Maternal non-steroidal anti-inflammatory drug exposure during pregnancy and risk of miscarriage: a systematic review and meta-analysis

Numerous studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs) might be associated with increased risk of miscarriage. However, these results are conflicting and inconclusive. We performed this systematic review and meta-analysis to assess the relationship between NSAIDs exposure and risk of miscarriage. A systematic literature search was conducted to identify relevant studies published from the time of database inception until June 2021. A total of ten studies involving 207,341 pregnant women were subjected to meta-analysis. There was no statistically significantly increased risk of miscarriage with the use of NSAIDs during pregnancy (OR = 1.37, 95% CI 0.99–1.88, p = 0.057). However, our findings showed that women exposed to NSAIDs around the time of conception were at increased risk of miscarriage (OR 2.32, 95% CI 1.16–4.66, p = 0.018). Furthermore, no significant association between NSAID use and miscarriage was evident during the first trimester of pregnancy (OR = 1, 95% CI = 0.83–1.2, p = 0.996), possibly attributable to the small sample size. Our findings indicate that NSAID exposure around the time of conception might be a risk factor for miscarriage. Further studies are needed to evaluate whether the risk varies by the type, dosage, or timing of NSAID exposure.