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CORK Bibliography: Fetal Alcohol Syndrome/Fetal Alcohol Effects

80 citations. January 2009 to present

Prepared: September 2012

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

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.

Copyright 2010, American Society of Addiction Medicine

Archer T. Effects of exogenous agents on brain development: Stress, abuse and therapeutic compounds. (review). CNS Neuroscience & Therapeutics 17(5): 470-489, 2011. (300 refs.)

The range of exogenous agents likely to affect, generally detrimentally, the normal development of the brain and central nervous system defies estimation although the amount of accumulated evidence is enormous. The present review is limited to certain types of chemotherapeutic and "use-and-abuse" compounds and environmental agents, exemplified by anesthetic, antiepileptic, sleep-inducing and anxiolytic compounds, nicotine and , and stress as well as agents of infection; each of these agents have been investigated quite extensively and have been shown to contribute to the etiopathogenesis of serious neuropsychiatric disorders. To greater or lesser extent, all of the exogenous agents discussed in the present treatise have been investigated for their influence upon neurodevelopmental processes during the period of the brain growth spurt and during other phases up till adulthood, thereby maintaining the notion of critical phases for the outcome of treatment whether prenatal, postnatal, or adolescent. Several of these agents have contributed to the developmental disruptions underlying structural and functional brain abnormalities that are observed in the symptom and biomarker profiles of the schizophrenia spectrum disorders and the fetal alcohol spectrum disorders. In each case, the effects of the exogenous agents upon the status of the affected brain, within defined parameters and conditions, is generally permanent and irreversible.

Copyright 2011, Wiley-Blackwell

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.

Copyright 2009, Research Society on Alcoholism

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.

Copyright 2011, National Institute on Alcohol Abuse and Alcoholism

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.

Copyright 2011, National Institute on Alcohol Abuse and Alcoholism

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.

Copyright 2011, Alcohol Research Documentation

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.

Copyright 2009, All India Institute of Medical Sciences

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.

Copyright 2009, Elsevier Science

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.

Copyright 2009, Research Society on Alcoholism

Cannon MJ; Dominique Y; O'Leary LA; Sniezek JE; Floyd RL. Characteristics and behaviors of mothers who have a child with fetal alcohol syndrome. Neurotoxicology and Teratology 34(1): 90-95, 2012. (32 refs.)

Fetal alcohol syndrome (FAS) is a leading cause of birth defects and developmental disabilities. The objective of this study was to identify the characteristics and behaviors of mothers of children with FAS in the United States using population-based data from the FAS Surveillance Network (FASSNet). FASSNet used a multiple source methodology that identified FAS cases through passive reporting and active review of records from hospitals, specialty clinics, private physicians, early intervention programs, Medicaid, birth certificates and other vital records, birth defects surveillance programs, and hospital discharge data. The surveillance included children born during January 1, 1995-December 31, 1997. In the four states included in our analysis - Arizona, New York, Alaska, and Colorado - there were 257 confirmed cases and 96 probable cases for a total of 353 FAS cases. Compared to all mothers in the states where surveillance occurred, mothers of children with FAS were significantly more likely to be older, American Indians/Alaska Natives, Black, not Hispanic, unmarried, unemployed, and without prenatal care, to smoke during pregnancy, to have a lower educational level, and to have more live born children. A significant proportion of mothers (9-29%) had another child with suspected alcohol effects. Compared to all US mothers, they were also significantly more likely to be on public assistance, to be on Medicaid at their child's birth, to have received treatment for alcohol abuse, to have confirmed alcoholism, to have used marijuana or cocaine during pregnancy, to have their baby screen positive for alcohol or drugs at birth, to have had an induced abortion, to have had a history of mental illness, to have been involved in binge drinking during pregnancy, and to have drunk heavily (7 days/week) during pregnancy. These findings suggest that it is possible to identify women who are at high risk of having a child with FAS and target these women for interventions.

Copyright 2012, Elsevier Science

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 (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.

