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CORK Bibliography: Prenatal Alcohol Exposure

79 citations. January 2009 to present

Prepared: September 2011

Burden MJ; Andrew C; Saint-Amour D; Meintjes EM; Molteno CD; Hoyme HE et al. The effects of fetal alcohol syndrome on response execution and inhibition: An event-related potential study. Alcoholism: Clinical and Experimental Research 33(11): 1994-2004, 2009. (77 refs.)

Background: Both executive function deficits and slower processing speed are characteristic of children with fetal alcohol exposure, but the temporal dynamics of neural activity underlying cognitive processing deficits in fetal alcohol spectrum disorder have rarely been studied. To this end, event-related potentials (ERPs) were used to examine the nature of alcohol-related effects on response inhibition by identifying differences in neural activation during task performance. Methods: We recorded ERPs during a Go/No-go response inhibition task in 2 groups of children in Cape Town, South Africa (M age = 11.7 years; range = 10 to 13)-one diagnosed with fetal alcohol syndrome (FAS) or partial FAS (FAS/PFAS; n = 7); the other, a control group whose mothers abstained or drank only minimally during pregnancy (n = 6). Children were instructed to press a "Go" response button to all letter stimuli presented except for the letter "X," the "No-go" stimulus, which occurred relatively infrequently. Results: Task performance accuracy and reaction time did not differ between groups, but differences emerged for 3 ERP components-P2, N2, and P3. The FAS/PFAS group showed a slower latency to peak P2, suggesting less efficient processing of visual information at a relatively early stage (similar to 200 ms after stimulus onset). Moreover, controls showed a larger P2 amplitude to Go versus No-go, indicating an early discrimination between conditions that was not seen in the FAS/PFAS group. Consistent with previous literature on tasks related to cognitive control, the control group showed a well-defined, larger N2 to No-go versus Go, which was not evident in the FAS/PFAS group. Both groups showed the expected larger P3 amplitude to No-go versus Go, but this condition difference persisted in a late slow wave for the FAS/PFAS group, suggesting increased cognitive effort. Conclusions: The timing and amplitude differences in the ERP measures suggest that slower, less efficient processing characterizes the FAS/PFAS group during initial stimulus identification. Moreover, the exposed children showed less sharply defined components throughout the stimulus and response evaluation processes involved in successful response inhibition. Although both groups were able to inhibit their responses equally well, the level of neural activation in the children with FAS/PFAS was greater, suggesting more cognitive effort. The specific deficits in response inhibition processing at discrete stages of neural activation may have implications for understanding the nature of alcohol-related deficits in other cognitive domains as well.

Bertrand J. Interventions for children with fetal alcohol spectrum disorders (FASDs): Overview of findings for five innovative research projects. Research in Developmental Disabilities 30(5): 986-1006, 2009

It is well established that prenatal exposure to alcohol causes damage to the developing fetus, resulting in a spectrum of disorders known as fetal alcohol spectrum disorders (FASDs). Although our understanding of the deficits and disturbances associated with FASDs is far from complete, there are consistent findings indicating these are serious, lifelong disabilities-especially when these disabilities result from central nervous system damage. Until recently, information and strategies for interventions specific to individuals with FASDs have been gleaned from interventions used with people with other disabilities and from the practical wisdom gained by parents and clinicians through trial and error or shared through informal networks. Although informative to a limited degree, such interventions have been implemented without being evaluated systematically or scientifically. The purpose of this article is to provide a brief overview of a general intervention framework developed for individuals with FASDs and the methods and general findings of five specific intervention research studies conducted within this framework. The studies evaluated five different interventions in five diverse locations in the United States, with different segments of the FASD population. Nonetheless, all participants showed improvement in the target behaviors or skills, with four studies achieving statistical significance in treatment Outcomes. important lessons emerged from these five interventions that may explain Success: including parent education or training, teaching children specific skills they would usually learn by observation or abstraction, and integration into existing systems of treatment. A major implication of these research studies for families dealing with FASDs is that there are now interventions available that can address their children's needs and that can be presented as scientifically validated and efficacious to intervention agents such as schools, social services, and mental health providers. In the field of FASD research and clinical service, a common theme reported by families has been that clinicians and professionals have been reluctant to diagnose their children because there were no known effective treatments. Results of these five studies dispel that concern by demonstrating several interventions that have been shown to improve the lives of individuals with FASDs and their families.

Kelly SJ; Leggett DC; Cronise K. Sexually dimorphic effects of alcohol exposure during development on the processing of social cues. Alcohol and Alcoholism 44(6): 555-560, 2009. (35 refs.)

Aims: The study used an animal model of fetal alcohol spectrum disorders (FASD) to investigate the impact of alcohol exposure during a period equivalent to all three trimesters in humans on social recognition memory. It was hypothesized that the effects on specific aspects of social recognition memory would be sexually dimorphic. Methods: This study exposed rats to ethanol during both the prenatal and early postnatal periods. Two control groups included a group exposed to the administration procedures but not ethanol and a non-treated group. At similar to 90 days, all rats were tested repeatedly in a test of social recognition memory with a juvenile animal of the same sex. Experimental rats of both sexes were allowed to investigate an unknown juvenile for either 2, 3 or 5 min and then, after a delay of 30, 60, 120 and 180 min, were allowed to investigate the same juvenile for 5 min. Results: Male rats investigated the juvenile for much longer than female rats. Ethanol-exposed male rats showed a deficit in recognition memory that was evident with longer delays when the initial investigation time was either 2- or 3-min long. In contrast, ethanol-exposed female rats showed a deficit in recognition memory only when the initial investigation period was of 2 min. Measurement of oxytocin receptor binding in the amygdala region indicated that ethanol exposure lowered oxytocin receptor binding in females but not males. Conclusions: The results suggest that ethanol exposure during development caused a deficit in memory duration but not encoding in males and a deficit in encoding but not memory duration in females. The deficit in ethanol-exposed females may be related to changes in oxytocin receptors in the amygdala.

Santhanam P; Li ZH; Hu XP; Lynch ME; Coles CD. Effects of prenatal alcohol exposure on brain activation during an arithmetic task: An FMRI study. Alcoholism: Clinical and Experimental Research 33(11): 1901-1908, 2009. (41 refs.)

Background: While behavioral studies have established that prenatal alcohol exposure (PAE) can result in diminished arithmetic processing capability, the underlying neural correlates of this deficit are still unclear. The aim of the present study was to use functional magnetic resonance imaging to determine the effect of PAE on neuronal activation during a subtraction task. Methods: Participants were young adults from a low socio-economic status population who were identified prenatally; the sample consisted of healthy unexposed controls (n = 17) and PAE who were subdivided based on the presence (n = 19) or absence of physical dysmorphic signs (n = 18). Multiple regression analysis was used to determine extent of activation and percent signal change during arithmetic processing, using a letter-matching task as the baseline. Region of interest analysis of activation was performed in the native space and normalized for each individual to compensate for the considerable variability in head size observed in the alcohol-exposed population. Results: An exposure-dependent response was observed in task performance and neuronal activation. Dysmorphic PAE individuals showed significantly lower task-related performance and activation in regions known to be associated with arithmetic processing, including left superior and right inferior parietal regions and medial frontal gyrus, while the nondysmorphic PAE group was generally intermediate but not significantly different from the control group in task performance and activation. Conclusions: Results indicate that there is a range of effects of PAE on arithmetic processing and that the severity of this deficit may be dependent on degree of impairment demonstrated by the exposed individual. Evidence of physical dysmorphia may be indicative of functional damage to regions associated with arithmetic calculation, resulting in markedly impaired neuronal recruitment.

Fryer SL; Schweinsburg BC; Bjorkquist OA; Frank LR; Mattson SN; Spadoni AD et al. Characterization of white matter microstructure in fetal alcohol spectrum disorders. Alcoholism: Clinical and Experimental Research 33(3): 514-521, 2009. (49 refs.)

Exposure to alcohol during gestation is associated with CNS alterations, cognitive deficits, and behavior problems. This study investigated microstructural aspects of putative white matter abnormalities following prenatal alcohol exposure. Diffusion tensor imaging was used to assess white matter microstructure in 27 youth (age range: 8 to 18 years) with (n = 15) and without (n = 12) histories of heavy prenatal alcohol exposure. Voxelwise analyses, corrected for multiple comparisons, compared fractional anisotropy (FA) and mean diffusivity (MD) between groups, throughout the cerebrum. Prenatal alcohol exposure was associated with low FA in multiple cerebral areas, including the body of the corpus callosum and white matter innervating bilateral medial frontal and occipital lobes. Fewer between-group differences in MD were observed. These data provide an account of cerebral white matter microstructural integrity in fetal alcohol spectrum disorders and support extant literature showing that white matter is a target of alcohol teratogenesis. The white matter anomalies characterized in this study may relate to the neurobehavioral sequelae associated with gestational alcohol exposure, especially in areas of executive dysfunction and visual processing deficits.

Guerri C; Bazinet A; Riley EP. Foetal alcohol spectrum disorders and alterations in brain and behaviour. (review). Alcohol and Alcoholism 44(2): 108-114, 2009. (116 refs.)

The term 'Foetal Alcohol Spectrum Disorders (FASD)' refers to the range of disabilities that may result from prenatal alcohol exposure. This article reviews the effects of ethanol on the developing brain and its long-term structural and neurobehavioural consequences. Brain imaging, neurobehavioural and experimental studies demonstrate the devastating consequences of prenatal alcohol exposure on the developing central nervous system (CNS), identifying specific brain regions affected, the range of severity of effects and mechanisms involved. In particular, neuroimaging studies have demonstrated overall and regional volumetric and surface area reductions, abnormalities in the shape of particular brain regions, and reduced and increased densities for white and grey matter, respectively. Neurobehaviourally, FASD consists of a continuum of long-lasting deficits affecting multiple aspects of cognition and behaviour. Experimental studies have also provided evidence of the vulnerability of the CNS to the teratogenic effects of ethanol and have provided new insight on the influence of risk factors in the type and severity of observed brain abnormalities. Finally, the potential molecular mechanisms that underlie the neuroteratological effects of alcohol are discussed, with particular emphasis on the role of glial cells in long-term neurodevelopmental liabilities.

Dodge NC; Jacobson JL; Molteno CD; Meintjes EM; Bangalore S; Diwadkar V et al. Prenatal alcohol exposure and interhemispheric transfer of tactile information: Detroit and Cape Town findings. Alcoholism: Clinical and Experimental Research 33(9): 1628-1637, 2009. (55 refs.)

Background: Previous research has demonstrated that heavy prenatal alcohol exposure affects the size and shape of the corpus callosum (CC) and compromises interhemispheric transfer of information. The aim of this study was to confirm the previous reports of poorer performance on a finger localization test (FLT) of interhemispheric transfer in a cohort of heavily exposed children and to extend these findings to a cohort of moderately exposed young adults. Methods: In Study 1, the FLT was administered to 40 heavily exposed and 23 nonexposed children from the Cape Coloured community of Cape Town, South Africa, who were evaluated for fetal alcohol syndrome (FAS) dysmorphology and growth. Anatomical images of the CC were obtained using structural MRI on a subset of these children. In Study 2, the FLT was administered to a cohort of 85 moderate-to-heavily exposed young adults participating in a 19-year follow-up assessment of the Detroit Prenatal Alcohol Exposure cohort, whose alcohol exposure had been ascertained prospectively during gestation. Results: In Study 1, children with FAS showed more transfer-related errors than controls after adjustment for confounding, and increased transfer-related errors were associated with volume reductions in the isthmus and splenium of the CC. In Study 2, transfer-related errors were associated with quantity of alcohol consumed per occasion during pregnancy. More errors were made if the mother reported binge drinking (>= 5 standard drinks) during pregnancy than if she drank regularly (M >= 1 drink/day) without binge drinking. Conclusions: These findings confirm a previous report of impaired interhemispheric transfer of tactile information in children heavily exposed to alcohol in utero and extend these findings to show that these deficits are also seen in more moderately exposed individuals, particularly those exposed to binge-like pregnancy drinking.

Kelly Y; Sacker A; Gray R; Kelly J; Wolke D et al. Light drinking in pregnancy, a risk for behavioural problems and cognitive deficits at 3 years of age? International Journal of Epidemiology 38(1): 129-140, 2009. (50 refs.)

Background: The objective of this study was to determine whether there was an association between mothers' light drinking during pregnancy and risk of behavioural problems, and cognitive deficits in their children at age 3 years. Methods Data from the first two sweeps of the nationally representative prospective UK Millennium Cohort study were used. Drinking patterns during pregnancy and behavioural and cognitive outcomes were assessed during interviews and home visits. Behavioural problems were indicated by scores falling above defined clinically relevant cut-offs on the parent-report version of the Strengths and Difficulties Questionnaire (SDQ). Cognitive ability was assessed using the naming vocabulary subscale from the British Ability Scale (BAS) and the Bracken School Readiness Assessment (BSRA). Results There was a J-shaped relationship between mothers drinking during pregnancy and the likelihood of high scores (above the cut-off) on the total difficulties scale of the SDQ and the conduct problems, hyperactivity and emotional symptom SDQ subscales. Children born to light drinkers were less likely to score above the cut-offs compared with children of abstinent mothers. Children born to heavy drinkers were more likely to score above the cut-offs compared with children of abstinent mothers. Boys born to mothers who had up to 1-2 drinks per week or per occasion were less likely to have conduct problems (OR 0.59, 95% CI 0.45-0.77) and hyperactivity (OR 0.71, 95% CI 0.54-0.94). These effects remained in fully adjusted models. Girls were less likely to have emotional symptoms (OR 0.72, 95% CI 0.51-1.01) and peer problems (OR 0.68, 95% CI 0.52-0.92) compared with those born to abstainers. These effects were attenuated in fully adjusted models. Boys born to light drinkers had higher cognitive ability test scores [standard deviations, (95% CI)] BAS 0.15 (0.08-0.23) BSRA 0.24 (0.16-0.32) compared with boys born to abstainers. The difference for BAS was attenuated on adjustment for socio-economic factors, whilst the difference for BSRA remained statistically significant. Conclusions: Children born to mothers who drank up to 1-2 drinks per week or per occasion during pregnancy were not at increased risk of clinically relevant behavioural difficulties or cognitive deficits compared with children of abstinent mothers. Heavy drinking during pregnancy appears to be associated with behavioural problems and cognitive deficits in offspring at age 3 years whereas light drinking does not.

