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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 (eg preterm birth, pre-eclampsia). 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 term and show an association between preterm labour and higher cff-DNA levels in the 2nd, 3rd trimester and at onset of PTB 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.