Identification of Microbial DNA in Maternal Plasma After PPROM

Using Metagenomic Next-generation Sequencing to Identify Microbial DNA in Maternal Plasma in Cases of Preterm Premature Rupture of Membranes

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.

Study Overview

• Status: Completed
• Conditions: Preterm Rupture of Membranes
• Intervention / Treatment: Diagnostic test: mNGS

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.

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

• Study Contact: Name: Nasim C Sobhani, MD; Phone Number: (415) 502-3231; Email: Nasim.Sobhani@UCSF.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PPROM; Preterm premature rupture of membranes between 16 0/7 and 33 6/7 weeks gestation	Diagnostic test: mNGS; Metagenomic next generation sequencing for microbial DNA
Healthy controls; Gestational-age-matched controls without preterm premature rupture of membranes or other pregnancy complications	Diagnostic test: mNGS; Metagenomic next generation sequencing for microbial DNA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of latency	Time between PPROM and delivery	From study enrollment to date of delivery, up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal infectious morbidity	Composite of fever, intrauterine infection, sepsis, postpartum endometritis, surgical site infection, and administration of antibiotics	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	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	At time of placental delivery
Perinatal demise	Composite of intrauterine fetal demise and neonatal demise	From study enrollment to 28 days of life
Admission to neonatal intensive care unit (NICU)		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
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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Nasim C Sobhani, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2020
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: March 10, 2020
• First Submitted That Met QC Criteria: March 19, 2020
• First Posted (Actual): March 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: April 6, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Rupture; Premature Birth; Fetal Membranes, Premature Rupture
• Other Study ID Numbers: 10-00505-JD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No