THURSDAY, May 14, 2026 (HealthDay News) -- There is no evidence of an association between first-trimester exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and major congenital malformations (MCMs), according to a study published online May 14 in PLOS Medicine.Ariel Avraham Hasidim, from Ben-Gurion University of the Negev in Be'er-Sheva, Israel, and colleagues evaluated the association between first-trimester NSAID exposure and the risk for MCMs among 264,858 singleton pregnancies (20,202 exposed-to-NSAID pregnancies) in a retrospective register-based cohort study.The researchers found the most commonly used NSAIDs were ibuprofen (5.1 percent), diclofenac (1.6 percent), and naproxen (1.2 percent). As a class and for individual NSAIDs, there was no association for MCMs overall (8.2 versus 7.0 percent; matched-adjusted-relative risk [aRR], 0.99) or with organ system-specific MCMs, including cardiovascular (matched-aRR, 1.05), musculoskeletal (matched-aRR, 1.03), central nervous system (matched-aRR, 0.77), cleft palate (matched-aRR, 0.95), gastrointestinal (matched-aRR, 1.03), and genitourinary (matched-aRR, 0.99) malformations. Additionally, there were no significant dose-response associations with MCMs across cumulative NSAID exposure: short term (one to seven defined-daily-dose [DDD]: matched-aRR, 1.06), medium term (eight to 21 DDD: matched-aRR, 1.10), and long-term (>21 DDD: matched-aRR, 1.24)."Our results provide reassuring evidence that NSAID use in early pregnancy is not associated with major birth defects," the authors write. "These findings can help both pregnant women and physicians make informed decisions about managing pain and fever in early pregnancy."Abstract/Full Text.Sign up for our weekly HealthDay newsletter