Fetal Alcohol Spectrum Disorder (FASD) Review PDF

J Dev Phys Disabil (2011) 23:143–167 DOI 10.1007/s10882-010-9204-2 R E V I E W A RT I C L E Fetal Alcohol Spectrum Disorder: A Review of Neurodevelopmental Findings and Interventions Krista Davis & Mary Desrocher & Timothy Moore Published online: 18 May 2010 # Springer Science+Business Media, LLC...

J Dev Phys Disabil (2011) 23:143–167 DOI 10.1007/s10882-010-9204-2 R E V I E W A RT I C L E Fetal Alcohol Spectrum Disorder: A Review of Neurodevelopmental Findings and Interventions Krista Davis & Mary Desrocher & Timothy Moore Published online: 18 May 2010 # Springer Science+Business Media, LLC 2010 Abstract Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term that describes a range of neuropsychological and behavioral deficits resulting from prenatal exposure to alcohol. The dysfunctions that emerge from alcohol exposure during gestation are irreversible and, largely preventable. As such, there is an imperative need to understand the underlying features of the disorder in order to inform preventative measures, early diagnosis, and treatment. This paper provides a comprehensive review of literature investigating the neuropsychological, behavioral, and neurobiological features of FASD. Research on treatment and interventions for FASD is appraised in terms of its limitations and recommendations for future research are proposed. Keywords Fetal alcohol spectrum disorder. Fetal alcohol syndrome. Intervention. Treatment Within the Western world, Fetal Alcohol Spectrum Disorder (FASD) is considered the most preventable cause of congenital neurobehavioral impairment (see Nash et al. 2006). The deleterious effect of prenatal alcohol exposure on the fetus has been alluded to throughout history. However, it was only in the 1970’s that the scientific community began exploring the issue more methodically. In a series of papers Jones and colleagues (Jones and Smith 1973; Jones et al. 1973) characterized a number of deficits that resulted from maternal alcohol consumption. It was Jones and Smith (1973) who first coined the term “Fetal Alcohol Syndrome” (FAS). Since publication of these landmark articles, the study of prenatal alcohol exposure has become a field K. Davis : M. Desrocher Department of Psychology, York University, Toronto, Ontario, Canada T. Moore (*) Department of Psychology, Glendon College, York University, 2275 Bayview Avenue, Toronto, Ontario M4N 3M6, Canada e-mail: [email protected] 144 J Dev Phys Disabil (2011) 23:143–167 burgeoning with researchers exploring multiple facets of the disorder including the effects of alcohol exposure on animal models, the underlying neurobiology and behavioral phenotype in humans, and, more recently, interventions to help rectify resultant damages. Alcohol consumption during pregnancy has a teratogenic effect on the embryo and fetus. Deficits that result from prenatal alcohol exposure lie on a continuum from subtle neuropsychological and behavioral dysfunction to the more severe deficits seen in FAS. FASD is a more recent term that describes a wide range of deficits that ensue from prenatal alcohol consumption. Fetal Alcohol Syndrome, alcohol-related birth defects (ARBD), alcohol-related neurodevelopmental disorder (ARND), and fetal alcohol effects (FAE) are all part of the fetal alcohol spectrum (Kyskan and Moore 2005). FAS, however, describes the most severe of the deficits found on the continuum and is characterized by distinctive facial dysmorphology, growth retardation, and central nervous system dysfunction. Although FAS is the most discernible condition, many individuals with prenatal alcohol exposure suffer from a range of adaptive and cognitive deficits despite lacking the diagnostic facial features. Epidemiology Canada-wide prevalence rates for FASD have yet to be established; however comprehensive studies from the United States have reported that FAS occurs at a rate from 0.2–2.0 per 1,000 live births (Riley and McGee 2005) and that FASD occurs at a much higher rate of 9.1 per 1,000 live births (Sampson et al. 1997). While rates in the United States may provide some insight into circumstances in Canada, diversity of the Canadian population calls for more thorough research. Within Canada only small segments of the population have been studied; however, these epidemiological studies demonstrate some of the unique issues that affect Canadian society. For instance, provincial-wide incidence rates that were gathered in Saskatchewan from 1988–1992 indicated that FAS occurred in approximately 0.589 cases of every 1,000 live births (Habbick et al. 1996). In Northern Manitoba FAS was found to occur in 7.1 per every 1,000 births (Williams et al. 1999). Robinson et al. (1987) carried out an epidemiological study on a remote Aboriginal population in British Columbia and found extremely high rates of FASD at 190 per 1,000 live births. While some Aboriginal communities tend to have higher rates of FASD than the rest of the population (Square 1997), sweeping generalizations about a cultural susceptibility are not empirically defensible (Atcheson 2010). It is important to keep in mind that there are several issues that arise in the collection of epidemiological data on prenatal alcohol exposure (May and Gossage 2001). Rates of FASD are more difficult to determine than rates of FAS since children who do not display the common facial characteristics of FAS may go undetected. For instance, the neuropsychological and behavioral deficits found in children with FASD may not necessarily be recognized as symptoms of prenatal alcohol exposure when physical features are lacking. Moreover, Northern commu- nities in Canada often lack access to the comprehensive health care that is found in urban centers. These communities are unlikely to possess resources to carry out the J Dev Phys Disabil (2011) 23:143–167 145 complex process in diagnosing FAS, thereby leading to a number of undiagnosed cases (Nash et al. 2006). It is clear that more comprehensive research is needed to identify prevalence rates of FASD amongst the Canadian population. Costs As long as alcohol consumption remains a common occurrence within Western society, risk for prenatal exposure to alcohol will prevail. A majority of both Canadian and American populations consumes alcohol. According to the Centers for Disease Control (2007) in the United States, approximately 61% of adults drank alcohol in a 1 year period. Moreover, the Canadian Addictions Survey from 2004 revealed that an estimated 79.3% of the population over the age of 15 had consumed alcohol in a 1 year time span (Collin 2006). While alcohol consumption rates in Canada and the United States remain steady, a more serious concern is the rise in binge drinking behaviors over the past several years. Tsai et al. (2007) tracked prevalence of binge drinking in women of child bearing age (18–44) across a two year time span. They discovered that rates of binge drinking increased substantially between 2001 and 2003. Both maternal alcohol consumption and prenatal alcohol exposure will remain pressing issues in society given that binge drinking has been associated with FAS and has been found to cause significantly harmful damages to the fetus (Maier and West 2001). The personal and psychological costs of prenatal alcohol exposure will become evident throughout the article. However, it is worth making special note of the staggering economic and social costs associated with FASD. Abel and Sokol (1987) carried out a study to determine the financial cost of FAS in the United States. Using an incidence rate of 1.9 per every 1,000 live births the estimated costs totaled $321 million per year. The cost analysis used by Abel and Sokol (1987) was based on growth retardation, surgical repair, treatment of sensorineural problems, and mental retardation. Abel and Sokol (1991) later carried out a more conservative analysis of economic costs based on an incidence rate of 0.33 per every 1,000 live births. Estimated costs totaled $74.6 million per year. In a more recent Canadian study, Stade et al. (2006) determined that the costs associated with FASD in Canada were $344,208,000 per year for children between the ages of 1 and 21. Included in their cost analysis were medical, educational, and social service expenses, as well as indirect costs such as productivity losses. Given the steady rate of alcohol consumption, the increase in binge drinking behaviors amongst women of childbearing age, and the resultant costs of FASD, it is clear that prenatal alcohol exposure is an issue that requires immediate attention and intervention. Risk Factors The range of deficits found in FASD is associated with various risk factors of alcohol consumption during pregnancy. Risk factors related to blood-alcohol concentration are considered to have the most significant impact on resulting alcohol related birth defects (Chudley et al. 2005; Riley and McGee 2005). These 146 J Dev Phys Disabil (2011) 23:143–167 variables include amount of alcohol that reaches the embryo or fetus and the timing of alcohol exposure. Amount of alcohol in the fetal blood stream is directly related to maternal consumption patterns (e.g., how often and how much alcohol is consumed). Researchers that have explored the timing of prenatal alcohol exposure have found that exposure during the first trimester leads to a disruption in the migration, proliferation, and organization of brain cells (Cook et al. 1990; Miller 1993, 1996). Furthermore, research using animal models has found that alcohol exposure during the period equivalent to the first trimester in humans resulted in distinct facial dysmorphology and malformations of the brain (Kotch and Sulik 1992). Exposure in the third trimester has been linked to ethanol-induced damage to the cerebellum, hippocampus, and prefrontal cortex (Borges and Lewis 1983; Livy et al. 2003; Riley and McGee 2005; Sutherland et al. 1997). There are several alternative risk factors that do not have the same linear relationship with resulting deficits as those affected by blood alcohol concentration. Genetics, for instance, may impact the effects that prenatal alcohol consumption has on the fetus. Genetics play a role in determining rate at which the body metabolizes alcohol and may also influence the body’s sensitivity to alcohol (Riley and McGee 2005). Individuals who have inherited a sensitivity to alcohol may be more susceptible to the damaging effects of prenatal exposure. There also are a number of social risk factors related to maternal alcohol consumption during pregnancy. Sood et al. (2001) carried out a comprehensive study of factors that affected prenatal alcohol consumption in women who sought help from a university-based maternity clinic. It was found that the level of prenatal alcohol exposure increased when the following factors were present: the biological mother was the primary caregiver, maternal age was high, maternal education level was low, maternal drug use, child custody changes within the family, paternal drug use, and low socioeconomic status. Chudley et al. (2005), however, warn that these risk factors may be interrelated and vary from one population to the next, making it difficult to discern the relative risk of differing social factors. Presentation Physical Features Children exposed to high levels of alcohol in utero often display a distinct set of facial malformations. Discriminating features