Adverse Health Outcomes in Offspring Associated With Fetal Alcohol Exposure: A Systematic Review of Clinical and Preclinical Studies With a Focus on Metabolic and Body Composition Outcomes

Abstract

Prenatal alcohol exposure (PAE) results in well-characterized neurological, behavioral, and cognitive deficits in offspring. However, the effects on other health outcomes have not been comprehensively described. We used a systematic review methodology to survey published clinical and preclinical studies investigating a broad range of health outcomes in offspring with PAE. This study specifically reports on outcomes related to metabolism and body composition. The literature was systematically searched across 4 electronic databases (PubMed, CINAHL, Embase, and Web of Science), resulting in 3,230 articles following duplicate removal. Titles and abstracts were reviewed against specific inclusion/exclusion criteria, with 242 articles meeting the criteria for full-text assessment of eligibility. Articles with ineligible study type were removed (127) and articles added from reference lists (15) and an updated search closer to submission (9) for a total of 139 studies. Although 5 health domains were identified, here we focus on metabolism and body composition. Details of alcohol exposure, offspring demographics, and sample sizes were tabulated and quality of reporting assessed. Findings were summarized for body composition (percentage fat mass), physiological and molecular outcomes related to glucose metabolism, and outcomes related to lipid metabolism. There were 32 included studies (2 case-control, 1 prospective longitudinal cohort, and 29 preclinical). Studies had a range of alcohol exposures, both dosage and timing, although all clinical studies had heavy PAE and/or evidence of fetal alcohol syndrome in offspring. The preclinical studies provided evidence of glucose intolerance and/or insulin resistance; dyslipidemia and/or hypercholesterolemia; and increased adiposity in offspring with PAE. Due to the paucity of clinical studies, we recommend further studies be conducted to obtain a complete assessment of long-term metabolic health outcomes in children and adults with PAE, particularly in those diagnosed with fetal alcohol spectrum disorder.

Keywords: FASD; Fetal Alcohol Exposure; Glucose Tolerance; Insulin Sensitivity; Metabolic Syndrome.