Evaluation of the German biographic screening interview for fetal alcohol spectrum disorder (BSI-FASD).

Alcohol consumption during pregnancy may lead to permanent damage in the offspring, including fetal alcohol spectrum disorders (FASD), which have an estimated prevalence of 1-8% worldwide. In adulthood, diagnosing FASD is time-consuming and costly. This study aimed to evaluate the discriminatory power of a German screening instrument for FASD in adults-the biographic screening interview (BSI-FASD). In an open-label comparative cohort study wherein a one-time survey was administered per participant, we compared 22 subjects with confirmed FASD with control groups of 15 subjects diagnosed with attention deficit hyperactivity disorder (ADHD), 20 subjects with alcohol or opiate dependence, 18 subjects with depression, and 31 controls without prenatal alcohol exposure. The BSI-FASD was found to be resource-efficient, user-friendly, comprehensible, and easily applicable. It provided an overall good convergent and discriminant validity with a sensitivity of 0.77 (adapted 0.86) and specificities between 0.70 and 1.00. The BSI-FASD subdomains differed in their power to differentiate FASD from the groups. This study established that the BSI-FASD is an efficient instrument to screen adults with suspected FASD. The BSI-FASD may facilitate future diagnostic evaluation and thereby contribute to improved treatment of affected individuals.

Fatty acid ethyl esters in meconium and substance use in adolescence.

Prenatal alcohol exposure (PAE) continues to be a serious public health problem, yet no reliable clinical tools are available for assessing levels of drinking during pregnancy. Fatty acid ethyl esters (FAEEs), the nonoxidative metabolites of ethanol measured in meconium, are potential biomarkers to quantify the level of PAE. The association between the concentrations of FAEEs from meconium and adolescent substance use and related problems was examined in a prospective birth-cohort of adolescents exposed to alcohol and drugs in utero. FAEEs were quantified with gas chromatography via a flame ionization detector. Meconium was analyzed for FAEEs in 216 newborns; 183 of them (81 boys, 102 girls) were assessed at age 15 for alcohol, tobacco, and marijuana use using biologic assays and self-report. Substance use problems were assessed using the Problem Oriented Screening Instrument for Teenagers. Findings from multivariable logistic regression analyses indicated that, after controlling for other prenatal drug exposure and covariates, higher concentrations of FAEEs (ethyl myristate, ethyl palmitate, ethyl oleate, ethyl linoleate, ethyl linolenate, and ethyl arachidonate) were related to a greater likelihood of marijuana use and experiencing substance use problems, but not tobacco or alcohol use, at age 15. Elevated levels of FAEEs in meconium may be promising markers for PAE, identifying newborns at risk for early substance use and developing substance use problems.

Implications of altered maternal cytokine concentrations on infant outcomes in children with prenatal alcohol exposure.

Excessive alcohol consumption has been shown to increase serum plasma levels of numerous immune cytokines. Maternal immune activation and elevated cytokines have been implicated in certain neurological disorders (e.g., autism and schizophrenia) in the offspring. We investigated the hypothesis that elevated cytokines during pregnancy are a risk factor in women who gave birth to a child with Fetal Alcohol Spectrum Disorder (FASD) or a child with neurobehavioral impairment, regardless of prenatal alcohol exposure. Moderate to heavy alcohol-exposed (AE) (N = 149) and low or no alcohol-exposed (LNA) (N = 92) women were recruited into the study during mid pregnancy (mean of 19.8 ± 5.8 weeks' gestation) in two regions of Ukraine: Khmelnytsky and Rivne. Maternal blood samples were obtained at enrollment into the study at early to mid-pregnancy and during a third-trimester follow-up visit and analyzed for plasma cytokines. Children were examined at 6 and/or 12 months of age and were classified as having FASD if their mothers reported alcohol use and if they had at least one standardized score (Bayley Scales of Infant Development II Mental Development Index [MDI], or Psychomotor Development Index [PDI]) below 85 with the presence or absence of physical features of FASD. In multivariate analyses of maternal cytokine levels in relation to infant MDI and PDI scores in the entire sample, increases in the ratio of TNF-α/IL-10 and IL-6/IL-10 were negatively associated with PDI scores at 6 months (p = 0.020 and p = 0.036, respectively) and 12 months (p = 0.043 and p = 0.029, respectively), and with MDI scores at 12 months (p = 0.013 and p = 0.050, respectively). A reduction in the odds ratio of having an FASD child was observed with increasing levels of IL-1ß, IL-2, IL-4, IL-6, and IL-10 in early to mid-pregnancy and IL-1ß and IL-10 during late pregnancy. However, women that failed to increase IL-10 levels in the third trimester in order to maintain the balance of pro- and anti-inflammatory cytokines had an elevated risk of having an FASD child, specifically a significant increase in the odds ratio of FASD with every one-unit log increase in late pregnancy TNF-α/IL-10 levels (aOR: 1.654, CI: 1.096-2.495, p = 0.017). These data support the concept that disruptions in the balance between pro- and anti-inflammatory cytokines may contribute to neurobehavioral impairment and alter the risk of FASD.

