Prenatal Alcohol Exposure, Biomarkers and Foetal Alcohol Spectrum Disorders

Foetal Alcohol Spectrum Disorders (FASD) is the term used to describe neurobehavioural disorders associated with prenatal alcohol exposure ranging from the most severe foetal alcohol syndrome (FAS) with facial dysmorphology, through partial foetal alcohol syndrome (pFAS) to alcohol-related birth defects (ARBD). Many of the cognitive impairments associated with FASD are similar to those seen in Attention Deficit Hyperactivity Disorder (ADHD), Autistic Spectrum Disorders and other such conditions. There are considerable problems in diagnosing FASD and evidence of more than minimal exposure to ethanol during pregnancy is an important criterion. Information on the mother’s alcohol consumption during pregnancy may not be available, or may be inaccurate. Furthermore, approximately half of children affected by FASD may not exhibit signs of CNS dysfunction until they are preschool or school-age when the child and the mother may have become separated.
Early accurate differential diagnosis would enable the most effective treatments to be used. Ideally biomarkers would be identified which would enable confirmation of prenatal alcohol exposure. The use of meconium as an accessible foetal source of fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG) and ethyl sulfate (EtS) is frequently considered, but this is only applicable for the first few days of the neonate’s life. The use of neonatal blood phosphatidylethanol (PEth) has also been discussed, but again the longevity of this biomarker is short. More recently results from animal studies of neonatal plasma microRNA biomarkers and changes to histone modifications have provided new opportunities, and DNA methylation has been suggested as a potential biomarker. Our own work suggests that prenatal alcohol exposure may induce long-lived changes in brain derived neurotrophic factor (BDNF) and brain aminopeptidase activity which may be reflected in changes in plasma or urine.
In the light of the evidence that many foetuses are exposed to alcohol but do not exhibit any degree of FASD, this review will assess the evidence of reliability of emerging enduring markers of prenatal alcohol exposure and explore whether they correlate only with prenatal alcohol exposure or also with FASD.