Whole Body Effects of PAE Across the Life Span: Early Markers of & Clinical Interventions for Children and Adolescents in Ukraine

项目摘要 许多合并症在儿童和青少年中被确定为相对常见的 产前酒精暴露(PAE)或胎儿酒精谱系障碍(FASD)，包括睡眠障碍， 高血压，不正常的饮食行为，改变的生长模式，以及共病的抑郁和焦虑。在……里面 此外，新出现的数据表明，几种发育性成人疾病，如糖尿病， 动脉粥样硬化、心血管疾病和自身免疫性疾病的比例过高，且发病年龄较早。 在患有FASD的成年人中。必须更好地了解这些疾病的患病率和共生性。 尽可能早地在患有PAE的儿童和青少年的生命过程中，最好是在亚临床阶段 以临床上有意义的方式进行干预。建立在现有的胎儿酒精问题合作倡议的基础上 频谱障碍(CIFASD)在乌克兰的纵向队列研究，我们的目标是填补这一关键的知识空白 两种方式。首先，我们将比较亚临床和临床体征/症状的发生率和特征 当前和发展中的代谢性疾病和其他慢性疾病及其致病因素 患有PAE的儿童/青少年与120名没有/最低PAE的儿童/青少年年龄匹配。这包括 比较病前或合并高血压、高脂血症、血糖受损的患病率 耐受性/胰岛素抵抗和心血管疾病，并比较生长参数、体格 活动，饮食摄入量，不良童年经历，睡眠障碍，焦虑和 抑郁症。第二，我们将比较一组结构或功能的实验测量结果 有助于阐明同一组300人中PAE相关合并症的发病机制 儿童和青少年。实验测量包括毛细血管微血管、端粒长度和 MiRNA的表达模式。可操作的发现将在个人层面转化为临床 为参与者和照顾者提供指导。此外，为了与以下目标之一保持一致 CIFASD5，这项研究的结果将直接告知未来儿童和青少年的干预目标，以帮助 补救、改善或防止研究中确定的临床前或临床状况的进展 评估。我们还将与CIFASD联盟中的其他调查人员合作，以互动 解决联合会在改进FASD诊断和治疗方面的总体目标。

Project Summary Numerous comorbidities have been identified as relatively common among children and adolescents with prenatal alcohol exposure (PAE) or fetal alcohol spectrum disorders (FASDs) including sleep disturbances, hypertension, abnormal eating behaviors, altered growth patterns, and comorbid depression and anxiety. In addition, emerging data suggest that several adult diseases of developmental origin, such as diabetes, atherosclerosis, cardiovascular and autoimmune disorders are over-represented and have earlier age at onset in adults with FASDs. It is imperative to better understand the prevalence and co-occurrence of these disorders as early as possible in the life course of children and adolescents with PAE, ideally at the sub-clinical stage, in order to intervene in clinically meaningful ways. Building on the existing Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) longitudinal cohort study in Ukraine, we aim to fill this critical gap in knowledge in two ways. First, we will compare the prevalence and characteristics of subclinical and clinical signs/symptoms of current and developing metabolic and other chronic diseases and contributing factors in 180 children/adolescents with PAE age-matched to 120 children/adolescents with no/minimal PAE. This includes comparing prevalence of premorbid or comorbid hypertension, hyperlipidemia, impaired glucose tolerance/insulin resistance, and cardiovascular disease and also comparing growth parameters, physical activity, dietary intake, adverse childhood experiences, sleep disturbances, and measures of anxiety and depression. Second, we will compare findings on a panel of experimental measures of structure or function that can help illuminate mechanisms of PAE-related comorbidities across the lifespan in the same cohort of 300 children and adolescents. Experimental measures include capillary microvasculature, telomere length, and patterns of miRNA expression. Findings that are actionable will translate on the individual level to clinical guidance provided to the participant and caregiver. Furthermore, in keeping with one of the primary goals of CIFASD5, findings of this study will directly inform future intervention targets in children and adolescents to help remediate, ameliorate or prevent progression of pre-clinical or clinical conditions identified in the study evaluations. We will also work collaboratively with other investigators in the CIFASD Consortium to interactively address the overall goals of the Consortium in improving diagnosis and treatment of FASD.