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.

Project Narrative A better understanding of the prevalence and co-occurrence of relatively common comorbidities among children and adolescents with prenatal alcohol exposure (PAE) is essential in order to intervene in clinically meaningful ways. These complex comorbid conditions are often the most challenging, disruptive, and costly health issues that families with a child affected by alcohol must cope. This study will document the prevalence and co- occurrence of early-stage indicators of possible or probable future chronic disease in children/adolescents with PAE.