925: Non-reportable cell-free DNA: patient preferences, utility of repeat draw, and outcomes

Abstract

To investigate predictors of a repeat non-reportable (NR) cell-free DNA (cfDNA) result and evaluate its association with adverse pregnancy outcomes. This was a retrospective cohort study of patients with NR cfDNA results from a maternal fetal medicine center from March 2013 to June 2018. A NR result for chromosomes 21, 18, 13 or sex chromosomes was categorized as NR. A NR result for a microdeletion but negative testing for above chromosomes were excluded. The primary outcome was aneuploidy or microarray abnormality on prenatal or postnatal genetic testing. Secondary outcomes evaluated were maternal characteristics, testing laboratory and methodology, and pregnancy and neonatal outcomes. Statistical analysis was performed utilizing Student’s t-test and Fisher’s exact test. Forty-six patients had NR cfDNA results, of which 31 (67.4%) had low fetal fraction (FF). Mean maternal age was 34.2 ± 4.9 years, and median gestational age at initial blood draw was 10.4 weeks (IQR 10.1 – 11.6). Median body mass index (BMI) was 28.1 kg/m2 (IQR 23.6 – 32.6), and 43% were obese. Of these patients, 6 (13%) chose diagnostic testing, 38 (82.7%) opted for a repeat blood draw, and 2 (4.3%) declined additional testing. On repeat cfDNA sampling, 15 (39.5%) had a NR result and 23 (60.5%) had a reported result. Maternal age and BMI did not significantly differ in patients with a persistent NR result (p > 0.05); they were more likely to have maternal comorbidities (p = 0.04) and a FF < 4% at time of initial blood draw (p = 0.05). Obtaining a reportable or NR result on redraw did not differ by laboratory or testing method (p > 0.05). Patients with a repeat NR result were significantly more likely to undergo diagnostic testing (66.7% vs 4.3%, p < 0.01), which yielded an aneuploidy result in 20% of patients. Pregnancy outcomes did not significantly differ in patients with a repeat NR result (p > 0.05), detailed in the table. Almost half of repeat testing following a NR cfDNA result will again be NR. Repeat NR result is more likely in patients with medical comorbidities and FF < 4% at initial blood draw. It is associated with a 20% incidence of aneuploidy but not associated with an increased risk of adverse pregnancy outcomes. These test characteristics are important to consider when counseling patients on management following an initial NR cfDNA result.