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

项目摘要 许多合并症已被确定为儿童和青少年中相对常见， 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、异常饮食行为、改变的生长模式以及抑郁和焦虑共病。在 此外，新出现的数据表明，几种发育起源的成人疾病，如糖尿病， 动脉粥样硬化、心血管和自身免疫性疾病的发病率过高，且发病年龄较早 有FASD的成年人。当务之急是更好地了解这些疾病的患病率和共同发生 在PAE儿童和青少年的生命过程中尽早，理想情况下在亚临床阶段， 以有临床意义的方式进行干预。在现有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，我们的目标是填补知识的这一关键空白， 两种方式。首先，我们将比较亚临床和临床体征/症状的患病率和特征 目前和发展中的代谢和其他慢性疾病和促成因素，180 年龄匹配的PAE儿童/青少年与120例无/极轻微PAE的儿童/青少年。这包括 比较发病前或共病高血压、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，身体 活动，饮食摄入，不良的童年经历，睡眠障碍，焦虑和 萧条其次，我们将比较一组结构或功能的实验测量结果， 可以帮助阐明300人的同一队列中PAE相关合并症在整个生命周期中的机制 儿童和青少年。实验测量包括毛细血管微血管，端粒长度， miRNA的表达模式。可操作的发现将在个人层面转化为临床 为参与者和护理人员提供指导。此外，根据《公约》的主要目标之一， CIFASD 5，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 治疗、改善或预防研究中发现的临床前或临床状况的进展 评价。我们还将与CIFASD联盟的其他研究人员合作， 解决联盟在改善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.