644 The impact of maternal autoimmune disease on first-trimester cell-free fetal DNA

Abstract

Maternal autoimmune disease (AID) is associated with increased incidence of indeterminate cell-free DNA (cfDNA) results from low fetal fraction (FF), possibly due to increased maternal cfDNA release from chronic inflammation. We sought to evaluate differences in first-trimester cfDNA FF for women with AID on no therapy versus those on immune modulator (IM) therapy compared to controls. Retrospective, single institution cohort study of a previously validated cfDNA test using whole genome sequencing. AID included systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and other. IM therapies included biologics, corticosteroids, hydroxychloroquine, azathioprine, and IVIG. Women on anticoagulation were excluded. An indeterminate result was defined as FF<4%. We evaluated the association between maternal AID, treatment modality, and FF using ANOVA, chi square, and regression analyses, adjusting for body mass index (BMI), fetal sex, and gestational age at sample collection. 1475 patients were included. Mean gestational age was 14.3 (±4.4) weeks and mean BMI 26.9kg/m2 (±6.7). Overall, 3% (N=42) had a documented AID, with 25 on no therapy and 17 on IM therapy. There was a significant stepwise decrease in mean FF, with 12.0%, 10.4% and 9.6% in the control, AID on IM therapy, and AID on no therapy groups, respectively (p=0.03) [Figure 1A]. An inverse relationship was observed in the rate of indeterminate results from 3% to 6% to 24% for controls, AID on IM therapy, and AID on no therapy, respectively (p<0.001) [Figure 1B]. Logistic regression showed an increased odds of an indeterminate result for women with AID on no therapy compared to controls, OR 9.1 (95%CI 3.2, 25.7). Linear regression showed a significant decrease in FF for women with AID on no therapy compared to controls, β -2.0 (95%CI -3.8, -0.2). Women with AID on no therapy have higher rates of indeterminate cfDNA results compared to controls. Treatment of AID with IM therapies may improve FF, which could be further evaluated in future studies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)