NSAID use near conception is associated with early miscarriage in women with BMI <25

Reference

Li DK, Ferber JR, Odouli R, Quesenberry C. Use of nonsteroidal anti-inflammatory drugs during pregnancy and the risk of miscarriage. Am J Obstet Gynecol 2018;219(3):275.e1-e8.

Synopsis

NSAIDs have a plausible biological mechanism for association with miscarriage by interfering with the prostaglandin production necessary for successful embryonic implantation. These investigators studied the association of NSAIDs with miscarriage in a well-designed prospective cohort study with special attention to timing and duration of use. Pregnant members of an integrated healthcare system (Kaiser Permanente Northern California) were invited to participate if they had a confirmed pregnancy test result and fell into 1 of 3 categories; exposed to NSAIDs only, exposed to acetaminophen only, or not exposed to either. Women who used both types of medications or who used aspirin were excluded. A total of 1097 women were enrolled. Participants were interviewed in person to collect detailed information about exposure to NSAIDs and acetaminophen, as well as to gather information about the pregnancy, reproductive history, medical conditions, and other potential confounders such as age, race/ethnicity, education level, smoking, and fever in the pregnancy. Timing and duration of medication use were ascertained, but dosage information was insufficient. Women with NSAID or acetaminophen use were followed up for miscarriage starting at the gestational age of the positive pregnancy test result, unless medication was initiated at a later time. Results were presented mainly as adjusted, although adjustments for confounders had minimal impact on the unadjusted results. NSAID use in the first 2 weeks from conception was associated with increased risk of miscarriage as compared with the unexposed group (adjusted hazard ratio [HR] 1.89; 95% CI 1.31 - 2.71), while use that started later was not (adjusted HR 0.89; 0.43 - 1.85). More than 14 days of use was associated with a higher rate of miscarriage than 14 days or less (aHR 2.10 vs aHR 1.36; test for trend P <.01). The association was stronger for miscarriage at less than 8 weeks' gestation (aHR 4.08; 2.25 - 7.41). Only women with a BMI of less than 25 were at increased risk for miscarriage with early NSAID exposure (aHR 3.78; 2.04 - 6.99; NS for women with BMI of 25 or higher).