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.

Prevalence and factors associated with alcohol consumption during pregnancy

“…Ethanol may also inhibit the transport of cofactors critical for fetal growth and development, such as biotin and vitamin B6. 2 The risk of infant births with low birth weight (<2500g for the term newborn) or small for gestational age increases linearly in mothers who consume a daily dose of alcohol (about 10g absolute alcohol) or more. 24 A survey of 1,964 pregnant women in a public maternity hospital in the city of São Paulo found that the higher the alcohol consumption, the lower the weight, the head circumference and the length of newborns.…”

“…Other supplements, such as folic acid, Lglutamine, boric acid and choline also appear to minimize the harmful effects of alcohol on embryofetal development and may play a therapeutic role in the future. 2 Since there is no safe amount of alcohol intake during pregnancy and any amount can affect embryofetal development, 2,11 we recommend that the material published by the Ministry of Health to inform both health professionals and the general public points out the importance of abstaining from alcohol consumption throughout pregnancy explicitly, not only in the first trimester. Promoting advertising campaigns on the subject can also be an additional measure of health education.…”

“…1,2 It causes hemodynamic changes in pregnant women who compromise placental blood flow and circulates freely through all the body's fluid compartments, including vasculature, interstitial and intracellular fluids. 3 Thus, the alcohol concentration is the same in a pregnant woman as in the conceptus, causing the amniotic fluid to remain impregnated with unmodified alcohol (ethanol) and acetaldehyde.…”

“…Alcohol acts in different ways, depending on the type of brain cell and embryofetal development stage, which can lead to structural and functional changes: cell death, impaired new cell formation, changes in cell migration, production of neurotransmitters and synapse formation. 2,5 In 1973, a specific phenotype was identified and defined in children born to female alcoholics, called "fetal alcohol syndrome" (FAS). This is an irreversible condition characterized by typical craniofacial anomalies, intra and extrauterine growth restriction, central nervous system dysfunction (including neurological abnormalities, behavioral changes, neuropsychomotor developmental delay and intellectual disability) and various associated malformations, mainly cardiac, ocular, kidney and spinal.…”

FASD: folic acid and formic acid — an unholy alliance in the alcohol abusing mother

“…To our knowledge there is no published literature linking folic acid deficiency and formic acid to FASD, although numerous studies suggest alcohol-mediated oxidative stress as the possible mechanism (Dreosti 1993;Brocardo et al 2011;Muralidharan et al 2015;Gupta et al 2016;Sarmah et al 2016;Sogut et al 2017). Thus, treatment using nutrients that have antioxidant properties, such as folic acid, appear promising.…”