Copyright 2009, Research Society on Alcoholism

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.

Copyright 2010, Wiley-Blackwell

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.

Copyright 2009, Research Society on Alcoholism

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.

Copyright 2010, Elsevier Science

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.

Copyright 2010, Research Society on Alcoholism

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.

Copyright 2009, Georg Thime Verlag

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.

Copyright 2009, Research Society on Alcoholism

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.

Copyright 2010, Oxford University Press

Eaton LA; Kalichman SC; Sikkema KJ; Skinner D; Watt MH; Pieterse D et al. Pregnancy, alcohol intake, and intimate partner violence among men and women attending drinking establishments in a Cape Town, South Africa township. Journal of Community Health 37(1): 208-216, 2012. (49 refs.)

The highest rates of fetal alcohol syndrome worldwide can be found in South Africa. Particularly in impoverished townships in the Western Cape, pregnant women live in environments where alcohol intake during pregnancy has become normalized and interpersonal violence (IPV) is reported at high rates. For the current study we sought to examine how pregnancy, for both men and women, is related to alcohol use behaviors and IPV. We surveyed 2, 120 men and women attending drinking establishments in a township located in the Western Cape of South Africa. Among women 13.3% reported being pregnant, and among men 12.0% reported their partner pregnant. For pregnant women, 61% reported attending the bar that evening to drink alcohol and 26% reported both alcohol use and currently experiencing IPV. Daily or almost daily binge drinking was reported twice as often among pregnant women than non-pregnant women (8.4% vs. 4.2%). Men with pregnant partners reported the highest rates of hitting sex partners, forcing a partner to have sex, and being forced to have sex. High rates of alcohol frequency, consumption, binge drinking, consumption and binge drinking were reported across the entire sample. In general, experiencing and perpetrating IPV were associated with alcohol use among all participants except for men with pregnant partners. Alcohol use among pregnant women attending shebeens is alarmingly high. Moreover, alcohol use appears to be an important factor in understanding the relationship between IPV and pregnancy. Intensive, targeted, and effective interventions for both men and women are urgently needed to address high rates of drinking alcohol among pregnant women who attend drinking establishments.

Copyright 2012, Springer

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.

Copyright 2009, Wiley-Liss

Fraser SL; Muckle G; Abdous BB; Jacobson JL; Jacobson SW. Effects of binge drinking on infant growth and development in an Inuit sample. Alcohol 46(3): 277-283, 2012. (52 refs.)

Prenatal exposure to an average of 0.5 oz absolute alcohol per day (the equivalent of 7 standard drinks per week) during pregnancy has been found to be associated with numerous adverse effects on pre- and postnatal development. In the animal model, concentrated alcohol exposure has been found to lead to more adverse effects than exposure to the same total quantity of alcohol ingested in smaller doses over a longer period of time. The primary aim of this study is to determine whether, in a population where binge drinking is common but total alcohol consumption across pregnancy is low, prenatal exposure to alcohol is associated with effects on prenatal growth, visual acuity and cognitive development during infancy. The second aim is to determine which of several indicators of alcohol consumption best predicts pre- and postnatal outcomes. Data were collected from 216 Inuit women and their infants living in Nunavik, the northern region of Quebec. Maternal interviews were conducted during mid-pregnancy and at 1 and 6 months postpartum. Birth weight, length, and head circumference were assessed at delivery. Visual acuity and cognitive development were assessed at 6 months of age. In this population in which infrequent heavy episodic drinking is common, even occasional binge exposure was associated with reduced prenatal growth and poorer visual acuity at 6 months of age. A simple dichotomous measure of binge drinking during pregnancy provided the best predictor of fetal growth and 6-month acuity. The population studied here is unusual in terms of its pattern of binge alcohol consumption. To our knowledge, this is the first study to observe effects of binge drinking during pregnancy on infant growth and development in a sample where the average daily alcohol intake is low (<0.5 ounces).

