TOPLINE:

Early exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) from 2 weeks before conception to 20 weeks of pregnancy was associated with an 83% increased risk for miscarriage compared with no exposure, with flurbiprofen demonstrating a more than threefold higher risk among the commonly prescribed NSAIDs.

METHODOLOGY:

• Researchers conducted a nationwide population-based retrospective cohort study to evaluate the association between early exposure to NSAIDs during pregnancy and the risk for miscarriage.
• They used data from a French registry and included 4,857,907 pregnancies (median maternal age, 30 years) from 2013 to 2019, comprising 4,671,366 live births, 22,875 stillbirths, and 163,666 miscarriages. Of these, 349,294 pregnancies were exposed to NSAIDs, and 4,508,613 were not.
• Exposure to NSAIDs was determined using prescription data spanning 2 weeks before conception until the end of pregnancy; pregnancies were considered exposed from 3 days after the first dispensation to account for NSAIDs prescribed to treat early miscarriage symptoms rather than cause them.
• The outcome was miscarriage before the end of the 20th week of gestation, assessed from the sixth week of pregnancy to minimise misclassification of very early losses.

TAKEAWAY:

• Early exposure to NSAIDs was associated with an 83% higher risk for miscarriage between the sixth and 20th weeks of pregnancy than no exposure (hazard ratio [HR], 1.83; 95% CI, 1.81-1.86).
• The risk for miscarriage varied across NSAIDs, with exposure to flurbiprofen showing the strongest association (HR, 3.28; 95% CI, 3.15-3.41), followed by mefenamic acid (HR, 2.43; 95% CI, 2.12-2.79), ketoprofen (HR, 2.25; 95% CI, 2.18-2.33), indomethacin (HR, 1.93; 95% CI, 1.32-2.81), ibuprofen (HR, 1.89; 95% CI, 1.85-1.94), morniflumate (HR, 1.68; 95% CI, 1.26-2.23), and naproxen (HR, 1.09; 95 % CI, 1.01-1.18) compared with no exposure.
• When very early miscarriages (before the sixth week) were included in sensitivity analyses, the risk was similar to that in the main analysis (HR, 1.82; 95% CI, 1.79-1.84); although longer lag periods reduced the risk estimate (no lag: HR, 2.25; 95% CI, 2.21-2.28 and 7-day lag: HR, 1.56; 95% CI, 1.54-1.59), the association remained significant throughout.

IN PRACTICE:

"These findings support the need for careful restriction and close monitoring of NSAID use not only in late pregnancy but also in the early stages," the authors wrote.

"Our findings support the results of some previous studies and strengthen the rationale of the current recommendations for the cautious use of NSAIDs during the first trimester of pregnancy," they added.

SOURCE:

The study was led by Chi-Hong Duong, High-dimensional Biostatistics for Drug Safety and Genomics, Centre for Epidemiology and Population Health, Villejuif, France. It was published online on March 18, 2026, in BMJ Open.

LIMITATIONS:

The analysis relied on healthcare administrative databases, which do not capture important confounders such as smoking status and alcohol consumption. The study lacked data on unrecognised miscarriages, especially those occurring in the early stages of pregnancy. The lack of data on dosage and treatment duration in the databases precluded assessment of dose-response relationships.

DISCLOSURES:

This study received funding from the French National Agency for Medicines and Health Products Safety and the French National Research Agency. The authors declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.