Astley SJ; Aylward EH; Olson HC; Kerns K; Brooks A; Coggins TE et al. Magnetic resonance imaging outcomes from a comprehensive magnetic resonance study of children with fetal alcohol spectrum disorders. Alcoholism: Clinical and Experimental Research 33(10): 1671-1689, 2009. (68 refs.)

Background: Magnetic resonance (MR) technology offers noninvasive methods for in vivo assessment of neuroabnormalities. Methods: A comprehensive neuropsychological/psychiatric battery, coupled with MR imaging, (MRI), MR spectroscopy (MRS), and functional MRI (fMRI) assessments, were administered to children with fetal alcohol spectrum disorders (FASD) to determine if global and/or focal abnormalities could be identified, and distinguish diagnostic subclassifications across the spectrum. The 4 study groups included: (i) fetal alcohol syndrome (FAS)/partial FAS (PFAS); (ii) static encephalopathy/alcohol exposed (SE/AE); (iii) neurobehavioral disorder/alcohol exposed (ND/AE) as diagnosed with the FASD 4-Digit Code; and (iv) healthy peers with no prenatal alcohol exposure. Presented here are the MRI assessments that were used to compare the sizes of brain regions between the 4 groups. The neuropsychological/behavioral, MRS, and fMRI outcomes are reported separately. Results : Progressing across the 4 study groups from Controls to ND/AE to SE/AE to FAS/PFAS, the mean absolute size of the total brain, frontal lobe, caudate, putamen, hippocampus, cerebellar vermis, and corpus callosum length decreased incrementally and significantly. The FAS/PFAS group (the only group with the 4-Digit FAS facial phenotype) had disproportionately smaller frontal lobes relative to all other groups. The FAS/PFAS and SE/AE groups [the 2 groups with the most severe central nervous system (CNS) dysfunction] had disproportionately smaller caudate regions relative to the ND/AE and Control groups. The prevalence of subjects in the FAS/PFAS, SE/AE, and ND/AE groups that had 1 or more brain regions, 2 or more SDs below the mean size observed in the Control group was 78, 58, and 43%, respectively. Significant correlations were observed between size of brain regions and level of prenatal alcohol exposure, magnitude of FAS facial phenotype, and level of CNS dysfunction. Conclusions: Magnetic resonance imaging provided further validation that ND/AE, SE/AE, and FAS/PFAS as defined by the FASD 4-Digit Code are 3 clinically distinct and increasingly more affected diagnostic subclassifications under the umbrella of FASD. Neurostructural abnormalities are present across the spectrum. MRI could importantly augment diagnosis of conditions under the umbrella of FASD, once population-based norms for structural development of the human brain are established.

Youngentob SL; Glendinning JI. Fetal ethanol exposure increases ethanol intake by making it smell and taste better. Proceedings of the National Academy of Sciences 106(13): 5359-5364, 2009

Human epidemiologic studies reveal that fetal ethanol exposure is highly predictive of adolescent ethanol avidity and abuse. Little is known about how fetal exposure produces these effects. It is hypothesized that fetal ethanol exposure results in stimulus-induced chemosensory plasticity. Here, we asked whether gestational ethanol exposure increases postnatal ethanol avidity in rats by altering its taste and odor. Experimental rats were exposed to ethanol in utero via the dam's diet, whereas control rats were either pair-fed an iso-caloric diet or given food ad libitum. We found that fetal ethanol exposure increased the taste-mediated acceptability of both ethanol and quinine hydrochloride (bitter), but not sucrose (sweet). Importantly, a significant proportion of the increased ethanol acceptability could be attributed directly to the attenuated aversion to ethanol's quinine-like taste quality. Fetal ethanol exposure also enhanced ethanol intake and the behavioral response to ethanol odor. Notably, the elevated intake of ethanol was also causally linked to the enhanced odor response. Our results demonstrate that fetal exposure specifically increases ethanol avidity by, in part, making it taste and smell better. More generally, they establish an epigenetic chemosensory mechanism by which maternal patterns of drug use can be transferred to offspring. Given that many licit (e.g., tobacco products) and illicit (e.g., marijuana) drugs have noteworthy chemosensory components, our findings have broad implications for the relationship between maternal patterns of drug use, child development, and postnatal vulnerability.

Simmons RW; Levy SS; Riley EP; Madra NM; Mattson SN. Central and peripheral timing variability in children with heavy prenatal alcohol exposure. Alcoholism: Clinical and Experimental Research 33(3): 400-407, 2009. (53 refs.)

The study examined whether prenatal alcohol exposure is associated with increased motor timing variability when the timing response is partitioned into central clock variability, which indexes information processing at the central nervous system (CNS) level and motor delay variability, which reflects timing processes at the level of the peripheral nervous system. Eighteen children with histories of prenatal alcohol exposure and 22 control children were assigned to young (7 to 11 years) or older (12 to 17 years) groups. Children tapped a single response key with the index finger in synchrony with a series of externally generated tones (the paced phase). At the conclusion of these tones, children continued tapping (the continuation phase) while attempting to maintain the same rate of tapping imposed by the paced phase. Two blocks of tapping were completed with inter-tone-intervals set at either 400 or 900 milliseconds. Inter-response interval, central clock variability, and motor delay variability produced during the continuation phase were the dependent variables. Mean inter-response interval for the 4 groups did not differ for either time interval. Central clock variability produced by the young alcohol-exposed group was significantly greater than the two older groups for the 400 millisecond interval and all other groups for the 900 millisecond interval. Motor delay variability produced by the young alcohol-exposed group was significantly greater than the other three groups for both time intervals. Central and motor delay variability in children with and without alcohol exposure was directly related to the duration of the interval to be reproduced. Central and peripheral timing variability was significantly greater for the young alcohol-exposed children. This atypical timing may be related to the teratogenic effects of alcohol, although the negative effects are limited to younger alcohol-exposed children since there were no differences in central and peripheral timing variability between the older alcohol-exposed children and controls.

Fast DK; Conry J. Fetal alcohol spectrum disorders and the criminal justice system. (review). Developmental Disabilities Research Reviews 15(3): 250-257, 2009. (58 refs.)

The life-long neurological impairments found in people with fetal alcohol spectrum disorders (FASDs), including learning disabilities, impulsivity, hyperactivity, social ineptness, and poor judgment, can increase susceptibility to victimization and involvement in the criminal justice system (CJS). Individuals with FASDs become involved in the CJS as complainants, witnesses, and accused. Their disabilities, resulting from the prenatal alcohol exposure, must be considered at all stages in the legal process. Adverse experiences, such as having a dysfunctional family background, mental health problems, and substance use disorders, are compounding factors. Experiencing physical, sexual, and emotional abuse also increases the risk that these individuals will become involved in the CJS. It is critical that everyone involved in the CJS receives education and training to understand FASD and the implications for the individual offender. A comprehensive medical-legal report, prepared by professionals experienced with FASD, can help judges and lawyers understand the complex interactions among brain damage, genetics and the environment. Corrections workers and probation officers need to comprehend the significance of FASD and how it affects the offender's abilities to understand and follow rules and probation orders. Caregivers and parents need to be involved whenever possible. Early recognition of the disabilities associated with FASDs may help reduce the over-representation of this group in the CJS.

Premji SS; Semenic S. Do Canadian prenatal record forms integrate evidence-based guidelines for the diagnosis of a FASD? Canadian Journal of Public Health 100(4): 274-280, 2009. (58 refs.)

Objectives: Prenatal alcohol exposure is a significant public: health issue with lifelong psychological, emotional and financial costs associated with caring for an affected individual. In 2005, the Public Health Agency of Canada and Health Canada's First Nations and Inuit Health Branch developed evidence-based guidelines for the diagnosis of a Fetal Alcohol Spectrum Disorder (FASD). We examined the extent to which prenatal records across Canadian provinces and territories currently integrate key recommendations from these guidelines. Methods: A content analysis of prenatal record forms retrieved from each Canadian province and territory (N = 12) was conducted to identify all questions or intervention prompts related to prenatal screening, exposure assessment, counseling or referral for maternal alcohol use during pregnancy Findings were reviewed in relation to recommendations extrapolated from the Canadian guidelines and the FASD literature. Results: All the prenatal record forms contained questions to assess maternal alcohol use during pregnancy. However, the dimensions of alcohol consumption assessed and the format, wording and number of items related to each dimension varied markedly across provinces/territories. Only five prenatal record forms included a validated screening tool to identify risky alcohol drinking behaviour. Most of the forms lacked prompts to encourage providers to intervene or refer pregnant clients with high-risk drinking behaviour. Conclusion: Integration of the Canadian recommendations into Canadian prenatal record forms may be an effective public health strategy for helping identify pregnancies at high risk for alcohol exposure, reducing the incidence of a FASD through appropriate prenatal intervention and referral, and facilitating early diagnosis of a FASD.

Rodriguez A; Olsen J; Kotimaa AJ; Kaakinen M; Moilanen I; Henriksen TB et al. Is prenatal alcohol exposure related to inattention and hyperactivity symptoms in children? Disentangling the effects of social adversity. Journal of Child Psychology and Psychiatry and Allied Disciplines 50(9): 1073-1083, 2009. (42 refs.)

Background: Studies concerning whether exposure to low levels of maternal alcohol consumption during fetal development is related to child inattention and hyperactivity symptoms have shown conflicting results. We examine the contribution of covariates related to social adversity to resolve some inconsistencies in the extant research by conducting parallel analyses of three cohorts with varying alcohol consumption and attitudes towards alcohol use. Methods: We compare three population-based pregnancy-offspring cohorts within the Nordic Network on ADHD from Denmark and Finland. Prenatal data were gathered via self-report during pregnancy and birth outcomes were abstracted from medical charts. A total of 21,678 reports concerning inattention and hyperactivity symptoms in children were available from the Strengths and Difficulties Questionnaire or the Rutter Scale completed by parents and/or teachers. Results: Drinking patterns differed cross-nationally. Women who had at least some social adversity (young, low education, or being single) were more likely to drink than those better off in the Finnish cohort, but the opposite was true for the Danish cohorts. Prenatal alcohol exposure was not related to risk for a high inattention-hyperactivity symptom score in children across cohorts after adjustment for covariates. In contrast, maternal smoking and social adversity during pregnancy were independently and consistently associated with an increase in risk of child symptoms. Conclusions: Low doses of alcohol consumption during pregnancy were not related to child inattention/hyperactivity symptoms once social adversity and smoking were taken into account.

Greenbaum RL; Stevens SA; Nash K; Koren G; Rovet J. Social cognitive and emotion processing abilities of children with fetal alcohol spectrum disorders: A comparison with attention deficit hyperactivity disorder. (review). Alcoholism: Clinical and Experimental Research 33(10): 1656-1670, 2009. (110 refs.)

Background: Although children with Fetal Alcohol Spectrum Disorders (FASDs) are at high risk of attention deficit hyperactivity disorder (ADHD), direct comparisons show distinct cognitive phenotypes in the 2 diagnoses. However, these groups have not been directly compared for social problems or social cognition, nor has social cognition been directly examined in FASDs. Objectives: To compare FASDs and ADHD groups on social cognition tasks and determine whether deficient social cognition and emotion processing predict behavioral problems and social skills. Methods: Studied were 33 children with FASDs, 30 with ADHD, and 34 normal controls (NC). All received tasks of social cognition and emotion processing. Parents and teachers rated children on measures of completed questionnaires assessing child's behavioral problems and social skills using the Child Behavior Checklist, Teacher Report Form, and Social Skills Rating Scale. Children received 3 subtests from the Saltzman-Benaiah and Lalonde (2007) Theory of Mind Task as a measure of social cognition and 4 subtests from the Minnesota Test of Affective Processing (Lai et al., 1991) to assess emotion processing. Results : Parents and teachers reported more behavior problems and poorer social skills in children in FASD and ADHD than NC groups. FASDs demonstrated significantly weaker social cognition and facial emotion processing ability than ADHD and NC groups. Regression analyses identified social cognition as a significant predictor of behavior problems and emotion processing as a significant predictor of social skills. Conclusions: Children with FASDs show a distinct behavioral profile from children with ADHD. Difficulties in social cognition and emotion processing in children with FASDs may contribute to their high incidence of social behavioral problems.

Abel EL. Fetal alcohol syndrome: Same old, same old. (editorial). Addiction 104(8): 1274-1275, 2009. (9 refs.)

Wozniak JR; Muetzel RL; Mueller BA; McGee CL; Freerks MA; Ward EE et al. Microstructural corpus callosum anomalies in children with prenatal alcohol exposure: An extension of previous diffusion tensor imaging findings. Alcoholism: Clinical and Experimental Research 33(10): 1825-1835, 2009. (89 refs.)