Copyright 2012, Elseiver Science

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.

Copyright 2009, Resarch Society on Alcoholism

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

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

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.

Copyright 2009, Society for the Study of Addiction to Alcohol and Other Drugs

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.

Copyright 2009, Research Society on Alcoholism

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.

Copyright 2009, Oxford University Press

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.

Copyright 2010, Research Society on Alcoholism

Ingersoll KS; Hettema JE; Cropsey KL; Jackson JP. Preconception markers of dual risk for alcohol and smoking exposed pregnancy: Tools for primary prevention. Journal of Women's Health 20(11): 1627-1633, 2011. (36 refs.)

Objective: Effective preconception primary prevention strategies are needed for women who are at dual risk for alcohol and smoking exposed pregnancies. The current study seeks to identify risk factors that can be used to target intervention strategies at women who are at dual risk. Methods: During a 2-year period from January 2007 through December 2009, 109 women at dual risk for alcohol exposed pregnancy (AEP) and smoking exposed pregnancy (SEP) and 108 women at risk only for AEP were recruited from central Virginia cities. All participants completed a battery of instruments, including assessments of sexual, smoking, and alcohol history and current behavior in each area. Results: Several factors differentiated women at dual risk for SEP/AEP vs. AEP alone, including lower educational level and employment, higher frequency of sexual intercourse, less use of contraception, and higher frequency of alcohol use and mental disorders. Conclusions: Several measurable factors differentiate SEP/AEP women, and these factors could be used to efficiently target primary prevention. The increased severity of women at dual risk of SEP/AEP on a variety of factors demonstrates the importance of preconception prevention efforts for these women.

Copyright 2011, Mary Ann Liebert Inc

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.

Copyright 2010, Birkhauser Verlag AG

Katwan E; Adnams C; London L. Childhood behavioural and developmental disorders: Association with maternal alcohol consumption in Cape Town, South Africa. (editorial). South African Medical Journal 101(10): 724+, 2011. (10 refs.)

Current maternal alcohol consumption, especially binge drinking, is strongly associated with childhood behavioural and/or developmental disorders (BDDs) in a population attending tertiary hospital ambulatory services. BDDs were also associated with maternal alcohol use 6 months before pregnancy. An association with BDDs could not be conclusively demonstrated for drinking during pregnancy, but this may have been influenced by under-reporting and reduced study power due to misclassification of exposure. We cannot rule out the a priori suspicion that some mild BDDs in children in the Western Cape could be undiagnosed fetal alcohol spectrum disorder. Nonetheless, the study highlighted the important impact of current maternal alcohol use on behaviour and development of children. Future research on the impact of maternal alcohol use on childhood development should include examination of environmental and social factors contributing to this increased risk. Upstream interventions aimed at reducing alcohol-related harms may also contribute to reducing the burden of BDDs.

Copyright 2011, South Africa Medical Association

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.

Copyright 2009, Oxford University Press

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.

Copyright 2009, Oxford University Press

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.

Copyright 2009, John Wiley & Sons

Kim O; Park K. Prenatal alcohol consumption and knowledge about alcohol consumption and fetal alcohol syndrome in Korean women. Nursing & Health Sciences 13(3): 303-308, 2011. (26 refs.)

The study investigated prenatal alcohol consumption and knowledge of alcohol risks and fetal alcohol syndrome among Korean women. The participants were 221 Korean women who attended the post-partum care centers in Seoul, Korea. The data included the participants' background characteristics, quantity-frequency typology, Student Alcohol Questionnaire, and a scale on the participants' knowledge of fetal alcohol syndrome. Alcohol was consumed during pregnancy by 12.7% of the participants. Of these, 60.7% drank alcohol with their spouse. A few participants reported that nurses identified their drinking habits and gave them information on alcohol consumption and fetal alcohol syndrome. Most of the participants did not have the opportunity for prenatal counseling about fetal alcohol syndrome. The knowledge level regarding alcohol risks and fetal alcohol syndrome among the participants was poor. Alcohol consumption before pregnancy was significantly related to prenatal alcohol consumption. Prenatal alcohol consumption was not related to knowledge about alcohol consumption and fetal alcohol syndrome. The assessment of alcohol consumption and counseling about alcohol are needed for pregnant women in order to prevent fetal alcohol syndrome.