Neural correlates of verbal memory in youth with heavy prenatal alcohol exposure.

Prenatal alcohol exposure can impact both brain development and neurobehavioral function, including verbal learning and recall, although the relation between verbal recall and brain structure in this population has not been examined fully. We aimed to determine the structural neural correlates of verbal learning and recall in youth with histories of heavy prenatal alcohol exposure using a region of interest (ROI) approach. As part of an ongoing multisite project, subjects (age 10-16 years) with prenatal alcohol exposure (AE, n = 81) and controls (CON, n = 81) were tested using the CVLT-C and measures of cortical volume, surface area, and thickness as well as hippocampal volume were derived from MRI. Group differences in brain and memory indices were tested with ANOVA. Multiple regression analyses tested whether brain ROIs significantly predicted memory performance. The AE group had lower scores than the CON group on all CVLT-C variables (ps ≤ .001) and volume and surface area (ps < .025), although results varied by ROI. No group differences in cortical thickness were found. The relations between cortical structure and memory performance differed between group among some ROIs, particularly those in the frontal cortex, generally with smaller surface area and/or thinner cortex predicting better performance in CON but worse performance in AE. Cortical surface area appears to be the most sensitive index to the effects of prenatal alcohol exposure, while cortical thickness appears to be the least sensitive. These findings also indicate that the neural correlates of verbal memory are altered in youth with heavy prenatal alcohol exposure compared to controls.

Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that individuals carrying the ADHD risk alleles of the dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) genes may be especially sensitive to their effects. METHODS: Functional MRI data, information on prenatal adversities and genetic data were available for 239 adolescents and young adults participating in the multicentre ADHD cohort study NeuroIMAGE (average age 17.3 yr). We analyzed the effects of DRD4 and DAT1, prenatal exposure to alcohol and smoking and their interactions on ADHD severity, response inhibition and neural activity. RESULTS: We found no significant gene × environment interaction effects. We did find that the DRD4 7-repeat allele was associated with less superior frontal and parietal brain activity and with greater activity in the frontal pole and occipital cortex. Prenatal exposure to smoking was also associated with lower superior frontal activity, but with greater activity in the parietal lobe. Further, those exposed to alcohol had more activity in the lateral orbitofrontal cortex, and the DAT1 risk variant was associated with lower cerebellar activity. LIMITATIONS: Retrospective reports of maternal substance use and the cross-sectional study design restrict causal inference. CONCLUSION: While we found no evidence of gene × environment interactions, the risk factors under investigation influenced activity of brain regions associated with response inhibition, suggesting they may add to problems with inhibiting behaviour.

With Bated Breath: diagnosis of respiratory illness.

This essay recounts the author's experience of diagnosis of a rare respiratory condition in order to invite a broader reflection on the nature of diagnosis. Diagnosis is a pivotal moment in one's illness experience, and it can be viewed as both a closure of possibilities and an opening of new, unanticipated ones. The notion of anticipation is also important to the illness experience, in that anticipation and waiting characterize the illness experience generally--in waiting rooms, anticipating test results--as well as the change in one's attitude towards the future, which becomes fearsome in illness.

The effects of prenatal exposure to alcohol and environmental tobacco smoke on risk for ADHD: a large population-based study.

