Mitochondrial DNA Triggering Epidural Related Maternal Fever

NCT ID: NCT04045223

Last Updated: 2022-01-03

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-07-01
• Study Completion Date: 2021-06-30

Brief Summary

Background: Giving birth is a critical moment for the mother and the fetus, potentially accompanied by stress, tissue damage, cell injury, placental hypoxia and sometimes multisystem vascular syndrome known as preeclampsia. Epidural analgesia with a local anesthetic is a common anesthetic approach during labor. Local anesthetics inhibit the oxidative phosphorylation and impair the synthesis of ATP, resulting in mitochondrial dysfunction and increased reactive oxygen species. Especially when the high demand of ATP during pregnancy cannot be reached, apoptosis will occur in an anaerobic environment. During apoptosis 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. These DAMPs are evolutionary conserved and have structural similarity to their bacterial ancestor. 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 and hypoxia.

Objective: The aim of this study is to investigate to role of epidural analgesia during birth, quantifying the copy number of circulating cell-free mitochondrial DNA in maternal serum and the placenta compared to controls. The investigators hypothesize that epidural analgesia with a local anesthetic has an effect on cell-free mitochondrial DNA levels, promoting the pathogenesis of ERMF and early inflammation. In addition, circulating mitochondrial DNA could be a potent biomarker for cell damage, early placenta hypoxia/insufficiency or preeclampsia.

Methods: For this study the investigators planned 3 groups each consisting of 15 patients. The intervention group (group 1) will be women with vaginal delivery having epidural analgesia and developing fever before delivery. The control group (group 2) will be women with vaginal delivery having an epidural analgesia without developing fever before delivery. Women with vaginal delivery without an epidural analgesia will serve as additional control (group 3). Blood will be taken at arrival at the delivery ward and immediately after delivery from a peripheral venous line. In addition, venous blood from the umbilical vein will be drawn postpartum. Axillary temperature will be measured routinely using a thermometer in a routine clinical fashion. Circulating cell-free mitochondrial DNA and other immunological markers will be quantified in maternal and umbilical cord (fetal) serum by real time quantitative PCR and statistical analysis will be performed by non-parametric tests.

Conditions

Mitochondrial DNA; Epidural Related Maternal Fever (ERMF)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Epidural analgesia and fever

Group 1 will be patients with vaginal delivery and having an epidural analgesia that develop fever during delivery.

Blood samples

Intervention Type: OTHER

Maternal blood will be taken at arrival at the delivery unit and after delivery. Furthermore, placental blood will be taken after delivery.

Epidural analgesia and no fever

Group 2 will be patients with vaginal delivery and having an epidural analgesia that do not develop fever during delivery.

Blood samples

Intervention Type: OTHER

Maternal blood will be taken at arrival at the delivery unit and after delivery. Furthermore, placental blood will be taken after delivery.

No epidural analgesia

Group 3 serves as additional control group and consists of patients having no epidural analgesia and no fever.

Blood samples

Intervention Type: OTHER

Maternal blood will be taken at arrival at the delivery unit and after delivery. Furthermore, placental blood will be taken after delivery.

Interventions

Blood samples

Maternal blood will be taken at arrival at the delivery unit and after delivery. Furthermore, placental blood will be taken after delivery.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• women
• between 18 and 45 years
• Para 0 or Para 1
• Gestational week
• Elective procedure 37±0 to 42±0

Exclusion Criteria

• younger than 18 years
• Emergency procedures
• No written consent
• Fever <2 weeks
• Intraoperative conversion from one anesthetic or surgical procedure to another one.
• preeclampsia
• HELLP syndrome
• intrauterine growth reduction
• gestational diabetes mellitus
• autoimmune disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Ass.-Prof. PD Dr. Klaus Ulrich Klein

Principle Investigator, Klaus Ulrich Klein; MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Anesthesia, General Intensive Care and Pain Management,Medical University of Vienna

Vienna, , Austria

Countries

Austria

Other Identifiers

2119/2017

Identifier Type: -

Identifier Source: org_study_id