Risk for a fetal chromosome abnormality when low fetal fraction results in 'no call' by NIPT

Objectives:

To assess the frequency of fetal chromosome abnormalities in women who receive a „no-call” result from non-invasive prenatal testing due to low fetal fraction (FF); and to identify the subset of women at highest risk and who would most benefit from immediate referral for ultrasound and/or diagnostic testing.

Methods:

Clinical follow-up was obtained for women who received a „no-call” due to low FF. A fetal – fraction-based risk (FFBR) model incorporating prior risk with maternal weight (MW)- and gestational age-adjusted FF to determine risk for chromosome abnormality was developed. A high FFBR score of ≥1/100 indicated elevated risk for triploidy, trisomy 18 (T18), or trisomy 13 (T13).

Results:

Of 1350 cases, 202 cases were lost to follow-up/had missing information and were excluded. Of the 1148 cases with an outcome – 1006 (87.6%) were confirmed/presumed normal, 48 (4.2%) had confirmed chromosomal abnormality, 9 (0.8%) had a suspected chromosomal abnormality. Eighty-five (7.4%) pregnancies ended in pregnancy loss. The FFBR algorithm assigned 564 (49%) cases a high FFBR score and 584 (51%) a low FFBR score. High-FFBR-score cases had a greater proportion of FF-related chromosomal abnormalities than women with low FFBR scores (7.1% vs. 1.4%) and more fetal deaths (14.7% vs. 2.7%).

Conclusion:

Low FF is associated with a high risk for fetal death, triploidy, T18, and T13, but not T21. The FFBR algorithm identified a high-risk subgroup of 'no-call' cases due to low FF that should be immediately referred for additional testing. Cases with a low FFBR cases may benefit from a redraw.