{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T06:26:16Z","timestamp":1778826376999,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T00:00:00Z","timestamp":1627948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["DD001184"],"award-info":[{"award-number":["DD001184"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2021,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Use of nonsteroidal anti\u2010inflammatory drugs (NSAIDs) during pregnancy may increase risk for neural tube defects (NTDs), including spina bifida. Folic acid intake can prevent NTDs, but it is not known whether it modifies any risks associated with NSAID use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To assess the impact of periconceptional NSAID use on the risk of spina bifida overall and stratified by folic acid intake.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>We analyzed 1998\u20132015 data from the Slone Epidemiology Center Birth Defects Study, a multi\u2010site, case\u2013control study. Mothers were interviewed to identify sociodemographic factors, behaviors, and exposures during pregnancy. Periconceptional NSAID use was defined as use of aspirin, ibuprofen, naproxen, or COX2 inhibitors within the month before or after the last menstrual period. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for NSAID use, adjusted for study center and race\/ethnicity stratified by average daily folic acid intake above (\u201chigh FA\u201d) or below (\u201clow FA\u201d) 400\u2009mcg\/day.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We compared mothers of 267 infants with spina bifida to mothers of 6,233 nonmalformed controls. Among control mothers, 20% used NSAIDS periconceptionally (16% ibuprofen, 4% aspirin, 3% naproxen, and &lt;1% COX\u20102 inhibitors). For any NSAID use, the aORs among low FA and high FA women were 1.70 (95% CI [1.13, 2.57]) and 1.09 (95% CI [0.69, 1.71]), respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We observed a small increase in the risk for spina bifida among infants born to women who used NSAIDs periconceptionally, but this risk was limited to those who had inadequate folic acid intake.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1944","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T05:00:21Z","timestamp":1628053221000},"page":"1257-1266","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Periconceptional nonsteroidal anti\u2010inflammatory drug use, folic acid intake, and the risk of spina bifida"],"prefix":"10.1002","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2894-0523","authenticated-orcid":false,"given":"Daina B.","family":"Esposito","sequence":"first","affiliation":[{"name":"Department of Epidemiology Boston University School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha E.","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Boston University School of Public Health  Boston Massachusetts USA"},{"name":"Slone Epidemiology Center at Boston University  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen A.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Boston University School of Public Health  Boston Massachusetts USA"},{"name":"Slone Epidemiology Center at Boston University  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7610-6288","authenticated-orcid":false,"given":"Sarah C.","family":"Tinker","sequence":"additional","affiliation":[{"name":"National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha M.","family":"Werler","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Boston University School of Public Health  Boston Massachusetts USA"},{"name":"Slone Epidemiology Center at Boston University  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23100"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2017.1299768"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1380"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2820197"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199911113412006"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/openhrt-2016-000550"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2011.11.019"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annepidem.2017.09.003"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annepidem.2017.10.010"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067407"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2011.02.029"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17445-X"},{"issue":"14","key":"e_1_2_8_14_1","first-page":"1","article-title":"Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects","volume":"41","author":"MMWR Recomm Rep","year":"1992","journal-title":"MMWR Recommendations and Reports. Morbidity and Mortality Weekly Report. Recommendations and Reports"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2004.10.598"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpp.2000.112052"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20085"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36324"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2013.05.047"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20772"},{"key":"e_1_2_8_21_1","unstructured":"Research C for DE and FDA. (2019).FDA Drug Safety Communication: FDA has reviewed possible risks of pain medicine use during pregnancy. FDA [Internet]. Retrieved fromhttp:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-drug-safety-communication-fda-has-reviewed-possible-risks-pain-medicine-use-during-pregnancy"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022174"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a010070"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2005.02.100"},{"issue":"1","key":"e_1_2_8_25_1","first-page":"1","article-title":"Updated estimates of neural tube defects prevented by mandatory folic acid fortification \u2010 United States, 1995\u20132011","volume":"64","author":"Williams J.","year":"2015","journal-title":"MMWR. Morbidity and Mortality Weekly Report"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3182a6643c"}],"container-title":["Birth Defects Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.1944","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bdr2.1944","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.1944","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:30:46Z","timestamp":1693355446000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdr2.1944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,3]]},"references-count":25,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2021,10,15]]}},"alternative-id":["10.1002\/bdr2.1944"],"URL":"https:\/\/doi.org\/10.1002\/bdr2.1944","archive":["Portico"],"relation":{},"ISSN":["2472-1727","2472-1727"],"issn-type":[{"value":"2472-1727","type":"print"},{"value":"2472-1727","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,3]]},"assertion":[{"value":"2021-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}