Recent reports have revealed an increased risk of spontaneous abortion associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy. To further examine this association, we propose to conduct a cohort study among the members of the Kaiser Permanente Medical Care Program (KPMCP). All KPMCP women who have a positive pregnancy test performed in one of the 13 KPMCP facilities and who speak either English or Spanish will be screened for their NSAID use during pregnancy to identify NSAID-exposed women. Using methods developed in an earlier study of electromagnetic field exposure and the risk of spontaneous abortion, we will recruit 1500 pregnant women: 500 NSAID-exposed women and 500 unexposed women; to control for confounding by indication, we will also recruit 500 women who have used acetaminophen, but neither NSAIDs nor aspirin because acetaminophen shares many similar indications with NSAIDs, but has a different pharmacological effect. Detailed information on prenatal NSAID use and other medications will be ascertained during an in-person interview as soon as the positive pregnancy is identified. Any subsequent NSAID use after the interview will be further ascertained at the end of pregnancy or at 20 weeks of gestation. Self-reported NSAID use will be confirmed by medication bottles, prescription records, and the KPMCP pharmacy databases that capture all prescription NSAIDs and nonprescription NSAID obtained at KPMCP pharmacies. Spontaneous abortion and other pregnancy outcomes will be ascertained through linkage to the KPMCP databases and review of medical records. Unidentified pregnancy outcomes will be ascertained through follow-up telephone interviews. Cox proportional hazard regression will be used to examine the risk of spontaneous abortion associated with periconceptional NSAID use. In addition, the risk associated with dose, timing, and duration of NSAID use as well as other characteristics of NSAID use including current/past use and cumulative dose will be examined. The proposed study will be the first population-based prospective cohort study specifically designed to examine the risk of spontaneous abortion associated with prenatal NSAID use. The findings from this study will provide valuable information on the safety of periconceptional NSAID use that has significant public health implications because of the widespread use of NSAIDs in the general population and among women of reproductive age. ? ?