include microcephaly, short palpebral fissures, a smooth philtrum, and a thin upper lip. Other associated features include epicanthal folds, a low nasal bridge, minor ear anomalies, and micrognathia (Riley and McGee 2005). These facial features are not widespread across the FASD continuum; only a small portion of children—those who would usually meet the criteria for FAS, display these facial characterizations. The extent of facial malformations found in children may also vary depending on the degree and timing of exposure. Facial dysmorphology is often considered the cornerstone of FAS; however, there are a number of alternative syndromes that share similar facial features (e.g., Cornelia de Lange Syndrome). For this reason, facial features cannot be used on their own to diagnose FAS. J Dev Phys Disabil (2011) 23:143–167 147 Children with prenatal alcohol exposure have also been found to be small for their age. Growth deficits have been shown to be symmetrical—impacting height, weight, and circumference of the head to the same extent (Larkby and Day 1997). These deficits appear to last throughout childhood, but are somewhat ameliorated following growth spurts during puberty (Larkby and Day 1997). Deficits in growth rate are thought to be directly related to the amount of alcohol that reaches the fetus during development, with greater amounts of exposure leading to greater dysfunction in developmental growth (Larkby and Day 1997). Neuropsychological Features and Underlying Neurobiology Alcohol acts as a teratogen causing impairment to development of the embryo and fetus following gestational exposure. The neuropsychological deficits that result from prenatal alcohol exposure can have devastating lifelong effects. Many of these deficits are traced to regions of the brain that have sustained damage during fetal development. Recent studies have employed advanced imaging technology that has provided researchers with opportunity to explore brain anomalies of individuals at different points of the FASD spectrum. Understanding the link between neuropsy- chological deficits and underlying brain dysmorphology can help guide future treatment and intervention. This section begins with a look at some of the overall deficits in neuropsychological functioning and neurobiology, and is followed by a description of more specific deficits and, where available, associated brain anomalies. Overall Intellectual Functioning One of the most widespread findings of FASD research has been that prenatal alcohol exposure can have detrimental effects on overall intelligence. Children who have been exposed prenatally to alcohol have been found to have lower overall intellectual functioning (Mattson et al. 1997) that persists well into adolescence (Howell et al. 2006). However, intelligence scores have been found to vary greatly between children within this population. Streissguth et al. (1991) explored intelligence scores of 40 individuals with prenatal alcohol exposure and found that the scores varied from as low as 20 to as high as 114. Interestingly, Mattson et al. (1997) found that cognitive functioning was affected even in children who did not show the facial dysmorphology characteristic of FAS. This finding indicates that underlying brain damage can result in lowered intellectual functioning, even when external physical damage is not present. Overall reduction of the cranial vault and corresponding reductions in brain size have been commonly reported in individuals with prenatal alcohol exposure (see Riley and McGee 2005). More recent research, however, has found that reductions in brain size are not universal across all areas of the brain. Magnetic Resonance Imaging (MRI) studies have demonstrated that the more severe cases of alcohol exposure, most often found in those diagnosed with FAS, led to specific patterns of hypoplasia (i.e. underdevelopment of specific brain areas; Archibald et al. 2001). Exploring reductions in brain volume using a volumetric approach has allowed researchers to discover these patterns. The volumetric approach compares specific brain region volumes to other regions of the brain in order to determine relative 148 J Dev Phys Disabil (2011) 23:143–167 reductions. Using this method Archibald et al. (2001) found that reductions were more prominent in the parietal lobes relative to the occipital and temporal lobes. Furthermore, current studies have found that areas of white matter are particularly susceptible to heavy prenatal alcohol exposure compared to gray matter (Archibald et al. 2001; Sowell et al. 2008). Learning and Memory One area of functioning that has received much research attention is learning and memory. Mattson, Riley et al. (1996) found that children with FAS showed impairments in learning word lists and recalling them after a period of delay. Poor performance may have been related to the high frequency of intrusion errors and perseveration amongst alcohol exposed subjects. Interestingly, the deficits in learning and memory were apparent in some children even when mental age was controlled for, suggesting that learning and memory deficits go beyond that which would be expected by lower intellectual functioning. The hippocampus, a structure of the limbic system, plays an integral role in learning and memory functions. Reduction in the size of this structure is commonly observed in children with prenatal alcohol exposure. A closer look at the hippocampus using MRI has revealed that damage is not symmetrical; rather, the decrease in volume was more significant in the left temporal lobe than the right temporal lobe (Riikonen et al. 1999). Animal studies of rats exposed prenatally to alcohol also demonstrate abnormal development and function of the hippocampus (Berman and Hannigan 2000). The primary role of the hippocampus is to consolidate short-term memories into long-term memories (Mattson et al. 2001). As such, deficits in spatial and verbal memory amongst children with FASD are thought to be associated with damages to the hippocampus (Mattson et al. 2001). For instance, Uecker and Nadel (1996) report that children with FAS displayed spatial memory dysfunction that was similar to deficits seen in patients with right temporal lobe lobectomies and excisions to the hippocampus. Language Children with FASD have also been found to show deficits in their language abilities. For instance, research conducted by Mattson et al. (1996) revealed that children with prenatal alcohol exposure and FAS performed more poorly on tasks measuring word comprehension and naming ability when compared to controls matched for chronological as well as mental age. Reaction Time Measures of reaction time are frequently used to examine cognitive and neural functioning. Several researchers have reported slow processing speed among children with prenatal alcohol exposure (Burden et al. 2005; Jacobson et al. 1993, 1994; Kable and Coles 2004). Simmons et al. (2002) found that children with prenatal alcohol exposure performed slowly on choice reaction time tasks (i.e. making a differential response to more than one stimulus) compared to controls in both premotor and motor conditions. Premotor reaction time reflects the speed of cognitive and perceptual processing, whereas motor reaction time reflects the actual motor reflex involved in responding to stimuli (Simmons et al. 2002). These results indicate that children with prenatal alcohol exposure display reduced speed of information processing as well as peripheral execution. J Dev Phys Disabil (2011) 23:143–167 149 Motor Functioning Children with prenatal alcohol exposure display deficits in a number of areas of motor functioning, including delayed motor development, fine motor dysfunction, tremors, weak grasp, and poor hand-eye coordination (Jones et al. 1973; Roebuck et al. 1998; Wacha and Obrzut 2007). One study employing neuropsychological testing also revealed that children with prenatal alcohol exposure display deficits in fine motor speed (Mattson and Riley 1998). Moreover, animal studies have consistently found impairments in balance following prenatal exposure to alcohol (Meyer et al. 1990; Thomas et al. 1996). One of the main structures responsible for motor functioning is the cerebellum. The cerebellum controls motor functions such as posture, balance, and coordination (Spadoni et al. 2007). Damage to the cerebellum is thought to be associated with many of the motor deficits found in children with prenatal alcohol exposure. In fact, animal studies have consistently linked resulting motor deficits with damage to the cerebellum. For instance, Meyer et al. (1990) found that rats exposed to ethanol during the brain growth spurt, when the cerebellum undergoes rapid development, displayed prominent postural and gait deficits. Similarly, Thomas et al. (1996) found that bingelike alcohol exposure in rats during the third trimester had damaging effects on both the cerebellum and corresponding motor development. It is important to note that while studies have consistently found reductions in volume of the cerebellum (Archibald et al. 2001; Mattson et al. 1992), researchers who have looked more closely at these volumetric reductions have discovered that the reductions are not uniform. For instance, Sowell et al. (1996) found that the anterior vermis was reduced in size relative to the posterior vermis. The basal ganglia are another structure responsible for motor activity as well as procedural learning (Mattson et al. 2001; Spadoni et al. 2007). The basal ganglia are found at the center with connections that extend to cortical and subcortical motor areas of the brain. Research studies on children with prenatal alcohol exposure have repeatedly found the basal ganglia to be reduced in size compared to normally developing children (Archibald et al. 2001; Mattson et al. 1992, 1994). Damage to the basal ganglia in children with prenatal alcohol exposure may also be responsible for some of the motor deficiencies that are commonly reported in this population (Clark et al. 2000). When controlling for overall reductions in the cranial vault it was determined that reductions were not uniform across the basal ganglia, but were specific to the caudate nucleus relative to other portions of the structure (Archibald et al. 2001; Mattson et al. 1992, 1994). The caudate nucleus has neural connections that extend to areas of the frontal lobe and, is therefore, thought to be involved in cognitive and executive functions (Mattson et al. 2001; Niccols 2007). Reductions in the caudate nucleus may be related to deficits in spatial memory, perseveration, and set shifting that are commonly found in children with prenatal alcohol exposure (Mattson et al. 1994; Spadoni et al. 2007). Visuospatial Functioning Numerous researchers have reported that children with prenatal alcohol exposure show deficits in visuospatial functioning (Aronson and Hagberg 1998; Carmichael-Olson et al. 1998; Coles et al. 2002; Janzen et al. 1995; Mattson and Riley 1998; Uecker and Nadel 1996). In a study by Sowell et al. (2008) children with FASD were found to display poor performance on visuospatial 150 J Dev Phys Disabil (2011) 23:143–167 measures of the Rey-Osterrieth Complex Figure Test (Osterrieth 1944; Rey 1941) when compared to a control group. However, these deficits have not been found to be entirely universal. Rather, Mattson, Gramling et al. (1996) found that visuospatial functioning