FETAL ALCOHOL SYNDROME

The life effect of Fetal Alcohol Syndrome

The life effect of Fetal Alcohol Syndrome

Introduction

Fetal alcohol syndrome (FAS) is characterized by cardiac defects, fetal growth restriction, neurodevelopmental delays, and craniofacial malformations. In a recent epidemiologic study, periconceptional alcohol use was associated with cardiac birth defects, specifically conotruncal (outflow) defects and transposition of the great arteries. The FAS-related outflow tract congenital birth defects are similar to those that we reported in Avian's models that were exposed acutely to the therapeutic drug lithium or to an elevated dose of the metabolic intermediary homocysteine. We demonstrated that a single exposure to lithium or to homocysteine during gastrulation of vertebrate development induced cardiac valve defects by modulating canonical Wnt/ß-catenin signaling. We provided evidence that folic acid (folate) alone or in combination with myoinositol can rescue the adverse effects on cardiac development that are induced by lithium, homocysteine, and Wnt3A. It had been reported that ethanol suppresses Wnt/ß-catenin signaling in bone marrow stromal cells, which provides further credence to the possibility of alcohol interacting with the canonical Wnt pathway during cardiogenesis. Because of the similarities between cardiac birth defects that are associated with FAS and those induced by lithium, homocysteine, or canonical Wnt exposure, we investigated whether alcohol (ethanol) impacts Wnt/ß-catenin signaling and can be protected by folate (Bailey, 2008).

The mechanism by which alcohol induces congenital defects is not known, nor is it known how early in gestation the damage occurs. The gastrulation stage of gestation is targeted specifically in our studies, because it is an especially vulnerable period in pregnancy during which cardiac, neural crest, and neural cell fates are being specified. The cardiac effects of alcohol exposure during this early period of development have not been defined, specifically in relation to the canonical Wnt pathway, which is an important regulatory pathway in cardiac progenitor cell fate specification. The specification signaling cascade that involves canonical Wnt/ß-catenin is active during gestation when a woman may be unaware she is pregnant. In the human, our targeted experimental window extrapolates to 16-18 days after conception. We also analyzed whether there is a potential for folate or folate/myoinositol to protect the embryo from ethanol's adverse effects on development (Knofler, 2007).

Discussion and Analysis

Fetal alcohol syndrome is one of a group of birth defects commonly grouped together as fetal alcohol spectrum disorders (FASD), also known as fetal alcohol effects. These disorders include a range of effects that can occur or develop in individuals whose biological mother drank alcohol during pregnancy. These effects can include physical, mental, behavioral, and/or learning disabilities, with possible lifelong implications. The umbrella term FASD includes FAS, partial fetal alcohol syndrome (PFAS), alcohol-related birth defects (ARBD), and alcohol-related neurodevelopmental disorder (ARND) (Bailey, 2008).

Alcohol use during pregnancy is the leading known preventable cause of mental retardation and birth defects in the United States. Because alcohol easily passes through the placental barrier and the fetus is less well equipped to physically process and eliminate alcohol than its mother, the fetus tends to receive a higher concentration of alcohol ...