CSF/Serum Biomarkers in Predicting PND/Persistent Pain After Cesarean
Condition: Perinatal Depression; Chronic Pain
MeSH terms: Asphyxia Neonatorum; Chronic Pain; Depression
Study type: Observational

Summary: 
      The aim is to investigate if inflammatory biomarkers in the blood and cerebrospinal fluid
      (CSF) are associated with the development of perinatal depression and/or persistent pain
      after cesarean delivery.

      This study will obtain CSF and blood samples in 70 parturients. All parturients will be
      assessed for perinatal depression and persistent pain, and the presence/absence of these
      outcomes will be correlated to changes in the inflammatory biomarkers within the samples
      collected. If present, consistent changes in biomarkers correlating with perinatal depression
      or persistent pain may be utilised as a predictive tool and facilitate early treatment for
      these conditions.
    

Detailed description: 
      Persistent pain and perinatal depression (PND) contribute significantly to maternal morbidity
      and mortality after cesarean delivery. Neuroinflammation has been associated with both
      persistent pain and perinatal depression, and may therefore be a common etiological process,
      however, little is known of the association between neuroinflammation and persistent pain or
      PND in parturients undergoing cesarean delivery.

      Aim 1: To compare neuroinflammatory cytokine profiles (in CSF and plasma samples within 48
      hours after surgery) between the cohort of parturients that develop the composite outcome of
      persistent pain or PND (defined below), versus the cohort of parturients that did not develop
      this outcome.

      Aim 2. To determine the correlation between the neuroinflammatory cytokine profiles of CSF
      and plasma.

      Exploratory aim: To determine the change in plasma inflammatory cytokine profile from the
      antenatal to the postnatal period, and correlate this change with preoperative quantitative
      sensory tests, acute postsurgical pain severity, and development of persistent pain and/or
      PND. To examine proteomics in CSF and correlate with persistent pain and/or PND.

      This is a prospective cohort study of 70 adult parturients undergoing elective cesarean
      delivery at Duke University Hospital. After obtaining informed consent, baseline demographic
      data, the Edinburgh Postnatal Depression Scale (EPDS), mechanical temporal summation (MTS),
      and pain-pressure threshold (PPT) tests will be administered. During IV cannulation, 10ml of
      blood will be collected, and up to 10ml CSF will be collected during spinal anesthesia. After
      cesarean delivery, pain scores, analgesia requirements, and data on adverse events will be
      collected. Additional 10ml of blood will be collected within 48 hours post-surgery during
      inpatient hospital stay. During the routine 6-week postnatal follow up, EPDS scores will be
      recorded, and at 3-months, EPDS and persistent pain assessment will be conducted over the
      phone.

      Based on a composite endpoint of persistent pain (pain at 3 months after surgery) or PND
      (EPDS of 10 or greater, during pregnancy or within 3 months after delivery), parturients will
      be stratified into "study" or "control" cohorts. Using a validated multiplex quantitative
      proteomic approach, candidate biomarkers will be quantified and correlated against the
      composite outcome using two-sided Mann-Whitney U test. Correlation between CSF and plasma
      cytokines will be assessed using spearman correlation. The exploratory aim will be analyzed
      with generalized linear models.
    

Intervention name(s): No intervention
Intervention type(s): Other
Intervention description(s): No intervention
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Tertiary care hospital, specialist obstetric unit
      
Biospecimen description: 
      Blood and CSF samples
    
Keywords: Neuroinflammation; Biomarker; Cesarean delivery; Cytokines; Cerebrospinal fluid