deficits were specific to local stimuli, while global stimuli functioning remained intact. Global stimuli in this study consisted of large letters or shapes that were constructed from several local stimuli (smaller letters or shapes). These deficits in visuospatial functioning may lead to difficulties in writing abilities and processing fine details of visual information (Mattson et al. 1996). Interestingly, researchers exploring cortical thickness in areas of the brain found that poor performance on visuospatial functioning tasks was related to abnormalities in cortical thickness (Sowell, Mattson et al. 2008). When tested on visuospatial measures, children with FASD performed more poorly than the typically developing control group. Among control subjects in this study, it was found that the thinner the cortex was in areas of the parietal, left occipital, right frontal, and temporal cortices, the better performance was on visuospatial functioning tasks. Cortical thinning in these areas is considered a part of normal development, whereby synaptic pruning leads to neural efficiency and higher intellectual functioning (Shaw et al. 2006; Sowell, Mattson et al. 2008). Children with FASD, however, did not show this same pattern of cortical thinning. Alcohol exposed children displayed cortical thickness in large areas of the parietal, frontal, and temporal cortices. Moreover, areas of cortical thinness in children with FASD were associated with poor performance, the opposite of what was found in the control group. These results suggest that children with prenatal alcohol exposure may experience atypical patterns of pruning and mylenation during development, which may impede neural connections and processing speed leading to poor performance on visuospatial tasks (Sowell, Mattson et al. 2008). Executive Functioning The focus of research on prenatal alcohol exposure has shifted more recently to exploring deficits in executive and behavioral functioning. The area of the brain thought to be responsible for executive functioning and behavioral control is the frontal lobes. Executive functioning is often described as a group of cognitive abilities which include self-regulation, working memory, set-shifting, cognitive flexibility, inhibition, and planning and organization (Pennington and Ozonoff 1996). Research has shown that children with prenatal alcohol exposure show impairments in several areas of executive functioning including cognitive flexibility, response inhibition, planning, reasoning, and working memory (Kodituwakku et al. 1995; Mattson et al. 1999; Rasmussen 2005). Deficits in these areas may also explain some of the behavioral and social impairments commonly reported in children with prenatal alcohol exposure such as poor judgment, the inability to plan ahead, the inability to understand consequences, and impulsivity (Mattson et al. 1999; Niccols 2007). Patients with prenatal alcohol exposure exhibit behaviors that are often described as similar to those diagnosed with frontal lobe lesions, suggesting that there is some connection between damage to the frontal lobe area and deficits in executive and behavioral functioning (Connor et al. 2000). Despite the abundance of research on deficits in executive and behavioral functioning, studies that have explored brain damage using volumetric and voxel- based analyses have failed to show reductions to the frontal lobe areas (Sowell et al. 2002). However, recent studies comparing regions using the whole-brain J Dev Phys Disabil (2011) 23:143–167 151 technique have found reduced brain growth in regions of the left ventral portion of the frontal lobes (Sowell et al. 2002). Damage to this area may explain some of the deficits that individuals with prenatal alcohol exposure demonstrate in executive and behavioral functioning. Sowell et al. (2002) used structural MRI imaging to explore regional brain shape abnormalities. Using the whole-brain imaging technique researchers explored the cortical surfaces of patients with a history of severe prenatal alcohol exposure. The whole-brain technique is able to pick up anomalies that may not have been evident in previous volumetric and voxel-based analyses. This study was able to uncover brain growth reductions in the orbitofrontal lobe that may accompany specific executive functioning deficits such as inhibiting inappro- priate behaviors. Using Single Photon Emission Computed Tomography (SPECT) analyses Riikonen et al. (1999) found that children with prenatal alcohol exposure experienced abnormal blood supplies to the right frontal region of the brain. Because SPECT is able to pick up on mild abnormalities in blood flow, the dysfunction in the frontal lobe area may not have been recognized by traditional brain imaging techniques such as MRI or computed tomography. The pattern of blood flow found in children with prenatal alcohol exposure has also been observed in children with Attention Deficit Hyperactivity Disorder (ADHD) and may be related to some of the similar behavioral deficits between the two populations (Riikonen et al. 1999). Finally, researchers using functional MRI studies have also found that children with FASD show abnormal activation in the frontal lobes and prefrontal cortex when carrying out working memory tasks compared to controls (Connor and Mahurin 2001; Malisza et al. 2005). Animal studies, which allow researchers more experimental control, have revealed that damage to the frontal area of the brain leads to functional deficits. Mihalick et al. (2001) found that rats that underwent prenatal ethanol exposure displayed significant cell loss in the medial prefrontal cortex; this cell loss was found to be associated with impaired reversal learning. Behavioral Functioning One of the more recent goals in the field of prenatal alcohol exposure is to define the behavioral phenotype of children with FASD in order to create diagnostic tools that will lead to early interventions. Children with FASD are commonly described as hyperactive and inattentive. In fact, a large portion of children with FASD would also qualify for a diagnosis of ADHD (Riley and McGee 2005). Coles et al. (1997) explored the attentional profiles of children with ADHD and FASD and discovered that there were unique differences between the two populations. When compared on variables of encoding, shifting, sustaining, and focusing, children with prenatal alcohol exposure had more difficulties with tasks involving encoding and shifting, whereas children with ADHD had more difficulties with tasks involving sustaining and focusing (Coles et al. 1997). Further studies suggest that children with ADHD are characterized more by issues of impulsivity than are children with FASD (Calarco et al. 2003). Children with FASD are also commonly reported by both teachers and parents to display externalizing and internalizing behaviors. Researchers have begun to explore some of these behavioral deficits through personality tests and behavior checklists. Roebuck et al. (1999) administered the Personality Inventory for Children (Wirt et al. 152 J Dev Phys Disabil (2011) 23:143–167 1984) and found that those with prenatal alcohol exposure scored higher on the following behavioral measures than matched controls: depression, delinquency, anxiety, withdrawal, hyperactivity, psychosis, and social skill deficits. Similarly, a study by Nash et al. (2006) compared children with FASD to controls on the Child Behavior Checklist (Achenbach and Rescorla 2001) and found that children with FASD scored higher on measures of hyperactivity, inattention, lying and cheating, lack of guilt, and disobedience. Compared to children with ADHD, children with FASD scored higher on: lack of guilt, acting younger than their age, cruelty, and stealing (Nash et al. 2006). Some of the attentional problems that are commonly reported in children with FASD are thought to be related to atypicality of the corpus callosum, an area of the brain that has also been found to show abnormalities in children with ADHD (Hynd et al. 1991). The corpus callosum is a large bundle of nerve fibers that allows the left and right hemispheres of the brain to communicate with one another. Children with prenatal alcohol exposure show differences in volume ranging from a thinning of the corpus callosum to complete agenesis of the corpus callosum (i.e. complete absence of the structure; Riley et al. 1995). When controlling for overall reduction in brain size, however, the anterior and posterior regions of the corpus callosum were significantly smaller than the rest of the structure (Riley et al. 1995). Sowell et al. (2001) also found severe displacement of the corpus callosum in children with prenatal alcohol exposure. It has been suggested that agenesis of the corpus callosum in children with FASD may be related to some of the attentional deficits that are common amongst the two populations (Riley et al. 1995), however, it is important to keep in mind that the attentional differences between the two populations suggests that behavioral manifestations may be a result of distinct underlying neurocognitive deficits (Coles et al. 1997). Because the corpus callosum is responsible for a wide variety of functions that requires communication between the hemispheres, damage to this structure has also been linked to deficits in a number of other areas including: learning, reading, verbal memory, and executive and psychosocial functioning (Wacha and Obrzut 2007). Children with prenatal alcohol exposure who display agenesis of the corpus callosum show difficulties in tasks that require interhemispheric interaction (Riley et al. 1995; Roebuck-Spencer et al. 2002, 2004). Roebuck-Spencer et al. (2004) recruited 21 children with FASD and 17 non-exposed children matched for age, ethnicity, and sex. A computerized version of The Bimanual Coordination Test (Brown 1991; Marion et al. 2003) was used to test the speed and accuracy of coordinating the use of two hands. This test provides a measure of the interaction between the hemispheres and the ability to coordinate activities using the corpus callosum. As the complexity of the tasks increased the children with FASD performed more variably and poorly than controls. This was thought to be related to the increased demands on the interaction between hemispheres, confirming the finding that children with FASD have impaired callosal functioning. Interestingly, in another study the greater the displacement of the corpus callosum the greater deficits were in verbal learning skills (Sowell et al. 2001). Overall, the various neuropsychological deficits that correlate with callosal anomalies suggest that greater variability in shape, displacement, and size is associated with decreased functioning in a number of motor and cognitive functions in children with prenatal alcohol exposure (Spadoni et al. 2007). J Dev Phys Disabil (2011) 23:143–167 153 Social Skills Another area of interest is the deficits in social skills that children and adolescents with prenatal alcohol exposure exhibit. Compared to controls, children with FASD display deficits in their interpersonal relationship skills that go beyond the deficits that would be expected with lower intelligence (Thomas et al. 1998). Because deficits in social behavior are also found in animal models, it has been suggested that these social deficits are a result of the prenatal alcohol exposure as opposed to environmental