Labor Epidural Anesthesia and Postpartum Depression Risk: Prospective Observation Study and Mendelian Randomization Analysis

Postpartum depression is a common mental disorder in mothers. Although the association between pain and depression is generally accepted, it remains uncertain whether labor epidural analgesia can effectively reduce the risk of postpartum depression. The objective of this study was to investigate the association between labor epidural analgesia and postpartum depression. A total of 146 parturients with a single-term cephalic pregnancy who were preparing for vaginal delivery were recruited for this observational prospective study. The parturients were divided into a labor epidural analgesia group and a control group (routine care) by preference, with 73 in each group. Sociodemographic characteristics and peripartum data of the parturients were collected. Postpartum depression was defined as a score of ≥ 13 on the Edinburgh Postnatal Depression Scale (EPDS) at 6-weeks postpartum. Multivariable logistic analysis was applied to explore the risk factors for postpartum depression, and Mendelian randomization analyses were used to provide supporting evidence for the association between labor epidural analgesia and postpartum depression at the genetic level. Single-nucleotide polymorphisms associated with epidural or spinal anesthesia and postpartum depression were identified from publicly available genetic dataset of the United Kingdom biobank and FinnGen database. There was no statistically significant difference in the incidence of postpartum depression at 6-weeks postpartum between the epidural and non-epidural groups [12 (16.4%) vs 7 (9.6%), P = 0.219]. The multivariable logistic model suggested that prepartum EPDS scores, satisfaction with income and marital status, pain level before anesthesia, and comorbidity during pregnancy were independent predictors of postpartum depression incidence. Mendelian randomization analyses indicated that neither labor epidural (OR = 0.90, 95% CI: 0.78-1.05; P = 0.18) nor spinal anesthesia (OR = 1.10, 95% CI: 0.96-1.27; P = 0.17) potentially reduced the risk of postpartum depression. These findings imply that administration of labor epidural analgesia during delivery has no influence on the incidence of postpartum depression. The study protocol was registered in Chinese Clinical Trial Registry (ChiCTR2300078957).