{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:55:51Z","timestamp":1793051751478,"version":"4.5.0"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,6,3]],"date-time":"2015-06-03T00:00:00Z","timestamp":1433289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>The aim of the study was to characterize the extent of indication bias resulting from the excessive use of NSAIDs on the days preceding a spontaneous abortion to relieve pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used data from a retrospective cohort study assessing the risk for spontaneous abortions following exposure to NSAIDs. Three definitions of exposure for cases of spontaneous abortions were compared, from the first day of pregnancy until the day of spontaneous abortion and until 3 and 2 days before a spontaneous abortion. Statistical analysis was performed using multivariate time programmed Cox regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A sharp increase was observed in the dispensation of indomethacin, diclofenac and naproxen, and a milder increase was found in the use of ibuprofen during the week before a spontaneous abortion. Non\u2010 selective COX inhibitors in general and specifically diclofenac and indomethacin were found to be associated with spontaneous abortions when the exposure period was defined until the day of spontaneous abortion (hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.04, 1.28; HR 1.31, 95% CI 1.08, 1.59 and HR 3.33, 95% CI 2.09, 5.29, respectively). The effect disappears by excluding exposures occurring on the day before the spontaneous abortion for non\u2010selective COX inhibitors and on the last week before the spontaneous abortion for indomethacin. In general, decreasing HRs were found with the exclusion of exposures occurring on the days immediately before the spontaneous abortion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The increased use of NSAIDs during the last few days that preceded a spontaneous abortion to relieve pain associated with the miscarriage could bias studies assessing the association between exposure to NSAIDs and spontaneous abortions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12653","type":"journal-article","created":{"date-parts":[[2015,4,7]],"date-time":"2015-04-07T03:20:10Z","timestamp":1428376810000},"page":"750-754","source":"Crossref","is-referenced-by-count":15,"title":["NSAIDs and spontaneous abortions \u2013 true effect or an indication bias?"],"prefix":"10.1111","volume":"80","author":[{"given":"Sharon","family":"Daniel","sequence":"first","affiliation":[{"name":"Departments of Public Health, Faculty of Health Sciences Ben\u2010Gurion University of the Negev, Soroka Medical Center  Beer\u2010Sheva Israel"},{"name":"Departments of Pediatrics, Faculty of Health Sciences Ben\u2010Gurion University of the Negev, Soroka Medical Center  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon","family":"Koren","sequence":"additional","affiliation":[{"name":"The Motherisk Program, Division of Clinical Pharmacology\u2010Toxicology, Hospital for Sick Children The University of Toronto  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eitan","family":"Lunenfeld","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Health Sciences Ben\u2010Gurion University of the Negev, Soroka Medical Center  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Levy","sequence":"additional","affiliation":[{"name":"Departments of Public Health, Faculty of Health Sciences Ben\u2010Gurion University of the Negev, Soroka Medical Center  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,3]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"259","volume-title":"Current Diagnosis & Treatment, Obstetrics & Gynecology","author":"Prernoll M","year":"2007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(80)90061-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(02)04694-0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198807283190401"},{"key":"e_1_2_8_6_1","first-page":"170","volume-title":"Williams Gynecology","author":"Hoffman BL","year":"2011"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2005.02.100"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.120453"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2011.07.013"},{"key":"e_1_2_8_10_1","first-page":"959","volume-title":"Goodman & Gilman's The Pharmacological Basis of Therapeutics","author":"Grosser T","year":"2011"},{"key":"e_1_2_8_11_1","first-page":"273","volume-title":"Current Diagnosis & Treatment, Obstetrics & Gynecology","author":"Roman APM","year":"2007"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1756-185X.2012.01769.x"},{"key":"e_1_2_8_13_1","unstructured":"GuillermoR MuntherAK.Pregnancy and Rheumatic Disease.2013; Available at:https:\/\/www.rheumatology.org\/Practice\/Clinical\/Patients\/Diseases_And_Conditions\/Pregnancy_and_Rheumatic_Disease\/. 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