225: Clinical implications of low fetal fraction in pregnancies with negative cell free DNA testing

Abstract

Fetal cell free DNA (cfDNA) in the maternal circulation is thought to be primarily of placental origin. We sought to determine if fetuses with a low fetal fraction (FF) in the first trimester are more likely to be affected by placental- mediated conditions, primarily low birth weight. This is a retrospective cohort study of women who had negative cfDNA screening <14 weeks gestation and delivered a viable infant between July 2016 and June 2018 at a single institution. Women with a multiple gestation or abnormal cfDNA screen were excluded. Women who had a non-reportable cfDNA result were included if their re-draw was negative. FF≤5%ile were considered to have a low FF. The primary outcome was birth weight ≤10%ile using growth curves generated by Oken et al. Secondary outcomes included birth weight ≤5%ile, abruption, hypertensive disorder of pregnancy, stillbirth, and a composite outcome. Chi-squared tests were used for comparisons. Multivariable logistic regressions calculated odds ratios for the primary and secondary outcomes, adjusting for maternal age, BMI, gestational age at draw, parity, chronic hypertension, and tobacco use. Of the 2034 women included, the mean FF was 10.0% (SD 3.4%) and a FF<5.3% was considered low (n=101). For all women, 66.4% had cfDNA testing at 12 weeks gestation, the median BMI was 24.0 (IQR 21.6-27.5), 42.3% were nulliparous, 1.8% had a diagnosis of chronic hypertension, and 0.7% used tobacco. Compared to pregnancies with a higher FF, there was no significant difference in the incidence of birth weight ≤10%ile in women with a low FF (11.9 vs 8.0%, p=0.17), though the comparison was limited by small sample size. Among secondary outcomes, birth weight ≤5%ile and the composite outcome were significantly higher in the low FF group. In the multivariable analysis, low FF was associated with an increased odds of birth weight ≤10%ile [aOR 2.20 (95%CI 1.12-4.30)], birth weight £5%ile [aOR 3.23 (95%CI 1.35-7.74)], and the composite adverse outcome [aOR 1.91 (95%CI 1.10-3.33)]. Low FF (≤5%ile) among women with negative cfDNA results in the first trimester is associated with increased odds of low birth weight, similar to women with a low PAPP-A. Future studies are needed to determine if a low FF should prompt screening for growth restriction given the potential implications of this recommendation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)