5 Perinatal and genetic outcomes associated with no call cfDNA results in 18,496 pregnancies

Abstract

Failed or no call cell free DNA (cfDNA) testing confers an increased risk of aneuploidy, but few series include complete obstetric, infant, and genetic outcomes. We hypothesized that failed tests would be associated with aneuploidy and adverse perinatal outcomes. Secondary analysis of a multicenter prospective study of SNP-based cfDNA; confirmatory genetic testing was performed in all cases during pregnancy or after birth. Demographics, pregnancy outcomes, and confirmatory genetic results were compared between no call and resulted cases. Univariate analysis compared differences between groups; odds ratios (OR) were calculated after adjusting for BMI, gestational age at draw, and black race. Results applying an updated algorithm after study completion were also compared. 18,496 women had both cfDNA screening and genetic confirmation. A first draw result was reported in 17,885 while 611 (3.3%) were no calls; 320/435 (73.6%) redraws gave a result, leaving 291 as no calls. No calls were associated with higher BMI, later gestational age, lower fetal fraction, and black race. T13, 18, or 21 was confirmed in 1.6% of no calls vs 0.7% with a result (p=.013). After adjustment for confounders, the aOR for aneuploidy was 2.2 (95% CI 1.1,4.5) after a first no call; this increased to 3.8 (95% CI 1.7, 8.4) after the second. Livebirths occurred in 94.9% with a no call vs 98.8% with a result (p< .001; aOR for livebirth: 0.17 [95% CI 0.10, 0.28]). PTB < 28, 34, and 37wks and preeclampsia were all higher after a no call. All risks were higher after a second no call result (Table). With the updated algorithm, the no call rate decreased to 0.6% and the adverse associations were further increased. The association with perinatal outcomes persisted in euploid pregnancies. Patients with no call cfDNA results are at increased risk for aneuploidy; this risk is further increased with a second no call. The risk of other adverse perinatal outcomes is also increased, including in euploid pregnancies.