{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:32:03Z","timestamp":1790775123947,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2011,6,10]],"date-time":"2011-06-10T00:00:00Z","timestamp":1307664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We describe a boy who was exposed to misoprostol and methotrexate in the first trimester of gestation as a result of a failed medical abortion. He presented with severe growth retardation, skull defects, proptotic eyes, cleft palate, and severe micrognathia. There were bilateral defects of the upper and lower extremities, missing and hypoplastic ribs, and undescended testicles. He had clinical features of pulmonary hypoplasia with severe persistent pulmonary hypertension and remained ventilator\u2010dependent until he expired. An autopsy revealed brain anomalies consistent with arrhinencephaly. Methotrexate is frequently used in conjunction with misoprostol to induce medical abortion, an off\u2010label use as abortifacient. Both of these medications are well\u2010established teratogens and have an X classification during pregnancy. Data from eight patients who were exposed to both medications in the first trimester indicate a significant teratogenic risk to the developing fetus. Reported anomalies include growth retardation, absence or hypoplasia of the frontal bones, craniosynostosis, large fontanelle, ocular hypertelorism, short palpebral fissures, wide nasal bridge, malformed and low\u2010set ears, and micrognathia. Skeletal anomalies are frequent consisting of syndactyly, mesomelic shortening of the forearms, missing ribs, dislocated hips, and talipes equinovarus. The findings in our case are consistent with the pattern of abnormalities that have been reported in the literature. In addition, our patient had severe pulmonary hypoplasia and arrhinencephaly, anomalies that have not been described previously. This case adds to the documentation of the teratogenic effects of methotrexate and misoprostol on the developing fetus. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.34037","type":"journal-article","created":{"date-parts":[[2011,6,10]],"date-time":"2011-06-10T19:37:16Z","timestamp":1307734636000},"page":"1723-1728","source":"Crossref","is-referenced-by-count":25,"title":["Methotrexate and misoprostol teratogenicity: Further expansion of the clinical manifestations"],"prefix":"10.1002","volume":"155","author":[{"given":"Chahira","family":"Kozma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayashree","family":"Ramasethu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,6,10]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20503"},{"key":"e_1_2_4_3_1","first-page":"159","article-title":"Uses of misoprostol in obstetrics and gynecology","volume":"2","author":"Allen R","year":"2009","journal-title":"Rev Obst Gynecol"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/GRF.0b013e3181a2b026"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199802)57:2<51::AID-TERA2>3.0.CO;2-9"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-7824(99)00029-3"},{"key":"e_1_2_4_7_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1K550"},{"key":"e_1_2_4_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20001211)95:4<297::AID-AJMG1>3.0.CO;2-K"},{"key":"e_1_2_4_9_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2003.131"},{"key":"e_1_2_4_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420360111"},{"key":"e_1_2_4_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199907)60:1<10::AID-TERA5>3.0.CO;2-H"},{"key":"e_1_2_4_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/13.4.1063"},{"key":"e_1_2_4_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420230205"},{"key":"e_1_2_4_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420150211"},{"key":"e_1_2_4_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420470605"},{"key":"e_1_2_4_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jp.7211563"},{"key":"e_1_2_4_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)12363-7"},{"key":"e_1_2_4_18_1","first-page":"CD002855","article-title":"Medical methods for first trimester abortion","volume":"2","author":"Kulier R","year":"2004","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_4_19_1","first-page":"2360","article-title":"Low dose methotrexate in the first trimester of pregnancy: Results of a French collaborative study","volume":"31","author":"Lewden B","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_4_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/92.10.551"},{"key":"e_1_2_4_21_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1080\/09709274.2007.11905976","article-title":"Methotrexate induced gross malformations in chick embryos","volume":"21","author":"Natekar PE","year":"2007","journal-title":"J Hum Ecol"},{"key":"e_1_2_4_22_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-0913"},{"key":"e_1_2_4_23_1","first-page":"1872","article-title":"Low dose weekly methotrexate in early pregnancy. 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