factors (Kelly et al. 2000). Many of these social skill deficits are thought to be related to some of the problems in executive functioning that were addressed above. For instance, lying and cheating behaviors found among children with FASD are thought to be associated with inability to understand cause and effect reasoning and to inhibit inappropriate behaviors (Rasmussen et al. 2008). Secondary Disabilities Individuals with FASD who experience neuropsychological and behavioral deficits are often at risk of acquiring secondary disabilities throughout their lives. Secondary disabilities are those that evolve across development and could potentially improve through proper interventions (Streissguth et al. 1997). Streissguth et al. completed a study assessing the secondary disabilities amongst 415 patients with prenatal alcohol exposure. The authors developed the Life History Interview to assess secondary disabilities and risk and protective factors amongst patients. They found six main secondary disabilities including (percentage of individuals who reported concerns in brackets): mental health problems (90%), disrupted school experience (60%), trouble with the law (60%), confinement for inpatient treatment or incarceration (50%), inappropriate sexual behavior (50%), and alcohol/drug problems (30%). The level of secondary disabilities amongst individuals with prenatal alcohol exposure is disconcerting as it signifies impairment in quality of life and a costly impact on society (Streissguth et al. 1997). A better understanding of the disorder and appropriate interventions are desperately needed to prevent the development of secondary disabilities. Treatment and Intervention To date, there has been a wealth of scientific research on presentation and etiology of FASD. However, there has been a relatively limited amount of research investigating methods of treatment and intervention. This section provides an overview of research on the treatment of FASD in animal models and the neuropsychological, behavioral, pharmacological, and cognitive interventions in humans. Reasons for the paucity of research in the area of FASD treatment are also explored. Research Findings Animal Research As demonstrated above, children exposed to alcohol in utero experience a number of neuropsychological deficits. Several researchers have begun to explore treatment options that can help ameliorate targeted deficits in children with FASD. One line of research has sought to rectify damage that occurs to different areas of the brain exposed to ethanol in animal models. Guerri et al. (2005) 154 J Dev Phys Disabil (2011) 23:143–167 tested the role of antioxidants in preventing cell death caused by exposure to ethanol in rats. Antioxidants were delivered simultaneously to rat pups receiving ethanol diets. They found that antioxidants either decreased or prevented apoptotic death in the cerebral cortex of ethanol exposed rats. The authors also suggested that ethanol antagonists, which block the actions of ethanol, may be able to prevent or even mitigate the teratogenic effects of prenatal alcohol exposure. Another area of research that has received increasing attention is the use of choline supplements as a treatment for prenatal alcohol exposure. Several studies have found choline to alter brain development leading to improvements in cognitive functioning in animal models (Guerri et al. 2005). For instance, Thomas et al. (2000) found that postnatal choline supplements significantly improved performance on visuospatial discrimination tasks in rats. Thomas et al. (2004) also found that choline supplements reduced the number of errors on a serial spatial discrimination reversal learning task and reduced hyperactivity, both of which are caused by ethanol exposure. Conversely, choline supplements have not been able to reduce the motor deficits, suggesting that choline specifically targets deficits in visuospatial functioning (Thomas et al. 2004). A recent study by Ryan et al. (2008) provides increasing support for use of choline supplements in mitigating deficits caused by alcohol exposure, specifically in the area of spatial memory. In this study rat pups were first subjected to ethanol exposure during the period equivalent to the third trimester brain growth spurt in humans. Following ethanol exposure, rat pups were treated with choline injections during postnatal days 11–20, 21–30, or 11–30. The control groups did not receive any choline treatment, but were injected with a saline solution from post natal days 11–30. All subjects were tested on a Morris water maze spatial learning task, in which the rats had to follow spatial cues to find a platform hidden in a tank of opaque water. During training, completion of the maze was impaired amongst subjects exposed to ethanol. However, during testing, subjects that received both early and late choline treatments preformed at levels that were similar to the non- exposed groups. While the researchers were not able to determine the exact neural targets of the choline treatment, they suggest that choline improves the functioning of the hippocampus, an area that suffers damage following ethanol exposure and is responsible for spatial learning (Berman and Hannigan 2000). Results from this study are promising for humans as they demonstrate that choline treatments may mitigate spatial learning deficits even after the damage from alcohol exposure has finalized. Since FASD is not usually diagnosed until later in life, choline treatments may be an effective treatment for older children while the brain is still developing (Ryan et al. 2008). Although choline supplements have not been found to have an effect on motor abilities, intensive skill training in animal models has been found to improve functioning in this area. In a study by Guerri et al. (2005) rat pups were exposed to binge-like alcohol consumption during the period in which the cerebellum is especially susceptible to the teratogenic effects of alcohol. They were then provided with 20 days of complex motor task training. When later tested on parallel bar, rotating rod traversals, and rope climbing tasks, the rats who received training improved significantly and were able to perform at a level similar to other trained animals. Improvements in motor functioning following intensive skill training were J Dev Phys Disabil (2011) 23:143–167 155 associated with significantly more synapses and more complex dendritic modifica- tions, suggesting that the brain in ethanol exposed rats preserves the capacity for plasticity. In another study, McGough et al. (2009) found that insulin like growth factor-I (IGF-I) was also able to attenuate the effects of ethanol on motor coordination in rats. According to McGough et al. (2009), insulin like growth factor is “neuro- potective against ethanol-related toxicity and promotes white matter production following a number of insults” (p.40). Reductions in the concentration of IGF-I in the fetal brain have been found following exposure to ethanol during pregnancy (Breese et al. 1993; Singh et al. 1996). Rat pups in the McGough et al. (2009) study were exposed to ethanol during the period equivalent to the third trimester in humans. Following exposure rat pups received IGF-I treatments and were tested on a number of tasks measuring overactivity, motor coordination, and spatial learning. It was found that the group with ethanol exposure that had received IGF-I treatments performed comparably to the control group on a task of motor coordination, while the group exposed to ethanol that did not receive IGF-I treatments performed significantly worse. Performance on the tasks assessing activity level and spatial learning were not affected by the IGF-I treatments. The motor task used in this study required balance and fine motor coordination, which is thought to be controlled mainly by the cerebellum. As such, the authors suggest that effects of IGF-I may directly influence the cerebellum or other motor areas of the brain. In sum, it appears that treatments such as antioxidants, supplements, and growth factors administered to rat pups during gestation and following birth have been found to rectify some of the cell damage caused by ethanol. These substances target specific areas of the brain and related functional deficits to ameliorate damages. While the above studies have only been tested in animal models, they provide some promise for the future use of such treatments among humans exposed to alcohol in utero. Human Interventions Interventions for children with FASD have focused on the improvement of school performance and cognitive functions that impact academics. Kable et al. (2007) carried out an interesting investigation of an intervention program aimed at improving math functioning amongst children with prenatal alcohol exposure. The intervention program, entitled Math Interactive Learning Experience (MILE), was developed to address the underlying neuropsychological deficits of arithmetic disabilities in children with FASD. This intervention was unique in that it aimed to improve specific underlying deficits as opposed to intervening with overall math skills. For instance, to address slow processing speed, instructors employed slow paced instructions and interactive tasks. To address deficits in visuospatial functioning and working memory children used tangible tools (i.e. vertical number lines) to compute basic math functions. To address issues with interhemispheric communication, participants were provided “repetitive experiences...in which participants were required to label, a left hemisphere function, their visual-spatial perceptions, a right hemisphere function” (Kable et al. 2007, p. 1428). Finally, instructors addressed graphomotor skills (Conry 1990) by teaching children column alignment and start points. During the intervention children were also provided with feedback and mediation when they committed errors. Children diagnosed with FAS 156 J Dev Phys Disabil (2011) 23:143–167 or partial FAS were divided into two groups, those who received the math treatment and those who received standard psychoeducational treatment only. While improve- ments were made in both groups on the Test of Early Mathematics Ability 2nd edition (Ginsburg and Baroody 1990), selected math-related subtests from the Bracken Early Concept Scales Revised (Bracken 1998), and the Number Writing Task (Coles et al. 2004), the math treatment group made significantly greater improvements in math knowledge. These results suggest that proper teaching methods, which address underlying neurodevelopmental deficits in children with prenatal alcohol exposure, can significantly enhance learning and skill deficits. Adnams et al. (2007) carried out a similar study that aimed at improving underlying language and literacy skills of children exposed prenatally to alcohol. Adnams et al. (2007) recruited a sample of 40 children diagnosed with FASD and 25 non-exposed children. Children diagnosed with FASD were split into two groups. The first group received Language and Literacy Training (LLT) while the other group received no training. The LLT program consisted of 38 h of intervention over a nine month period. Training focused on the development of phonological awareness, reading, spelling, and semantics. The program utilized multi-sensory stimulation exercises. For example, trainers would articulate sounds aloud while pairing with pictures