Uncovering The Relationship Between Opioid Use And Postpartum Depression: Evidence From A Two-Sample Mendelian Randomization Study

Background and Objective: Opioid use during pregnancy is a significant public health concern that has been associated with adverse maternal and fetal outcomes. This study aims to investigate the association between the genetic liability for prescription opioid medication and postpartum depression (PPD) using a Two-Sample Mendelian Randomization (MR) approach. By reducing the risk of residual confounding found in traditional observational studies, we can comprehend how MR can further improve our understanding of this issue. Design, setting, and participants: We conducted a 2-sample MR using summary statistics from genome-wide association studies (GWAS) to determine associations of prescription opioid use with PPD. Selected relevant single nucleotide polymorphisms from GWASs have a threshold P less than 5x10-6 and R2 ≤ 0.001. The GWAS data comprised participants of European ancestry included in the UK Biobank and FinnGen biobanks. We performed sensitivity analyses to assess bias due to genetic pleiotropy. Main outcomes and measures: Postpartum depression Results: The primary analysis included 78,808 participants with a record of prescription opioid use, 13,657 participants with PPD, and 236,178 without PPD. Per doubling in the genetically predicted population prevalence of opioid use, the odds of developing PPD increased by 12% (OR = 1.12, [95% CI] = [1.05, 1.20], p = 0.002). This finding was further validated by sensitivity analyses controlling for genetically predicted cofounders. Conclusions and relevance: The findings of these robust MR analyses additionally demonstrate a potential causal association between opioid use and PPD when considering traditional observational studies suggesting a relationship between opioid use and PPD. While replication is necessary, these findings may inform further investigation of the opioid epidemic related to maternal mental health