1053 Abnormal placentation and affect on fetal fraction of cell-free DNA

Abstract

Abnormal placentation may affect fetal fraction (FF) of cell-free fetal DNA (cffDNA). Second-trimester cffDNA fraction is higher in pregnancies complicated by placenta previa (PP) alone, but not with placenta accreta spectrum (PAS) compared to women with normal placentation. Since concurrent PP and PAS occurs frequently, we hypothesized a decrease in the FF due to PAS might be masked in patients with concurrent placenta previa. We compared women with normal placentation to cases of PAS, PP, or PAS+PP, all of whom had non-invasive prenatal screening (NIPS). Assuming a standard deviation of 3% for the population and using an α of .05 and β of .8, we estimated that we need at least six subjects in each group to detect a difference of 6% in means of cffDNA fraction. Data was abstracted from electronic medical records. PAS spectrum disorders were confirmed histologically and/or clinically. We used the Shapiro-Francia test to assess the distribution of our data for normality. Normally distributed data were compared with unpaired t-test. Data with non-normal distribution were compared with the Mann-Whitney test. Percentages were compared with Fisher's exact test. We studied 10 cases of normal placentation, 9 cases of PAS, 8 cases of PAS+PP, and 6 cases with PP. There were no significant differences between the groups, including maternal age, ethnicity, pre-pregnancy body mass index, previous cesarean deliveries, pregnancy-induced hypertension, autoimmune disease, treatment with anti-coagulants, median gestational age when blood sample was collected, or commercial laboratory where NIPS was performed. The mean FF of cffDNA from patients with PAS was significantly lower than those with normal placentation or with PAS+PP, i.e., 95% confidence interval for the difference between means, .3 to 6.9% and .3 to 7.8, respectively (p< .05). The difference between PP and other groups were not statistically significant. The pathogenesis leading to PAS is associated with low fetal fraction of cffDNA in the maternal serum. This association is masked among those with concurrent PAS and PP.