Cell-free fetal DNA and spontaneous preterm birth

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.