Association between low fetal fraction of cell free DNA at the early second-trimester and adverse pregnancy outcomes

Objective: The purpose of this study was to examine whether low fetal fraction (FF) of cell free DNA is associated with risks of adverse pregnancy outcomes. Methods: This was a historical cohort study of 2191 women with singleton pregnancies who had non-invasive prenatal test (NIPT) at 13 to 26 weeks of gestation. Data were collected from prenatal screening system and hospital records. Main outcome was the subsequent diagnosis of gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), preeclampsia (PE), pregnancy induced hypertension (PIH) and pre-term birth (PTB). Logistic regression analysis was performed to evaluate the association between LFF and adverse pregnancy outcomes. Results: The prevalence of GDM, ICP, PE, PIH and PTB was 23.87% (523), 4.02% (88), 2.92% (64), 2.83% (62) and 6.85% (150), respectively. Low FF, defined as less than the 10th percentile, was associated with an increased risk of PE (adjusted OR = 2.06, 95% CI: 1.07-3.98) and early PTB (< 34 weeks' gestation: adjusted OR = 3.09, 95% CI: 1.21-7.92). In addition, low FF, defined as less than the 5th percentile, was associated with an increased risk of low birth weight babies (< 2500 g: adjusted OR = 2.50, 95% CI: 1.01-6.17). However, there was no significant association between low FF and GDM, as well as ICP and PIH. Conclusion: Our study provides evidence that low FF is associated with PE and early PTB. Further exploration of the clinical significance of low FF is warranted.