Copyright 2011, Wiley-Blackwell

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.

Copyright 2009, Lippincott, Williams & Wilkins

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.

Copyright 2010, Elsevier Science

Kully-Martens K; Denys K; Treit S; Tamana S; Rasmussen C. A review of social skills deficits in individuals with fetal alcohol spectrum disorders and prenatal alcohol exposure: Profiles, mechanisms, and interventions. (review). Alcoholism: Clinical and Experimental Research 36(4): 568-576, 2012. (97 refs.)

Background: Individuals gestationally exposed to alcohol experience a multitude of sociobehavioral impairments, including deficits in adaptive behaviors such as social skills. Methods: The goal of this report is to critically review research on social skills deficits in individuals with prenatal alcohol exposure, including individuals with and without fetal alcohol spectrum disorders (FASD). Results: Social deficits are found in alcohol-exposed children, adults, and adolescents with and without a clinical presentation. These deficits tend to persist across the lifespan and may even worsen with age. Social deficits in this population appear to be independent of facial dysmorphology and IQ and are worse than can be predicted based on atypical behaviors alone. Abnormalities in neurobiology, executive function, sensory processing, and communication likely interact with contextual influences to produce the range of social deficits observed in FASD. Conclusions: Future investigations should strive to reconcile the relationship between social skills deficits in FASD and variables such as gender, age, cognitive profile, and structural and functional brain impairments to enable better characterization of the deficits observed in this population, which will enhance diagnosis and improve remediation.

Copyright 2012, Research Society on Alcoholism

Li Q; Fisher WW; Peng CZ; Williams AD; Burd L. Fetal alcohol spectrum disorders: A population based study of premature mortality rates in the mothers. Maternal and Child Health Journal 16(6): 1332-1337, 2012. (36 refs.)

Fetal alcohol spectrum disorders (FASD) are associated with an increase in risk for mortality for people with an FASD and their siblings. In this study we examine mortality rates of birth mothers of children with FASD, using a retrospective case control methodology. We utilized the North Dakota FASD Registry to locate birth certificates for children with FASD which we used to identify birth mothers. We then searched for mothers' death certificates. We then compared the mortality rates of the birth mothers with an age matched control group comprised of all North Dakota women who were born and died in the same year as the birth mother. The birth mothers of children with FASD had a mortality rate of 15/304 = 4.93%; (95% CI 2.44-7.43%). The mortality rate for control mothers born in same years as the FASD mothers was 126/114,714 = 0.11% (95% CI 0.09-0.13%). Mothers of children with an FASD had a 44.82 fold increase in mortality risk and 87% of the deaths occurred in women under the age of 50. Three causes of death (cancer, injuries, and alcohol related disease) accounted for 67% of the deaths in the mothers of children with FASD. A diagnosis of FASD is an important risk marker for premature death in the mothers of children diagnosed with an FASD. These women should be encouraged to enter substance abuse treatment.

Copyright 2012, Springer

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.

Copyright 2010, Wiley-Blackwell

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.

Copyright 2010, Sage Publications

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.

Copyright 2010, Research Society on Alcoholism

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.

Copyright 2011, MDPI AG

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.

Copyright 2011, National Institute on Alcohol Abuse and Alcoholism

May PA; Tabachnick BG; Gossage JP; Kalberg WO; Marais AS; Robinson LK et al. Maternal risk factors predicting child physical characteristics and dysmorphology in fetal alcohol syndrome and partial fetal alcohol syndrome. Drug and Alcohol Dependence 119(1-2): 18-27, 2011. (63 refs.)

