mtDNA as Novel Biomarker for Intra-amniotic Infection (mtDNA)

Circulating Cell-free Mitochondrial as a Novel Biomarker for Intra-amniotic Infection in Obstetrics

Finding a predictive biomarker for IAI could improve the clinical outcome for the mother and the neonate. The aim of this study is to quantify the copy number of circulating cell-free mitochondrial DNA in maternal serum and the placenta compared to controls.the investigators hypothesise that circulating cell-free mitochondrial DNA levels could help predict the likelihood of early inflammation in IAI. In addition, mitochondrial DNA could be a promotor triggering the pathogenesis of systemic inflammation.

Study Overview

• Status: Unknown
• Conditions: Preterm Premature Rupture of Membrane
• Intervention / Treatment: Biological: Blood sampling

Detailed Description

Background: Intra-amniotic infection (IAI) or chorioamnionitis is a common condition seen in obstetrics leading to labor abnormalities such as uterine atony, postpartum bleeding and preterm labor (Schrag et al., 2006). Further adverse effects such as perinatal death, asphyxia, sepsis, pneumonia, respiratory distress and especially neurodevelopmental delay and cerebral palsy are associated with IAI (Buhimschi et al., 2009; Holzman, Lin, Senagore, & Chung, 2007). Diagnosing IAI can be challenging due to its very heterogeneous clinical signs, which are often very insensitive for this condition. Clinical findings such as fever, tachycardia and maternal leukocytosis leave room for multiple differential diagnoses. During apoptosis (due to hypoxia, cell damage or infection) the cell membrane integrity is disturbed, releasing the cytoplasm into the blood circulation. Circulating cell-free mitochondrial DNA acts as a damage associated molecular pattern (DAMP) by activating the innate immune system leading to inflammation (Matzinger, 1994). These DAMPs are evolutionary conserved and have structural similarity to their bacterial ancestor (Zhang et al., 2010). Therefore, cell-free mitochondria can act as a potent agent triggering the immune system in an autoimmune manner as well as a biomarker for cell damage due to infection.

Objective: Finding a predictive biomarker for IAI could improve the clinical outcome for the mother and the neonate. The aim of this study is to quantify the copy number of circulating cell-free mitochondrial DNA in maternal serum and the placenta compared to controls. Investigators hypothesize that circulating cell-free mitochondrial DNA levels could help predict the likelihood of early inflammation in IAI. In addition, mitochondrial DNA could be a promotor triggering the pathogenesis of systemic inflammation.

Methods: For this study the investiagtors planned 2 groups each consisting of 30 patients. The control group are pregnant women without IAI. The intervention group will be women with premature preterm rupture of membranes (pProm), suffering from IAI (meeting the diagnostic criteria for IAI suggested by the National Institute of Child Health and Human Development Workshop). 12ml of venous blood will be drawn from a peripheral venous line in addition to routine blood tests, when the patient arrives at the ward (2 weeks before delivery). A further 12ml of venous blood will be taken from the peripheral venous line, during delivery (during delivery). In addition, 12ml of venous blood will be drawn from the placenta postpartum. In total, 36 ml of blood will be withdrawn in each patient. Circulating cell-free mitochondrial DNA will be quantified in maternal and placental serum by real time quantitative PCR and statistical analysis will be performed by non-parametric tests.

Design: Single center, prospective, observational pilot trial.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Herbert Kiss, MD, PhD; Phone Number: +43140400; Email: herbert.kiss@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Herbert Kiss, MD, PhD; Phone Number: +43140400

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women

Description

Inclusion Criteria:

• Pregnant women 2 weeks before scheduled elective caesarian section at term (control group)
• Pregnant women in week 22+0 until week 28+0 who are admitted because of pPROM (intervention group)
• aged between 18 and 45 years
• Provide signed and dated informed consent

Exclusion Criteria:

• Women younger than 18 years
• No written consent
• Patients suffering from any autoimmune disease

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study Group; The intervention group will be women with premature preterm rupture of membranes (pProm), suffering from IAI	Biological: Blood sampling; Serial blood sampling
Control Group; Pregnant women without IAI	Biological: Blood sampling; Serial blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
mtDNA in Plasma	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Herbert Kiss, MD, PhD, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 5, 2017
• Primary Completion (ANTICIPATED): June 30, 2018
• Study Completion (ANTICIPATED): December 31, 2018

Study Registration Dates

• First Submitted: October 1, 2017
• First Submitted That Met QC Criteria: October 10, 2017
• First Posted (ACTUAL): October 11, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 11, 2017
• Last Update Submitted That Met QC Criteria: October 10, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Pregnancy Complications; Obstetric Labor Complications; Rupture; Fetal Membranes, Premature Rupture
• Other Study ID Numbers: 1115/2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Biomarker pilot trial

Drug and device information, study documents

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