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

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.

Grant Number: 5U01AA014835-22
NIH Institute/Center: NIH
Principal Investigator: CHRISTINA CHAMBERS