Reply to: assessing the association between postpartum depression and caesarean section under general anaesthesia

Editor, We thank Geng et al. for their thoughtful comments on our recently published systematic review and meta-analysis in this journal.1 They raise important concerns about several potential confounders, including indications for general anaesthesia (GA), pre-existing antenatal depression or psychiatric disorders, and post-caesarean analgesic management, which may not have been fully controlled or reported in the included studies and could influence the observed association. These issues warrant careful consideration. We agree that, in studies exploring potential causal relationships, appropriate control and balance of confounding variables are essential to minimise bias and avoid overinterpretation of associations. Establishing causality in this context is inherently challenging. Although randomised controlled trials are the methodological gold standard, random allocation of anaesthetic technique for Caesarean section is often neither ethical nor feasible, particularly in urgent or high-risk obstetric situations. No eligible randomised trials addressing this context were identified in our systematic search. Among available observational studies, cohort studies generally provide a stronger design than case-control or cross-sectional studies for examining temporal associations, while partially mitigating certain forms of selection bias.2 For this reason, we restricted our analyses to cohort studies. Our primary objective was to synthesise the existing evidence regarding the association between anaesthetic technique and postpartum depression (PPD), thereby identifying potential knowledge gaps and guiding future research directions. Nonetheless, residual confounding remains an inherent limitation of observational studies. To further address this concern, we conducted an additional sensitivity analysis restricted to studies that more comprehensively accounted for key confounders, including contraindications to neuraxial anaesthesia, obstetric complications necessitating GA, and pre-existing psychiatric conditions. These studies applied propensity score matching to balance these key confounders and other baseline demographic characteristics between GA and non-GA groups.3–5 The association between GA and increased risk of PPD remained statistically significant in this analysis (pooled adjusted odds ratio 1.29, 95% confidence interval 1.05 to 1.57), consistent with our main findings. Other unmeasured factors may still contribute to the observed association. As discussed in our original manuscript and highlighted by Geng et al., postoperative pain intensity and analgesic consumption may influence the risk of PPD and could represent important mediators or confounders.6 However, these variables were not consistently reported in the included studies. Future prospective cohort studies incorporating detailed peri-operative pain assessments and management strategies will be essential to further clarify their role in this association. In summary, our findings suggest that Caesarean section under GA may be associated with a higher risk of PPD. Given the limited number of high-quality studies and the possibility of residual confounding, this association should be interpreted cautiously. Large-scale, methodologically rigorous prospective studies are warranted to further minimise potential bias and refine our understanding of this relationship.