Gene-Environment Influences on Fetal Alcohol Syndrome: State of the Science

Gloria Giarratano, PhD, APRN, CNS and Angelique White Williams, DNS, APRN, CNS, CCHC

Abstract

Alcohol ingestion during pregnancy continues to be a major medical, social, and public health problem. This article will review the state of the science and current research concerning the adverse effects of alcohol on fetal and child development. Genetic-based research will be presented as a relatively new area of knowledge that may lend insight into determining how risk of injury and susceptibility to more severe consequences of fetal alcohol syndrome can be influenced by genetic determinants, such as maternal alcohol metabolism. The health care professional’s role in prevention, providing early diagnosis, physical and mental health assessments, and promoting family advocacy will be overviewed.

Keywords: genetics , genetic nursing , Fetal alcohol syndrome

INTRODUCTION

In 2005, the U.S. Surgeon General's Advisory on Alcohol Use in Pregnancy urged women who were pregnant or who may become pregnant to abstain from using all alcohol (1, 2 ). No amount of alcohol is considered safe for consumption during pregnancy. This policy was fougm who have characteristic facial anomalies, growth deficits, and central nervous system problems.

Prenatal alcohol exposure is the most preventable cause of birth defects, developmental disabilities, and mental retardation in the U.S. (3nce of FAS is combined with all other alcohol-related conditions, the overall effects of prenatal alcohol exposure is estimated to affect 10 out of 1000 live births (5).

STATE OF THE SCIENCE

Since the characterization of FAS more than 30 years ago, there has been a plethora of research studies aimed toward increasing our understand e genetic links will be highlighted below. Recent discoveries of the genetic influences on predisposition to FASD, and the severity of complications leading to FAS, will impact how we screen at-risk women and newborns and how we target prevention efforts.

VARIATIONS THAT AFFECT FAS PHENOTYPE: ENVIRONMENT AND GENES

Maternal drinking patterns

FASD and FAS are not genetically inherited conditions. A child must be exposed to prenatal alcohol in order to be affected. However, there are believed to be variations in the susceptibility and severity of the conditions based on environment-gene interactions. The environmental impact of alcohol on the fetus may vary due to the timing and dosage of alcohol; the genetic make-up of the mother who consumes and metabolizes the alcohol; and the fetus, which responds to the toxic effects of alcohol and eventually metabolizes it in later development. Maternal drinking patterns and maternal metabolism are the two most important variables that affect the levels of blood alcohol concentration (BAC) and thus influence the severity of fetal brain injury (17, 18).

Genetic influences on alcohol intake and metabolism

Despite these findings, not all incidences of prenatal exposure to alcohol will result in FAS. The possibility that genetic risk factors play a role in the susceptibility to adverse effects was first considered when animal researchers noted that different strains of mice and chick research models were affected differently by alcohol exposure during gestation. Certain strains consistently experienced mg pattern. While intake is generally considered an environmental issue alone, there is now evidence that genetic variations may affect the amount of alcohol desired and the risk of dependency and addiction (25).

Table 1. Alcohol Dehydrogenase (ALDH) Enzyme Polymorphisms

Polymorphisms for ADH using Human genome Org.nomenclature	Speculated role in alcohol metabolism and risk for Fetal alcohol spectrum disorders
ADH1B*1	Associated with a slower rate of ethanol oxidation as compared with the two alternate alleles (see below). Predominately seen in European and American populations.
ADH1B*2	Associated with an increased rate of ethanol oxidation. Significantly more common in unaffected individuals exposed to prenatal alcohol, suggesting a protective role within either the mother or the fetus against FAS.
ADH1B*3	Associated with an increased rate of ethanol oxidation. More frequently found in African Americans and believed to enable more efficient metabolism of alcohol and thus demonstrates a protective role. Maternal allele indicated protective benefits in alcohol-exposed infants: improved birth weight and length; improved scores on the Bayley Mental Development Index (MDI).