and children were required to trace sandpaper letters by hand before writing letters out on their own. Tasks were also arranged hierarchically. For instance, children were first taught to sound out phonemes of short words, longer words, and then multisyllabic words. Reading and spelling were taught utilizing word cards and short stories; semantic training was taught through naming tasks and story comprehension. Children who received LLT training did not show significant improvements on general scholastic assessments; however, they did improve on more specific tests of language and literacy. The LLT group made significant improvements over the control group in areas of syllable manipulation, letter sound knowledge, written letters, word and non-word reading, and spelling. These findings confirm the conclusion that targeted cognitive interventions can increase perfor- mance of specific skills in children with FASD. Loomes et al. (2008) carried out an intervention study exploring weaknesses in working memory, an area found to be deficient in children with FASD (Burden, Jacobson, Sokol et al. 2005; Carmichael-Olson et al. 1998; Kodituwakku et al. 1995). Rehearsal training is one intervention that has been found to be effective in improving short-term memory in populations that experience cognitive deficits similar to those in FASD (Bowler 1991; Broadley and MacDonald 1993; Broadley et al. 1994; Comblain 1994). Loomes et al. (2008) thus predicted that children with FASD would also benefit from rehearsal training. Children with FASD were divided into a control group (n=16) and an experimental group (n=17) matched for age and gender when possible. Children were required to complete a digit span memory task where they were read a set of numbers and asked to repeat them back following a 10 s delay. During the first post-test, children in the experimental group were prompted to try repeating the numbers over and over again to themselves in order to help them remember the numbers, while the control group received no instructions. During the second post-test, 6–21 days later, children in the experimental group were again prompted to repeat the numbers to themselves in order to better remember the numbers, while children in the control group received no instructions. The J Dev Phys Disabil (2011) 23:143–167 157 experimental group showed a significant increase in digit span scores across sessions, whereas the control group showed no increase. Instructions were brief, but had a significant impact on working memory. As such, more in depth interventions targeted at increasing working memory may have positive effects on the academic and cognitive development of children with prenatal alcohol exposure. Researchers in South Africa have begun exploring classroom and educational interventions to address behavioral problems and cognitive functioning in children with FASD. Riley et al. (2003) tested the effects of Cognitive Control Therapy (CCT), an intervention that teaches children to understand their own unique learning styles, learning challenges, and trains them in self-observation and regulation (Kalberg and Buckley 2007; Riley et al. 2003). Riley et al. (2003) recruited a sample of children diagnosed with FAS and split them into an intervention (n=5) and control group (n=5) matched for age, language, socioeconomic status, grade, and locality of school. The intervention group received CCT for a period of 1 h per week for 10 months. Therapy focused on five metacognitive control domains including body positioning, movements, and self-awareness; focal attention; information processing with distracters; controlling external information; and categorizing information. While intelligence scores did not improve following the CCT intervention, teacher-rated behaviors of children with FAS did improve over the ten months (Riley et al. 2003). As such, CCT appears to be a promising intervention option for managing behavioral issues in children with FASD. Children with FASD are often at risk of having comorbid mental health problems (Burd et al. 2003). One of the most frequently diagnosed disorders among children with prenatal alcohol exposure is ADHD. As such, structured environments and structured tasks that are often utilized in the treatment of children with ADHD have also been found to assist children with FASD. For instance, environmental structure and simplicity allow children with FASD to focus on the task at hand, therefore aiding with attentional deficits. Environmental structure can be achieved in a number of different ways. For instance, keeping a child’s workspace simple and clear of visual clutter with minimal decorations can reduce distractibility (Kalberg and Buckley 2007). Visually structured environments may also be helpful and can include taping off sections of the workspace for specific activities, colour coding different areas around the workspace, and using arrows to guide and direct children. Finally, visual schedules can also help children to structure their time and prepare for transitions between activities (Kalberg and Buckley 2007). Highly structured tasks allow children to understand exactly what is expected of them (Kalberg and Buckley 2007). For instance, tasks should be colour coded and numbered, and children should be provided examples of the end result to assist in task completion (Kalberg and Buckley 2007). Because children with FASD are frequently diagnosed with ADHD, it is possible that a number of alternative interventions that have been successful with hyperactive and inattentive children may also assist children with FASD. Structured environments and tasks may be particularly beneficial given the attentional deficits that are more frequently reported amongst children with prenatal alcohol exposure. Researchers have also explored the role of ADHD medication in treating some of the ADHD symptom clusters in children with FASD. Doig et al. (2008) found that ADHD medication may be helpful in treating symptoms of hyperactivity/impulsivity 158 J Dev Phys Disabil (2011) 23:143–167 and opposition/defiance, but not symptoms of inattention, which are thought to occur more often in children with prenatal alcohol exposure. These results support findings from a study by Snyder et al. (1997), who found that stimulant medication for ADHD improved hyperactive parent-rated behaviors in a group of children diagnosed with FAS, but failed to improve sustained attention. The fact that stimulant medication failed to improve attentional deficits in children with FASD starkly contrasts the results of studies that have found that children with pure ADHD (Pelham et al. 1990) and developmental disorders (Aman et al. 1991) respond very well to such medication. ADHD medication may prove helpful for some children with FASD who present with hyperactive behaviors; however, attentional deficits may arise from different underlying neuropsychological dysfunction and may, therefore, not respond well to medication. Another type of intervention, Child Friendship Training (CFT), has been found to help ameliorate social skill deficits common in children with FASD (O’Connor et al. 2006). O’Connor et al. (2006) recruited a sample of 100 children divided into a treatment group and delayed treatment control group. The treatment group received twelve 90 min CFT sessions while parents received concurrent information sessions. Children were taught key social behaviors including communication and conversa- tion skills, how to play with other children, being a good sport and a good host, managing teasing and accusations, and conflict resolution. The facilitation of skills was taught through rules, modeling, rehearsal, feedback, homework, and parental coaching. Sessions for parents aimed at increasing knowledge on FASD and informing parents of the types of social skills being taught to their children. Compared to the delayed treatment group, children who underwent CFT exhibited an increase in knowledge of appropriate social behaviors; this knowledge persisted at a three month follow-up. While researchers did not conduct an independent evaluation of the children’s behaviors, parents did report an increase in their children’s social skills and a decrease in problem behaviors following training. The goal of many of the aforementioned interventions was to treat neuropsycho- logical and behavioral deficits early in life. Nevertheless, there remains a critical need for interventions that address secondary disabilities and fetal alcohol effects amongst adult populations. Grant et al. (2004) carried out a pilot community intervention for young women diagnosed with FASD. Participants were assigned case manager advocates who were trained in FASD interventions. Case managers were responsible for linking patients to services in the community that were knowledgeable in FASD and for training uninformed agencies. During the 12 month intervention period, case managers assisted clients in accessing in/outpatient treatment, assisted in family planning needs, established a network of service providers, connected patients with parenting support groups, and helped to secure stable housing. Participants were assessed during intake and again following treatment. The researchers reported a number of improved outcomes including a reduction in the amount of alcohol and substance abuse, and an increase in the use of contraceptives, mental health services, and stable housing. Because women with FASD are thought to be at an increased risk of drinking while pregnant, one of the goals of the study was to seek methods by which to prevent the birth of future generations of alcohol exposed children (Grant et al. 2004). In this sense, the pilot intervention appeared to be successful. J Dev Phys Disabil (2011) 23:143–167 159 Together the above intervention studies provide an encouraging future for the role of intervention programs in rectifying areas of cognitive and behavioral dysfunction that result from FASD. These research findings reveal that targeted intervention programs that are aimed at ameliorating specific functional deficits in areas such as, mathematics, language, literacy, social skills, working memory, and attention, can have a positive effect on functioning. Future Research While studies outlined in this paper provide some promise for treatment programs of FASD, there remains a clear need for additional research. Premji et al. (2006) completed a comprehensive review of the literature in order to identify research based interventions. Results of this meta-analysis were disconcerting. Premji et al. (2006) searched peer-reviewed and grey literature databases, and completed secondary searches that revealed only 10 empirically based treatment studies. Of these, only two were experimental, and one quasi experimental. The rest were either unable to be located or in a foreign language. The authors strongly recommended expanding experimental research on FASD interventions, especially in light of the fact that early intervention can help to maximize the potential of children living with FASD due to the plasticity of the brain in early childhood. Public information on interventions is available through networks in both Canada and the United States that provide educational resources on prenatal alcohol exposure. The Substance Abuse and Mental Health Service Administration in the United States, and FASlink in Canada are two networks that provide FASD resources on their websites. However, much of the intervention information provided by these organizations is based on knowledge from experienced parents, teachers, and professionals who have worked with FASD. Indeed, Zevenbergen and Ferraro (2001) have indicated that the majority of FASD intervention and treatment information available is based on clinician, teacher, and parental suggestions, rather than on empirical research. Generally speaking, intervention programs have little structure, limited empirical basis, and are difficult to find. This is exactly what was found by Mills et al. (2006) who assessed the various patterns of mental health service use among children with FASD in Canada. They found that services received by children with FASD were variable and lacked a definitive means of access. Furthermore, compared to children with ADHD, children with FASD were referred to mental health services less often (Mills et al. 2006). Given the degree of mental health needs among this population, children with prenatal alcohol exposure would be better cared for under multidisciplinary teams that can address a range of presenting issues (Burd, Klug et al. 2003; Mills et al. 2006). It is clear that there is a considerable need for empirically-based intervention research on FASD (Burd 2006). Intervening early in life can provide increased opportunities for managing neuropsychological and behavioral symptoms, as well as preventing secondary disabilities, such as incarceration, at a later age. Multi-modal treatment and intervention strategies will be essential in treating children with FASD due to the impairments that are found in a range of domains and to various degrees (Doig et al. 2008). 