This study evaluates the use of metagenomic next generation sequencing in identifying microbial DNA in plasma samples of patients with preterm premature rupture of membranes.

Although preterm premature rupture of membranes (PPROM) occurs in only 3% of pregnancies, it accounts for 30% of preterm births (PTB) and is associated with serious maternal and neonatal morbidity. An important factor in the underlying pathophysiology of PPROM and subsequent PTB is subclinical infection, which promotes a cascade of events that contribute to synthesis of prostaglandins, release of proinflammatory cytokines, infiltration of neutrophils, and activation of metalloproteases. Over time, enhanced activity of these infectious and inflammatory pathways contributes to the development of spontaneous labor and/or overt intraamniotic infection (IAI). Unfortunately, the majority of patients with PPROM do not manifest signs and symptoms of infection that are detectable by clinical examination, laboratory evaluation, and traditional microdiagnostic tests, and attempting to predict length of latency period and/or timing of delivery remains a clinical challenge. We propose the use of metagenomic next-generation sequencing (mNGS) to identify microbial DNA in maternal plasma following PPROM. We hypothesize that the presence and abundance of microbial DNA is associated with a shorter latency period and that an increase in the abundance of microbial DNA precedes delivery.

Inclusion Criteria:

• For PPROM group, preterm premature rupture of membranes between 16 0/7 and 33 6/7 weeks of gestation
• For control group, healthy pregnancy with no evidence of preterm premature rupture of membranes or other major complications

Exclusion Criteria:

• Maternal age < 18 years
• Major fetal congenital malformation

Pregnant patients with preterm premature rupture of membranes and gestational-age-matched controls