Background: Several studies have now shown corpus callosum abnormalities using diffusion tensor imaging (DTI) in children with fetal alcohol spectrum disorders (FASD) in comparison with nonexposed controls. The data suggest that posterior regions of the callosum may be disproportionately affected. The current study builds on previous efforts, including our own work, and moves beyond midline corpus callosum to probe major inter-hemispheric white matter pathways with an improved DTI tractographic method. This study also expands on our prior work by evaluating a larger sample and by incorporating children with a broader range of clinical effects including full-criteria fetal alcohol syndrome (FAS). Methods: Participants included 33 children with FASD (8 FAS, 23 partial FAS, 2 static encephalopathy) and 19 nonexposed controls between the ages of 10 and 17 years. Participants underwent DTI scans and intelligence testing. Groups (FASD vs. controls) were compared on fractional anisotropy (FA) and mean diffusivity (MD) in 6 white matter tracts projected through the corpus callosum. Exploratory analyses were also conducted examining the relationships between DTI measures in the corpus callosum and measures of intellectual functioning and facial dysmorphology. Results : In comparison with the control group, the FASD group had significantly lower FA in 3 posterior tracts of the corpus callosum: the posterior mid-body, the isthmus, and the splenium. A trend-level finding also suggested lower FA in the genu. Measures of white matter integrity and cognition were correlated and suggest some regional specificity, in that only posterior regions of the corpus callosum were associated with visual-perceptual skills. Correlations between measures of facial dysmorphology and posterior regions of the corpus callosum were nonsignificant. Conclusions: Consistent with previous DTI studies, these results suggest that microstructural posterior corpus callosum abnormalities are present in children with prenatal alcohol exposure and cognitive impairment. These abnormalities are clinically relevant because they are associated with cognitive deficits and appear to provide evidence of abnormalities associated with prenatal alcohol exposure independent of dysmorphic features. As such, they may yield important diagnostic and prognostic information not provided by the traditional facial characteristics.

Chase JR; Poolman MG; Fell DA. Contribution of NADH increases to ethanol's inhibition of retinol oxidation by human ADH isoforms. Alcoholism: Clinical and Experimental Research 33(4): 571-580, 2009. (50 refs.)

A decrease in retinoic acid levels due to alcohol consumption has been proposed as a contributor to such conditions as fetal alcohol spectrum diseases and ethanol-induced cancers. One molecular mechanism, competitive inhibition by ethanol of the catalytic activity of human alcohol dehydrogenase (EC 1.1.1.1) (ADH) on all-trans-retinol oxidation has been shown for the ADH7 isoform. Ethanol metabolism also causes an increase in the free reduced nicotinamide adenine dinucleotide (NADH) in cells, which might reasonably be expected to decrease the retinol oxidation rate by product inhibition of ADH isoforms. To understand the relative importance of these two mechanisms by which ethanol decreases the retinol oxidation in vivo we need to assess them quantitatively. We have built a model system of 4 reactions: (1) ADH oxidation of ethanol and NAD(+), (2) ADH oxidation of retinol and NAD(+), (3) oxidation of ethanol by a generalized Ethanol(oxidase) that uses NAD(+), (4) NADH(oxidase) which carries out NADH turnover. Using the metabolic modeling package ScrumPy, we have shown that the ethanol-induced increase in NADH contributes from 0% to 90% of the inhibition by ethanol, depending on (ethanol) and ADH isoform. Furthermore, while the majority of flux control of retinaldehyde production is exerted by ADH, Ethanol(oxidase) and the NADH(oxidase) contribute as well. Our results show that the ethanol-induced increase in NADH makes a contribution of comparable importance to the ethanol competitive inhibition throughout the range of conditions likely to occur in vivo, and must be considered in the assessment of the in vivo mechanism of ethanol interference with fetal development and other diseases.

Chiodo LM; Janisse J; Delaney-Black V; Sokol RJ; Hannigan JH. A metric of maternal prenatal risk drinking predicts neurobehavioral outcomes in preschool children. Alcoholism: Clinical and Experimental Research 33(4): 634-644, 2009. (98 refs.)

Fetal Alcohol Spectrum Disorders (FASDs), including Fetal Alcohol Syndrome, continue to be high-incidence developmental disorders. Detection of patterns of maternal drinking that place fetuses at risk for these disorders is critical to diagnosis, treatment, and prevention, but is challenging and often insufficient during pregnancy. Various screens and measures have been used to identify maternal risk drinking but their ability to predict child outcome has been inconsistent. This study hypothesized that a metric of fetal "at-risk" alcohol exposure (ARAE) derived from several indicators of maternal self-reported drinking would predict alcohol-related neurobehavioral dysfunctions in children better than individual measures of maternal alcohol consumption alone. Self-reported peri-conceptional and repeated maternal drinking during pregnancy were assessed with semi-structured interviews and standard screens, i.e., the CAGE, T-ACE, and MAST, in a prospective sample of 75 African-American mothers. Drinking volumes per beverage type were converted to standard quantity and frequency measures. From these individual measures and screening instruments, a simple dichotomous index of prenatal ARAE was defined and used to predict neurobehavioral outcomes in the 4- to 5-year-old offspring of these women. Study outcomes included IQ, attention, memory, visual-motor integration, fine motor skill, and behavior. Statistical analyses controlled for demographic and other potential confounders. The current "at-risk" drinking metric identified over 62% of the mothers as drinking at risk levels-23% more than the selection criterion identified-and outperformed all individual quantity and frequency consumption measures, including averages of weekly alcohol use and "binge" alcohol exposures (assessed as intake per drinking occasion), as well as an estimate of the Maternal Substance Abuse Checklist (Coles et al., 2000), in predicting prenatal alcohol-related cognitive and behavioral dysfunction in 4- to 5-year-old children. A metric reflecting multiple indices of "at-risk" maternal alcohol drinking in pregnancy had greater utility in predicting various prenatal alcohol-related neurobehavioral dysfunction and deficits in children compared to individual measures of maternal self-reported alcohol consumption or a previous maternal substance abuse index. Assessing fetal risk drinking in pregnant women was improved by including multiple indicators of both alcohol consumption and alcohol-related consequences and, if appropriate practical applications are devised, may facilitate intervention by health care workers during pregnancy and potentially reduce the incidence or severity of FASDs.

Gray R. Neurodevelopment and prenatal alcohol consumption. (editorial). Addiction 104(8): 1279-1280, 2009. (7 refs.)

Gray R; Mukherjee RAS; Rutter M. Alcohol consumption during pregnancy and its effects on neurodevelopment: What is known and what remains uncertain. Addiction 104(8): 1270-1273, 2009. (26 refs.)

It has been claimed that mothers' drinking during pregnancy may affect the neurodevelopment of around 1% of all children. If this is true, then prenatal alcohol exposure represents an important risk factor for neurodevelopmental problems, giving rise to a large burden of disability which could be potentially preventable. Evidence to support this idea has come from animal experiments and human observational studies. However, such findings need to be supported by more robust research designs. Because randomized controlled trials in this area are neither feasible nor ethical, suggestions are made for further research making more use of natural experiments.

Banakar MK; Kudlur NS; George S. Fetal alcohol spectrum disorder (FASD). Indian Journal of Pediatrics 76(11): 1173-1175, 2009. (8 refs.)

Fetal alcohol syndrome (FAS)is the leading cause of mental retardation worldwide but is also the foremost preventable cause of neurobehavioral and developmental abnormalities. It is equally important to know spectrum of disorders due to maternal alcoholism during pregnancy such as fetal alcohol spectrum disorder (FASD) in order to identify and treat affected child and family effectively. This article aims to create awareness among practising clinicians most of whom are only aware of phenotypical variant of FASD which is FAS. In this article we discuss those aspects of FASD relevant to the clinician such as: terminological ambiguity, assessment, diagnosis and prevention.

Kfir M; Yevtushok L; Onishchenko S; Wertelecki W; Bakhireva L; Chambers CD et al. Can prenatal ultrasound detect the effects of in-utero alcohol exposure? A pilot study. Ultrasound in Obstetrics and Gynecology 33(6): 683-689, 2009. (16 refs.)

Objectives The aim of this pilot study was to explore possible ultrasound parameters for the earl), detection of alcohol-mediated fetal somatic and central nervous system (CNS) maldevelopment. Maternal alcohol ingestion during pregnancy may lead to fetal alcohol spectrum disorders (FASD), which encompass a broad range of structural abnormalities including growth impairment, specific craniofacial features and CNS abnormalities. Early detection of fetuses at risk of FASD would support earlier interventions. Methods We performed a longitudinal prospective pilot stud), from 2004 to 2006 at two sites in Ukraine. A sample of pregnant women who reported consuming moderate-to-heavy amounts of alcohol participated in a comprehensive maternal interview, and received ultrasound evaluation of fetal growth and specific fetal brain measurements during the second and third trimesters. These measurements were compared with those collected from a group of pregnant women who consumed little-to-no alcohol during pregnancy, and who were recruited and followed in the same manner. Results: From 6745 screened women, 84 moderate-to-heavy alcohol users and 82 comparison women were identified and ultrasound examinations performed. After controlling for maternal smoking, alcohol-exposed fetuses had shorter mean femur length, caval-calvarial distance and frontothalamic measurements in the second trimester (P < 0.05), and alcobol-exposed fetuses also had shorter frontothalamic distance measurements in the third trimester relative to comparison fetuses (P < 0.05). In addition, after controlling for maternal smoking, both mean orbital diameter and biparietal diameter measurements were significantly smaller on average in the alcohol-exposed group in the third trimester relative to comparison fetuses (P < 0.05). Conclusions: Significant differences in selected somatic and brain measurements were noted between alcohol-exposed and comparison fetuses, suggesting these markers may be further explored for clinical utility in prenatal identification of affected children. Further study correlating these findings with alcohol-related physical features of the newborn and subsequent comparisons of neuro-developmental outcomes will help define potential uses of prenatal ultrasound for intervention and prevention of FASD.

Kulaga V; Pragst F; Fulga N; Koren G. Hair analysis of fatty acid ethyl esters in the detection of excessive drinking in the context of Fetal Alcohol Spectrum Disorders. Therapeutic Drug Monitoring 31(2): 261-266, 2009. (76 refs.)

A serious challenge in diagnosing fetal alcohol spectrum disorder (FASD) is the need to document alcohol use during pregnancy. Maternal/paternal alcohol abuse affects the likelihood of fetal alcohol exposure. and hence the occurrence of FASD. The objective of the current study was to document the use of the fatty acid ethyl ester (FAEE) hair test, a biomarker of excessive alcohol use, in parents at risk of having children with FASD and quantify the prevalence of alcohol use in this population. Hair samples submitted for FAEE testing between October 2005 and May 2007 were evaluated (n = 324). Subjects consisted of the parents of at-risk children. Samples were analyzed using a previously published method. Briefly, samples underwent a liquid-liquid extraction, followed by headspace solid phase microextraction, and were then analyzed by gas chromatography-mass spectrometry using deuterated FAEE as internal standards. Limit of detection and limit of quantification values, were between 0.01-0.04 ng/mg and 0.04-0.12 ng/mg, respectively. Positive levels for excessive drinking were ascertained using a Cutoff level of 0.5 ng/mg, offering 90% sensitivity and specificity. The rate of positive hair samples for excessive drinking was 33.3% (32.4% among women and 35.4% among men) (n = 324). The majority of samples (62%) had cumulative FAEE levels above a level that excludes strict abstinence (0.2 ng/mg) and many (19%) were highly positive (above 1.0 ng/mg). Of 26 FAEE hair tests for which women were reported to be pregnant, 38% had FAEE hair levels above 0.2 ng/mg and 19% tested positive for excessive drinking, with levels above 0.5 ng/mg; 12% had levels above 1.0 ng/mg. The high rate of positive FAEE results demonstrates that the FAEE hair test corroborates the clinical suspicion of alcohol use in parents of children at risk for FASD. Our results suggest that FAEE hair analysis may be a powerful tool in detecting excessive alcohol use in the perinatal period.

O'Leary CM; Bower C. Measurement and classification of prenatal alcohol exposure and child outdomes: Time for improvement. (editorial). Addiction 104(8): 1275-1276, 2009. (18 refs.)

Olsen J. Problems in studying fetoxic effects of alcohol. (editorial). Addiction 104(8): 1276-1278, 2009. (9 refs.)

Dolan GP; Stone DH; Briggs AH. A systematic review of continuous performance task research in children prenatally exposed to alcohol. Alcohol and Alcoholism 45(1): 30-38, 2010. (32 refs.)

Aims: The aim of this study was to review systematically, research investigating an association between the continuous performance task (CPT) in children and exposure to alcohol in utero, in order to identify any evidence of a specific deficit in performance. Methods: Seven electronic databases and three websites were searched. Papers were selected in accordance with specific inclusion criteria and scored in terms of the methodological quality using the Newcastle-Ottawa score. Marked methodological heterogeneity limited the validity of any statistical meta-analysis and a descriptive synthesis was performed instead. Results: A total of 14 papers were identified for inclusion. There was no consistent evidence of any association between prenatal alcohol exposure and correct responses, reaction time, commission or omission errors during CPT testing. Apparent trends in the reported results, however, suggest that a potential effect might have been missed. Conclusions: Identifying a specific profile of CPT performance may assist in the detection and management of attention deficits amongst children with prenatal alcohol exposure. Future research with more consistent measures of exposure and outcome is, however, required before any valid generalizations about CPT performance can be made.

Coles CD; Lynch ME; Kable JA; Johnson KC; Goldstein FC. Verbal and nonverbal memory in adults prenatally exposed to alcohol. Alcoholism: Clinical and Experimental Research 34(5): 897-906, 2010. (42 refs.)

Background: Neurocognitive effects of prenatal alcohol exposure in adulthood are not well documented. Questions persist regarding the extent to which there are specific, measurable effects beyond those associated with global ability deficits, whether individuals without the full fetal alcohol syndrome (FAS) demonstrate alcohol-related cognitive impairments, and whether observed memory effects are specific to a particular modality, i.e., verbal vs. visual/spatial domains. Methods: In this study, verbal and nonverbal selective reminding paradigms were used to assess memory function in 234 young adults (M age: 22.78, SD: 1.79). Alcohol exposure was quantified prenatally. Alcohol groups included: Individuals with physical effects of alcohol exposure (Dysmorphic group, n = 47); Exposed individuals without such effects (n = 74). Contrast groups included: Controls (n = 59) matched for ethnicity, socioeconomic status, and hospital of birth; Special Education contrast group (n = 54) included to control for disability status. Memory outcomes entailed total recall, delayed recall, and measures of encoding and retrieval, and learning over trials as indexed by slope. Results: Results: indicated that Dysmorphic individuals were significantly less efficient in memory performance than Controls on all of the outcomes measured, but they did not differ from those in the Special Education contrast group. The nondysmorphic, alcohol-exposed group was intermediate in their performance, suggesting a continuum of effects of prenatal exposure. Evaluation of the encoding and retrieval aspects of memory performance indicated that learning rather than forgetting accounted for the deficits associated with prenatal alcohol exposure. Finally, no interaction was found between modality of presentation (verbal and nonverbal) and effects of alcohol exposure on memory performance. Conclusion: These findings indicate that prenatal alcohol exposure is associated with persistent and specific effects on memory performance, and these problems result from less efficient encoding of information across both verbal and nonverbal modalities. Education and training efforts with this clinical group should take these characteristics into account.