160 J Dev Phys Disabil (2011) 23:143–167 Limitations and Future Research Research in the field of FASD has been expanding over the past 30 years. Most of this research has focused on understanding the neuropsychological and behavioral features of the disorder, as well as linking deficits to brain dysfunction. This knowledge base will be vital for formulating treatment programs and interventions to ameliorate the deficits that result from prenatal alcohol exposure. In moving forward it is important to look critically at the limitations of current research in order to improve future studies. It is clear that there is a need for more rigorous, large scale, and methodologically sound research on FASD. Deficits that result from prenatal alcohol exposure lie on a continuum and vary from one individual to the next. As a result, research findings cannot be generalized to all children with FASD. For instance, in the math intervention study by Kable et al. (2007) potential participants with an IQ of less than 50 were excluded from the study. Thus, results of this intervention program may only be suitable for a unique population of children. It will be important to test interventions with a variety of samples to determine strategies that are effective for children across the FASD continuum. Multiple methods of treatment will also be necessary to address the range of deficits that are found in children with FASD. Together this will allow clinicians to customize intervention programs to fit the needs and strengths of individual children. Another limitation frequently found in FASD research involves sampling. It is common for researchers to recruit subjects through affiliated hospitals and clinics. Nash et al. (2006) recruited their population through the Motherisk FAS clinic, while Riikonen et al. (1999) recruited their participants through the Central Hospital of Kymenlaakso. Patients who seek out treatment, however, may not be representative of the majority of people living with the disorder. Clinic-referred samples may represent the more extreme cases of prenatal alcohol exposure since these are families that are most likely to seek help. Studies using clinic-referred subjects neglect a unique population of children living in the community with prenatal alcohol exposure. Furthermore, clinical samples often include only children from urban centers who have access to diagnostic services. As previously mentioned, children from Northern rural communities in Canada lack access to comprehensive health care and, although they may be at an increased risk, they are often excluded from studies that use clinic samples. Due to the relative rarity of the disorder, sample sizes within many of the FASD studies remain small. For instance, a number of the studies discussed above used experimental group sample sizes with as few as 5 participants per cell. It will be important to validate research findings on larger samples of children with prenatal alcohol exposure. Additionally, researchers will need to follow up intervention results in order to assess the longevity of benefits in children with FASD. Finally, it will be critical to determine whether treatment success in animal models can be extended to humans. Adopting what Parke (2004) describes as a multisite, multi-investigator collaborative model may help to rectify some of the issues that are prominent in FASD research. This model promotes involvement of multiple sites, investigators, theoretical views, and designs. Collaboration among multiple clinics and community services, such as those discussed above, will lead to larger and more diverse J Dev Phys Disabil (2011) 23:143–167 161 samples. This collaborative process will not only allow researchers to generate valid and reliable results, but will also allow for the transfer of knowledge between interdisciplinary professionals. Finally, collaboration across multiple sites will allow for more structured and organized diagnostic protocols and treatment programs. Conclusions Since Jones and Smith’s (1973) first article coining the term FAS, researchers have made impressive advances in understanding the neuropsychological dysfunction and underlying brain dysmorphology caused by prenatal alcohol exposure. It is evident that exposure to alcohol during gestation can lead to permanent damage of the brain that results in a range of lifelong deficits in neurodevelopmental functioning. Deficits are found to be greatest amongst those exposed to high doses of alcohol and seem to lessen with decreases in exposure. Physical characteristics are found in only a small portion of children. Nevertheless, researchers have found that children display deficits in areas of neuropsychological and behavioral dysfunction regardless of the presence of physical features. Research employing MRI techniques has revealed that FASD- related neurological deficits are uncorrelated with facial abnormalities (Bookstein, Sampson et al. 2002; Bookstein, Streissguth et al. 2002). Consequently, a child without distinctive morphological features may be as severely impaired in functional skills as someone displaying the full range of traditional diagnostic criteria. This means that that critical aspects of FASD—organic brain damage and the concomitant cognitive shortfalls—are invisible to the naïve observer, thus allowing parents, teachers, social workers, police, and some doctors to “miss” the underlying pathology. Using advanced imaging techniques researchers have demonstrated that the overall reduction in brain size caused by prenatal alcohol exposure is a result of volume reductions to specific regions of the brain. Volumetric reductions have been found in the basal ganglia, corpus callosum, and cerebellum, while alterations have also been found in shape, tissue density, and symmetry throughout the bran (Riley and McGee 2005). Areas of neuropsychological functioning affected by prenatal alcohol exposure include: cognitive functioning, learning and memory, language, reaction time, motor functioning, visuospatial functioning, and executive function- ing. Children with prenatal alcohol exposure also show deficits in behavioral functioning such as delinquency, lying and cheating, inhibiting inappropriate behaviors, and social skills. Secondary disabilities, such as mental health problems and incarceration, develop throughout life and can have devastating effects on those with FASD. Knowledge of the above areas of disability are being used to determine patterns of dysfunction in individuals with FASD in order to develop more comprehensive diagnostic measures as well as effective treatments and interventions (Riley and McGee 2005; Nash et al. 2006). Ideally, prevention would be the most successful means of ameliorating damages caused by prenatal alcohol exposure, however, FASD is distressingly prevalent and, therefore, more research is needed to find empirical methods of treatment and intervention. FASD affects not only the individual, but families, the community, and society at large. The paucity of empirical research on interventions and treatment is daunting, but leaves much room for scientists to 162 J Dev Phys Disabil (2011) 23:143–167 use their knowledge and creativity in designing studies that will lead to effective programs and services for those with FASD. As research continues to develop in the field, it is essential that findings from basic research provide the foundation for improved intervention strategies and treatment programs. References Abel, E. L., & Sokol, R. J. (1987). Incidence of fetal alcohol syndrome and economic impact of FAS- related anomalies. Drug and Alcohol Dependence, 19, 51–70. Abel, E. L., & Sokol, R. J. (1991). A revised conservative estimate of the incidence of FAS and its economic impact. Alcoholism: Clinical and Experimental Research, 15, 514–524. Achenbach, T., & Rescorla, L. (2001). Manual for the ASEBA school-age forms and profiles. Burlington: Research Center for Children Youth and Families. Adnams, C. M., Sorour, P., Kalberg, W. O., Kodituwakku, P., Perold, M. D., Kotze, A., et al. (2007). Language and literacy outcomes from a pilot intervention study for children with fetal alcohol spectrum disorder in South Africa. Alcohol, 41, 403–414. Aman, M. G., Marks, R. E., Turbott, S. H., Wilsher, C. P., & Merry, S. N. (1991). Methylphenidate and Thioridazine in the treatment of intellectually subaverage children: effects on cognitive-motor performance. Journal of the American Academy of Child and Adolescent Psychiatry, 30, 816–824. Archibald, S. L., Fennema-Notestine, C., Gamst, A., Riley, E. P., Mattson, S. N., & Jernigan, T. L. (2001). Brain dysmorphology in individuals with severe prenatal alcohol exposure. Developmental Medicine and Child Neurology, 43, 148–154. Aronson, M., & Hagberg, B. (1998). Neuropsychological disorders in children exposed to alcohol during pregnancy: a follow-up study of 24 children to alcoholic mothers in Göteborg, Sweden. Alcoholism: Clinical and Experimental Research, 22, 321–324. Atcheson, J. (2010). FASD and Aboriginal peoples. Retrieved November 20, 2009, from http://fasdjustice. on.ca/incidence.html Berman, R. F., & Hannigan, J. H. (2000). Effects of prenatal alcohol exposure on the hippocampus: spatial behavior, electrophysiology, and neuroanatomy. Hippocampus, 10, 94–110. Bookstein, F. L., Sampson, P. D., Connor, P. D., & Streissguth, A. P. (2002). Midline corpus callosum is a neuroanatomical focus of fetal alcohol damage. The Anatomical Record, 269, 162–174. Bookstein, F. L., Streissguth, A. P., Sampson, P. D., Connor, P. D., & Barr, H. M. (2002). Corpus callosum shape and neurospsychological deficits in adult males with heavy fetal alcohol exposure. NeuroImage, 15, 