Postnatal Choline Supplementation in Children with Prenatal Alcohol Exposure

目前，有关对胎儿酒精谱系障碍(FASD)患者进行干预的文献非常多 有限，只发表了两项随机对照试验，但有很有希望的新治疗选择 还没有在人类身上应用过。最近的临床前研究戏剧性地表明，饮食 在啮齿动物出生前甚至出生后补充胆碱，直到第21-30天(相当于 人类童年)，减轻与产前酒精暴露相关的记忆和行为缺陷 (Thomas等人，2007年；Thomas等人，2000年)。我们提出了一个为期两年的项目，以评估可行性和 出生前酒精暴露的幼儿产后补充胆碱的耐受性观察 通过一项为期三年的双盲、安慰剂对照的先导研究，检验补充胆碱的疗效 改善这些儿童的认知和行为功能。在R21可行性阶段，20 年龄在12个月到54个月之间的儿童将随机服用9个月的胆碱 补充剂或安慰剂。6个月和9个月的随访将包括父母评级 行为、认知测量，包括早期学习的马伦量表和引出模仿(EI) 海马区范例和电生理测量，包括髓鞘形成相关的VEP测量 处理速度。根据在R21阶段收集的数据，将修改研究设计并 在R33阶段更大规模地实施。在R33阶段，40名儿童将被随机分配到 胆碱补充剂或安慰剂。后续措施将根据情况相同或略有修改 R21研究。研究结果将被用于设计一项更大规模的临床试验，以测试 出生前酒精暴露的幼儿产后补充胆碱。考虑到潜在的 对海马体发育、髓鞘形成和大脑发育的其他基本方面的影响 治疗可能对许多其他神经发育障碍具有重要的适用性。

At present, the literature on interventions for individuals with Fetal Alcohol Spectrum Disorders (FASD) is very limited, with only two published randomized controlled trials, yet there are promising new treatment options that have not been applied in humans. Recent pre-clinical studies have dramatically demonstrated that dietary choline supplementation pre-natally and even post-natally, as late as days 21-30 in the rodent (equivalent to human childhood), attenuates the memory and behavioral deficits associated with prenatal alcohol exposure (Thomas et al., 2007; Thomas et al., 2000). We propose a two-year project to evaluate the feasibility and tolerability of post-natal choline supplementation in young children with pre-natal alcohol exposure followed by a three-year double-blind, placebo-controlled pilot study examining the efficacy of choline supplementation in improving the cognitive and behavioral functioning of these children. In the R21 feasibility phase, 20 children between the ages of 12 months and 54 months will be randomized to nine months of choline supplementation or placebo. Follow-up visits at 6 months and 9 months will include parent ratings of behavior, cognitive measures including the Mullen Scales of Early Learning and an elicited imitation (EI) hippocampal paradigm, and electrophysiological measures including a VEP measure of myelination-associated processing speed. Based on data collected in the R21 phase, the study design will be modified and implemented on a larger scale in the R33 phase. During the R33 phase, 40 children will be randomized to choline supplementation or placebo. Follow-up measures will be the same or slightly modified based on the R21 study. Results of the studies will be used to design a larger, full-scale clinical trial to test the efficacy of post-natal choline supplementation in young children with pre-natal alcohol exposure. Given the potential effects on hippocampal development, myelination, and other basic aspects of brain development, this treatment may have significant applicability to a host of other neurodevelopmental disorders.