Amniotic fluid cell‐free DNA in preterm prelabor rupture of membranes

Abstract

Introduction We evaluated the levels of cell‐free nuclear DNA (nDNA) and cell‐free mitochondrial DNA (mtDNA) in the amniotic fluid supernatant from pregnancies complicated by preterm prelabor rupture of membranes (PPROM) based on evidence of microbial invasion of the amniotic cavity (MIAC) and/or intra‐amniotic inflammation (IAI). Material and methods A total of 155 women with PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. The levels of cell‐free nDNA and mtDNA in the amniotic fluid supernatant were assessed and quantified by real‐time polymerase chain reaction. Results The levels of cell‐free nDNA and mtDNA were higher in women with MIAC and IAI than in women without these conditions (nDNA: with MIAC: median 3.9 × 104 genome equivalent [GE]/mL vs without MIAC: median 1.2 × 104 GE/mL, with IAI: median: 5.3 × 104 GE/mL vs without IAI: median 1.2 × 104 GE/mL; mtDNA: with MIAC: median 9.2 × 105 GE/mL vs without MIAC: median 2.5 × 105 GE/mL, with IAI: median 1.1 × 106 GE/mL vs without IAI: median 2.5 × 105; all P values ≤ 0.01). Women with the microbial‐associated IAI showed the highest levels of cell‐free nDNA and mtDNA. Conclusions Cell‐free nDNA and mtDNA are constituents of the amniotic fluid supernatant from PPROM pregnancies. Both cell‐free nDNA and mtDNA are involved in the intra‐amniotic inflammatory response in women with PPROM.

Pathophysiological Implication of Pattern Recognition Receptors in Fetal Membranes Rupture: RAGE and NLRP Inflammasome

“…A study showed that 58% of patients with sterile intra-amniotic inflammation have histological chorioamnionitis features (infiltration of polynuclears at the level of the fetal membranes) [ 61 ]. Moreover, higher concentrations of alarmins such as HMGB1, S100β, heat shock protein 70, cell-free DNA and S100 proteins have been found within AF, maternal blood or even gestational tissues (placenta, FM) in cases of pPROM or chorioamnionitis [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]; these increased amounts of DAMPs, which can lead to an inflammatory stimulation by interacting with PRRs, might be the consequence of oxidative stress or senescence [ 70 , 71 ]. Finally, a study revealed that the in vivo inhibition (in a murine model) of the inflammatory pathway NFκB causes delays in lipopolysaccharide (LPS)-induced PTB, clearly showing the importance of inflammation in parturition [ 72 ].…”

Exosomes-Associated DNA—New Marker in Pregnancy Complications?

“…The latest study of NETosis associated with spontaneous abortion showed that chorioamniotic NETs were found to be increased in women with chorioamnionitis and preterm delivery [39]. Similarly, it was recently found that cfDNA of both mitochondrial and nuclear origins were elevated in amniotic fluids in pregnancies complicated by preterm prelabor rupture of membranes [40]. Certain inflammatory cytokines and chemokines contribute to the pathogenesis of spontaneous abortions, which is associated with inflammatory mechanisms, and are possibly associated with cfDNA [36].…”

Association between periodontal disease and preterm prelabour rupture of membranes

“…Women with PPROM at <34 weeks of gestation received a course of corticosteroids to accelerate lung maturation and were treated with tocolytics for 48 hr and antibiotics. Women characterized by both microbial invasion of the amniotic cavity and intra-amniotic infection beyond 28 gestational weeks were actively managed: women were treated only with corticosteroids and antibiotics, and either labour was induced or a caesarean section was performed within 72 hr of membrane rupture as previously described (Kacerovsky et al, 2018;Musilova et al, 2016). The remaining women with PPROM at >34 weeks were conservatively managed: labour was induced or an elective caesarean section was performed after gestational age 34 + 0 weeks.…”