Identification of Microbial DNA in Maternal Plasma After PPROM

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
PPROM	mNGS	Preterm premature rupture of membranes between 16 0/7 and 33 6/7 weeks gestation
Healthy controls	mNGS	Gestational-age-matched controls without preterm premature rupture of membranes or other pregnancy complications

Primary Outcome Measures

Name	Time	Method
Length of latency	From study enrollment to date of delivery, up to 24 weeks	Time between PPROM and delivery

Secondary Outcome Measures

Name	Time	Method
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
Admission to neonatal intensive care unit (NICU)	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
Intraventricular hemorrhage	From neonatal birth to neonatal hospital discharge, up to 1 year
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
NICU length of stay	From neonatal birth to neonatal hospital discharge, up to 1 year
Neonatal need for supplemental oxygen	From neonatal birth to neonatal hospital discharge, up to 1 year
Necrotizing enterocolitis	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

Locations (1): University of California, San Francisco
🇺🇸
San Francisco, California, United States

Receive instant email notifications about changes in this clinical trial

Receive instant email notifications about changes in this clinical trial