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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.<\/jats:p>","DOI":"10.1530\/rep-17-0619","type":"journal-article","created":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T20:21:18Z","timestamp":1513887678000},"page":"R137-R145","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":56,"title":["Cell-free fetal DNA and spontaneous preterm birth"],"prefix":"10.1093","volume":"155","author":[{"given":"Sara R","family":"van Boeckel","sequence":"first","affiliation":[{"name":"Tommy\u2019s Centre for Maternal and Fetal Health at the MRC Centre for Reproductive Health , University of Edinburgh, QMRI, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald J","family":"Davidson","sequence":"additional","affiliation":[{"name":"MRC Centre for Inflammation Research , University of Edinburgh, QMRI, 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