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Little is known about cyclobenzaprine's safety during pregnancy. We explored the association between maternal cyclobenzaprine exposure and risk of birth defects among offspring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We combined data from two large, multi\u2010site, population\u2010based case\u2013control studies in the United States. Cases were identified from birth defects registries across 10 states; controls were liveborn infants without birth defects randomly selected from the same catchment areas. Participants reported cyclobenzaprine use during the month before conception through the third month of pregnancy (\u201cpericonception\u201d) via computer\u2010assisted telephone interview. We used logistic regression to assess associations between periconceptional cyclobenzaprine exposure and selected structural birth defects. We calculated crude odds ratios (OR) with corresponding 95% confidence intervals (CI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our study included 33\u2009615 cases and 13\u2009110 controls. Overall, 51 case (0.15%) and 9 control (0.07%) participants reported periconceptional cyclobenzaprine use. We observed increased risk for all seven defects with \u22653 exposed cases: cleft palate (OR\u2009=\u20094.79, 95% CI 1.71\u201313.44), cleft lip (OR\u2009=\u20092.50, 95% CI 0.89\u20137.02), anorectal atresia\/stenosis (OR\u2009=\u20096.91, 95% CI 1.67, 28.65), d\u2010transposition of the great arteries (OR\u2009=\u20096.97, 95% CI 2.17\u201322.36), coarctation of the aorta (OR\u2009=\u20095.58, 95% CI 1.88\u201316.58), pulmonary valve stenosis (OR\u2009=\u20094.55, 95% CI 1.10\u201318.87), and secundum atrial septal defect (OR\u2009=\u20093.08, 95% CI 0.83\u201311.45).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Even in our large sample, cyclobenzaprine use was rare. Our estimates are unadjusted and imprecise so should be interpreted cautiously. These hypothesis\u2010generating results warrant confirmation and further research to explore possible mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.5619","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T11:35:58Z","timestamp":1679398558000},"page":"855-862","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Maternal cyclobenzaprine exposure and risk of birth defects in the National Birth Defects Prevention Study (1997\u20132011) and Birth Defects Study to Evaluate Pregnancy exposureS (2014\u20132018)"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4702-1007","authenticated-orcid":false,"given":"Sarah C.","family":"Fisher","sequence":"first","affiliation":[{"name":"Birth Defects Registry New York State Department of Health  Albany New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8420-5040","authenticated-orcid":false,"given":"Meredith M.","family":"Howley","sequence":"additional","affiliation":[{"name":"Birth Defects Registry New York State Department of Health  Albany New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2643-0397","authenticated-orcid":false,"given":"Emmy L.","family":"Tran","sequence":"additional","affiliation":[{"name":"Eagle Global Scientific LLC  Atlanta Georgia USA"},{"name":"Division of Birth Defects and Infant Disorders, National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth C.","family":"Ailes","sequence":"additional","affiliation":[{"name":"Division of Birth Defects and Infant Disorders, National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni A.","family":"Papadopoulos","sequence":"additional","affiliation":[{"name":"Birth Defects Registry New York State Department of Health  Albany New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy N.","family":"Nembhard","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Fay W. 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