FETAL ALCOHOL SYNDROME: DOSE-RESPONSE

胎儿酒精综合症：剂量反应

• 批准号: 3109023
• 负责人: STERLING K CLARREN
• 金额: $ 9.67万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-29 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3109023
• 关键词: alcoholic beverage consumption; animal birth weight; animal developmental psychology; blood chemistry; chronic brain damage; circadian rhythms; cognition disorders; congenital brain disorder; congenital ear disorder; congenital neuromuscular disorder; congenital oral /facial /cranial defect; congenital skeletal disorder; congenital vision disorder; dosage; electron microscopy; fetal alcohol syndrome; histopathology; infant animal; mother /embryo /fetus nutrition; neurochemistry; neuropsychological tests; neuropsychology; neurotoxins; neurotransmitter metabolism; nutrition related tag; postnatal growth disorder; prenatal growth disorder; sex development disorder; teratogens

At present, there are few data applicable to humans on the risks of intermittent alcohol use (binge drinking) in pregnancy. Such information is urgently needed by medical professionals counseling pregnant women, but for both ethical and practical reasons cannot be obtained from human studies. An alternate primate model is necessary. A recent pilot project demonstrating a binge model for fetal alcohol syndrome in the pigtailed macaque (Macaca nemestrina) found severe teratogenic effects in the animal exposed to 4.1 g/kg of ethanol once per week from mid-first trimester to term. Moderate effects were found in one of two animals exposed to 2.5 g/kg of ethanol over the same gestational period. In this study 39 additional females and their resultant infants will be evaluated. When added to the pilot project infants, there will be 6 groups of 7 animals each exposed to 0, 0.3, 0.6, 1.2, 2.5, or 4.1 g/kg of ethanol once/week throughout gestation. The mothers will be given the ethanol by gavage weekly from the first week after conception to term. Maternal weight gain, dietary intake and general health will be closely monitored. Serum ethanol degradation curves will be obtained after each dosage and after parturition. The infants will be observed for 6 months. Physical examinations for major and minor malformations at birth and at 6 months will be recorded. Roentgenograms and photographs will be obtained. A standardized battery of developmental and psychological tests will be applied. A complete autopsy at 6 months with extensive neuroanatomic and neurochemical studies will be done. The study will provide much needed information on variation in ethanol metabolism throughout pregnancy and when non-pregnant as well as on the dose-response curve for each physical, behavioral and neuroanatomic-neurochemical characteristic of the infant that is affected by periodic exposure to alcohol during gestation.

目前，几乎没有适用于人类的风险数据， 怀孕期间间歇性饮酒（暴饮）。 此类信息 孕妇咨询的医疗专业人员迫切需要， 由于伦理和实际的原因，不能从人类身上获得 问题研究 另一种灵长类动物模型是必要的。 最近的一个试点项目 展示了猪尾巴胎儿酒精综合征的狂欢模型， 猕猴（Macaca nemestrina）在动物中发现了严重的致畸作用 从妊娠中期至妊娠中期，每周一次暴露于4.1 g/kg乙醇 term. 在暴露于2.5 μ g/kg的2只动物中， g/kg乙醇。 在这项研究中，39 将评价额外的雌性和它们产生的婴儿。 当 加上试点项目的婴儿，将有6组7只动物 每只动物每周一次暴露于0、0.3、0.6、1.2、2.5或4.1 g/kg乙醇 整个妊娠期。 母亲们将被灌胃乙醇 从受孕后的第一周到足月，每周一次。 母体体重增加， 并会密切监察食物摄取量及一般健康情况。 血清乙醇 将在每次给药后和给药后获得降解曲线。 分娩 婴儿将被观察6个月。 物理 出生时和6个月时的主要和次要畸形检查 将被记录。 将获得X线片和照片。 一 一系列标准化的发展和心理测试将被 应用。 6个月时进行全面尸检， 将进行神经化学研究。 这项研究将提供急需的 关于整个妊娠期乙醇代谢变化的信息， 当未怀孕时以及在每次体检的剂量反应曲线上， 婴儿的行为和神经解剖-神经化学特征 怀孕期间定期接触酒精会影响胎儿的发育