Dalen K; Bruaroy S; Wentzel-Larsen T; Laegreid LM. Cognitive functioning in children prenatally exposed to alcohol and psychotropic drugs. Neuropediatrics 40(4): 162-167, 2009. (37 refs.)

Cognitive functioning was compared in 29 children diagnosed with fetal alcohol syndrome (FAS), 35 children with fetal alcohol effects (FAE), and 66 psychotropic drugs-exposed (PDE) children using Wechsler tests and the neuropsychological test battery NEPSY. In the FAS group, verbal IQ (VIQ = 78), performance IQ (PIQ = 77), and full scale IQ (FSIQ = 75) were significantly lower as compared to the FAE and PDE groups. In the PDE group VIQ and FSIQ were significantly higher than in the FAE group. In the FAS group, processing speed (PS) was significantly lower than the other three factors. In the FAE group, perceptual organization (PO) was significantly higher, whereas PS was significantly lower than the other factors. In the PDE group, verbal comprehension (VC) was significantly higher than the other factors. Attention subscales on the NEPSY were significantly lower in all the three groups. Prenatal alcohol exposure affects IQ levels more than exposure to psychotropic drugs. Attentional problems were found in all children when tested with the NEPSY in all groups.

Keil V; Paley B; Frankel F; O'Connor MJ. Impact of a social skills intervention on the hostile attributions of children with prenatal alcohol exposure. Alcoholism: Clinical and Experimental Research 34(2): 231-241, 2010. (74 refs.)

Background: Prenatal alcohol exposure (PAE) has been linked to a wide array of developmental deficits, including significant impairments in social skills. Given the extensive body of evidence linking social information-processing patterns with social behavior, it is possible that social information-processing may represent one mechanism of behavioral change. The present investigation sought to answer the question of whether a well-established social skills intervention decreased the hostile attributions of children with PAE. Further, was there a differential impact of the intervention on hostile attributions in the context of peer provocation versus group entry scenarios? Methods: Participants consisted of 100 children (51% male) with PAE between the ages of 6 and 12 years. Participants were randomly assigned to either a social skills intervention, Children's Friendship Training (CFT), or to a Delayed Treatment Control (DTC) condition. Results: Analyses indicated that the social skills intervention resulted in a significantly lower proportion of hostile attributions in peer group entry, but not peer provocation, scenarios. This decrease was maintained over a 3-month follow-up period. Conclusions: Deficits in social information-processing among individuals with PAE can be improved through social skills intervention, and these changes may lead to more positive developmental outcomes.

Lanting CI; Buitendijk SE; Crone MR; Segaar D; Gravenhorst JB; van Wouwe JP. Clustering of xocioeconomic, behavioural, and neonatal risk factors for infant health in pregnant smokers. PLoS one 4(12): e-8363, 2009. (31 refs.)

Background: Tobacco smoking is a major cause of morbidity and mortality, including during pregnancy. Although effective ways of promoting smoking cessation during pregnancy exist, the impact of these interventions has not been studied at a national level. We estimated the prevalence of smoking throughout pregnancy in the Netherlands and quantified associations of maternal smoking throughout pregnancy with socioeconomic, behavioural, and neonatal risk factors for infant health and development. Methodology/Principal Findings: Data of five national surveys, containing records of 14,553 Dutch mothers and their offspring were analyzed. From 2001 to 2007, the overall rate of smoking throughout pregnancy fell by 42% (from 13.2% to 7.6%) mainly as a result of a decrease among highly educated women. In the lowest-educated group, the overall rate of smoking throughout pregnancy was six times as high as in the highest-educated group (18.7% versus 3.2%). Prenatal tobacco smoke exposure was associated with increased risk of extremely preterm (<= 28 completed weeks) (OR 7.25; 95% CI 3.40 to 15.38) and small-for-gestational age (SGA) infants (OR 3.08; 95% CI 2.66 to 3.57). Smoking-attributable risk percents in the population (based on adjusted risk ratios) were estimated at 29% for extremely preterm births and at 17% for SGA outcomes. Infants of smokers were more likely to experience significant alcohol exposure in utero (OR 2.08; 95%CI 1.25 to 3.45) and formula feeding in early life (OR 1.91; 95% CI 1.69 to 2.16). Conclusions: The rates of maternal smoking throughout pregnancy decreased significantly in the Netherlands from 2001 to 2007. If pregnant women were to cease tobacco use completely, an estimated 29% of extremely preterm births and 17% of SGA infants may be avoided annually.

McCowan L; Horgan RP. Risk factors for small for gestational age infants. (review). Best Practice & Research in Clinical Obstetrics & Gynaecology 23(6): 779-793, 2009. (124 refs.)

There are many established risk factors for babies who are small for gestational age (SGA) by population birth weight centiles (usually defined as <10th centile). The confirmed maternal risk factors include short statute, low weight, Indian or Asian ethnicity, nulliparity, mother born SGA, cigarette smoking and cocaine use. Maternal medical history of: chronic hypertension, renal disease, anti-phospholipid syndrome and malaria are associated with increased SGA. Risk factors developing in pregnancy include heavy bleeding in early pregnancy, placental abruption, pre-eclampsia and gestational hypertension. A short or very long inter-pregnancy interval, previous SGA infant or previous stillbirth are also risk factors. Paternal factors including changed paternity, short stature and father born SGA also contribute. Factors associated with reduced risk of SGA or increased birth weight include high maternal milk consumption and high intakes of green leafy vegetables and fruit. Future studies need to investigate risk factors for babies SGA by customised centiles as these babies have greater morbidity and mortality than babies defined as SGA by population centiles.

O'Leary CM; Nassar N; Zubrick SR; Kurinczuk JJ; Stanley F; Bower C. Evidence of a complex association between dose, pattern and timing of prenatal alcohol exposure and child behaviour problems. Addiction 105(1): 74-86, 2010. (59 refs.)

Background: There is a lack of evidence regarding the effect of dose, pattern and timing of prenatal alcohol exposure and behaviour problems in children aged 2 years and older. Methods: A 10% random sample of women delivering a live infant in Western Australia (1995-96) were invited to participate in an 8-year longitudinal survey (78% response rate n = 2224); 85% were followed-up at 2 years, 73% at 5 years and 61% at 8 years. Alcohol consumption was classified by combining the overall dose, dose per occasion and frequency to reflect realistic drinking patterns. Longitudinal analysis was conducted using generalized estimating equations (GEE) to investigate the association between child behaviour as measured by the Child Behaviour Checklist at 2, 5 and 8 years of age and prenatal alcohol exposure collected 3 months postpartum for each trimester separately, adjusting for a wide range of confounding factors. Results: Low levels of prenatal alcohol were not associated with child behaviour problems. There were increased odds of internalizing behaviour problems following heavy alcohol exposure in the first trimester; anxiety/depression [adjusted odds ratio (aOR) 2.82; 95% confidence interval (CI) 1.07-7.43] and somatic complaints (aOR 2.74; 95% CI 1.47-5.12) and moderate levels of alcohol exposure increased the odds of anxiety/depression (aOR 2.24; 95% CI 1.16-4.34). Conclusions: Prenatal alcohol exposure at moderate and higher levels increased the odds of child behaviour problems with the dose, pattern and timing of exposure affecting the type of behaviour problems expressed. Larger studies with more power are needed to confirm these findings.

Schlotz W; Phillips DIW. Fetal origins of mental health: Evidence and mechanisms. (review). Brain, Behavior and Immunity 23(7): 905-916, 2009. (231 refs.)

The concept of fetal programming states that changes in the fetal environment during sensitive periods of organ development may cause long-lasting changes in the structure and functioning of these organs later in life and influence the risk for chronic diseases such as coronary heart disease and type 2 diabetes. Fetal growth is a summary marker of the fetal environment and is reflected by relatively easy-to-obtain measures of size at birth such as birth weight. In the last two decades, a body of evidence emerged linking fetal growth with behavioural and mental health outcomes later in life. Cognitive functioning and behavioural problems in childhood, in particular inattention/hyperactivity, have been shown to be inversely related to fetal growth. Although results are mixed, risk for personality disorders and schizophrenia seems to be linked with fetal growth and adversity, while the evidence for mood disorders is weak. Vulnerability for psychopathology may also be influenced by prenatal adversity. There is evidence for associations of fetal growth with temperament in childhood as well as stress reactivity and distress. The associations of fetal growth with mental health later in life are potentially caused by specific prenatal factors such as maternal smoking, alcohol, toxins/drugs, nutrition, psychosocial stress and infection during pregnancy. The mechanisms likely involve changes in neurodevelopment and in the set point of neuroendocrine systems, and there is evidence that prenatal adversity interacts with genetic and postnatal environmental factors. Future studies should examine the effects of specific prenatal factors and attempt to disentangle genetic and prenatal environmental effects.

Petkovic G; Barisic I. FAS prevalence in a sample of urban schoolchildren in Croatia. Reproductive Toxicology 29(2): 237-241, 2010. (44 refs.)

We present the results of active case ascertainment of fetal alcohol syndrome (FAS). This study included a sample of urban schoolchildren attending 1st to 4th grade elementary school and their mothers. Out of 912 mothers, 575 (63.04%) participated in the interview. Prenatal alcohol consumption was admitted by 15.47% and binge drinking by 3.13% of interviewed mothers. We evaluated 466(51.09%) schoolchildren for signs of FAS or partial fetal alcohol syndrome (PFAS) using revised Institute of Medicine (IOM) diagnostic criteria. Nineteen students had features consistent with FAS or PFAS. The observed prevalence of FAS is 3 children and of PFAS is 16 children among 466 students, based on 51% participation rate. The estimated prevalence of FAS is 6.44/1000, of PFAS 34.33/1000 and overall prevalence of FAS/PFAS 40.77/1000. This is the first study of FAS prevalence in Croatia and as far as we are aware the second study in Europe.

Velasquez MM; Ingersoll KS; Sobell MB; Floyd RL; Sobel LC; von Sternberg K. A dual-focus motivational intervention to reduce the risk of alcohol-exposed pregnancy. Cognitive and Behavioral Practice 17(2): 203-212, 2010. (26 refs.)

Project CHOICES developed an integrated behavioral intervention for prenatal alcohol exposure in women at high risk for alcohol-exposed pregnancies. Settings included primary care, university-hospital based obstetrical/gynecology practices, an urban jail, substance abuse treatment settings, and a media-recruited sample in three large cities. The intervention was based on motivational interviewing and targeted both adoption of effective contraception and reduction of alcohol use. Treatment included 4 manual-guided sessions delivered by mental health clinicians and I contraceptive counseling session delivered by a family planning clinician. This paper describes the rationale for treatment; the use of motivational interviewing and the transtheoretical model for a dual-focused approach to behavior change; the development of the Project CHOICES intervention; development of the study protocol and treatment manual; and selection, training, supervision, and monitoring of study counselors. Implications for future applications of the intervention are discussed.

Meintjes EM; Jacobson JL; Molteno CD; Gatenby JC; Warton C; Cannistraci CJ et al. An fMRI study of number processing in children with fetal alcohol syndrome. Alcoholism: Clinical and Experimental Research 34(8): 1450-1464, 2010. (78 refs.)

Background: Number processing deficits are frequently seen in children exposed to alcohol in utero. Methods: Functional magnetic resonance imaging was used to examine the neural correlates of number processing in 15 right-handed, 8- to 12-year-old children diagnosed with fetal alcohol syndrome (FAS) or partial FAS (PFAS) and 18 right-handed, age- and gender-matched controls from the Cape Coloured (mixed ancestry) community in Cape Town, South Africa, using Proximity Judgment and Exact Addition tasks. Results: Control children activated the expected fronto-parietal network during both tasks, including the anterior horizontal intraparietal sulcus (HIPS), left posterior HIPS, left precentral sulcus, and posterior medial frontal cortex. By contrast, on the Proximity Judgment task, the exposed children recruited additional parietal pathways involving the right and left angular gyrus and posterior cingulate/precuneus, which may entail verbally mediated recitation of numbers and/or subtraction to assess relative numerical distances. During Exact Addition, the exposed children exhibited more diffuse and widespread activations, including the cerebellar vermis and cortex, which have been found to be activated in adults engaged in particularly challenging number processing problems. Conclusions: The data suggest that, whereas control children rely primarily on the fronto-parietal network identified in previous studies to mediate number processing, children with FAS/PFAS recruit a broader range of brain regions to perform these relatively simple number processing tasks. Our results are consistent with structural neuroimaging findings indicating that the parietal lobe is relatively more affected by prenatal alcohol exposure and provide the first evidence for brain activation abnormalities during number processing in children with FAS/PFAS, effects that persist even after controlling statistically for group differences in total intracranial volume and IQ.

Thomas JD; Warren KR; Hewitt BG. Fetal alcohol spectrum disorders from research to policy. Alcohol Research & Health 33(1-2): 118-126, 2010. (63 refs.)

