Inflammation is known to play a key role in preterm and term parturition. Cell-free fetal
DNA (cff-
DNA) is present in the maternal circulation and increases with gestational age and some
pregnancy complications (e.g.
preterm birth,
preeclampsia). Microbial
DNA and adult
cell-free DNA can be pro-inflammatory through
DNA-sensing mechanisms such as
Toll-like receptor 9 and the Stimulator of
Interferon Genes (
STING) pathway. However, the pro-inflammatory properties of cff-
DNA, and the possible effects of this on pregnancy and parturition are unknown. Clinical studies have quantified cff-
DNA levels in the maternal circulation in women who deliver preterm and women who deliver at term and show an association between
preterm labor and higher cff-
DNA levels in the 2nd, 3rd trimester and at onset of
preterm birth symptoms. Together with potential pro-inflammatory properties of cff-
DNA, this rise suggests a potential mechanistic role in the pathogenesis of spontaneous
preterm birth. In this review, we discuss the evidence linking cff-
DNA to adverse pregnancy outcomes, including
preterm birth, obtained from preclinical and clinical studies.