Pregnancy outcomes and birth defects in offspring following Non-steroidal anti-inflammatory drugs exposure during pregnancy: A systematic review and meta-analysis.

There is a high global prevalence of NSAIDs during pregnancy. However, current evidence is largely conflicting regarding the safety of gestational NSAIDs use both for the pregnancy and offspring health. The aim of this study is to systematically review the relationship between NSAIDs use during pregnancy and the risk of adverse pregnancy outcomes and congenital abnormalities. Cohort studies and case control studies on congenital malformations, miscarriage and preterm birth in infants born to mothers who were exposed to NSAIDs during pregnancy were identified via PubMed, Medline, Embase, the Cochrane Library databases and the Reprotox® database from inception to 26 March 2021, and updated on 6 April 2023. On the whole, compared with the unexposed group, infants exposed to NSAIDs during early pregnancy showed a 28% increased risk of overall congenital anomalies (OR 1.28, 95%CI 1.16-1.40), and 19% for major birth defects (OR 1.19, 95%CI 1.08-1.30). Contrary to previous beliefs, there appeared to be a trend towards a higher risk of miscarriage among women who were exposed to NSAIDs during pregnancy, but the association was not statistically significant (OR 1.20, 95%CI 0.93-1.55). According to our study findings, the use of NSAIDs by pregnant women has been linked to a higher risk of congenital anomalies and a negative impact on preterm birth. Therefore, we advise pregnant women to carefully consider the potential benefits and risks before using NSAIDs during pregnancy.