CSF/Serum Biomarkers in Predicting PND/Persistent Pain After Cesarean

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.

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.

Eligibility Criteria:
Inclusion Criteria:

* American Society of Anesthesiologists (ASA) class 2 and 3
* English speaking
* 18 years or older
* Singleton pregnancy
* Gestational age \> 37 weeks
* Scheduled cesarean delivery under spinal or combined spinal epidural anesthesia

Exclusion Criteria:

* Intravenous drug or chronic opioid use
* Anti-depressant or anxiolytic drug use
* Allergy to standard of care drugs
* Cesarean delivery under general anesthesia or epidural anesthesia
* Pre-eclampsia needing magnesium sulfate
* Chronic PO/IV analgesic or glucocorticoids
* History of chronic pain syndromes