Attention deficit hyperactivity disorder (ADHD) is caused by the interaction of genetic and environmental factors. The objective of this study was to examine the effects of prenatal exposure to alcohol and environmental tobacco smoke (ETS). Among the 30,552 parents who responded to a survey, the answers of 19,940 who replied to questions on prenatal exposure to ETS, alcohol consumption, and completed the DuPaul Rating Scale were analyzed. Results revealed that risk of ADHD significantly increased as a result of exposure to alcohol by 1.55 times (95% CI 1.33-1.82), maternal smoking during pregnancy by 2.64 times (95% CI 1.45-4.80), and paternal smoking during pregnancy by 1.17 times (95% CI 1.98-1.39). When the subjects whose mothers did not smoke during pregnancy were divided into 4 groups, the prevalence was 1.16 times higher (95% CI 1.02-1.33) in the group exposed to ETS but not alcohol, 1.19 times higher (95% CI 0.91-1.57) in the group exposed to alcohol but not ETS, and 1.58 times higher (95% CI 1.31-1.91) in the group exposed to ETS and alcohol. The differences between the groups were statistically significantly (P<0.0001). This result shows that simultaneous exposure to ETS and alcohol during pregnancy increases the risk of ADHD.

[Potential therapy of intravenous neural stem cell transplantation for psychiatric disorder--a strategy for facilitation of neural network and behavioral recovery].

Recent clinical neuroimaging studies have revealed a possible relationship between morphological brain changes and the manifestation of psychiatric disorders such as depression, schizophrenia, and alcoholism. Although its biological mechanism is still unclear, the emerging evidence suggests that the alteration of neurogenesis is the key factor for the morphological brain changes of these psychiatric disorders. In our previous work, we analyzed the mechanism of neural network disruption by ethanol using cultured cells, and found a suppressive effect of ethanol on neural stem cell (NSC) differentiation. While, we also demonstrated that antidepressants, mood stabilizers and atypical antipsychotics stimulate NSC differentiation which was inhibited by ethanol. In the present work, we have demonstrated that the usefulness of intravenous transplantation of NSCs to fetal alcohol spectrum disorder (FASD) model rat for the purpose of reconstructing the impaired neural network and investigating the possibility of regenerative therapy for patients with neurobehavioral deficits of FASD. We have shown the potential migration of transplanted NSCs into the brain by visualizing a fluorescent cell marker and radioisotope, as well as the possible recovery of behavioral abnormalities observed in FASD model rats, such as memory/cognitive function, and social interaction. We further assessed the characteristics of transplanted cells in the brain and found that the GABAergic interneurons were increased in amygdale, DG, cingulated cortex areas in the model rat. In the amygdala and cingulate Cortex of model rats, number of parvalbumin positive cells was reduced and the NSC transplantation recovered these disturbances. Moreover, in the amygdala and cingulate cortex, intravenous NSC transplantation appears to regenerate expression of post-synaptic density protein 95 (PSD95) in FASD model rats. These results indicate that intravenous NSC transplantation has the potential to become a therapeutic intervention for FASD patients.

Cognitive aspects of fetal alcohol syndrome in young adults: two case studies / Aspectos Cognitivos da Síndrome Fetal Alcoólica em adultos jovens: dois estudos de caso

Fetal Alcohol Syndrome (FAS) includes a specific pattern of cognitive deficits, including language and speech disorders. Two adult participants were studied by means of the Examination of Language Test and a battery of complementary tests to evaluate oral and written language. Our data indicated great results of the participant who had psychopedagogical and speech-language assistance than the other who did not receive none intervention. These findings suggest that early diagnosis and intervention are crucial to minimize sequelae in FAS.

A Síndrome Fetal Alcóolica (SFA) inclui um padrão de déficit cognitivo, incluindo alterações de linguagem e fala. Estudou-se dois participantes adultos que foram diagnosticados com SFA na infância por meio do Teste de Exame de Linguagem e de uma bateria de testes complementares para avaliar aspectos da linguagem oral e escrita. Os dados indicaram que o participante que recebeu uma intervenção psicopedagógica apresentou melhores resultados que aquele que não tinha recebido nenhuma intervenção. Estes achados indicam que um diagnóstico precoce é fundamental para minimizar as sequelas da SFA.

Explanation of social inequalities in hyperactivity/inattention in children with prenatal alcohol exposure.

