PLoS Med
Early pregnancy NSAIDs not linked to birth defects
Clinical Takeaway: NSAIDs may be an option for selected patients who need pain or fever relief in the first trimester, but treatment should still be individualized and later-pregnancy NSAID cautions still apply.
Pain and fever are common in early pregnancy, but medication safety concerns can leave patients and clinicians with limited options. This study adds reassuring evidence for first-trimester use of common NSAIDs, including ibuprofen, diclofenac, and naproxen.
After matching and adjustment, NSAID exposure was not associated with major congenital malformations overall, despite higher unadjusted rates among exposed pregnancies. The matched adjusted relative risk was 0.99, and no increased risk was seen for cardiovascular, musculoskeletal, central nervous system, gastrointestinal, or genitourinary malformations.
The findings were consistent for individual drugs and across dose-response analyses. Short-, medium-, and longer-term cumulative NSAID exposure during the first trimester were not significantly associated with major birth defects.
Researchers analyzed 264,858 singleton pregnancies from the Southern Israeli Pregnancy Registry, including 20,202 with first-trimester NSAID exposure. The study was observational, exposure was based on dispensation rather than confirmed use, and spontaneous abortions were not captured.
“Our results provide reassuring evidence that NSAID use in early pregnancy is not associated with major birth defects,” the authors said.
The study findings apply to first-trimester exposure. Later in pregnancy, NSAIDs are generally avoided because use after 20 weeks can cause fetal kidney dysfunction and low amniotic fluid and use around 30 weeks or later can prematurely close the ductus arteriosus.
Source: Hasidim AA. PLoS Med. 2026 May 14. First-trimester nonsteroidal anti-inflammatory drugs exposure and risk of major congenital malformations