{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:15:09Z","timestamp":1791976509202,"version":"4.4.0"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,6,4]],"date-time":"2014-06-04T00:00:00Z","timestamp":1401840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Centers for Disease Control and Prevention to the Centers for Birth Defects Research and Prevention","award":["PA96043"],"award-info":[{"award-number":["PA96043"]}]},{"name":"Centers for Disease Control and Prevention to the Centers for Birth Defects Research and Prevention","award":["PA02081"],"award-info":[{"award-number":["PA02081"]}]},{"name":"Centers for Disease Control and Prevention to the Centers for Birth Defects Research and Prevention","award":["FOA DD09-001"],"award-info":[{"award-number":["FOA DD09-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>Methotrexate is an anti\u2010folate medication that is associated with increased risk of multiple birth defects. Using data from the National Birth Defects Prevention Study, a case\u2010control study of major birth defects in the United States, we examined mothers exposed to methotrexate. The study population included mothers of live\u2010born infants without major birth defects (controls) and mothers of fetuses or infants with a major birth defect (cases), with expected dates of delivery between October 1997 and December 2009. Mothers of cases and controls were asked detailed questions concerning pregnancy history, demographic information, and exposures in a telephone interview. Approximately 0.06% (n\u2009=\u200916\/27,623) of case and 0.04% (n\u2009=\u20094\/10,113) of control mothers reported exposure to methotrexate between 3 months prior to conception through the end of pregnancy. Of the 16 case infants, 11 (68.8%) had a congenital heart defect (CHD). The observed CHDs included atrial septal defects, tetralogy of Fallot, valvar pulmonary stenosis, ventricular septal defects (VSDs), and total anomalous pulmonary venous return. One case infant had microtia in addition to a VSD and another had VACTER association. Exposed cases without a CHD had one of the following birth defects: cleft palate, hypospadias, congenital diaphragmatic hernia, or craniosynostosis. Based on a limited number of methotrexate\u2010exposed mothers, our findings support recent case reports suggesting an association between early pregnancy exposure to methotrexate and CHDs. Because of the rarity of maternal periconceptional exposure to methotrexate, long\u2010term, population\u2010based case\u2010control studies are needed to confirm these findings and better evaluate the association between methotrexate and birth defects. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36625","type":"journal-article","created":{"date-parts":[[2014,6,4]],"date-time":"2014-06-04T14:04:51Z","timestamp":1401890691000},"page":"2212-2216","source":"Crossref","is-referenced-by-count":51,"title":["Maternal exposure to methotrexate and birth defects: A population\u2010based study"],"prefix":"10.1002","volume":"164","author":[{"given":"April L.","family":"Dawson","sequence":"first","affiliation":[{"name":"National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Riehle\u2010Colarusso","sequence":"additional","affiliation":[{"name":"National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennita","family":"Reefhuis","sequence":"additional","affiliation":[{"name":"National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Fernando","family":"Arena","sequence":"additional","affiliation":[{"name":"National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the National Birth Defects Prevention Study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1701-2163(16)30422-4"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0029-7844(03)00120-0"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwp226"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24034"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(90)90005-M"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420470605"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200011303432204"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23003"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0052-y"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780290703"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/92.10.551"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(68)80430-5"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0029-7844(01)01607-6"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-011-9913-z"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2011.06.014"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10012"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/14647273.2012.694571"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20199"},{"key":"e_1_2_6_20_1","unstructured":"U.S. Food and Drug Administration.Methotrexate sodium label information.http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2011\/011719s117lbl.pdf. 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