Exploratory Trial of Choline Supplementation for Fetal Alcohol Syndrome

补充胆碱治疗胎儿酒精综合症的探索性试验

• 批准号: 8418722
• 负责人: SANDRA W. JACOBSON
• 金额: $ 15.86万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-05 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8418722
• 关键词: Adherence; Adult; Adverse effects; Affect; Air; Alcohol abuse; Alcohol dependence; Alcohol-Related Disorders; Alcoholic beverage heavy drinker; Alcohols; Animal Model; Animals; Area; Auditory; Behavioral; Biological Assay; Biological Markers; Birth; Blinking; Body Weight; Brain; Brain Stem; Child; Choline; Cognitive; Cognitive deficits; Color; Communities; Conditioned Stimulus; Data; Development; Diet; Dietary History; Dietary Supplementation; Dietary intake; Disease; Double-Blind Method; Dysmorphology; Female of child bearing age; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal Alcohol Syndrome; Fetal Growth; Fetal alcohol effects; Folate; Genetic Polymorphism; Growth; Heavy Drinking; High Prevalence; Hour; Hyperactive behavior; Impairment; Incidence; Infant; Intake; Intervention; Learning; Mediating; Mothers; National Institute on Alcohol Abuse and Alcoholism; Neurocognitive; Neurocognitive Deficit; Nutrient; Nutritional; Outcome Study; Pattern; Placebo Control; Placebos; Plasma; Population; Postpartum Period; Pregnancy; Pregnancy Trimesters; Pregnant Women; Prenatal care; Prevalence; Prevention; Protocols documentation; Public Health; Randomized; Randomized Clinical Trials; Rattus; Recruitment Activity; Research; Research Priority; Risk; Sampling; Severities; South Africa; Stimulus; Supplementation; Treatment Efficacy; Woman; alcohol consumption during pregnancy; alcohol exposure; base; cognitive function; cohort; conditioning; design; fetal; interest; meetings; neural circuit; neurobehavioral; pregnant; prenatal; prenatal intervention; prevent; psychosocial; tool; way finding

DESCRIPTION (provided by applicant): Descriptive studies have documented poor fetal growth, dysmorphology, and a range of neurobehavioral deficits in infants and children with fetal alcohol spectrum disorder (FASD). Although the adverse effects associated with fetal alcohol exposure are well-known and numerous psychosocial interventions have been attempted, many women continue to drink heavily during pregnancy. Because psychosocial interventions are frequently ineffective, NIAAA has highlighted "the potential of maternal dietary supplementation with choline, folate, and other nutrients to interact with alcohol to reduce the risk of FASD" as a priority research area. This proposal is designed to gather feasibility, adherence, and preliminary data on a promising pharmacological intervention that could prevent or mitigate the severity of fetal alcohol-related impairment. Since 1998, we have conducted research on children born to mothers recruited during pregnancy in the Cape Coloured (mixed ancestry) community in Cape Town, South Africa, where there is an unusually high incidence of alcohol abuse and dependence in women of child-bearing age, very heavy alcohol consumption during pregnancy, and one of the highest rates of fetal alcohol syndrome (FAS) in the world. We have identified a strikingly consistent effect of prenatal alcohol exposure on eyeblink conditioning (EBC), a Pavlovian paradigm that involves contingent temporal pairing of a conditioned stimulus (a tone) with an unconditioned stimulus (an air puff). Not a single child with full FAS met criterin for conditioning, compared with 75% of non-exposed controls. Two-thirds of the other heavily exposed children also failed to meet criterion for conditioning. Because infants reach the same terminal levels of conditioning as adults, EBC can provide an early indicator of alcohol-related impairment and an important tool for evaluating the efficacy of a prenatal intervention. Animal studies have shown that choline supplementation during the equivalent of the 3rd trimester of pregnancy can protect against or mitigate some of the damage incurred by fetal alcohol exposure on EBC and cognitive function. We propose to conduct a randomized, double-blind exploratory trial to examine the feasibility of implementing a choline supplementation intervention in pregnancy, assess acceptability and adherence to the intervention protocol by heavy drinkers, obtain data on plasma choline levels in supplemented mothers and placebo controls and on the prevalence of polymorphisms that substantially alter endogenous choline synthesis in this population, and collect preliminary data regarding the efficacy of the intervention in mitigating fetal alcohol effects on infant EBC and other alcohol- related cognitive deficits. Sixty heavy drinking pregnant women from the Cape Coloured community who initiate prenatal care at or before 20 weeks gestation will receive either choline supplementation (n = 30) or placebo (n = 30) twice daily until delivery. Maternal and infant nutritional intake will be evaluated by dietary history and biological assay. Infants will be assessed for birth size, growth, and EBC and neurocognitive function at 6.5 months postpartum.

描述（由申请人提供）：描述性研究已经记录了患有胎儿酒精谱系障碍（FASD）的婴儿和儿童的胎儿生长不良、畸形和一系列神经行为缺陷。虽然胎儿接触酒精的不良影响是众所周知的，并且已经尝试了许多社会心理干预措施，但许多妇女在怀孕期间继续大量饮酒。由于心理社会干预往往无效，NIAAA强调了“母亲在饮食中补充胆碱、叶酸和其他营养素与酒精相互作用以降低FASD风险的潜力”