Factors Associated With Failed Routine Aneuploidy Cell-Free DNA Screening: A Systematic Review [14K]

Abstract

INTRODUCTION: Cell free DNA (cfDNA) is the recommended screening test for aneuploidy in women age 35 and over. We conducted a systematic review of factors associated with a failed cfDNA result following routine aneuploidy screening. METHODS: PubMed, Scopus, Clinicaltrials.gov and Cochrane were searched for articles from inception to October 2018. Patients undergoing routine cfDNA aneuploidy screening at ≥ 10 weeks gestational age and who had a viable pregnancy were included. Cohort studies and randomized controlled trials were included. Case reports and case series with less than five patients were excluded. The outcome was test failure. RESULTS: Our search yielded 756 results. 19 studies met our inclusion criteria and included 506,709 patients. Aneuploidy, maternal obesity, Low-Molecular Weight Heparin (LMWH), and IVF were associated with increased rates of test failure. 12 articles reported aneuploidy as an associated factor in inconclusive results, specifically triploidy and trisomies 13, 18, and 21. One study reported trisomy 9 in a result failure. In six studies, obesity was associated with higher failure rates. Failure rates in obese women was reported at 51.5% compared to 0.7% in non-obese women in one study. Two studies reported increased failure rates in women with LMWH. 75% of women who received failed results were on LMWH in one study. One study reported a 3% higher test failure rate in women who underwent in-vitro fertilization. CONCLUSION: Fetal aneuploidy, maternal obesity, LMWH, and IVF are associated with increased rates of failure in cfDNA following routine aneuploidy screening.