Nicotine Dependence and Risk of Postpartum Psychosis: A Large Real-World Cohort Study

Background Postpartum psychosis is a rare but severe mental health emergency that occurs within 60 days of delivery. Although nicotine is a well-established risk factor for psychosis in the general population, its potential association with postpartum psychosis remains underexplored. Prior research has shown that maternal smoking is associated with an increased risk of postpartum depression. Building on this evidence, our study aims to investigate whether nicotine dependence similarly increases the risk of postpartum psychosis. Methods A retrospective cohort study was conducted using the TriNetX database to identify females aged 15-45 with documented deliveries. Two cohorts were formed based on the presence or absence of nicotine dependence during pregnancy. The primary outcome was postpartum psychosis up to 60 days after birth. Risk differences and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to compare incident postpartum psychosis; Kaplan-Meier survival curves and log-rank tests were used to assess time to event. Hazard ratios (HRs) were estimated using Cox proportional hazards regression. Propensity score matching was conducted to balance demographics and pre-existing mental, behavioral, and neurodevelopmental disorders between cohorts. Results The nicotine dependence and control cohorts comprised 155,280 and 1,291,177 patients, respectively. After propensity matching, 154,123 women were included in each group. Postpartum psychosis occurred in 158 patients (0.11%) in the nicotine-exposed cohort and 70 patients (0.05%) in the matched control cohort (p=0.001). Despite the increased relative risk, the absolute incidence of postpartum psychosis remained low in both cohorts. Nicotine dependence was associated with a significantly increased risk of postpartum psychosis (RR (95% CI) = 2.29 (1.73-3.04)). Survival analysis demonstrated a higher hazard of postpartum psychosis among nicotine-exposed patients (hazard ratio 2.27, 95% CI 1.71-3.01; log-rank p < 0.001). Conclusion Nicotine dependence is associated with increased risk of postpartum psychosis within 60 days after delivery. These findings suggest that nicotine exposure may represent a clinically relevant risk factor for postpartum psychosis. Further studies incorporating behavioral and socioeconomic data are warranted to clarify underlying mechanisms and inform targeted prevention strategies.