New study published in PLOS Medicine finds no increased risk of major birth defects from common NSAIDs like ibuprofen and naproxen during early pregnancy.

Common nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen taken during the first trimester of pregnancy do not appear to be associated with an elevated risk of major congenital malformations, according to a study published in PLOS Medicine. The research, conducted by Sharon Daniel from Ben-Gurion University of the Negev and Clalit Health Services in Israel, analyzed data from 264,858 singleton pregnancies between 1998 and 2018.

The study found that among these pregnancies, 7.6% were exposed to NSAIDs during the first trimester—most commonly ibuprofen (5.1%), diclofenac (1.6%), and naproxen (1.2%). Major congenital malformations were identified from linked clinical, hospitalization, and termination records. The researchers adjusted for various maternal and pregnancy characteristics including age, ethnicity, diabetes, obesity, folic acid use, and the reason for NSAID use.

The study did not observe an association between NSAID exposure and major congenital malformations overall (8.2% vs 7.0% in unexposed pregnancies; matched adjusted relative risk = 0.99). No individual drug was associated with increased risks of specific types of birth defects, and dose-response analyses showed no significant link between cumulative NSAID exposure and birth defect risk.

The authors conclude that their findings provide "reassuring evidence" that early use of ibuprofen in pregnancy is not linked to major birth defects. Dr. Sharon Daniel emphasized the importance of these results for both pregnant women and healthcare providers, stating, "Our study can help guide decisions about managing pain and fever during early pregnancy."

Dr. Ariel Hasidim highlighted a key aspect of the research: addressing gaps in real-world data. He some individuals may have used NSAIDs without them being recorded, which could influence results. To mitigate this issue, the team employed special analysis techniques to assess how missing information might have affected their findings.

"This study is reassuring for many expecting mothers and healthcare providers," said Dr. Daniel. "It provides crucial information about the safety of commonly used pain relievers during early pregnancy."

The research underscores the need for further studies to explore potential risks associated with NSAID use in later stages of pregnancy, as well as other medications that may be taken by pregnant women.

Publication details: Hasidim AA, et al. First-trimester nonsteroidal anti-inflammatory drugs exposure and risk of major congenital malformations: A retrospective register-based cohort study, PLOS Medicine (2026). DOI: 10.1371/journal.pmed.1005063

Journal information: PLoS Medicine