BACKGROUND: Hyperactivity and inattention are major effects of prenatal alcohol exposure (PAE). Although predominantly women from the high social class consume alcohol during pregnancy, children from the low social class are particularly affected by the adverse effects of PAE. This study aimed to test the hypothesis of a social gradient in hyperactivity/inattention in children with PAE. METHODS: Children with PAE (N=996) enrolled in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were studied. KiGGS was designed and conducted by Robert Koch Institute (RKI) as a nationwide representative survey on the health of German children and adolescents aged 0-17 years. The data include information given by parents and adolescents on the physical and mental health, sociodemographic features, life circumstances and conditions. RESULTS: PAE children with a middle and low parental socioeconomic status (SES) are on a higher risk of developing hyperactivity/inattention compared to those with high parental SES. Cultural-behavioral factors had the strongest effect in the explanation of social inequalities in hyperactivity/inattention among children with PAE. CONCLUSIONS: Cultural-behavioral factors, particularly health-related behaviors, need a significant improvement in children from the low and middle social class. To reduce social inequalities in hyperactivity in children with PAE, interventions have to focus on the dietary and television habits of the child by reaching parents from the low and middle social class.

Relation over time between facial measurements and cognitive outcomes in fetal alcohol-exposed children.

BACKGROUND: The identification of individuals exposed prenatally to alcohol can be challenging, with only those having the characteristic pattern of facial features, central nervous system abnormality, and growth retardation receiving a clinical diagnosis of fetal alcohol syndrome (FAS). METHODS: Seventeen anthropometric measurements were obtained at 5 and 9 years from 125 Cape Town, South African children, studied since birth. The children were divided into 3 groups: FAS or partial FAS (PFAS), heavily exposed nonsyndromal (HE), and non-alcohol-exposed controls (C). Anthropometric measurements were evaluated for mean group differences. Logistic regression models were used to identify the subset of anthropometric measures that best predicted group membership. Anthropometric measurements were examined at the 2 ages in relation to prenatal alcohol exposure obtained prospectively from the mothers during pregnancy. Correlation of these facial measurements with key neurobehavioral outcomes including Wechsler Intelligence Scales for Children-IV IQ and eyeblink conditioning was used to assess their utility as indicators of alcohol-related central nervous system impairment. RESULTS: Significant group differences were found for the majority of the anthropometric measures, with means of these measures smaller in the FAS/PFAS compared with HE or C. Upper facial widths, ear length, lower facial depth, and eye widths were consistent predictors distinguishing those exposed to alcohol from those who were not. Using longitudinal data, unique measures were identified that predicted facial anomalies at one age but not the other, suggesting the face changes as the individual matures. And 41% of the FAS/PFAS group met criteria for microtia at both ages. Three of the predictive anthropometric measures were negatively related to measures of prenatal alcohol consumption, and all were positively related to at least 1 neurobehavioral outcome. CONCLUSIONS: The analysis of longitudinal data identified a common set of predictors, as well as some that are unique at each age. Prenatal alcohol exposure appears to have its primary effect on brain growth, reflected by smaller forehead widths, and may suppress neural crest migration to the branchial arches, reflected by deficits in ear length and mandibular dimensions. These results may improve diagnostic resolution and enhance our understanding of the relation between the face and the neuropsychological deficits that occur.

Cognitive-adaptive disabilities.

Cognitive-adaptive disabilities (CADs) are not frequently seen in the general pediatric setting. Yet, given the high rates of comorbidity in that population, they commonly demand a lot of time and effort on the part of clinicians. One aspect of comorbidity is the degree to which psychiatric disorders occur in children, adolescents, and young adults with CADs. This article reviews the epidemiology, associated psychopathology, and pharmacologic treatment of selected CADs.

[Promising therapy of neural stem cell transplantation for FASD model--neural network reconstruction and behavior recovery].