233–251. Borges, S., & Lewis, P. D. (1983). Effects of ethanol on postnatal cell acquisition in the rat cerebellum. Brain Research, 271, 388–391. Bowler, D. M. (1991). Rehearsal training and short-term free-recall of sign and word labels by severely handicapped children. Journal of Intellectual Disability Research, 35, 13–124. Bracken, B. A. (1998). Bracken Concept Scale-Revised Examiners Manual. San Antonio: The Psychological Corporation. Breese, C. R., D’Costa, A., Ingram, R. L., Lenham, J., & Sonntag, W. E. (1993). Long-term suppression of insulin-like growth factor-1 in rats after in utero ethanol exposure: Relationship to somatic growth. Journal of Pharmacology and Experimental Therapeutics, 264, 448–456. Broadley, I., & MacDonald, J. (1993). Teaching short term memory skills to children with Down’s syndrome. Down Syndrome Research and Practice, 1, 56–62. Broadley, I., MacDonald, J., & Buckley, S. (1994). Are children with Down’s syndrome able to maintain skills learned from a short-term memory training programme? Down Syndrome Research and Practice, 2, 116–122. Brown, W. S. (1991). The Bimanual Coordination Test: Version 1. Pasadena: Travis. Burd, L. J. (2006). Interventions in FASD: we must do better. Child: Care, Health and Development, 33, 398–400. Burd, L. J., Cotsonas-Hassler, T. M., Martsolf, J. T., & Kerbeshian, J. (2003). Recognition and management of fetal alcohol syndrome. Neurotoxicology and Teratology, 25, 681–688. Burd, L. J., Klug, M. G., Martsolf, J. T., & Kerbeshian, J. (2003). Fetal alcohol syndrome: neuropsychiatric phenomics. Neurotoxicology and Teratology, 25, 697–705. J Dev Phys Disabil (2011) 23:143–167 163 Burden, M. J., Jacobson, S. W., & Jacobson, J. L. (2005). Relation of prenatal alcohol exposure to cognitive processing speed and efficiency in childhood. Alcoholism: Clinical and Experimental Research, 29, 1473–1483. Burden, M. J., Jacobson, S. W., Sokol, R. J., & Jacobson, J. L. (2005). Effects of prenatal alcohol exposure on attention and working memory at 7.5 years of age. Alcoholism: Clinical and Experimental Research, 29, 443–452. Calarco, K. E., Mattson, S. N., Robertson, B., & Riley, E. P. (2003). Heavy prenatal alcohol exposure or ADHD? Errors make the difference. Journal of the International Neuropsychological Society, 9, 152. Carmichael-Olson, H., Feldman, J. J., Streissguth, A. P., Sampson, P. D., & Bookstein, F. L. (1998). Neuropsychological deficits in adolescents with fetal alcohol syndrome: clinical findings. Alcoholism: Clinical and Experimental Research, 22, 1998–2012. Centers for Disease Control and Prevention. (2007). Alcohol use. Retrieved November 18, 2009, from http://www.cdc.gov/nchs/fastats/alcohol.htm Chudley, A. E., Conry, J., Cook, J. L., Loock, C., Rosales, T., & LeBlanc, N. (2005). Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. Canadian Medical Association Journal, 172, S1–S21. Clark, C. M., Li, D., Conry, J., Conry, R., & Loock, C. (2000). Structural and functional brain integrity of fetal alcohol syndrome in nonretarded cases. Pediatrics, 105, 1096–1099. Coles, C. D., Platzman, K. A., Raskind-Hood, C. L., Brown, R. T., Falek, A., & Smith, I. E. (1997). A comparison of children affected by prenatal alcohol exposure and attention deficit, hyperactivity disorder. Alcoholism: Clinical and Experimental Research, 21, 150–161. Coles, C. D., Platzman, K. A., Lynch, M. A., & Freides, D. (2002). Auditory and visual sustained attention in adolescents prenatally exposed to alcohol. Alcoholism: Clinical and Experimental Research, 26, 263–272. Coles, C. D., Kable, J. A., Dent, D., & Lee, D. (2004). Socio-cognitive habilitation with children with FAS. Alcoholism: Clinical and Experimental Research, 28, 719A. Collin, C. (2006). Substance abuse issues and public policy in Canada: V. alcohol and related harms. Retrieved November 20, 2009, from http://www2.parl.gc.ca/Content/LOP/ResearchPublications/ prb0620-e.htm Comblain, A. (1994). Working memory in Down’s syndrome: training the rehearsal strategy. Down Syndrome Research and Practice, 2, 123–126. Connor, P., & Mahurin, R. (2001). A preliminary study of working memory in fetal alcohol damage using fMRI. Journal of the International Neuropsychological Society, 7, 206. Connor, P. D., Sampson, P. D., Bookstein, F. L., Barr, H. M., & Streissguth, A. P. (2000). Direct and indirect effects of prenatal alcohol damage on executive function. Developmental Neuropsychology, 18, 331–354. Conry, J. (1990). Neuropsychological deficits in fetal alcohol syndrome and fetal alcohol effects. Alcoholism: Clinical and Experimental Research, 14, 650–655. Cook, T. R., Keiner, J. A., & Yen, A. (1990). Ethanol causes accelerated Gl arrest in differentiating HL-60 cells. Alcoholism: Clinical and Experimental Research, 14, 695–703. Doig, J., McLennan, J. D., & Gibbard, W. B. (2008). Medication effects on symptoms of attention deficit/ hyperactivity disorder in children with fetal alcohol spectrum disorder. Journal of Child and Adolescent Psychopharmacology, 18, 365–371. Ginsburg, H. P., & Baroody, A. J. (1990). Test of early mathematics ability. Austin: PRO-ED. Grant, T., Huggins, J., Connor, P., Pedersen, J. Y., Whitney, N., & Streissguth, A. (2004). A pilot community intervention for young women with fetal alcohol spectrum disorders. Community Mental Health Journal, 40, 499–511. Guerri, C., Pascual, M., Garcia-Minguillán, M. C., Charness, M. E., Wilkemeyer, M. F., Klinstova, A. Y., et al. (2005). Fetal alcohol effects: potential treatments from basic science. Alcoholism: Clinical and Experimental Research, 29, 1074–1079. Habbick, B. F., Nanson, J. L., Snyder, R. E., Casey, R. E., & Schulman, A. L. (1996). Foetal alcohol syndrome in Saskatchewan: unchanged incidence in a 20-year period. Canadian Journal of Public Health, 87, 204–207. Howell, K. K., Lynch, M. E., Platzman, K. A., Smith, G. H., & Coles, C. D. (2006). Prenatal alcohol exposure and ability, academic achievement, and school functioning in adolescence: a longitudinal follow-up. Journal of Pediatric Psychology, 31, 116–126. Hynd, G. W., Semrud-Clikeman, M., Lorys, A. R., Novey, E. S., Ellopulos, D., & Lyytinen, H. (1991). Corpus callosum morphology in attention deficit-hyperactivity disorder: morphometric analysis of MRI. Journal of Learning Disabilities, 24, 141–146. 164 J Dev Phys Disabil (2011) 23:143–167 Jacobson, S. W., Jacobson, J. L., Sokol, R. J., Martier, S. S., & Ager, J. W. (1993). Prenatal alcohol exposure and infant information processing ability. Child Development, 64, 1706–1721. Jacobson, S. W., Jacobson, J. L., & Sokol, R. J. (1994). Effects of fetal alcohol exposure on infant reaction time. Alcoholism: Clinical and Experimental Research, 18, 1125–1132. Janzen, L. A., Nanson, J. L., & Block, G. W. (1995). Neuropsychological evaluation of preschoolers with fetal alcohol syndrome. Neurotoxicology and Teratology, 17, 273–279. Jones, K. L., & Smith, D. W. (1973). Recognition of the fetal alcohol syndrome in early infancy. The Lancet, 2, 999–1001. Jones, K. L., Smith, D. W., Ulleland, C. N., & Streissguth, A. P. (1973). Pattern of malformation in offspring of chronic alcoholic mothers. The Lancet, 1, 1267–1271. Kable, J. A., & Coles, C. D. (2004). The impact of prenatal alcohol exposure on neurophysiological encoding of environmental events at six months. Alcoholism: Clinical and Experimental Research, 28, 489–496. Kable, J. A., Coles, C. D., & Taddeo, E. (2007). Socio-cognitive habilitation using the math interactive learning experience program for alcohol-affected children. Alcoholism: Clinical and Experimental Research, 31, 1425–1434. Kalberg, W. O., & Buckley, D. (2007). FASD: what types of intervention and rehabilitation are useful? Neuroscience and Biobehavioral Review, 31, 278–285. Kelly, S. J., Day, N., & Streissguth, A. P. (2000). Effects of prenatal alcohol exposure on social behavior in humans and other species. Neurotoxicology and Teratology, 22, 143–149. Kodituwakku, P. W., Handmaker, N. S., Cutler, S. K., Weathersby, E. K., & Handmaker, S. D. (1995). Specific impairments in self-regulation in children exposed to alcohol prenatally. Alcoholism: Clinical and Experimental Research, 19, 1558–1564. Kotch, L. E., & Sulik, K. K. (1992). Experimental fetal alcohol syndrome: proposed pathogenic basis for a variety of associated facial and brain anomalies. American Journal of Medical Genetics, 44, 168–176. Kyskan, C. E., & Moore, T. E. (2005). Global perspectives on fetal alcohol syndrome: assessing practices, policies, and campaigns in four English-speaking countries. Canadian Psychology, 46, 153–165. Larkby, C., & Day, N. (1997). The effects of prenatal alcohol exposure. Alcohol Health and Research World, 21, 192–198. Livy, D. J., Miller, E. K., Maier, S. E., & West, J. R. (2003). Fetal alcohol exposure and temporal vulnerability: effects of binge-like alcohol exposure on the developing rat hippocampus. Neuro- toxicology and Teratology, 25, 447–458. Loomes, C., Rasmussen, C., Pei, J., Manji, S., & Andrew, G. (2008). The effect of rehearsal training on working memory span of children with fetal alcohol spectrum disorder. Research in Developmental Disabilities, 29, 113–124. Maier, S. E., & West, J. R. (2001). Drinking patterns and alcohol-related birth defects. Alcohol Research & Health, 25, 168–174. Malisza, K. L., Allman, A., Shiloff, D., Jakobson, L., Longstaffe, S., & Chudley, A. E. (2005). Evaluation of spatial working memory function in children and adults with fetal alcohol spectrum disorders: a functional magnetic resonance imaging study. Pediatric Research, 58, 1150–1157. Marion, S. D., Kilian, S. C., Naramor, T. L., & Brown, W. S. (2003). Normal development of bimanual coordination: visuomotor and interhemispheric contributions. Developmental Neuropsychology, 23, 399–421. Mattson, S. N., & Riley, E. P. (1998). A review of the neurobehavioral deficits in children with fetal alcohol syndrome and prenatal exposure to alcohol. Alcoholism: Clinical and Experimental Research, 22, 279–294. Mattson, S. N., Riley, E. P., Jernigan, T. L., Ehlers, C. L., Delis, D. C., Jones, K. L., et al. (1992). Fetal alcohol syndrome: a case report of neuropsychological, MRI, and EEG assessment of two children. Alcoholism: Clinical and Experimental Research, 16, 1001–1003. Mattson, S. N., Riley, E. P., Jernigan, T. L., Garcia, A., Kaneko, W. M., Ehlers, C. L., et al. (1994). A decrease in the size of the basal ganglia following prenatal alcohol exposure: a preliminary report. Neurotoxicology and Teratology, 16, 283–289. Mattson, S. N., Gramling, L., Riley, E. P., Delis, D. C., & Jones, K. L. (1996). Global-local processing in children prenatally exposed to alcohol. Child Neuropsychology, 2, 165–175. Mattson, S. N., Riley, E. P., Delis, D. C., Stern, C., & Jones, K. L. (1996). Verbal learning and memory in children with fetal alcohol syndrome. Alcoholism: Clinical and Experimental Research, 20, 810–816. Mattson, S. N., Riley, E. P., Gramling, L., Delis, D. C., & Jones, K. L. (1997). Heavy prenatal alcohol exposure with or without physical features of fetal alcohol syndrome leads to IQ deficits. Journal of Pediatrics, 131, 718–721. J Dev Phys Disabil (2011) 23:143–167 165 Mattson, S. N., Goodman, A. M., Caine, C., Delis, D. C., & Riley, E. P. (1999). Executivefunctioning in children with heavy prenatal alcohol exposure. Alcoholism: Clinical and Experimental Research, 23, 1808–1815. Mattson, S. N., Schonfeld, A. M., & Riley, E. P. (2001). Teratogenic