Background: Previous research in South Africa revealed very high rates of fetal alcohol syndrome (FAS), of 46-89 per 1000 among young children. Maternal and child data from studies in this community summarize the multiple predictors of FAS and partial fetal alcohol syndrome (PFAS). Method: Sequential regression was employed to examine influences on child physical characteristics and dysmorphology from four categories of maternal traits: physical, demographic, childbearing, and drinking. Then, a structural equation model (SEM) was constructed to predict influences on child physical characteristics. Results: Individual sequential regressions revealed that maternal drinking measures were the most powerful predictors of a child's physical anomalies (R(2) = .30, p < .001), followed by maternal demographics (R(2) = .24, p < .001), maternal physical characteristics (R(2) = .15,p < .001), and childbearing variables (R(2) = .06, p < .001). The SEM utilized both individual variables and the four composite categories of maternal traits to predict a set of child physical characteristics, including a total dysmorphology score. As predicted, drinking behavior is a relatively strong predictor of child physical characteristics (beta = 0.61, p < .001), even when all other maternal risk variables are included; higher levels of drinking predict child physical anomalies. Conclusions: Overall, the SEM model explains 62% of the variance in child physical anomalies. As expected, drinking variables explain the most variance. But this highly controlled estimation of multiple effects also reveals a significant contribution played by maternal demographics and, to a lesser degree, maternal physical and childbearing variables.

Copyright 2011, Elsevier Science

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.

Copyright 2009, Elsevier Science

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.

Copyright 2010, Wiley-Blackwell

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.

Copyright 2010, John Wiley & Sons

Mullally A; Cleary BJ; Barry J; Fahey TP; Murphy DJ. Prevalence, predictors and perinatal outcomes of peri-conceptional alcohol exposure-retrospective cohort study in an urban obstetric population in Ireland. BMC Pregnancy and Childbirth 11: 27, 2011. (18 refs.)

Background: Evidence-based advice on alcohol consumption is required for pregnant women and women planning a pregnancy. Our aim was to investigate the prevalence, predictors and perinatal outcomes associated with peri-conceptional alcohol consumption. Methods: A cohort study of 61,241 women who booked for antenatal care and delivered in a large urban maternity hospital between 2000 and 2007. Self-reported alcohol consumption at the booking visit was categorised as low (0-5 units per week), moderate (6-20 units per week) and high (>20 units per week). Results: Of the 81% of women who reported alcohol consumption during the peri-conceptional period, 71% reported low intake, 9.9% moderate intake and 0.2% high intake. Factors associated with moderate alcohol consumption included being in employment OR 4.47 (95% CI 4.17 to 4.80), Irish nationality OR 16.5 (95% CI 14.9 to 18.3), private health care OR 5.83 (95% CI 5.38 to 6.31) and smoking OR 1.86 (95% CI 1.73 to 2.01). Factors associated with high consumption included maternal age less than 25 years OR 2.70 (95% CI 1.86 to 3.91) and illicit drug use OR 6.46 (95% CI 3.32 to 12.60). High consumption was associated with very preterm birth (<32 weeks gestation) even after controlling for socio-demographic factors, adjusted OR 3.15 (95% CI 1.26-7.88). Only three cases of Fetal Alcohol Syndrome were recorded (0.05 per 1000 total births), one each in the low, moderate and high consumption groups. Conclusions: Public Health campaigns need to emphasise the importance of peri-conceptional health and pre-pregnancy planning. Fetal Alcohol Syndrome is likely to be under-reported despite the high prevalence of alcohol consumption in this population.

Copyright 2011, BioMedical Central

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.)

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.

Copyright 2010, Society for the Study of Addiction to Alcohol and Other Drugs

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

Ortega-Garcia JA; Gutierrez-Churango JE; Sanchez-Sauco MF; Martinez-Aroca M; Delgado-Marin JL; Sanchez-Solis M et al. Head circumference at birth and exposure to tobacco, alcohol and illegal drugs during early pregnancy. Child's Nervous System 28(3): 433-439, 2012. (29 refs.)

