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.
Study Type
OBSERVATIONAL
Enrollment
70
Metagenomic next generation sequencing for microbial DNA
University of California, San Francisco
San Francisco, California, United States
Length of latency
Time between PPROM and delivery
Time frame: From study enrollment to date of delivery, up to 24 weeks
Maternal infectious morbidity
Composite of fever, intrauterine infection, sepsis, postpartum endometritis, surgical site infection, and administration of antibiotics
Time frame: From study enrollment to date of delivery, up to 30 weeks
Neonatal infectious morbidity
Composite of fever, sepsis, administration of antibiotics, and need for blood/urine/cerebrospinal fluid (CSF) cultures
Time frame: From neonatal birth to neonatal hospital discharge, up to 1 year
Histopathological signs of infection
Histopathological signs of infection on routine post-delivery examination of placenta, membranes, and umbilical cord
Time frame: At time of placental delivery
Perinatal demise
Composite of intrauterine fetal demise and neonatal demise
Time frame: From study enrollment to 28 days of life
Admission to neonatal intensive care unit (NICU)
Time frame: From neonatal birth to neonatal hospital discharge, up to 1 year
NICU length of stay
Time frame: From neonatal birth to neonatal hospital discharge, up to 1 year
Neonatal need for supplemental oxygen
Time frame: From neonatal birth to neonatal hospital discharge, up to 1 year
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Respiratory distress syndrome
Time frame: From neonatal birth to neonatal hospital discharge, up to 1 year
Necrotizing enterocolitis
Time frame: From neonatal birth to neonatal hospital discharge, up to 1 year
Intraventricular hemorrhage
Time frame: From neonatal birth to neonatal hospital discharge, up to 1 year