effects of alcohol on brain and behavior. Alcohol Research and Health, 25, 185–191. May, P. A., & Gossage, J. P. (2001). Estimating the prevalence of fetal alcohol syndrome: a summary. Alcohol Research and Health, 25, 159–167. McGough, N. N. H., Thomas, J. D., Dominguez, H. D., & Riley, E. P. (2009). Insulin-like growth factor-I mitigates motor coordination deficits associated with neonatal alcohol exposure in rats. Neuro- toxicology and Teratology, 31, 40–48. Meyer, L. S., Kotch, L. E., & Riley, E. P. (1990). Alterations in gait following ethanol exposure during the brain growth spurt in rats. Alcoholism: Clinical and Experimental Research, 14, 23–27. Mihalick, S. M., Crandall, J. E., Langlois, J. C., Krienke, J. D., & Dube, W. V. (2001). Prenatal ethanol exposure, generalized learning impairment, and medial prefrontal cortical deficits in rats. Neuro- toxicology and Teratology, 23, 453–462. Miller, M. W. (1993). Migration of cortical neurons is altered by gestational exposure to ethanol. Alcoholism: Clinical and Experimental Research, 17, 304–314. Miller, M. W. (1996). Limited ethanol exposure selectively alters the proliferation of precursor cells in the cerebral cortex. Alcoholism: Clinical and Experimental Research, 20, 139–143. Mills, R. M. T., McLennan, J. D., & Caza, M. M. (2006). Mental health and other service use by young children with fetal alcohol spectrum disorder. Journal of FAS International, 4(1), 1–11. Nash, K., Rovet, T., Greenbaum, R., Fantus, E., Nulman, I., & Koren, G. (2006). Identifying the behavioural phenotype in fetal alcohol spectrum disorder: sensitivity, specificity and screening protocol. Archives of Women’s Mental Health, 9, 181–186. Niccols, A. (2007). Fetal alcohol syndrome and the developing socio-emotional brain. Brain and Cognition, 65, 135–142. O’Connor, M. J., Frankel, F., Paley, B., Schonfeld, A. M., Carpenter, E., Laugeson, E. A., et al. (2006). A controlled social skills training for children with fetal alcohol spectrum disorders. Journal of Consulting and Clinical Psychology, 74, 639–648. Osterrieth, P. A. (1944). Le test de copie d’une figure complexe. Archives de Psychologie, 30, 206–356. Parke, R. D. (2004). The society for research in child development at 70: progress and promise. Child Development, 75, 1–24. Pelham, W. E., Jr., Harper, G. W., McBurnett, K., Milich, R., Murphy, D. A., Clinton, J., et al. (1990). Methylphenidate and baseball playing in ADHD children: who’s on first? Journal of Consulting and Clinical Psychology, 58, 130–133. Pennington, B. F., & Ozonoff, S. (1996). Executive functions and developmental psychopathology. Journal of Child Psychology and Psychiatry, 37, 51–87. Premji, S., Benzies, K., Serrett, K., & Hayden, K. A. (2006). Research-based interventions for children and youth with a fetal alcohol spectrum disorder: revealing the gap. Child: Care, Health and Development, 33, 389–397. Rasmussen, C. (2005). Executive functioning and working memory in fetal alcohol spectrum disorder. Alcoholism: Clinical and Experimental Research, 29, 1359–1367. Rasmussen, C., Talwar, V., Loomes, C., & Andrew, G. (2008). Brief report: lie telling in children with fetal alcohol spectrum disorder. Journal of Pediatric Psychology, 33, 220–226. Rey, A. (1941). L’examen psychologique dans les cas d’encephalopathie traumatique. Archives de Psychologie, 28, 286–340. Riikonen, R., Salonen, I., Partanen, K., & Verho, S. (1999). Brain perfusion SPECT and MRI in foetal alcohol syndrome. Developmental Medicine and Child Neurology, 41, 652–659. Riley, R. P., & McGee, C. L. (2005). Fetal alcohol spectrum disorders: an overview with emphasis on changes in brain and behavior. Experimental Biology and Medicine, 230, 357–365. Riley, E. P., Mattson, S. N., Sowell, E. R., Jernigan, T. L., Sobel, D. F., & Jones, K. L. (1995). Abnormalities of the corpus callosum in children prenatally exposed to alcohol. Alcoholism: Clinical and Experimental Research, 19, 1198–1202. Riley, E. P., Mattson, S. N., Li, T., Jacobson, S. W., Coles, C. D., Kodituwakku, P. W., et al. (2003). Neurobehavioral consequences of prenatal alcohol exposure: an international perspective. Alcoholism: Clinical and Experimental Research, 27, 362–373. Robinson, G. C., Conry, J. L., & Conry, R. F. (1987). Clinical profile and prevalence of fetal alcohol syndrome in an isolated community in British Columbia. Canadian Medical Association Journal, 137, 203–207. 166 J Dev Phys Disabil (2011) 23:143–167 Roebuck, T. M., Simmons, R. W., Mattson, S. M., & Riley, E. P. (1998). Prenatal exposure to alcohol affects the ability to maintain postural balance. Alcoholism: Clinical and Experimental Research, 22, 252–258. Roebuck, T. M., Mattson, S. N., & Riley, E. P. (1999). Behavioral and psychosocial profiles of alcohol- exposed children. Alcoholism: Clinical and Experimental Research, 23, 1070–1076. Roebuck, T. M., Mattson, S. N., & Riley, E. P. (2002). Interhemispheric transfer in children with heavy prenatal alcohol exposure. Alcoholism: Clinical and Experimental Research, 26, 1863–1871. Roebuck-Spencer, T. M., Mattson, S. N., Marion, S. D., Brown, W. S., & Riley, E. P. (2004). Bimanual coordination in alcohol-exposed children: role of the corpus callosum. Journal of the International Neuropsychological Society, 10, 536–548. Ryan, S. H., Williams, J. K., & Thomas, J. D. (2008). Choline supplementation attenuates learning deficits associated with neonatal alcohol exposure in the rat: effects of varying the timing of choline administration. Brain Research, 1237, 91–100. Sampson, P. D., Streissguth, A. P., Bookstein, F. L., Little, R. E., Clarren, S. K., Dehaene, P., et al. (1997). Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. Teratology, 56, 317–326. Shaw, P., Greenstein, D., Lerch, J., Clasen, L., Lenroot, R., Gogtay, N., et al. (2006). Intellectual ability and cortical development in children and adolescents. Nature, 440, 676–679. Simmons, R. W., Wass, T., Thomas, J. D., & Riley, E. P. (2002). Fractionated simple and choice reaction time in children with prenatal exposure to alcohol. Alcoholism: Clinical and Experimental Research, 26, 1412–1419. Singh, S. P., Ehmann, S., & Snyder, A. K. (1996). Ethanol-induced changes in insulin-like growth factors and IGF gene expression in the fetal brain. Proceedings of the Society for Experimental Biology and Medicine, 212, 349–354. Snyder, J., Nanson, J., Snyder, R., & Block, G. (1997). A study of stimulant medication in children with FAS. In A. Streissguth & J. Kanter (Eds.), The challenge of fetal alcohol syndrome: Overcoming secondary disabilities (pp. 64–77). Seattle: University of Washington. Sood, B., Delaney-Black, V., Covington, C., Nordstorm-Klee, B., Ager, J., Templin, T., et al. (2001). Prenatal alcohol exposure and childhood behavior at age 6 to 7 years: I. Dose–response effect. Pediatrics, 108, 1–9. Sowell, E. R., Jernigan, T. L., Mattson, S. N., Riley, E. P., Sobel, D. F., & Jones, K. L. (1996). Alcoholism: Clinical and Experimental Research, 20, 31–34. Sowell, E. R., Mattson, S. N., Thompson, P. M., Jernigan, T. L., Riley, E. P., & Toga, A. W. (2001). Mapping callosal morphology and cognitive correlates: effects of heavy prenatal alcohol exposure. Neurology, 57, 235–244. Sowell, E. R., Thompson, P. M., Mattson, S. N., Tessner, K. D., Jernigan, T. L., Riley, E. P., et al. (2002). Regional brain shape abnormalities persist into adolescence after heavy prenatal alcohol exposure. Cerebral Cortex, 12, 856–865. Sowell, E. R., Johnson, A., Kan, E., Lu, L. H., Van Horn, J. D., Toga, A. W., et al. (2008). Mapping white matter integrity and neurobehavioral correlates in children with fetal alcohol spectrum disorders. The Journal of Neuroscience, 28, 1313–1319. Sowell, E. R., Mattson, S. N., Kan, E., Thompson, P. M., Riley, E. P., & Toga, A. W. (2008). Abnormal cortical thickness and brain-behavior correlation patterns in individuals with heavy prenatal alcohol exposure. Cerebral Cortex, 18, 136–144. Spadoni, A. D., McGee, C. L., Fryer, S. L., & Riley, E. P. (2007). Neuroimaging and fetal alcohol spectrum disorders. Neuroscience and Biobehavioral Reviews, 31, 239–245. Square, D. (1997). Fetal alcohol syndrome epidemic on Manitoba reserve. Canadian Medical Association Journal, 157, 59–60. Stade, B., Unger, W. J., Stevens, B., Beyene, J., & Koren, G. (2006). The burden of prenatal exposure to alcohol: measurement of cost. Journal of FAS International, 4(5), 1–14. Streissguth, A. P., Randels, S. P., & Smith, D. F. (1991). A test-retest study of intelligence in patients with fetal alcohol syndrome: implications for care. Journal of the American Academy of Child and Adolescent Psychiatry, 30, 584–587. Streissguth, A., Barr, H., Kogan, J., & Bookstein, F. (1997). Primary and secondary disabilities in fetal alcohol syndrome. In A. Streissguth & J. Kanter (Eds.), The challenge of fetal alcohol syndrome: Overcoming secondary disabilities (pp. 25–39). Seattle: University of Washington. Sutherland, R. J., McDonald, R. J., & Savage, D. D. (1997). Prenatal exposure to moderate levels of ethanol can have long-lasting effects on hippocampal synaptic plasticity in adult offspring. Hippocampus, 7, 232–238. J Dev Phys Disabil (2011) 23:143–167 167 Thomas, J. D., Wasserman, E. A., West, J. R., & Goodlett, C. R. (1996). Behavioral deficits induced by bingelike exposure to alcohol in neonatal rats: importance of developmental timing and number of episodes. Developmental Psychobiology, 29, 433–452. Thomas, S. E., Kelly, S. J., Mattson, S. N., & Riley, E. P. (1998). Comparison of social abilities of children with fetal alcohol syndrome to those of children with similar IQ scores and normal controls. Alcoholism: Clinical and Experimental Research, 22, 528–533. Thomas, J. D., La Fiette, M. H., Quinn, V. R. E., & Riley, E. P. (2000). Neonatal choline supplementation ameliorates the effects of prenatal alcohol exposure on a discrimination learning task in rats. Neurotoxicology and Teratology, 22, 703–711. Thomas, J. D., Garrison, M., & O’Neill, T. M. (2004). Perinatal choline supplementation attenuates behavioral alterations associated with neonatal alcohol exposure in rats. Neurotoxicology and Teratology, 26, 35–45. Thomas, J. D., O’Neill, T. M., & Dominquez, H. D. (2004). Perinatal choline supplementation does not mitigate motor coordination deficits associated with neonatal alcohol exposure in rats. Neuro- toxicology and Teratology, 26, 223–229. Tsai, J., Floyd, R. L., & Bertrand, J. (2007). Tracking binge drinking among U.S. childbearing–age women. Preventive Medicine, 44, 298–302. Uecker, A., & Nadel, L. (1996). Spatial locations gone awry: Object and spatial memory deficits in children with fetal alcohol syndrome. Neuropsychologia, 34, 209–223. Wacha, V. H., & Obrzut, J. E. (2007). Effects of fetal alcohol syndrome on neuropsychological function. Journal of Developmental Physical Disabilities, 19, 217–226. Williams, R. J., Odaibo, F. S., & McGee, J. M. (1999). Incidence of fetal alcohol syndrome in Northeastern Manitoba. Canadian Journal of Public Health, 90, 192–194. Wirt, R. D., Lachar, D., Klinedinst, J. K., & Seat, P. D. (1984). Multidimensional description of child personality: A manual for the Personality Inventory for Children. Los Angeles: Western Psychological Services. Zevenbergen, A. A., & Ferraro, F. R. (2001). Assessment and treatment of fetal alcohol syndrome in children and adolescents. Journal of Developmental and Physical Disabilities, 13, 123–136.