Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study

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Abstract
Objective To evaluate whether prenatal use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of miscarriage. Design Population based cohort study. Prenatal use of NSAIDs, aspirin, and paracetamol (acetaminophen) ascertained by in-person interview. Setting Kaiser Permanente Medical Care Program, a healthcare delivery system, in the San Francisco area of the United States. Participants 1055 pregnant women recruited and interviewed immediately after their positive pregnancy test. Median gestational age at entry to the study was 40 days. Main outcome measures Pregnancy outcomes up to 20 weeks of gestation. Results 53 women (5%) reported prenatal NSAID use around conception or during pregnancy. After adjustment for potential confounders, prenatal NSAID use was associated with an 80% increased risk of miscarriage (adjusted hazard ratio 1.8 (95% confidence interval 1.0 to 3.2)). The association was stronger if the initial NSAID use was around the time of conception or if NSAID use lasted more than a week. Prenatal aspirin use was similarly associated with an increased risk of miscarriage. However, prenatal use of paracetamol, pharmacologically different from NSAIDs and aspirin, was not associated with increased risk of miscarriage regardless of timing and duration of use. Conclusion Prenatal use of NSAIDs and aspirin increased the risk of miscarriage. These findings need confirmation in studies designed specifically to examine the apparent association.