ISOTRETINOIN TERATOGENICITY: OUTCOME AT AGE 10

异维A酸致畸性：10 岁时的结果

• 批准号: 2403279
• 负责人: JANE ADAMS
• 金额: $ 16.19万
• 依托单位: UNIVERSITY OF MASSACHUSETTS BOSTON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2403279
• 关键词: 13 cis retinoate; academic achievement; child (0-11); child behavior disorders; child mental disorders; congenital disorders; congenital nervous system disorder; congenital skeletal disorder; developmental neurobiology; embryo /fetus drug adverse effect; gestational age; human data; human pregnant subject; human subject; intelligence; longitudinal human study; middle childhood (6-11); neuropsychological tests; postnatal growth disorder; socioeconomics; teratogens

Isotretinoin, a potent human teratogen, has been available by prescription since 1982 for the treatment of severe cystic acne and related skin conditions. We have bee following a sample of 47 children who were identified prospectively during the first 60 days of gestation, as part of a larger study on pregnancy and outcome following embryonic exposure (Lammer et al 1985). Of these pregnancies, 17% ended in spontaneous abortion and a 23% risk for malformation was documented for fetuses that reached 20 weeks gestation (Lammer et al, 1987). The pattern of malformations includes central nervous system, craniofacial, thymic, and cardiac structures. The liveborn infants and controls from this original study are now being examined at the age of 5 years. At a current sample size of 44 cases and 40 controls, 43% of the exposed children have been found to be functioning in the subnormal range of general intelligence. This includes children with and without major malformations. A pattern of deficits in executive and spatial processing is suggested. The long-range consequences of these functional deficits at 5 years of age is specifically unknown, but may be expected to include characteristics such as attentional difficulties, math, and handwriting disorders. The purpose of this grant is to evaluate the developmental characteristics of this sample of embryonically exposed children at the age of 10 years using tests which will examine a range of physical and cognitive abilities as well as elaborate and extend our understanding of the specific functional deficits of these children. In addition, we also wish to examine the teratogenic outcome of additional children exposed during fetal development. This work will allow us to better understand relationships between structural and functional teratogenesis, and between stage at exposure, disruptions in brain development, and corresponding physical and mental development. Studies of Isotretinoin exposed children who have received both prenatal and postnatal medical care, and have been identified prospectively during gestation provide a unique opportunity to address these important issues in teratology in a reasonably unconfounded human sample.

异维诺因是一种有效的人畸胎毒药，可通过 自1982年以来的处方治疗严重的囊性痤疮和 相关的皮肤状况。 我们有47个孩子的样本后有蜜蜂 在妊娠的头60天中被前瞻性地识别 作为胚胎后妊娠和结果的更大研究的一部分 暴露（Lammer等，1985）。 在这些怀孕中，有17％的人结束了 记录了自发流产和23％的畸形风险 妊娠20周的胎儿（Lammer等，1987）。 这 畸形模式包括中枢神经系统，颅面， 胸腺和心脏结构。 活出生的婴儿和控制 这项原始研究现在正在5岁时进行检查。 在 当前样本量为44例和40个对照，43％的暴露 已经发现儿童在下正常范围内起作用 通用情报。 这包括有和没有专业的孩子 畸形。 执行和空间处理中缺陷的模式 建议。 这些功能缺陷的远程后果 在5岁的5岁时未知，但可能会包括 注意力困难，数学和笔迹等特征 疾病。 这笔赠款的目的是评估发展 该样本的胚胎暴露儿童的特征 使用测试的10岁年龄，该测试将检查一系列身体和 认知能力以及阐述并扩展我们对 这些孩子的特定功能缺陷。 此外，我们也 希望检查其他儿童暴露的致病结果 在胎儿发育期间。 这项工作将使我们能够更好地理解 结构和功能性致膜发生之间的关系以及 在暴露阶段之间，大脑发育中的破坏和 相应的身心发展。 异维诺因的研究 接受产前和产后医学的暴露儿童 护理，并在妊娠期间被前瞻性地确定 独特的机会来解决某人在畸胎学中的这些重要问题 相当不满意的人类样本。