Circulating Cell-free Mitochondrial DNA Triggering Epidural Related Maternal Fever (ERMF) in Obstetric Anesthesia: a Pilot Study

Mitochondrial DNA Triggering Epidural Related Maternal Fever

Sponsors

Lead sponsor: Medical University of Vienna

Source Medical University of Vienna
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.

Overall Status Recruiting
Start Date July 1, 2019
Completion Date July 31, 2020
Primary Completion Date July 31, 2020
Study Type Observational
Primary Outcome
Measure Time Frame
quantity of circulating cell-free mitochondrial DNA change from quantity of baseline mtDNA to quantity of mtDNA immediately after delivery
Enrollment 45
Condition
Intervention

Intervention type: Other

Intervention name: Blood samples

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

Eligibility

Sampling method: Non-Probability Sample

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

Gender: Female

Gender based: Yes

Minimum age: 18 Years

Maximum age: 45 Years

Healthy volunteers: No

Overall Contact

Last name: Christina Hafner, MD, PhD

Phone: + 43 1 40400 41000

Email: [email protected]

Location
facility status Department of Anesthesia, General Intensive Care and Pain Management,Medical University of Vienna
Location Countries

Austria

Verification Date

August 2019

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Medical University of Vienna

Investigator full name: Ass.-Prof. PD Dr. Klaus Ulrich Klein

Investigator title: Principle Investigator, Klaus Ulrich Klein; MD

Has Expanded Access No
Condition Browse
Arm Group

Arm group label: Epidural analgesia and fever

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

Arm group label: Epidural analgesia and no fever

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

Arm group label: No epidural analgesia

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

Patient Data Undecided
Study Design Info

Observational model: Cohort

Time perspective: Prospective

Source: ClinicalTrials.gov