Forty years ago, alcohol was not commonly recognized as a teratogen, an agent that can disrupt the development of a fetus. Today, we understand that prenatal alcohol exposure induces a variety of adverse effects on physical, neurological, and behavioral development. Research supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has contributed to the identification of the range and prevalence of fetal alcohol spectrum disorders (FASD), as well as methods for prevention and treatment of FASD. The worldwide prevalence and high personal and societal costs of FASD speak to the importance of this research. This article briefly examines some of the ways that NIAAA has contributed to our understanding of FASD, the challenges that we still face, and how this research is translated into changes in public policy.

Aliyu MH; Lynch O; Belogolovkin V; Zoorob R; Salihu HM. Maternal alcohol use and medically indicated vs. spontaneous preterm birth outcomes: A population-based study. European Journal of Public Health 20(5): 582-587, 2010. (36 refs.)

Background: The aetiology of preterm birth remains poorly understood. The purpose of this study is to investigate if an association exists between prenatal alcohol consumption and preterm birth and to determine if such an association differs by subcategories of preterm birth. Methods: We employed vital statistics data from the state of Missouri covering the period 1989-2005 (n = 1 221 677 singleton records). The outcome of interest was preterm birth, subclassified into medically indicated and spontaneous phenotypes. Multivariate logistic regression was used to generate adjusted odds ratios, with non-drinking mothers as the referent category. Results: Prenatal alcohol use was associated with elevated risk for preterm birth. The strength of association was more prominent for spontaneous preterm delivery {adjusted odds ratio (AOR) [95% confidence interval (CI)] = 1.34 (1.28-1.41)} than for medically indicated preterm birth [AOR (95% CI) = 1.16 (1.05-1.28)]. The overall risk for drinking-related spontaneous preterm birth increased with incremental rise in the number of drinks consumed per week (P for trend < 0.01). Conclusions: Prenatal alcohol use is a risk factor for preterm delivery, and especially for spontaneous preterm birth. These findings enhance our understanding of the aetiology of preterm birth and could be utilized in the development of appropriate prevention strategies that will assist in decreasing perinatal mortality and morbidity associated with preterm delivery.

Anderson BL; Dang EP; Floyd RL; Sokol R; Mahoney J; Schulkin J. Knowledge, opinions, and practice patterns of obstetrician-gynecologists regarding their patients' use of alcohol. Journal of Addiction Medicine 4(2): 114-121, 2010. (26 refs.)

Objective: To evaluate the evolution of fetal alcohol spectrum disorder prevention practices including awareness and use of recently published tools. Methods: Fellows of the American College of Obstetricians and Gynecologists were asked about their knowledge, opinions, and practice regarding alcohol-related care. Eight hundred obstetrician-gynecologists (ob-gyns) were selected; 48.1% returned the survey. Results: The majority (66.0%) indicated that occasional alcohol consumption is not safe during any period of pregnancy. There was no consensus when asked if alcohol's effect on fetal development is clear (46.9% thought it was clear and 45.9% did not). Most (82.2%) ask all pregnant patients about alcohol use only during patients' initial visit, whereas 10.6% ask during initial and subsequent visits. Most (78.5%) advise abstinence when pregnant women report alcohol use. When asked which validated alcohol risk screening tool they most commonly use with pregnant patients, 57.8% said they use no tool. Although 71.9% felt prepared to screen for risky or hazardous drinking, older ob-gyns indicated feeling significantly more unprepared than younger ob-gyns. "Patient denial or resistance to treatment" was the top issue affecting alcohol screening and "referral resources for patients with alcohol problems" was the resource needed most. Most ob-gyns were not aware of the National Institute on Alcohol Abuse and Alcoholism "Clinician's Guide" or the American College of Obstetricians and Gynecologists "Fetal Alcohol Spectrum Disorder Prevention Tool Kit." Conclusions: There are few changes in the alcohol-related screening and treatment patterns of ob-gyns since 1999; although perceived barriers and needs have changed. Interventions, including referral resources and continuing medical education training, are warranted.

Boyles AL; DeRoo LA; Lie RT; Taylor JA; Jugessur A; Murray JC et al. Maternal alcohol consumption, alcohol metabolism genes, and the risk of oral clefts: A population-based case-control study in Norway, 1996-2001. American Journal of Epidemiology 172(8): 924-931, 2010. (36 refs.)

Heavy maternal alcohol consumption during early pregnancy increases the risk of oral clefts, but little is known about how genetic variation in alcohol metabolism affects this association. Variants in the alcohol dehydrogenase 1C (ADH1C) gene may modify the association between alcohol and clefts. In a population-based case-control study carried out in Norway (1996-2001), the authors examined the association between maternal alcohol consumption and risk of oral clefts according to mother and infant ADH1C haplotypes encoding fast or slow alcohol-metabolizing phenotypes. Subjects were 483 infants with oral cleft malformations and 503 control infants and their mothers, randomly selected from all other livebirths taking place during the same period. Mothers who consumed 5 or more alcoholic drinks per sitting during the first trimester of pregnancy had an elevated risk of oral cleft in their offspring (odds ratio (OR) = 2.6, 95% confidence interval (CI): 1.4, 4.7). This increased risk was evident only in mothers or children who carried the ADH1C haplotype associated with reduced alcohol metabolism (OR= 3.0, 95% CI: 1.4, 6.8). There was no evidence of alcohol-related risk when both mother and infant carried only the rapid-metabolism ADH1C variant (OR = 0.9, 95% CI: 0.2, 4.1). The teratogenic effect of alcohol may depend on the genetic capacity of the mother and fetus to metabolize alcohol.

Chiodo LM; da Costa DE; Hannigan JH; Covington CY; Sokol RJ; Janisse J et al. The impact of maternal age on the effects of prenatal alcohol exposure on attention. Alcoholism: Clinical and Experimental Research 34(10): 1813-1821, 2010. (76 refs.)

Background: Prenatal exposure to alcohol has a variety of morphologic and neurobehavioral consequences, yet more than 10% of women continue to drink during pregnancy, placing their offspring at risk for fetal alcohol spectrum disorders (FASD). Identification of at-risk pregnancies has been difficult, in part, because the presence and severity of FASD are influenced by factors beyond the pattern of alcohol consumption. Establishing maternal characteristics, such as maternal age, that increase the risk of FASD is critical for targeted pregnancy intervention. Methods: We examined the moderating effect of maternal age on measures of attention in 462 children from a longitudinal cohort born to women with known alcohol consumption levels (absolute ounces of alcohol per day at conception) who were recruited during pregnancy. Analyses examined the impact of binge drinking, as average ounces of absolute alcohol per drinking day. Smoking and use of cocaine, marijuana, and opiates were also assessed. At 7 years of age, the children completed the Continuous Performance Test, and their teachers completed the Achenbach Teacher Report Form. Results: After controlling for covariates, stepwise multiple regression analyses revealed a negative relation between levels of prenatal binge drinking and several measures of attention. The interaction between alcohol consumption and maternal age was also significant, indicating that the impact of maternal binge drinking during pregnancy on attention was greater among children born to older drinking mothers. Conclusion: These findings are consistent with previous findings that children born to older alcohol-using women have more deleterious effects of prenatal alcohol exposure on other neurobehavioral outcomes.

Molteno CD; Jacobson SW; Carter RC; Jacobson JL. Infant symbolic play as an early indicator of fetal alcohol-related deficit. Infancy 15(6): 586-607, 2010. (43 refs.)

Infant symbolic play was examined in relation to prenatal alcohol exposure and socioenvironmental background and to predict which infants met criteria for fetal alcohol syndrome (FAS) at 5 years. A total of 107 Cape-Colored, South African infants born to heavy drinking mothers and abstainers/light drinkers were recruited prenatally. Complexity of play, sociodemographic and psychological correlates of maternal alcohol use, and quality of parenting were assessed at 13 months, and intelligence quotient and FAS diagnosis at 5 years. The effect of drinking on spontaneous play was not significant after control for social environment. In contrast, prenatal alcohol and quality of parenting related independently to elicited play. Elicited play predicted 5-year Digit Span and was poorer in infants subsequently diagnosed with FAS/partial FAS and in nonsyndromal heavily exposed infants, compared with abstainers/light drinkers. Thus, symbolic play may provide an early indicator of risk for alcohol-related deficits. The independent effects of prenatal alcohol and quality of parenting suggest that infants whose symbolic play is adversely affected by alcohol exposure may benefit from stimulation from a responsive caregiver.

Eliasen M; Tolstrup JS; Andersen AMN; Gronbaek M; Olsen J; Strandberg-Larsen K. Prenatal alcohol exposure and autistic spectrum disorders: A population-based prospective study of 80,552 children and their mothers. International Journal of Epidemiology 39(4): 1074-1081, 2010. (42 refs.)

Methods: Participants were 80,552 children and their mothers enrolled in the Danish National Birth Cohort from 1996 to 2002. Alcohol consumption was obtained by self-report during pregnancy. Information on ASD was obtained from the Danish Central Psychiatry Register. Follow-up ended on February 2008. Data were analysed by means of Cox regression. Results In total, 401 children were diagnosed with ASD and 157 with infantile autism. No association was found between average alcohol consumption and ASD or infantile autism, respectively. For binge drinking, the adjusted hazard ratio (HR) for ASD was 0.72 [95% confidence interval (CI): 0.53-0.97] among women who binge drank once during pregnancy compared with women who did not binge drink. The corresponding HR for infantile autism was 0.61 (95% CI: 0.36-1.02). However, the HR for ASD was 0.84 (95% CI: 0.51-1.36) when restricting the analysis to first-time pregnancies conceived within 6 months of trying. No estimate was made for infantile autism due to low number of cases. No association was seen for more than one binge episode and for the timing of binge drinking. Conclusion: Our findings do not support that a low prenatal alcohol exposure increases the risk of ASD or infantile autism. The lower risk for women who binge drank once during pregnancy is most likely non-causal.

Hipp JA; Hipp JD; Atala A; Soker S. Ethanol alters the osteogenic differentiation of amniotic fluid-derived stem cells. Alcoholism: Clinical and Experimental Research 34(10): 1714-1722, 2010. (53 refs.)

Background: Fetal alcohol spectrum disorder (FASD) is a set of developmental defects caused by prenatal alcohol exposure. Clinical manifestations of FASD are highly variable and include mental retardation and developmental defects of the heart, kidney, muscle, skeleton, and craniofacial structures. Specific effects of ethanol on fetal cells include induction of apoptosis as well as inhibition of proliferation, differentiation, and migration. This complex set of responses suggests that a bioinformatics approach could clarify some of the pathways involved in these responses. Methods: In this study, the responses of fetal stem cells derived from the amniotic fluid (AFSCs) to treatment with ethanol have been examined. Large-scale transcriptome analysis of ethanol-treated AFSCs indicates that genes involved in skeletal development and ossification are up-regulated in these cells. Therefore, the effect of ethanol on osteogenic differentiation of AFSCs was studied. Results: Exposure to ethanol during the first 48 hours of an osteogenic differentiation protocol increased in vitro calcium deposition by AFSCs and increased alkaline phosphatase activity. In contrast, ethanol treatment later in the differentiation protocol (day 8) had no significant effect on the activity of alkaline phosphatase. Conclusions: These results suggest that transient exposure of AFSCs to ethanol during early differentiation enhances osteogenic differentiation of the cells.

Long L; Li Y; Wang YD; He QY; Li M; Cai XD et al. The preventive effect of oral EGCG in a fetal alcohol spectrum disorder mouse model. Alcoholism: Clinical and Experimental Research 34(11): 1929-1936, 2010. (39 refs.)

Background: Fetal alcohol spectrum disorder (FASD) is a challenging public health problem. Previous studies have found an association between FASD and oxidative stress. In the present study, we assessed the role of oxidative stress in ethanol-induced embryonic damage and the effect of (-)-epigallocatechin-3-gallate (EGCG), a powerful antioxidant extracted from green tea, on the development of FASD in a murine model. Methods: Pregnant female mice were given intraperitoneal ethanol (25%, 0.005 to 0.02 ml/g) on gestational day 8 (G8) to establish the FASD model. On G10.25, mice were sacrificed and embryos were collected and photographed to determine head length (HL), head width (HW), and crown rump length (CRL). For mice given EGCG, administration was through a feeding tube on G7 and G8 (dose: 200, 300, or 400 mg/kg/d, the total amount for a day was divided into 2 equal portions). G10.25 embryos were evaluated morphologically. Brain tissues of G9.25 embryos were used for RT-PCR and western blotting of neural marker genes and proteins and detection of oxidative stress indicators. Results: Administration of ethanol to pregnant mice on G8 led to the retardation of embryonic growth and down-regulation of neural marker genes. In addition, administration of ethanol (0.02 ml/g) led to the elevation of oxidative stress indicators [hydrogen peroxide (H2O2) and malondialdehyde (MDA)]. Administration of EGCG on G7 and G8 along with ethanol on G8 ameliorated the ethanol-induced growth retardation. Mice given EGCG (400 mg/kg/d) along with ethanol had embryo sizes and neural marker genes expression similar to the normal controls. Furthermore, EGCG (400 mg/kg on G7 and G8) inhibited the increase in H2O2 and MDA. Conclusions: In a murine model, oxidative stress appears to play an important role in ethanol-induced embryonic growth retardation. EGCG can prevent some of the embryonic injuries caused by ethanol.

Mattson SN; Roesch SC; Fagerlund A; Autti-Ramo I; Jones KL; May PA et al. Toward a neurobehavioral profile of fetal alcohol spectrum disorders. Alcoholism: Clinical and Experimental Research 34(9): 1640-1650, 2010. (47 refs.)

