{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T17:33:23Z","timestamp":1760204003577},"reference-count":14,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,7,20]],"date-time":"2004-07-20T00:00:00Z","timestamp":1090281600000},"content-version":"vor","delay-in-days":49,"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":[[2004,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> Congenital membranous ventricular septal defects (VSD) have been shown to close during postnatal development in rats [Solomon et al., Teratology 55:185\u2013194, 1997]. Although they may differ in size, spontaneous and treatment\u2010related VSD are histologically similar; however, the postnatal fate of treatment\u2010induced VSD is not known. The objective of this study was to determine if treatment\u2010induced VSD persist throughout postnatal development. <jats:bold>METHODS:<\/jats:bold> Groups of 40 female rats were given oral doses of trimethadione (TMD) at 400\u2009mg\/kg\/day (200 b.i.d.) or 600\u2009mg\/kg\/day (300 b.i.d.) on Gestation Days (GD) 9 and 10. Twenty dams in each group were designated for Cesarean section and 20 were allowed to deliver and rear their offspring to Postnatal Day (PND) 21. The integrity of the ventricular septum was evaluated in fetuses (GD 21) and pups (PND 21). <jats:bold>RESULTS:<\/jats:bold> The incidence of membranous VSD was 0.6, 7.6, and 49.8% per litter in the Control, 400, and 600\u2009mg\/kg groups, respectively, on GD 21. Both the incidence and severity of VSD increased with dose. The VSD at 400\u2009mg\/kg were small in size and initially detected by the presence of blood flowing through the defect from the closed right ventricle. In the 600\u2009mg\/kg dose group, the VSD, although still membranous, were larger and more readily detected without the need to examine the blood flow. At 600\u2009mg\/kg, not only were the VSD larger than those in the Control or the 400\u2009mg\/kg group, 10.1% per litter of the affected fetuses had other vessel anomalies associated with the VSD, which were incompatible with pup survival. On PND 21, VSD was noted in 0.3, 0, and 6.4% per litter evaluated in the Control, 400, and 600\u2009mg\/kg groups, respectively. This demonstrates that the small, isolated treatment\u2010related VSD can resolve postnatally; however, the closure of the larger or more severe VSD may be prolonged or may not occur at all. Although TMD exposure reduced group mean fetal weights at both dose levels, there was no difference between the mean weight of fetuses with VSD and those fetuses without VSD in the same group. <jats:bold>CONCLUSION:<\/jats:bold> Treatment\u2010induced VSD close postnatally, and appears to be a delay in cardiac development not associated with fetal weight. The timing of closure and survivability during closure is dependent on the severity of the VSD. Further characterization of the two sizes of VSD may provide diagnostic clarity; however, the current data support the smaller VSD as a variation with no significant impact on viability and growth, and the more severe VSD to be a malformation. <jats:italic>Birth Defects Res B<\/jats:italic> 71:185\u2013190, 2004. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrb.20011","type":"journal-article","created":{"date-parts":[[2004,7,20]],"date-time":"2004-07-20T15:09:22Z","timestamp":1090336162000},"page":"185-190","source":"Crossref","is-referenced-by-count":23,"title":["Postnatal closure of membranous ventricular septal defects in Sprague\u2010Dawley rat pups after maternal exposure with trimethadione"],"prefix":"10.1002","volume":"71","author":[{"given":"Tammye L.","family":"Fleeman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregg D.","family":"Cappon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark E.","family":"Hurtt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,7,20]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-135-9-200111060-00011"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.10067"},{"key":"e_1_2_5_4_1","first-page":"111","volume-title":"Handbook of developmental toxicology","author":"DeSesso JM","year":"1997"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1047951100007174"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01886-7"},{"key":"e_1_2_5_7_1","volume-title":"Human embryology and teratology","author":"O'Rahilly R","year":"2001"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-0705.2000.00202.x"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(95)00358-4"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/fn.81.1.F61"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199703)55:3<185::AID-TERA3>3.0.CO;2-1"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/tcm.1770040203"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1047951100012968"},{"key":"e_1_2_5_14_1","first-page":"453","volume-title":"Developmental cardiology: morphogenesis and function","author":"Veuthey S","year":"1990"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199704)55:4<249::AID-TERA5>3.0.CO;2-W"}],"container-title":["Birth Defects Research Part B: Developmental and Reproductive Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdrb.20011","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdrb.20011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T16:00:21Z","timestamp":1700236821000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdrb.20011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,6]]},"references-count":14,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2004,6]]}},"alternative-id":["10.1002\/bdrb.20011"],"URL":"https:\/\/doi.org\/10.1002\/bdrb.20011","archive":["Portico"],"relation":{},"ISSN":["1542-9733","1542-9741"],"issn-type":[{"value":"1542-9733","type":"print"},{"value":"1542-9741","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,6]]}}}