Mitochondrial DNA Triggering Epidural Related Maternal Fever
Condition: Mitochondrial DNA; Epidural Related Maternal Fever (ERMF)
MeSH terms: Fever
Study type: Observational

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.
    


Intervention name(s): Blood samples
Intervention type(s): Other
Intervention description(s): Maternal blood will be taken at arrival at the delivery unit and after delivery. Furthermore, placental blood will be taken after delivery.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients must meet inclusion criteria and must give written consent. Informed consent will
        be obtained only for conscious patients preoperative. The cause of admission will be noted,
        baseline demographics and clinical history will be recorded. Patients included are giving
        birth at the Department of Obstetrics and Feto-Maternal Medicine at the Medical University
        of Vienna between July 2019 and July 2020. We are expecting to need to observe 15 patients
        per group in order to prove our hypothesis in this pilot study.
      
Biospecimen description: 
      cell-free mitochondrial DNA