We aimed to assess the effects of exposure to tobacco smoke, alcohol and illegal drugs during early pregnancy on the head circumference (HC) at birth of otherwise healthy neonates. A follow-up study from the first trimester of pregnancy to birth was carried out in 419 neonates. An environmental reproductive health form was used to record data of substance exposure obtained during the first obstetric visit at the end of the first trimester. A multiple linear regression model was created for this purpose. Alcohol intake during pregnancy and medical ionizing radiation exposure were the most significant predictors of HC. The mothers' alcohol consumption increased with the mothers' and fathers' education level, net family income and fathers' alcohol consumption. In contrast, maternal smoking decreased with increasing mothers' and fathers' education level and net family income. About 13% of the surveyed embryos were exposed to illegal drugs. Mild to moderate alcohol consumption diminishes the at-birth HC of theoretically healthy newborns in a linear form. There was no threshold dose. We perceived a need for increasing the awareness, and for training, of health care professionals and parents, in regard to risks of alcohol consumption and for recommending abstinence of these substances in both parents during pregnancy. It should also be remembered that medical ionizing radiation should be performed only during the first half of the cycle in fertile women. We think that our study has an important social impact as it affords data for implementing policies for promoting "healthy pregnancies".

Copyright 2012, Springer

Paintner A; Williams AD; Burd L. Fetal alcohol spectrum disorders. Implications for Ccild neurology, Part 2: Diagnosis and management. (review). Journal of Child Neurology 27(3): 355-362, 2012. (45 refs.)

In part 1, we discussed the mechanism of alcohol exposure, dosimetry, and the teratogenic pathways of damage to the fetus. In part 2, we review the diagnosis of fetal alcohol spectrum disorders and the developmental implications of prenatal alcohol exposure. Fetal alcohol spectrum disorders are associated with increased rates of mental retardation, seizure disorders, brain malformations, and premature mortality. The risk of comorbid disorders is increased among this population, which enhances phenotype severity and complexity of management. Recurrence rates are high and younger siblings tend to be more severely affected. Detection of prenatal alcohol use warrants substance abuse intervention, which can avoid exposure in subsequent pregnancies. Fetal alcohol spectrum disorders are common developmental disorders with a phenotype that is influenced by both age and development and require long-term management. Child neurologists are essential in the diagnosis and management of fetal alcohol spectrum disorders.

Copyright 2012, Sage Publications

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.

Copyright 2009, American Psychiatric Association

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

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: The educational resources for health professionals have potential to contribute to reducing prenatal alcohol exposure and FASD.

Copyright 2011, Sage Publication

Pei J; Denys K; Hughes J; Rasmussen C. Mental health issues in fetal alcohol spectrum disorder. (review). Journal of Mental Health 20(5): 473-483, 2011. (48 refs.)

Background. High numbers of individuals with Fetal Alcohol Spectrum Disorders (FASD) have been described as having mental health problems. Aims. This article summarizes research about mental health problems in FASD and considers related developmental and environmental issues. Method. A computer-based literature search was conducted in the databases Medline, PsycINFO, Google Scholar, Academic Search Complete, and Education Resources Information Centre for articles addressing the prevalence and types of mental health issues in individuals affected by FASD. Results. High rates of mental disorders within the FASD and prenatal alcohol exposure (PAE) population were found to be consistently reported for both internalizing and externalizing disorders. Moreover, problems that emerge in childhood may reflect a convergence of genetic, environmental, and neurophysiological factors that persist into adulthood. Conclusions. Researchers are beginning to document the impacts of PAE on later mental health development. Further longitudinal study is needed to determine whether there is an increasing severity of mental health deficits and consequences with age, and whether any such changes reflect increasingly deteriorating environmental factors or brain-based factors. Additionally, research is needed to design interventions to better address the unique mental health needs of this population.

