Background and Aims Effective pain management is critical for postpartum recovery. While commonly prescribed, systematically-reviewed data regarding efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) are limited. Moreover, guidelines suggest avoiding NSAIDs in women with hypertensive disorders of pregnancy (HDP) due to risks of hypertension and adverse events (AE). However, these AE have not been consistently observed in cohort studies and randomised controlled trials (RCTs) following postpartum NSAID use. This systematic review aims to provide further insight into the postpartum safety and efficacy of NSAIDs. Method A systematic review of eight databases and four clinical trial registries was conducted in July 2020 (PROSPERO Protocol CRD42020196054). RCTs which assessed the safety and/or efficacy of NSAIDs in postpartum women after the year 2000 were included. The primary outcome was incidence of hypertension, with secondary outcomes categorised into three groups: hypertension, secondary safety and efficacy. Data were tabulated and analysed using R (version 4.0.2). Due to heterogeneity in study design, NSAIDs were analysed in a single group and compared with other medications (including paracetamol, opioids, and local anaesthetics) grouped based on mechanism to facilitate meta-analysis. Risk of bias was assessed using the RoB 2 tool with a plan to assess quality of evidence for the primary outcome. Results 12,172 records were identified with the inclusion of 92 RCTs. Eight studies, with four that included women with HDP, reported hypertension-related data (Table 1). The primary outcome was included in one RCT. Secondary safety outcomes such as acute kidney injury or eclampsia were not reported. The odds of nausea, vomiting and sedation were similar between groups. NSAIDs were effective when compared with placebo, as assessed by mean differences (MD) in visual assessment scores (VAS) at 12 hours (MD -1.57, 95% confidence intervals (CI) -2.47 to -0.66), 24 hours (MD -0.82, 95% CI -1.42 to -0.22) and need for additional analgesia (odds ratio 0.17, 95% CI 0.05 to 0.61). There were no significant differences in VAS between NSAIDs and other comparators at 12 and 24 hours. Further interpretation of results is limited due to heterogeneity in intervention and comparator groups, inclusion criteria and reported outcomes. Conclusion Our study confirms the efficacy of NSAIDs for postpartum pain, but current data are inconclusive regarding the risk of developing hypertension. Available data do not demonstrate trends toward AE although further research is required to determine long term, clinically-relevant outcomes to guide decision making.

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