Preterm Rupture of Membranes
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DIAGNOSTIC_TESTmNGS
Metagenomic next generation sequencing for microbial DNA
Sponsors
University of California, San Francisco
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Length of latency | From study enrollment to date of delivery, up to 24 weeks | Time between PPROM and delivery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neonatal infectious morbidity | From neonatal birth to neonatal hospital discharge, up to 1 year | Composite of fever, sepsis, administration of antibiotics, and need for blood/urine/cerebrospinal fluid (CSF) cultures |
| Histopathological signs of infection | At time of placental delivery | Histopathological signs of infection on routine post-delivery examination of placenta, membranes, and umbilical cord |
| Perinatal demise | From study enrollment to 28 days of life | Composite of intrauterine fetal demise and neonatal demise |
| Admission to neonatal intensive care unit (NICU) | From neonatal birth to neonatal hospital discharge, up to 1 year | — |
| Maternal infectious morbidity | From study enrollment to date of delivery, up to 30 weeks | Composite of fever, intrauterine infection, sepsis, postpartum endometritis, surgical site infection, and administration of antibiotics |
| Neonatal need for supplemental oxygen | From neonatal birth to neonatal hospital discharge, up to 1 year | — |
| Respiratory distress syndrome | From neonatal birth to neonatal hospital discharge, up to 1 year | — |
| Necrotizing enterocolitis | From neonatal birth to neonatal hospital discharge, up to 1 year | — |
| Intraventricular hemorrhage | From neonatal birth to neonatal hospital discharge, up to 1 year | — |
| NICU length of stay | From neonatal birth to neonatal hospital discharge, up to 1 year | — |
Countries
United States
Outcome results
None listed