Adverse Effects of Dipyrone (Metamizole) Use During Pregnancy on Offspring Health: A Systematic Review and Meta-Analysis

Abstract

Background This meta-analysis and systematic review aimed to review the health outcomes of offspring following dipyrone use during pregnancy.Methods A systematic literature search was conducted in MEDLINE, Embase, and the Cochrane Library to identify clinical trials or observational studies investigating women who used dipyrone during pregnancy published up to 22 March 2024. Two independent reviewers were responsible for the data extraction. The data were analyzed using odds ratios (ORs) with 95% confidence intervals (CIs) and a random effects model. Sensitivity analyses were performed using Bayesian Markov Chain Monte Carlo methods.Results Six case-control studies and four prospective cohort studies met the inclusion criteria. There was no evidence of associations with congenital anomalies (OR 1.18, 95% CI 0.80–1.63; I2 = 33.73%; 3 cohorts and 1 case-control, n = 67,374), major congenital anomalies (OR 1.06, 95% CI 0.47–2.37; I2 = 0%; 2 cohorts, n = 1,356), infant leukemia (OR 1.25, 95% CI 0.86–2.22; I2 = 72.82%; 3 case-controls, n = 1,686), fetal death (OR 0.81, 95% CI 0.57–1.14; 3 cohorts, n = 6,380), prematurity (OR 0.99, 95% CI 0.80–1.21; I2 = 0%; 3 cohorts, n = 6,194), low birth weight, constriction of the ductus arteriosus, or renal and cardiac disorders. There is insufficient evidence to exclude oligohydramnios and patent ductus arteriosus in second- and third-trimester exposures. All analyses were of very low certainty.Conclusion There is no evidence indicating that maternal use of dipyrone causes substantial harm to offspring. According to the sensitivity analyses, exposure during the first and second trimesters was not associated with any negative outcomes. Some observed outcomes, particularly in the third trimester of pregnancy, merit further research.