Iridic and retinal coloboma associated with prenatal methimazole exposure.
American Journal of Medical Genetics Part A (Impact Factor: 2.3). 01/2006; 139A(2):156-8. DOI:10.1002/ajmg.a.30917
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ABSTRACT: Gastroschisis is a major malformation which requires immediate surgical care to return the exposed viscera to the abdominal cavity, parenteral nutrition until bowel motility permits oral feedings, and evaluation for coexisting malformations. Almost all cases are diagnosed prenatally using midtrimester ultrasound and maternal serum alphafetoprotein measurement. This allows most infants to be delivered in a tertiary care facility where the best mode of delivery and neonatal management can be determined. About 10% of infants with gastroschisis will have other malformations. Half of these are considered related to the gastroschisis (intestinal atresia or stenosis, malrotation, cryptorchidism, amyoplasia, urinary tract obstruction). Other associated malformations occur which are not recognized to be secondary to the gastroschisis. Prominent among these are cardiac and limb defects. Fetal and neonatal mortality are increased, but neither appear related to lethal malformations. © 2008 Wiley-Liss, Inc.American Journal of Medical Genetics Part C Seminars in Medical Genetics 08/2008; 148C(3):219 - 230. · 4.44 Impact Factor
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ABSTRACT: Hyperthyroidism during pregnancy is treated with the antithyroid drugs (ATD) propylthiouracil (PTU) and methimazole (MMI). PTU currently is recommended as the drug of choice during early pregnancy. Yet, despite widespread ATD use in pregnancy, formal studies of ATD teratogenic effects have not been performed. We examined the teratogenic effects of PTU and MMI during embryogenesis in mice. To span different periods of embryogenesis, dams were treated with compounds or vehicle daily from embryonic day (E) 7.5 to 9.5 or from E3.5 to E7.5. Embryos were examined for gross malformations at E10.5 or E18.5 followed by histological and micro-CT analysis. Influences of PTU on gene expression levels were examined by RNA microarray analysis. When dams were treated from E7.5 to E9.5 with PTU, neural tube and cardiac abnormalities were observed at E10.5. Cranial neural tube defects were significantly more common among the PTU-exposed embryos than those exposed to MMI or vehicle. Blood in the pericardial sac, which is a feature indicative of abnormal cardiac function and/or abnormal vasculature, was observed more frequently in PTU-treated than MMI-treated or vehicle-treated embryos. Following PTU treatment, a total of 134 differentially expressed genes were identified. Disrupted genetic pathways were those associated with cytoskeleton remodeling and keratin filaments. At E 18.5, no gross malformations were evident in either ATD group, but the number of viable PTU embryos per dam at E18.5 was significantly lower from those at E10.5, indicating loss of malformed embryos. These data show that PTU exposure during embryogenesis is associated with delayed neural tube closure and cardiac abnormalities. In contrast, we did not observe structural or cardiac defects associated with MMI exposure except at the higher dose. We find that PTU exposure during embryogenesis is associated with fetal loss. These observations suggest that PTU has teratogenic potential.PLoS ONE 01/2012; 7(4):e35213. · 3.73 Impact Factor
- Canadian Journal of Ophthalmology 10/2011; 46(5):446-7. · 1.15 Impact Factor
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