Identification of Microbial DNA in Maternal Plasma After PPROM

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Preterm Rupture of Membranes

Intervention / Treatment
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* Diagnostic Test: mNGS


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PPROM<br>Preterm premature rupture of membranes between 16 0/7 and 33 6/7 weeks gestation | Diagnostic Test: mNGS<br>* Metagenomic next generation sequencing for microbial DNA<br>|
| Healthy controls<br>Gestational-age-matched controls without preterm premature rupture of membranes or other pregnancy complications | Diagnostic Test: mNGS<br>* Metagenomic next generation sequencing for microbial DNA<br>|

What is the study measuring?
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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 |