Background: A primary goal of recent research is the development of neurobehavioral profiles that specifically define fetal alcohol spectrum disorders (FASD), which may assist differential diagnosis or improve treatment. In the current study, we define a preliminary profile using neuropsychological data from a multisite study. Methods: Data were collected using a broad neurobehavioral protocol from 2 sites of a multisite study of FASD. Subjects were children with heavy prenatal alcohol exposure and unexposed controls. The alcohol-exposed group included children with and without fetal alcohol syndrome (FAS). From 547 neuropsychological variables, 22 variables were selected for analysis based on their ability to distinguish children with heavy prenatal alcohol exposure from nonexposed controls. These data were analyzed using latent profile analysis (LPA). Results: The results indicated that a 2-class model best fit the data. The resulting profile was successful at distinguishing subjects with FAS from nonexposed controls without FAS with 92% overall accuracy; 87.8% of FAS cases and 95.7% of controls were correctly classified. The same analysis was repeated with children with heavy prenatal alcohol exposure but without FAS and nonexposed controls with similar results. The overall accuracy was 84.7%; 68.4% of alcohol-exposed cases and 95% of controls were correctly classified. In both analyses, the profile based on neuropsychological variables was more successful at distinguishing the groups than was IQ alone. Conclusions: We used data from 2 sites of a multisite study and a broad neuropsychological test battery to determine a profile that could be used to accurately identify children affected by prenatal alcohol exposure. Results indicated that measures of executive function and spatial processing are especially sensitive to prenatal alcohol exposure.

Parker T; Maviglia MA; Lewis PT; Gossage JP; May PA. Psychological distress among Plains Indian mothers with children referred to screening for Fetal Alcohol Spectrum Disorders. Substance Abuse Treatment, Prevention, and Policy 5(e-article 22), 2010

Background: Psychological distress (PD) includes symptoms of depression and anxiety and is associated with considerable emotional suffering, social dysfunction and, often, with problematic alcohol use. The rate of current PD among American Indian women is approximately 2.5 times higher than that of U.S. women in general. Our study aims to fill the current knowledge gap about the prevalence and characteristics of PD and its association with self-reported current drinking problems among American Indian mothers whose children were referred to screening for fetal alcohol spectrum disorders (FASD). Methods: Secondary analysis of cross-sectional data was conducted from maternal interviews of referred American Indian mothers (n = 152) and a comparison group of mothers (n = 33) from the same Plains culture tribes who participated in an NIAAA-funded epidemiology study of FASD. Referred women were from one of six Plains Indian reservation communities and one urban area who bore children suspected of having an FASD. A 6-item PD scale (PD-6, Cronbach's alpha = .86) was constructed with a summed score range of 0-12 and a cut-point of 7 indicating serious PD. Multiple statistical tests were used to examine the characteristics of PD and its association with self-reported current drinking problems. Results: Referred and comparison mothers had an average age of 31.3 years but differed (respectively) on: education (Copyright 2010, BioMed Central

Shepard TH; Barr M; Brent RL; Hendrickx A; Kochhar D; Oakley G et al. An updated history of the Teratology Society. (review). Birth Defects Research. Part A: Clinical and Molecular Teratology 88(5): 263-285, 2010. (24 refs.)

BACKGROUND: The 49-year history of the Teratology Society is reviewed. An abbreviated history is outlined in table form, with listings of the Warkany Lectures, the Continuing Education Courses, and officers of the society. The original article was updated to include the years 2000 to 2010. METHODS: A year-by-year description of the events is given, including the scientific and social content of the annual meetings and changes in the business of the society, in many cases using comments from the past presidents. The valuable and unique diversity of the members is discussed and illustrated, presenting the disciplines and main research areas of the presidents. The number of submitted abstracts and the various categories are tabulated, averaging the number and type over successive periods. A significant increase in the number of abstracts dealing with epidemiology and developmental biology is evident. The society's development is compared to that of a human, and the question was asked by Shephard et al. (2000): Have we reached the maturational stage of old age or senescence, or is the society still maturing gracefully? This question needs further discussion by all the members. By 2010, many positive changes are happening to revitalize the society. RESULTS: During the past 50 years, we have developed the scientific basis to prevent birth defects caused by rubella, alcoholism, and folate deficiency, as well as other prenatal exposures. We are now taking advantage of advances in many fields to begin shaping the Teratology Society of the 21st century. CONCLUSIONS: We must now engage in political battles to obtain the resources needed to conduct further research and to implement prevention programs, as well as to provide care and rehabilitation for persons with birth defects.

Simmons RW; Thomas JD; Levy SS; Riley EP. Motor response programming and movement time in children with heavy prenatal alcohol exposure. Alcohol 44(4): 371-378, 2010. (49 refs.)

The present experiment assessed motor response programming and movement time in children with histories of heavy prenatal alcohol exposure (PEA). Alcohol-exposed children between the ages of 7 and 17 years were classified into two groups: Fetal Alcohol Syndrome (FAS: n = 9) and children with PEA (PEA: n = 19) but who did not have the defining characteristics of FAS. The FAS and PEA children were compared with non alcohol-exposed children (NC: n = 23) when completing two tasks: a simple reaction time task (RT alone condition) and a reaction plus movement task (RT + Move condition). The movement involved responding to an imperative stimulus signal and depressing three target buttons in a set sequence. Participants completed 24 trials each for the RT alone and RT Move response conditions. Results indicated no significant differences in performance among FAS, PEA, and NC groups during the RT alone condition. However, during the RT Move condition, the FAS group produced significantly longer and more variable RTs than the PEA and NC groups, which produced comparable RTs. The FAS group also produced significantly slower movement times when moving to all three targets, whereas movement time variability did not significantly differ as a function of group. The observed results indicate children with FAS experience deficits in response programming and movement time production.

Vangipuram SD; Lyman WD. Ethanol alters cell fate of fetal human brain-derived stem and progenitor cells. Alcoholism: Clinical and Experimental Research 34(9): 1574-1583, 2010. (61 refs.)

Background: Prenatal ethanol (ETOH) exposure can lead to fetal alcohol spectrum disorder (FASD). We previously showed that ETOH alters cell adhesion molecule gene expression and increases neurosphere size in fetal brain-derived neural stem cells (NSC). Here, our aim was to determine the effect of ETOH on the cell fate of NSC, premature glial-committed precursor cells (GCP), and premature neuron-committed progenitor cells (NCP). Methods: NSC, GCP, and NCP were isolated from normal second-trimester fetal human brains (n = 3) by positive selection using magnetic microbeads labeled with antibodies to CD133 (NSC), A2B5 (GCP), or PSA-NCAM (NCP). As a result of the small percentage in each brain, NSC were cultured in mitogenic media for 72 hours to produce neurospheres. The neurospheres from NSC and primary isolates of GCP and NCP were used for all experiments. Equal numbers of the 3 cell types were treated either with mitogenic media or with differentiating media, each containing 0 or 100 mM ETOH, for 120 hours. Expression of Map2a, GFAP, and O4 was determined by immunoflourescence microscopy and western blot analysis. Fluorescence intensities were quantified using Metamorph software by Molecular Devices, and the bands of western blots were quantified using densitometry. Results: ETOH in mitogenic media promoted formation of neurospheres by NSC, GCP, and NCP. Under control conditions, GCP attached and differentiated, NSC and NCP formed neurospheres that were significantly smaller in size than those in ETOH. Under differentiating conditions, Map2a expression increased significantly in NSC and GCP and reduced significantly in NCP, and GFAP expression reduced significantly in GCP and NCP, and Gal-C expression reduced significantly in all 3 cell types in the presence of ETOH compared to controls. Conclusions: This study shows that ETOH alters the cell fate of neuronal stem and progenitor cells. These alterations could contribute to the mechanism for the abnormal brain development in FASD.

Zoorob R; Aliyu MH; Hayes C. Fetal alcohol syndrome: Knowledge and attitudes of family medicine clerkship and residency directors. Alcohol 44(4): 379-385, 2010. (15 refs.)

Fetal alcohol spectrum disorders (FASD) are the leading preventable causes of developmental disabilities with serious permanent consequences. Regardless of the increased awareness of fetal alcohol syndrome (FAS), 13% of women in the United States drink alcohol during pregnancy. Health care professionals do not routinely assess the frequency and quantity of alcohol use by their patients. This study examined the knowledge, skills, and practices of family medicine residency and clerkship directors and assessed the time devoted and format of FAS curricula in the programs. A self-administered anonymous survey was sent to the residency and clerkship directors (N = 571). Response rate of clerkship directors was 52% and residency directors 46%. Both groups showed high level of knowledge of FASD and of alcohol counseling practices for pregnant women. Although almost two thirds of the residency programs had FASD integrated in the curriculum, an equivalent fraction of predoctoral programs did not. More than half of the clerkship directors without FASD in their curriculum agreed that a need exists for its inclusion. These findings raise important medical education and policy issues and provide insight into the disparity in FASD content of curricula between predoctoral and family medicine residency programs in the United States. The role of physician counseling in primary prevention of FAS should continue to be stressed in predoctoral and residency education.

Burden MJ; Westerlund A; Muckle G; Dodge N; Dewailly E; Nelson CA et al. The effects of maternal binge drinking during pregnancy on neural correlates of response inhibition and memory in childhood. Alcoholism: Clinical and Experimental Research 35(1): 69-82, 2011. (63 refs.)

Background: Although an extensive literature has documented a broad range of cognitive performance deficits in children with prenatal alcohol exposure, little is known about how the neurophysiological processes underlying these deficits may be affected. Event-related potentials (ERPs), which reflect task-specific changes in brain electrical activity, provide a method for examining multiple constituents of cognitive processing at the neural level. Methods: We recorded ERPs in 217 children from Inuit communities in Arctic Quebec (M age = 11.3 years) during 2 different tasks-Go/No-go response inhibition and continuous recognition memory. Children were classified as either alcohol-exposed (ALC) or controls (CON) depending on whether the mother reported binge drinking during pregnancy. Results: Both groups performed comparably in terms of accuracy and reaction time on the tasks, and both tasks elicited the expected effects on ERPs when responses were compared across conditions. However, the ALC group showed slower P2 latencies on Go/No-go, suggesting an altered neurophysiological response associated with initial visual processing of the stimuli. On the memory task, the ALC group showed reduced FN400 amplitude to New items, known as the familiarity effect, and reduced amplitude for the late positive component, possibly reflecting impairment in memory retrieval. Conclusions: These findings show that, even in tasks in which alcohol-exposed children exhibit behavioral performance that is comparable to controls, fetal alcohol exposure is associated with altered neurophysiological processing of response inhibition and recognition memory. The data suggest that fetal alcohol exposure is associated with reduced efficiency in the initial extracting of the meaning of a stimulus, reduced allocation of attention to the task, and poorer conscious, explicit recognition memory processing.

Chiodo LM; Sokol RJ; Delaney-Black V; Janisse J; Hannigan JH. Validity of the T-ACE in pregnancy in predicting child outcome and risk drinking. Alcohol 44(7/8, special issue): 595-603, 2010. (73 refs.)

Preventing fetal alcohol spectrum disorders (FASDs) requires detection of in-pregnancy maternal risk drinking. The widely used T-ACE screen has been applied in various ways, although the impact of those different uses on effectiveness is uncertain. We examined relations among different T-ACE scoring criteria, maternal drinking, and child outcome. Self-reported across-pregnancy maternal drinking was assessed in 75 African-American women. The different T-ACE criteria used varied the level of drinking that defined tolerance (two or three drinks) and the total T-ACE score cut-points (two or three). Receiver operator curves and regression analysis assessed the significance of relations. Increasing the total T-ACE score cut-point to 3 almost doubled specificity in detecting risk drinking whereas maintaining adequate sensitivity, equivalent to that in the original report, and identified substantially more neurobehavioral deficits in children. Redefining tolerance at three drinks did not improve T-ACE effectiveness in predicting outcomes. This study is among the first to show the ability of an in-pregnancy T-ACE assessment to predict child neurodevelopmental outcome. In addition, increasing the total T-ACE score criterion (from 2 to 3) improved identification of non-drinking mothers and unaffected children with little loss in detection of drinkers and affected children. Efficient in-pregnancy screens for risk drinking afford greater opportunities for intervention that could prevent/limit FASDs.

Denny CH; Tsai J; Floyd RL; Green PP. Alcohol use among pregnant and nonpregnant women of childbearing age --- United States, 1991--2005. MMWR. Morbidity and Mortality Weekly Review 58(19): 529-532, 2009. (10 refs.)

Alcohol consumption during pregnancy is a risk factor for poor birth outcomes, including fetal alcohol syndrome, birth defects, and low birth weight. To examine the prevalence of any alcohol use and binge drinking among pregnant women and nonpregnant women of childbearing age in the United States and to characterize the women with these alcohol use behaviors, CDC analyzed 1991--2005 data from Behavioral Risk Factor Surveillance System (BRFSS) surveys. The findings indicated that the prevalence of any alcohol use and binge drinking among pregnant and nonpregnant women of childbearing age did not change substantially from 1991 to 2005. During 2001--2005, the highest percentages of pregnant women reporting any alcohol use were aged 35--44 years (17.7%), college graduates (14.4%), employed (13.7%), and unmarried (13.4%). Greater percentages of pregnant women with at least some college education (11.2%), or a college degree or more (14.4%), reported alcohol use than pregnant women with a high school diploma or less (8.5%) (AORs = 1.4 and 1.9, respectively). A greater percentage of employed pregnant women (13.7%) reported alcohol use than unemployed pregnant women (8.3%, AOR = 1.5), and a greater percentage of unmarried pregnant women (13.4%) reported alcohol use than married pregnant women (10.2%, AOR = 2.2) In addition, a greater percentage of employed pregnant women (2.3%) reported binge drinking, compared with unemployed pregnant women (1.3%, AOR = 1.8), and a greater percentage of unmarried pregnant women (3.6%) reported binge drinking than married pregnant women (1.1%, AOR = 4.4).

Public Domain

du Toit MM; Smith M; Odendaal HJ. The role of prenatal alcohol exposure in abruptio placentae. South African Medical Journal 100(12): 832-835, 2010. (25 refs.)

