Use of dipyrone during pregnancy and risk of congenital anomalies: a systematic review

Abstract

Purpose: This study aimed to summarize the evidence on the teratogenic effects of dipyrone used during pregnancy.

Methods: Databases (MEDLINE, EMBASE, Cochrane Library, CINAHL, Web of Science, Lilacs, SciELO, SCOPUS, OasisBR, and OpenGray) were reviewed until September 2023. We included studies that compared pregnant women who used dipyrone during any gestational period with those who used other analgesics or did not use any analgesics during the same gestational period. The outcome assessed was the presence of any congenital anomaly. Two reviewers independently conducted the review process, and a third reviewer resolved any disagreements. The risk of bias was assessed using the Joanna Briggs Institute tool for observational studies. The reviewed data synthesis is presented in narrative form.

Results: The search retrieved 2045 results, of which seven studies were included in the review, four were case‒control studies, and three were cohort studies involving 153,562 participants. The congenital anomalies evaluated varied across studies, with unspecified congenital anomalies predominating. Five of seven studies found no association between dipyrone and congenital anomalies. In a case‒control study, a positive association was found between dipyrone use and isolated congenital cataracts compared to two control groups; in another study, a positive association for unspecified congenital anomalies was observed in only one of the two control groups analyzed. In all studies, a high risk of bias was identified, especially regarding measuring the exposure, outcome, and assessment of confounding factors.

Conclusion: There is not enough evidence to define the risk of congenital anomalies associated with dipyrone use during pregnancy.

Registration: CRD 42022333041.

Keywords: Congenital anomalies; Dipyrone; Observational studies; Pregnancy; Systematic review.