{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T11:13:14Z","timestamp":1774523594827,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,2,24]],"date-time":"2004-02-24T00:00:00Z","timestamp":1077580800000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt B"],"published-print":{"date-parts":[[2004,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> The antiepileptic drug valproic acid (VPA) is well known to cause neural tube and skeletal defects in both humans and animals. The amidic VPA analogues valpromide (VPD) and valnoctamide (VCD) have much lower teratogenicity than VPA inducing exencephaly in mice. The objective of this study was to investigate the teratogenic effects of VPA, VPD, and VCD on the skeleton of NMRI mice. <jats:bold>METHODS:<\/jats:bold> Pregnant NMRI mice were given a single subcutaneous injection of VPA (400 and 800\u2009mg\/kg), VPD (800\u2009mg\/kg), or VCD (800\u2009mg\/kg) on the morning of gestation day (GD) 8. Cesarean section was carried out on GD 18. Live fetuses were double\u2010stained for bone and cartilage and their skeletons were examined. <jats:bold>RESULTS:<\/jats:bold> Significant increases in fetal loss and exencephaly rate were observed with VPA at 800\u2009mg\/kg compared to the vehicle control. There were no significant differences between either VPD or VCD and the control groups for any parameter at cesarean section. A number of abnormalities were dose\u2010dependently induced at high incidences by VPA in both the cartilage and bone of vertebrae, ribs and sternum. In contrast, lower frequencies of abnormality were exhibited with VPD and VCD than VPA in all skeletons affected by VPA. <jats:bold>CONCLUSIONS:<\/jats:bold> These findings clearly indicate that VPD and VCD are distinctly less teratogenic than VPA in the induction of not only neural tube defects, but also skeletal abnormalities. A structure\u2010teratogenicity relationship of VPA on the skeleton is suspected. <jats:italic>Birth Defects Res B<\/jats:italic> 71:47\u201353, 2004. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrb.10057","type":"journal-article","created":{"date-parts":[[2004,2,26]],"date-time":"2004-02-26T20:25:46Z","timestamp":1077827146000},"page":"47-53","source":"Crossref","is-referenced-by-count":27,"title":["Amidic modification of valproic acid reduces skeletal teratogenicity in mice"],"prefix":"10.1002","volume":"71","author":[{"given":"Akinobu","family":"Okada","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Kurihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinobu","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meir","family":"Bialer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michio","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,2,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420490317"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(97)90194-6"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200009010-00003"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420470207"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00315032"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199120020-00003"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-3659(99)00037-1"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0272-0590(88)90112-1"},{"key":"e_1_2_6_10_1","first-page":"560","article-title":"Disposition 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