-risk patients, especially those with a second cell-free DNA test failure.

Analysis of retest reliability for pregnant women undergoing cfDNA testing with a no-call result

“…The no-call rates of the cfDNA tests were assessed by various technologies, and methods based on MPS were subtotaled to have the lowest no-call rate (1.58%) [ 5 ]. The no-call rate in our center based on the MPS platform was 1.12% (111/9871), which is lower than that in previous studies [ 5 , 8 , 13 , 14 ]. The most important reason is that the no-call rate in the current study was calculated based on whether a result was obtained after sequencing, and problems of previous processes, including sampling, delivery, tracking, and plasma preparation, were not considered.…”

“…The primary cause of no-call test results in the current study was data fluctuation, mainly due to sample degradation, library preparation, and other technical reasons. However, previous studies have demonstrated that the most common reason for no-call test results is low FFs [ 7 , 8 ]. Different definitions of test failure or no-call test results should be considered.…”

“…In the retrospective analysis of Liu et al, the women with a no-call cfDNA test result were divided into a high-risk group and a low-risk group according to maternal age and maternal serum screening (MSS). They demonstrated that high-risk pregnant women with a no-call cfDNA test result are at increased risk of adverse pregnancy outcomes [ 8 ].…”

Incidental Detection of Malignancies With Cell-Free DNA Screening

“…Providers are encouraged to contact the laboratory directly with questions about uncertain results and request information from the medical team to assist with interpretation or clarification 13 . Atypical results can occur for a number of reasons (ie, low fetal fraction, laboratory processing issues), some of which may be rectified with a new blood sample 32 . When maternal malignancy is suspected, repeat cfDNA screening is not recommended.…”

“…13 Atypical results can occur for a number of reasons (ie, low fetal fraction, laboratory processing issues), some of which may be rectified with a new blood sample. 32 When maternal malignancy is suspected, repeat cfDNA screening is not recommended. If it is unclear from the laboratory report whether maternal malignancy should be considered, a laboratory counselor or laboratory director can be contacted for clarification.…”