Copyright 2011, Informa Healthcare

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.

Copyright 2010, Elsevier Science

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.

Copyright 2009, Canadian Public Health Association

Rasmussen C; Kully-Martens K; Denys K; Badry D; Henneveld D; Wyper K et al. The effectiveness of a community-based intervention program for women at-risk for giving birth to a child with fetal alcohol spectrum disorder (FASD). Community Mental Health Journal 48(1): 12-21, 2012. (34 refs.)

The goal of this study was to determine whether the First Steps program (modeled after the Parent-Child Assistance Program) resulted in improved outcomes among women at-risk for giving birth to a child with FASD. We conducted a retrospective analysis of data on 70 participants in the First Steps program. Clients were high risk and faced many life challenges, including: being on welfare, substance abuse, physical and sexual abuse as children, mental health issues, criminal activity, and unplanned pregnancies. We found a significant increase in birth control use and decrease in welfare rates from pre- to post-program. At program exit, many participants were abstinent from alcohol and/or drugs and the majority did not experience a subsequent pregnancy. Clients also showed significant increases in goals and decreases in needs from pre-to post-program. The First Steps program demonstrated promising outcomes for women at-risk for giving birth to a child with FASD.

Copyright 2012, Springer

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.

Copyright 2009, Wiley-Blackwell

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.

Copyright 2010, Elsevier Science

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.

Copyright 2011, Elsevier Science

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.)

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.

Copyright 2010, Wiley-Liss

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.

Copyright 2009, Research Society on Alcoholism

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.

Copyright 2010, Elsevier Science

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.)

[NB. From 1898 publication.]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.

Copyright 2011, Oxford Press

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.

Copyright 2010, National Institute on Alcohol Abuse and Alcoholism

Valenzuela CF; Morton RA; Diaz MR; Topper L. Does moderate drinking harm the fetal brain? Insights from animal models. (review). Trends In Neurosciences 35(5): 284-292, 2012. (86 refs.)

Although public health campaigns advise pregnant women to abstain from ethanol, drinking during pregnancy is pervasive. Here, we highlight recent studies that have clearly demonstrated long-lasting neurobehavioral deficits in the offspring of laboratory animals exposed to moderate levels of ethanol during development. Alterations in learning, memory, motor coordination, social behavior, and stress responses were identified in these animals. Increased vulnerability to substance abuse was also demonstrated. These behavioral alterations have been associated with impairments in neurotransmitter systems, neuromodulators, and/or synaptic plasticity in several brain regions. With this review we hope to contribute to a better appreciation of the potential effects of developmental exposure to moderate ethanol levels, leading to better interventions aimed at relieving fetal alcohol spectrum disorders.

Copyright 2012, Elsevier Science

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.

Copyright 2010, Research Society on Alcoholism

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.

Copyright 2009, Research Society on Alcoholism

Yildiz S; Sezer S; Boyar H; Cece H; Ziylan SZ; Vural M et al. Impact of passive smoking on uterine, umbilical, and fetal middle cerebral artery blood flows. Japanese Journal of Radiology 29(10): 718-24, 2011

The aim of this study was to evaluate the influence of passive maternal smoking on blood flow velocities in arteries of the fetal-placental-maternal circulation. A total of 79 pregnant women in their third trimester, including 33 passive smokers, 23 active smokers, and 23 nonsmoking controls, were enrolled in the study. Fetal biophysical indices were evaluated with B-mode scanning, whereas blood flow waveforms of uterine, umbilical, and fetal middle cerebral (MCA) arteries were analyzed with Doppler ultrasonography. There were significant differences among active smokers vs. passive smokers vs. controls with regard to the presence of a uterine artery diastolic notch (39.1% vs. 18.2% vs. 4.3%; P = 0.012); ratio of peak systolic/end-diastolic velocity of fetal MCA [3.73 1.27 vs. 4.26 1.20 vs. 5.00 2.15, analysis of variance (ANOVA) P = 0.026]; resistance index of fetal MCA (0.74 0.08 vs. 0.75 0.07 vs. 0.80 0.09; ANOVA P = 0.014); ratio of fetal MCA/umbilical artery resistance index (1.27 0.20 vs. 1.24 0.14 vs. 1.39 0.21; ANOVA P = 0.011); and ratio of fetal MCA/umbilical artery pulsatility index (1.56 0.44 vs. 1.63 0.43 vs. 1.97 0.54; ANOVA P = 0.046). Effects of passive maternal smoking on the fetal-placental-maternal unit were comparable to those with active maternal smoking as determined by the means of increased resistance in the maternal vasculature and adaptive changes of cerebroplacental circulation for maintaining fetal cerebral circulation.

