title: An Update on Fetal Alcohol Syndrome-Pathogenesis, Risks, and Treatment.
abstract: Alcohol is a well-established teratogen that can cause variable physical and behavioral effects on the fetus. The most severe condition in this spectrum of diseases is known as fetal alcohol syndrome (FAS). The differences in maternal and fetal enzymes, in terms of abundance and efficiency, in addition to reduced elimination, allow for alcohol to have a prolonged effect on the fetus. This can act as a teratogen through numerous methods including reactive oxygen species (generated as by products of CYP2E1), decreased endogenous antioxidant levels, mitochondrial damage, lipid peroxidation, disrupted neuronal cell-cell adhesion, placental vasoconstriction, and inhibition of cofactors required for fetal growth and development. More recently, alcohol has also been shown to have epigenetic effects. Increased fetal exposure to alcohol and sustained alcohol intake during any trimester of pregnancy is associated with an increased risk of FAS. Other risk factors include genetic influences, maternal characteristics, for example, lower socioeconomic statuses and smoking, and paternal chronic alcohol use. The treatment options for FAS have recently started to be explored although none are currently approved clinically. These include prenatal antioxidant administration food supplements, folic acid, choline, neuroactive peptides, and neurotrophic growth factors. Tackling the wider impacts of FAS, such as comorbidities, and the family system have been shown to improve the quality of life of FAS patients. This review aimed to focus on the pathogenesis, especially mechanisms of alcohol teratogenicity, and risks of developing FAS. Recent developments in potential management strategies, including prenatal interventions, are discussed.
authors.affiliation: School of Medicine, Imperial College London, London, UK.
authors.forename: Keshav K
authors.initials: KK
authors.lastname: Gupta
authors.affiliation: School of Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Gupta
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Shirasaka
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects* / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology* / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011788:Quality of Life; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000431:Ethanol
keywords: Alcohol; Fetal Alcohol Syndrome; Prenatal Treatment; Teratogenicity