Objective. To investigate the association between preconception and prenatal alcohol use and abruptio placentae. Methods. A case-control study of women with the clinical diagnosis of abruptio placentae, 65 cases and 66 controls, at Tygerberg Academic Hospital, Western Cape, South Africa. Women in whom a retroplacental blood clot, covering at least 15% of the placental surface, was found at delivery at 24 weeks' gestation or later were asked to complete a timeline follow-back questionnaire to determine their alcohol intake 12 and 3 months before and during pregnancy. The same questionnaire was administered to a control group of high-risk women who had no antepartum haemorrhage. Outcome. Women who drank alcohol 12 months before conception were more than 4 times more likely to develop abruptio placentae than the control group (odds ratio (OR) 4.49, p=0.00009). Women who drank alcohol 3 months prior to conception were 3 times more likely to develop abruptio placentae than the control group (OR 3.06, p=0.003). Drinking alcoholic beverages during pregnancy carried a more than 3 times greater risk of developing abruptio placentae (OR 3.52, p=0.0006). In the study group, women consumed a mean of 13.6, 12.0 and 11.2 standard drinks in a typical week at 12 and 3 months before and during pregnancy, respectively. The study group demonstrated a binge-drinking pattern, with two to four sessions per month. Conclusion. An association was found between preconception and prenatal consumption of alcohol and abruptio placentae.

Goodlett CR. Fetal alcohol spectrum disorders: New perspectives on diagnosis and intervention. (editorial). Alcohol 44(7/8, special issue): 579-582, 2010. (32 refs.)

Johnson ME; Robinson RV; Corey S; Dewane SL; Brems C; Casto LD. Knowledge, attitudes, and behaviors of health, education, and service professionals as related to fetal alcohol spectrum disorders. International Journal of Public Health 55(6): 627-635, 2010. (27 refs.)

We explored differences in fetal alcohol spectrum disorders (FASD) knowledge, attitudes, and behaviors across six groups of professionals in key position to provide primary and secondary prevention efforts (physicians, educators, correctional staff, social workers, public health nurses, and substance abuse counselors). Achieving a 60.1% response rate, 2,292 professionals returned surveys, providing data on basic knowledge of FAS, FASD-associated risks and cognitive deficits, and willingness to confront and recommend treatment to alcohol-consuming pregnant women. Across groups, findings revealed ample FASD knowledge and willingness to confront and recommend treatment to alcohol-consuming pregnant women that increases as consumption becomes more frequent and severe. However, results revealed significant between-group differences data that provide valuable guidance for targeted future FASD education efforts. Public health initiatives regarding FASD have been effective in increasing knowledge among a broad range of professionals. However, between-group differences indicate the need for targeted, discipline-specific interventions. These differences highlight the need for all professional groups to provide a consistent public health message regarding maternal alcohol consumption.

Kulaga V; Shor S; Koren G. Correlation between drugs of abuse and alcohol by hair analysis: Parents at risk for having children with fetal alcohol spectrum disorder. Alcohol 44(7/8, special issue): 615-621, 2010. (63 refs.)

The fatty acid ethyl esters (FAEEs) hair test, a biomarker of excessive alcohol exposure, has demonstrated its potential for use in fetal alcohol spectrum disorder (FASD) diagnosis. FASD may be compounded by polydrug exposure. Our objective was to determine the likelihood of positive FAEE test among parents testing positive for other drugs of abuse. Samples submitted for FAEE hair analysis by Children's Aid Societies between October 2005 and May 2007, also concurrently tested for cocaine, cannabinoids, opiates, methamphetamine, amphetamine, benzodiazepines, methadone, and/or oxycodone, were included in our analysis. Subjects consisted of parents suspected of using excessive amounts of alcohol. Parents testing positive for drugs of abuse had a significantly increased risk for testing positive for high FAEE. Mothers testing positive for heavy chronic alcohol use were found to have a threefold increased risk of testing positive for cocaine (odds ratio = 3.26, 1.1-9.7). Our results suggest that parents abusing stimulants are at risk of high alcohol exposure, which put their unborn children at risk for FASD.

Lowe P; Lee E; Yardley L. Under the influence? The construction of foetal alcohol syndrome in UK Newspapers. Sociological Research Online 15: e-article 4, 2010. (30 refs.)

Today, alongside many other proscriptions, women are expected to abstain or at least limit their alcohol consumption during pregnancy. This advice is reinforced through warning labels on bottles and cans of alcoholic drinks. In most (but not all) official policies, this is linked to a risk of Foetal Alcohol Syndrome (FAS) or one of its associated conditions. However, given that there is little medical evidence that low levels of alcohol consumption have an adverse impact on the foetus, we need to examine broader societal ideas to explain why this has now become a policy concern. This paper presents a quantitative and qualitative assessment of analysis of the media in this context. By analysing the frames over time, this paper will trace the emergence of concerns about alcohol consumption during pregnancy. It will argue that contemporary concerns about FAS are framed around a number of pre-existing discourses including alcohol consumption as a social problem, heightened concerns about children at risk and shifts in ideas about the responsibility of motherhood including during the pre-conception and pregnancy periods. Whilst the newspapers regularly carried critiques of the abstinence position now advocated, these challenges focused did little to refute current parenting cultures.

Rosenberg MJ; Wolff CR; El-Emawy A; Staples MC; Perrone-Bizzozero NI; Savage DD. Effects of moderate drinking during pregnancy on placental gene expression. Alcohol 44(7/8, special issue): 673-690, 2010. (67 refs.)

Many children adversely affected by maternal drinking during pregnancy cannot be identified early in life using current diagnostic criteria for fetal alcohol spectrum disorder (FASD). We conducted a preliminary investigation to determine whether ethanol-induced alterations in placental gene expression may have some utility as a diagnostic indicator of maternal drinking during pregnancy and as a prognostic indicator of risk for adverse neurobehavioral outcomes in affected offspring. Pregnant Long-Evans rats voluntarily consumed either a 0 or 5% ethanol solution 4 h each day throughout gestation. Ethanol consumption produced a mean maternal daily intermittent peak serum ethanol concentration of 84 mg/dL. Placentas were harvested on gestational day 20 for gene expression studies. Microarray analysis of more than 28,000 genes revealed that the expression of 304 known genes was altered twofold or greater in placenta from ethanol-consuming dams compared with controls. About 76% of these genes were repressed in ethanol-exposed placentas. Gene expression changes involved proteins associated with central nervous system development; organ morphogenesis; immunological responses; endocrine function; ion homeostasis; and skeletal, cardiovascular, and cartilage development. To date, quantitative real-time polymerase chain reaction analysis has confirmed significant alterations in gene expression for 22 genes, including genes encoding for three calcium binding proteins, two matrix metalloproteinases, the cannabinoid 1, galanin 2 and toll-like receptor 4, iodothyronine deiodinase 2, 11-beta hydroxysteroid dehydrogenase 2, placental growth factor, transforming growth factor alpha, gremlin 1, and epithelial growth factor (EGF)-containing extracellular matrix protein. These results suggest that the expression of a sufficiently large number of placental mRNAs is altered after moderate drinking during pregnancy to warrant more detailed investigation of the placenta as a biomarker system for maternal drinking during pregnancy and as an early indicator of FASD. Furthermore, these results provide new insights into novel mechanisms on how ethanol may directly or indirectly mediate its teratogenic effects through alterations in placental function during pregnancy.

Salihu HM; Kornosky JL; Lynch O; Alio AP; August EM; Marty PJ. Impact of prenatal alcohol consumption on placenta-associated syndromes. Alcohol 45(1): 73-79, 2011. (31 refs.)

The biology of placental and fetal development suggests that alcohol may play a significant role in increasing the risk of feto-infant morbidity and mortality, but study results are inconsistent and the mechanism remains poorly defined. Previous studies have not examined the risk of placenta-associated syndromes (PASs: defined as the occurrence of either placental abruption, placenta previa, preeclampsia, small for gestational age, preterm, or stillbirth) as a unique entity. Therefore, we sought to examine the relationship between prenatal alcohol use and the risk of PAS among singleton births in the Missouri maternally linked data files covering the period 1989-2005. Logistic regression with adjustment for intracluster correlation was used to generate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Compared with nondrinkers, drinkers were more likely to be smokers, 35 years of age or older, black, and multiparous. Drinkers had an increased risk of PAS (OR = 1.26, 95% CI = 1.22,1.31) when compared with their nondrinking counterparts. The risk of PAS was progressively amplified with increasing prenatal alcohol consumption (P for trend <.01). Women who reported consuming five or more alcoholic drinks per week had more than twofold increased risk of PASs, whereas women in the lowest drinking category (one to two drinks per week) had only a slight increased risk of PAS (OR = 1.09, 95% CI = 1.05, 1.14). Enhanced understanding of the mechanism by which prenatal alcohol consumption leads to PAS may aid in the development of more targeted interventions designed to prevent adverse pregnancy outcomes. Screening women for alcohol use may assist providers in protecting developing fetuses from the potential dangers of prenatal alcohol use.

Willford JA; Chandler LS; Goldschmidt L; Day NL. Effects of prenatal tobacco, alcohol and marijuana exposure on processing speed, visual-motor coordination, and interhemispheric transfer. Neurotoxicology and Teratology 32(6): 580-588, 2010. (120 refs.)

Deficits in motor control are often reported in children with prenatal alcohol exposure (PAE). Less is known about the effects of prenatal tobacco exposure (PTE) and prenatal marijuana exposure (PME) on motor coordination, and previous studies have not considered whether PTE, PAE, and PME interact to affect motor control. This study investigated the effects of PTE, PAE, and PME as well as current drug use on speed of processing, visual-motor coordination, and interhemispheric transfer in 16-year-old adolescents. Data were collected as part of the Maternal Health Practices and Child Development Project. Adolescents (age 16, n = 320) participating in a longitudinal study of the effects of prenatal substance exposure on developmental outcomes were evaluated in this study. The computerized Bimanual Coordination Test (BCT) was used to assess each domain of function. Other important variables, such as demographics, home environment, and psychological characteristics of the mother and adolescent were also considered in the analyses. There were significant and independent effects of PTE, PAE, and PME on processing speed and interhemispheric transfer of information. PTE and PME were associated with deficits in visual-motor coordination. There were no interactions between PAE. PTE, and PME. Current tobacco use predicted deficits in speed of processing. Current alcohol and marijuana use by the offspring were not associated with any measures of performance on the BCT.

Aros S; Mills JL; Iniguez G; Avila A; Conley MR; Troendle J et al. Effects of prenatal ethanol exposure on postnatal growth and the insulin-like growth factor axis. Hormone Research in Paediatrics 75(3): 166-173, 2011. (42 refs.)

Aims:To study the effect of in-utero alcohol exposure on the insulin-like growth factor axis (IGF) and leptin during infancy and childhood, considering that exposed children may exhibit pre- and postnatal growth retardation. Methods: We prospectively identified heavily drinking pregnant women who consumed on average 4 or more drinks of ethanol per day (>= 48 g/day) and assessed growth in 69 of their offspring and an unexposed control group of 83 children, measuring serum IGF-I (radioimmunoassay), IGF-II (immunoradiometric assay, IRMA), insulin-like growth factor-binding protein 3 (IGFBP-3) (IRMA) and leptin (IRMA) at 1 month and 1, 2, 3, 4, and 5 years of age. Results: IGF-II levels increased with age in both groups, but the rate of increase was significantly higher in exposed children, and levels were significantly higher in ethanol-exposed children at 3, 4, and 5 years of age. In exposed children, IGF-I levels were higher at 3 and 4 years and leptin levels were significantly lower at 1 and 2 years. Exposed subjects showed a much lower correlation between IGF-I and growth parameters than unexposed subjects. Conclusion: Exposure to ethanol during pregnancy increases IGF-I and IGF-II and decreases leptin during early childhood. The increase in serum IGF-II concentrations in ethanol-exposed children suggests that this hormone should be explored as a potential marker for prenatal alcohol exposure.

Bay B; Kesmodel US. Prenatal alcohol exposure: A systematic review of the effects on child motor function. (review). Acta Obstetricia et Gynecologica Scandinavica 90(3): 210-226, 2011. (55 refs.)

Objective. To systematically review the available evidence on the effects of prenatal alcohol exposure on motor function in humans. Design. Systematic review. Population. Pregnant women and their offspring. Methods. The search strategy included Medline, Embase, The Cochrane Library and Scopus. The authors read titles and abstracts, and the articles that met the predefined criteria for inclusion were obtained and the full text read. The articles were assessed for quality using the Newcastle-Ottawa Quality Assessment Scale. Main outcome measures. Motor function measured on standardized or validated tests. Results. The search resulted in 311 titles and abstracts, of which 39 were found relevant for inclusion. The findings of this review suggest a negative effect when the maternal consumption exceeded a certain level. Of all studies reporting a maternal intake of more than four drinks/day, only one study showed no effect on motor function, and of all studies reporting intake levels of less than 10 drinks/week, only one study showed deficit on the children's motor function. Conclusions. While it appears consistent that high daily alcohol intake is associated with deficits in gross and fine motor function, and low weekly intake is not associated with such deficits, the issue of binge drinking is unsettled.

Gray R. Commentary: Sullivan on the offspring of the female criminal alcoholic. (editorial). International Journal of Epidemiology 40(2): 289-292, 2011. (23 refs.)

Payne JM; France KE; Henley N; D'Antoine HA; Bartu AE; O'Leary CM et al. RE-AIM evaluation of the Alcohol and Pregnancy Project: Educational resources to inform health professionals about prenatal alcohol exposure and fetal alcohol spectrum disorder. Evaluation & the Health Professions 34(1): 57-80, 2011. (29 refs.)