Copyright 2011, Japanese Society of Radiology

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.

Copyright 2009, National Academy of Sciences

Zammit S; Thomas K; Thompson A; Horwood J; Menezes P; Gunnell D et al. Maternal tobacco, cannabis and alcohol use during pregnancy and risk of adolescent psychotic symptoms in offspring. British Journal of Psychiatry 195(4): 294-300, 2009. (52 refs.)

Background: Adverse effects of maternal substance use during pregnancy on fetal development may increase risk of psychopathology. Aims To examine whether maternal use of tobacco, cannabis or alcohol during pregnancy increases risk of offspring psychotic symptoms. Method A longitudinal study of 6356 adolescents, age 12, who completed a semi-structured interview for psychotic symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Results Frequency of maternal tobacco use during pregnancy was associated with increased risk of suspected or definite psychotic symptoms (adjusted odds ratio 1.20, 95% CI 1.05-1.37, P=0.007). Maternal alcohol use showed a non-linear association with psychotic symptoms, with this effect almost exclusively in the offspring of women drinking >21 units weekly. Maternal cannabis use was not associated with psychotic Symptoms. Results for paternal smoking during pregnancy and maternal smoking post-pregnancy lend some support for a causal effect of tobacco exposure in utero on development of psychotic experiences. Conclusions: These findings indicate that risk factors for development of non-clinical psychotic experiences may operate during early development. Future studies of how in utero exposure to tobacco affects cerebral development and function may lead to increased understanding of the pathogenesis of psychotic phenomena.

Copyright 2009, Royal College of Psychiatrists

Zelner I; Shor S; Lynn H; Roukema H; Lum L; Eisinga K; Koren G. Neonatal screening for prenatal alcohol exposure: Assessment of voluntary maternal participation in an open meconium screening program. Alcohol 46(3): 269-276, 2012. (41 refs.)

Meconium fatty acid ethyl esters (FAEEs) are validated biomarkers of fetal alcohol exposure. Meconium FAEE testing can potentially be used as a screen by health-care professionals to identify neonates at-risk for Fetal Alcohol Spectrum Disorder, thereby permitting diagnostic follow-up of these children and early intervention in those who develop disabilities. The purpose of this study was to assess whether women would willingly partake in a screening program of this nature. This was determined by launching a pilot screening program for prenatal alcohol exposure in a high-risk obstetric unit previously shown to have a high prevalence of FAEE-positive meconium via anonymous meconium testing. The program involved voluntary testing of meconium for FAEEs and long-term developmental follow-up of positive cases through an existing public health program. The participation rate in the screening program was significantly lower than when testing was conducted anonymously (78% vs. 95%, respectively; p < 0.05), and the positivity rate was 3% in contrast to 30% observed under anonymous conditions (p < 0.001). These low rates suggest that the majority of mothers who consumed alcohol in pregnancy refused to participate. We conclude that despite the potential benefits of such screening programs, maternal unwillingness to consent, likely due to fear, embarrassment, and guilt, may limit the effectiveness of meconium testing for population-based open screening, highlighting the need for public education and social marketing efforts for such programs to be of benefit.

Copyright 2012, Elseiver Science

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.

Copyright 2010, Elsevier Science