Focus On: Biomarkers of Fetal Alcohol Exposure and Fetal Alcohol Effects
Bakhireva, Ludmila N., Savage, Daniel D., Alcohol Research
One of the ongoing challenges for the accurate diagnosis and treatment of children with fetal alcohol spectrum disorders (FASD) is the difficulty of confirming whether a mother drank during her pregnancy. Commonly used screening questionnaires often are unreliable, and current established biomarkers of alcohol consumption are not sensitive enough for use with many pregnant women. These limitations underscore the critical need to develop novel biomarkers with greater sensitivity for detecting moderate levels of drinking during pregnancy for longer periods of time after the last drinking episode. In addition, developing reliable biomarkers of fetal alcohol effects that can identify children at risk for adverse neurobehavioral outcomes could lead to behavioral interventions earlier in development. The use of animal models of FASD in biomarker development could accelerate progress in this challenging field of research. KEY WORDS: Maternal alcohol exposure; prenatal alcohol exposure; pregnancy; fetal alcohol effects; fetal alcohol spectrum disorders; prenatal diagnosis; screening and diagnostic method; biomarkers
Despite publicawareness campaigns and warning labels on alcoholic beverages, roughly one of every eight women in the United States continues to drink during her pregnancy. The term fetal alcohol syndrome (FAS) was first used in the 1970s to describe a specific pattern of malformations associated with prenatal alcohol exposure (Jones et al. 1974). The continuum of clinical presentations caused by prenatal alcohol exposure is known as fetal alcohol spectrum disorders (FASD). Attempts to accurately estimate the prevalence of FASD have been challenging because of numerous methodological issues, including diagnostic criteria, passive versus active surveillance, and difficulties with ascertainment of milder cases of FASD in the absence of fetal alcohol-induced birth defects. The prevalence of FAS ranges from 0.5 to 7.0 per 1,000 live births in the general population and up to 9.8 per 1,000 live births in highrisk groups (May et al. 2001, 2009). The prevalence of the entire continuum of FASD might be as high as 1 to 5 percent in young school children in the United States (Lupton et al. 2004; May et al. 2001, 2009), which is higher than the prevalence of autism spectrum disorders.
A large majority of fetal alcohol-affected children may show no physical evidence of prenatal alcohol-associated birth defects. In the absence of characteristic FAS dysmorphology, recognition of FASD requires confirmation of maternal drinking during pregnancy. However, maternal drinking histories are generally unreliable, and the utility of currently available biomarkers of alcohol exposure is limited. Thus, one of the critical challenges for the fetal alcohol research community is to develop better methods for detecting drinking during pregnancy. This article will examine current methods for detecting maternal and fetal alcohol exposure, including selfreporting and biomarkers. The limitations of current methods, however, underscore the critical need to develop new biomarkers with greater sensitivity for detecting moderate levels of drinking during pregnancy for longer periods of time after the last drinking episode. Thus future research needs are reviewed as well.
The development of more sensitive and reliable biomarkers for alcohol use could serve two important objectives in clinical intervention. First, the ability to identify more women who are drinking during pregnancy, particularly early in pregnancy, would allow providers to educate such patients about the dangers of drinking during pregnancy and provide counseling to reduce the risk of subsequent drinking episodes. Effective intervention at this point would benefit not only the mother and fetus but also could reduce the risks of fetal alcohol damage in subsequent pregnancies. Second, a biomarker, or perhaps a combination of biomarkers and other clinical measures, could provide an early indication of whether a newborn child is at risk for developing behavioral and/or cognitive problems later in life, creating opportunities for earlier postnatal interventions that may reduce longerterm adverse consequences. …