Academic journal article Alcohol Research

Advances in Diagnosis and Treatment of Fetal Alcohol Spectrum Disorders: From Animal Models to Human Studies

Academic journal article Alcohol Research

Advances in Diagnosis and Treatment of Fetal Alcohol Spectrum Disorders: From Animal Models to Human Studies

Article excerpt

Alcohol consumption during pregnancy can interfere with both embryonic and fetal development, producing a wide range of outcomes that fall under the rubric of fetal alcohol spectrum disorders (FASD). FASD is the nondiagnostic umbrella term used to refer to the full range of effects that can occur following prenatal alcohol exposure. Such exposure can produce a variety of effects, including physical birth defects, growth retardation, and facial dysmorphism, but the most profound effects are on the developing brain and accompanying cognition and behavior. The disabilities associated with prenatal alcohol are variable, influenced by numerous factors, and can have a lifelong impact. Therefore, early diagnosis and intervention are essential for improved clinical outcomes (Streissguth et al. 2004).

Animal models have played a critical role in research on FASD, including studies confirming that alcohol is indeed a teratogen and those providing insights into the mechanisms by which alcohol exerts its teratogenic effect. Researchers have used a wide variety of organisms to model the effects of prenatal alcohol exposure, which mimic both the physical and the behavioral alterations seen in human FASD (Wilson and Cudd 2011). These models allow researchers to experimentally control factors, including alcohol dose, pattern and timing of exposure, nutritional status, maternal factors, and genetics, that are known to influence and contribute to variability in clinical outcomes. Animal models also can help identify better strategies for diagnosing and treating FASD. This review will not directly compare the animal and human data because previous reviews have done this (Schneider et al. 2011). Rather, it will highlight and integrate translational research that might lead to advancements in the diagnosis and treatment of FASD. Furthermore, several psychosocial, academic, and behavioral interventions for FASD that recently have been discussed elsewhere (Paley and O'Connor 2011) are difficult to model in animals and thus will not be reviewed here. Instead, this review focuses on recent pharmacological, nutritional, and exercise interventions that have shown promise in preclinical studies and are progressing toward translation to the clinic.

Identification and Diagnosis

To obtain an accurate estimate of FASD prevalence and provide early intervention for affected individuals, it is critical to identify infants prenatally exposed to alcohol. Identification is less problematic on the severe end of the spectrum-where fetal alcohol syndrome (FAS) lies-because it is characterized by obvious growth retardation, central nervous system (CNS) dysfunction, and a specific pattern of craniofacial anomalies (see figure 1A). However, many, if not the majority, of individuals affected by prenatal alcohol exposure do not meet criteria for FAS (Bertrand et al. 2005), yet have significant neurobehavioral impairments (Mattson et al. 2013). These cases are referred to as alcoholrelated neurodevelopmental disorders (ARND) and are often difficult to identify because they lack the characteristic facial features and growth retardation seen in FAS. In fact, an ARND diagnosis requires confirmation of prenatal alcohol exposure, which often is unavailable or unreliable (see Riley et al. 2011 for a comparison of various diagnostic schemas for FAS and ARND). Finding novel ways to identify at-risk individuals for disabilities along the spectrum is critical, as is identifying effective interventions to mitigate these cognitive and behavioral effects.

The routine use of objective, validated, and highly specific markers of prenatal alcohol exposure would help improve FASD identification, which currently is hampered by a lack of good information. For example, a recent study (May et al. 2014a) found that only 33 percent of the mothers of children given a diagnosis of FAS provided information about their alcohol consumption. In addition, a large number of children with FASD are in adoptive situations or foster care, and there may be little knowledge of their alcohol exposure. …

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