The objective was to evaluate the Alcohol and Pregnancy Project that provided health professionals in Western Australia (WA) with educational resources to inform them about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder (FASD). The authors developed, produced, and distributed educational resources to 3,348 health professionals in WA. Six months later, they surveyed 1,483 of these health professionals. The authors used the RE-AIM framework (reach, effectiveness, adoption, implementation, and maintenance) to evaluate the project. The educational resources were effective in producing a 31% increase in the proportion of health professionals who routinely provided pregnant women with information about the consequences of drinking alcohol during pregnancy. One hundred percent of the settings adopted the project, it reached 96.3% of the target population, it was implemented as intended, and the resources were maintained (http: www.ichr.uwa.edu.au/alcoholandpregnancy). The educational resources for health professionals have potential to contribute to reducing prenatal alcohol exposure and FASD.

Robinson M; Oddy WH; McLean NJ; Jacoby P; Pennell CE; de Klerk NH et al. Low-moderate prenatal alcohol exposure and risk to child behavioral development: A prospective cohort study. (editorial). Obstetrical & Gynecological Survey 65(12): 759-760, 2010. (0 refs.)

The detrimental effects of fetal exposure to extreme levels of alcohol during pregnancy, such as the subsequent occurrence of childhood physical, cognitive, and behavioral deficits, are well known. Some investigators have suggested that there is a dose-response effect, with light drinking during pregnancy primarily affecting behavioral and adaptive functions and heavy drinking causing more serious developmental defects and problems. Accordingly, mild to moderate social drinking during pregnancy could be associated with long-term infant morbidity. The relatively few studies examining the long-term risk of fetal exposure to light-moderate levels of alcohol have failed to reach consensus, possibly due to deficiencies in study design. This prospective longitudinal cohort study investigated the effect of different levels of fetal alcohol exposure during pregnancy on child and adolescent behavioral development. The Western Australian Pregnancy Cohort (Raine) Study enrolled 2900 pregnancies between 1989 and 1991, with a 14-year follow-up. Maternal self-reported data for 5 levels of weekly alcohol intake were obtained at 18 and 34 weeks' gestation: no drinking, occasional drinking (up to one standard drink per week), light drinking (2-6 standard drinks per week), moderate drinking (7-10 standard drinks per week), and heavy drinking (11 or more standard drinks per week). A linear regression model was used to determine whether prenatal alcohol exposure could produce changes in Child Behavior Checklist scores over 14 years that reflected clinically meaningful differences in child behavioral development, after adjustment for maternal and sociodemographic confounders. Detailed clinical assessments of study children were conducted at birth, with follow-up conducted at 2, 5, 8, 10, and 14 years. The adjusted data showed that light and moderate drinking during the first 3 months of pregnancy resulted in Child Behavior Checklist z-scores indicative of positive behavior over 14 years. The z-scores reflected a clinically meaningful reduction in total, internalizing, and externalizing behavioral problems across the 14 years of follow-up. These findings suggest that low-moderate alcohol intake early in pregnancy is not associated with poor behavioral outcomes in offspring.

Sanders JL. What might have been: Sullivan may have impacted modern prenatal alcohol research under different circumstances. (editorial). International Journal of Epidemiology 40(2): 283-285, 2011. (21 refs.)

Simmons RW; Madra NJ; Levy SS; Riley EP; Mattson SN. Co-regulation of movement speed and accuracy by children with heavy prenatal alcohol exposure. Perceptual and Motor Skills 112(1): 172-182, 2011. (37 refs.)

The study investigated how children with heavy prenatal alcohol exposure regulate movement speed and accuracy during goal-directed movements. 16 children ages 7 to 17 years with confirmed histories of heavy in utero alcohol exposure, and 21 nonalcohol-exposed control children completed a series of reciprocal tapping movements between two spatial targets. 5 different targets sets were presented, representing a range of task difficulty between 2 and 6 bits of information. Estimates of percent error rate, movement time, slope, and linear fit of the resulting curve confirmed that for goal-directed, reciprocal tapping responses, performance of the group with prenatal alcohol exposure was described by a linear function, as predicted by Fitts' law, by sacrificing movement accuracy. The index of performance was the same for the two groups: it initially increased, then leveled off for more difficult movements.

Sullivan WC. A note on the influence of maternal inebriety on the offspring. (reprint from 1899). International Journal of Epidemiology 40(2): 278-282, 2011. (12 refs.)

Author's Introduction: The object of the following paper is to present the result of a number of observations touching certain aspects of the question of habitual inebriety, notably the r�le of maternal alcoholism as an agent in race degeneracy. . . . I have selected from the female population of Liverpool Prison, amongst whom habitual inebriety is very prevalent, a series of cases of chronic drunkards who have borne children; and from the history of these children, and more particularly from the indications given by the infant mortality, I have sought to illustrate the mode in which the maternal intoxication appears to have reacted on the development of the offspring. In the selection I have endeavoured, as far as possible, to choose cases in which alcoholism occurred uncomplicated by other degenerative factors. Author's Conclusion: The observations which we have thus briefly analysed enable us to form a fairly clear idea of the mode in which maternal inebriety reacts upon the offspring. We are familiar with the fact, clearly established by Morel, that the chronic alcoholism of one or both parents frequently appears as the first moment in the degenerative career of a family; that it represents a state of artificial degradation of the organism, capable of transmission in augmented force to the descendants, and culminating in some four generations in the extinction of the stock. In the case of maternal inebriety we have the same mode of action to consider, but with it, and very much more potent, we have the continued toxic influence exercised on the developing embryo throughout pregnancy. The brilliant researches of F�r� in the field of experimental teratology have sufficiently demonstrated the gravity of this influence. We have, further, to bear in mind the possible effect of alcoholic excesses during lactation. Lastly, reinforcing all these modes of influence, we have the detrimental effects, positive and negative, of the deterioration of the milieu as an indirect consequence of the mother's drunkenness.

Bailey BA; Sokol RJ. Prenatal alcohol exposure and miscarriage, stillbirth, preterm delivery, and sudden infant death syndrome. Alcohol Research & Health 34(1): 86-91, 2011. (39 refs.)

In addition to fetal alcohol syndrome and fetal alcohol spectrum disorders, prenatal alcohol exposure is associated with many other adverse pregnancy and birth outcomes. Research suggests that alcohol use during pregnancy may increase the risk of miscarriage, stillbirth, preterm delivery, and sudden infant death syndrome. This research has some inherent difficulties, such as the collection of accurate information about alcohol consumption during pregnancy and controlling for comorbid exposures and conditions. Consequently, attributing poor birth outcomes to prenatal alcohol exposure is a complicated and ongoing task, requiring continued attention to validated methodology and to identifying specific biological mechanisms.

Bakhireva LN; Savage DD. Biomarkers of Fetal Alcohol Exposure And Fetal Alcohol Effects. Alcohol Research & Health 34(1): 56-63, 2011. (55 refs.)

One of the ongoing challenges for the accurate diagnosis and treatment of children with fetal alcohol spectrum disorders (FASD) is the difficulty of confirming whether a mother drank during her pregnancy. Commonly used screening questionnaires often are unreliable, and current established biomarkers of alcohol consumption are not sensitive enough for use with many pregnant women. These limitations underscore the critical need to develop novel biomarkers with greater sensitivity for detecting moderate levels of drinking during pregnancy for longer periods of time after the last drinking episode. In addition, developing reliable biomarkers of fetal alcohol effects that can identify children at risk for adverse neurobehavioral outcomes could lead to behavioral interventions earlier in development. The use of animal models of FASD in biomarker development could accelerate progress in this challenging field of research.

Bakhireva LN; Wilsnack SC; Kristjanson A; Yevtushok L; Onishenko S; Wertelecki W et al. Paternal drinking, intimate relationship quality, and alcohol consumption in pregnant Ukrainian women. Journal of Studies on Alcohol and Drugs 72(4): 536-544, 2011. (53 refs.)

Objective: Maternal alcohol consumption during pregnancy and fetal alcohol spectrum disorders (FASDs) represent a significant public health problem. The influence of the male partner's alcohol consumption patterns and the quality of the partner's intimate relationship might be important factors to consider in the design of successful FASD prevention programs. Method: As part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, 166 pregnant women in two regions in Ukraine participated in an in-person interview at an average gestational age of 18-19 weeks. Subjects were classified cross-sectionally as abstainers/light drinkers (n = 80), defined as low or no consumption of alcohol in the periconceptional period and none in the most recent 2 weeks of pregnancy; discontinuers (n = 43), defined as moderate to heavy alcohol use in the periconceptional period but none during the most recent 2 weeks of pregnancy; or continuing drinkers (pi = 43), defined as continued moderate to heavy alcohol use within the most recent 2 weeks of pregnancy. Women also reported on their partner's drinking behavior and on the quality of their intimate relationship. Results: Heavy paternal drinking was significantly associated with both continuing maternal drinking in the most recent 2 weeks (adjusted odds ratio [OR] = 34.1; 95% CI [5.9, 195.8]) and being a risky drinker only around conception (adjusted OR = 27.0; 95% CI [5.0, 147.7]). In addition, women who consumed alcohol during pregnancy had lower mean scores for satisfaction with partners' relationship and ability to discuss problems (p < .05) compared with light drinkers/abstainers. Conclusions: This study suggests that development of partner-based interventions, as opposed to those solely focused on maternal drinking, might be warranted as a strategy to prevent FASD.

May PA; Fiorentino D; Coriale G; Kalberg WO; Hoyme HE; Aragon AS et al. Prevalence of children with severe fetal alcohol spectrum disorders in communities near Rome, Italy: New estimated rates are higher than previous estimates. International Journal of Environmental Research and Public Health 8(6): 2331-2351, 2011. (54 refs.)

Objective: To determine the population-based epidemiology of fetal alcohol syndrome (FAS) and other fetal alcohol spectrum disorders (FASD) in towns representative of the general population of central Italy. Methods: Slightly revised U. S. Institute of Medicine diagnostic methods were used among children in randomly-selected schools near Rome. Consented first grade children (n = 976) were screened in Tier I for height, weight, or head circumference and all children <= 10th centile on one of these measurements were included in the study. Also, teachers referred children for learning or behavioral problems. Children meeting either of these two criteria, along with randomly-selected controls, advanced to Tier II which began with a dysmorphology examination. Children with a possible FASD, and controls, advanced to Tier III for neurobehavioral testing, and their mothers were interviewed for maternal risks. Final diagnoses using indicators of dysmorphology, neurobehavior, and maternal risk were made in formally-structured, interdisciplinary case conferences. Results: Case control comparisons of physical, neurobehavioral, and maternal risk variables are presented for 46 children with an FASD and 116 randomly-selected controls without a diagnosis on the FASD continuum. Rates of diagnoses within the FASD continuum are then estimated from these in-school data via three different methods. The range of rates of FAS produced by these methods is between 4.0 to 12.0 per 1,000; Partial FAS ranges from 18.1 to 46.3 per 1,000; and an FASD was found in 2.3% to 6.3% of the children. Conclusions: These rates are substantially higher than previous estimates of FAS and overall FASD for the general populations of Western Europe and the U. S., and raise questions as to the total impact of FASD on mental deficit in mainstream populations of Western Europe and the United States where the majority are middle class and are not believed to be characterized by heavy episodic drinking.

May PA; Gossage JP. Maternal risk factors for fetal alcohol spectrum disorders not as simple as it might seem. Alcohol Research & Health 34(1): 15-26, 2011. (76 refs.)

Gathering information about drinking during pregnancy is one of the most difficult aspects of studying fetal alcohol spectrum disorders (FASD). This information is critical to linking specific risk factors to any particular diagnosis within the FASD continuum. This article reviews highlights from the literature on maternal risk factors for FASD and illustrates that maternal risk is multidimensional, including factors related to quantity, frequency, and timing of alcohol exposure; maternal age; number of pregnancies; number of times the mother has given birth; the mother's body size; nutrition; socioeconomic status; metabolism; religion; spirituality; depression; other drug use; and social relationships. More research is needed to more clearly define what type of individual behavioral, physical and genetic factors are most likely to lead to having children with FASD.

McGee CL; Bjorkquist OA; Riley EP; Mattson SN. Impaired language performance in young children with heavy prenatal alcohol exposure. Neurotoxicology and Teratology 31(2): 71-75, 2009. (31 refs.)

The aims of this study were to evaluate the language abilities of young children with heavy prenatal alcohol exposure and to determine if these abilities represent a relative strength or weakness for this population. Two matched groups of children (ages 3 to 5) completed the Clinical Evaluation of Language Fundamentals, Preschool version: 25 children with heavy prenatal alcohol exposure (ALC) and 26 non-exposed controls (CON). Consistent with previous research, the CON group had significantly higher full scale IQ (FSIQ) scores than the ALC group. Receptive and expressive language skills of the two groups were compared. The ALC group had significantly poorer language skills than the CON group and both groups had better receptive than expressive abilities. Language performance did not significantly deviate from what would be predicted by FSIQ for either group. These results indicate that receptive and expressive language abilities are impaired in children with heavy prenatal alcohol exposure but not more so than general intellectual functioning. However, these deficits are likely to impact the social interactions and behavioral adjustment of children with prenatal alcohol exposure.

Paley B; O'Connor MJ; Baillie SJ; Guiton G; Stuber ML. Integrating case topics in medical school curriculum to enhance multiple skill learning: Using fetal alcohol spectrum disorders as an exemplary case. Academic Psychiatry 33(2): 143-148, 2009. (10 refs.)

Objectives: This article describes the use of fetal alcohol spectrum disorders (FASDs) as a theme to connect the learning of basic neurosciences with clinical applications across the age span within a systems-based, integrated curricular structure that emphasizes problem-based learning. Methods: In collaboration with the Centers for Disease Control and Prevention (CDC) and the National Organization on Fetal Alcohol Syndrome, the Western Regional Training Center for Fetal Alcohol Exposure at UCLA developed and integrated educational materials on FASDs into the curriculum for first-year medical students. Results: Quantitative and qualitative evaluations suggested materials were effective in enhancing student knowledge and skills related to FASDs, as well as embryology, brain development, substance abuse, developmental psychopathology, and medical ethics. Conclusion: The use of a unifying theme integrating basic science and clinical information and skills is effective for medical student training in the prevention and treatment of common medical problems.