OBJECTIVES: It has been elucidated that psychiatric disorders are associated with impairment of the brain neural network. Reduction in brain size and hypoplasia of the basal ganglia and corpus callosum have been reported in Fetal Alcohol Spectrum Disorder (FASD). It is believed that the formation of the neural network is influenced by alcohol exposure during the fetal period. Additionally, it is well known that the functional expression of CNS consequences of prenatal alcohol exposure includes cognitive and attentional processes, as well as social behavioral problems. It has also been reported that abnormal 5-HT neuron development can be reversed by treatment with a 5-HT1A agonist in a prenatal alcohol exposure model. However, these treatments are prophylactic. Without early intervention, the consequences of FASD are permanent. Recently, emerging evidence suggest that many clinical symptoms observed in psychiatric disease are likely related to neural network disruptions including neurogenesis dysfunction. Neural stem cell (NSC) transplantation has been investigated in areas such as brain injury, stroke and neurodegenerative diseases and may be a way to reverse neurogenesis dysfunction. In the present work, we evaluated the usefulness of intravenous transplantation of NSCs in the FASD model rat focusing on the possibility of regenerative therapy, particularly regarding behavioral abnormalities, for FASD rats. RESULTS: Abnormal behaviors FASD model rats suggest that reduced social activity , and cognitive dysfunction are major symptoms in FASD patients. Intravenous NSC transplantation appeared to partially correct these behavioral abnormalities in FASD model rats. In the Amygdala areas intravenous NSC transplantation appears to have partially regaenerates expression of PSD95 in FASD model rats. CONCLUSIONS: The results suggest that intravenous NSC transplantation may be an advanced approach to recover neural network damage and CNS dysfunction in FASD and possibly other psychiatric disorders.

Psychological distress among Plains Indian mothers with children referred to screening for Fetal Alcohol Spectrum Disorders.

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 (

Prenatal alcohol exposure alters biobehavioral reactivity to pain in newborns.

OBJECTIVES: To examine biobehavioral responses to an acute pain event in a Cape Town, South Africa, cohort consisting of 28 Cape Colored (mixed ancestry) newborns (n = 14) heavily exposed to alcohol during pregnancy (exposed), and born to abstainers (n = 14) or light (< or = 0.5 oz absolute alcohol/d) drinkers (controls). METHODS: Mothers were recruited during the third trimester of pregnancy. Newborn data were collected on postpartum day 3 in the maternity obstetrical unit where the infant had been delivered. Heavy prenatal alcohol exposure was defined as maternal consumption of at least 14 drinks/wk or at least 1 incident of binge drinking/mo. Acute stress-related biobehavioral markers [salivary cortisol, heart rate (HR), respiratory sinus arrhythmia (RSA), spectral measures of heart rate variability (HRV), and videotaped facial actions] were collected thrice during a heel lance blood collection (baseline, lance, and recovery). After a feeding and nap, newborns were administered an abbreviated Brazelton Neonatal Behavioral Assessment Scale. RESULTS: There were no between-group differences in maternal age, marital status, parity, gravidity, depression, anxiety, pregnancy smoking, maternal education, or infant gestational age at birth (all ps > 0.15). In both groups, HR increased with the heel lance and decreased during the postlance period. The alcohol-exposed group had lower mean HR than controls throughout, and showed no change in RSA over time. Cortisol levels showed no change over time in controls but decreased over time in exposed infants. Although facial action analyses revealed no group differences in response to the heel lance, behavioral responses assessed on the Brazelton Neonatal Scale showed less arousal in the exposed group. CONCLUSIONS: Both cardiac autonomic and hypothalamic-pituitary-adrenal stress reactivity measures suggest a blunted response to an acute noxious event in alcohol-exposed newborns. This is supported by results on the Brazelton Neonatal Scale indicating reduced behavioral arousal in the exposed group. To our knowledge, these data provide the first biobehavioral examination of early pain reactivity in alcohol-exposed newborns and have important implications for understanding neuro-/biobehavioral effects of prenatal alcohol exposure in the newborn period.

Reversal of alcohol-induced learning deficits in the young adult in a model of fetal alcohol syndrome.

OBJECTIVE: To evaluate whether treatment with neuroprotective peptides to young adult mice prenatally exposed to alcohol reverses alcohol-induced learning deficits in a mouse model of fetal alcohol syndrome, whether the mechanism involves the N-methyl-d-aspartate (NMDA) and gamma-aminobutyric acid type A (GABAA) receptors, and whether it is related to glial cells. METHODS: C57Bl6/J mice were treated with alcohol (0.03 ml/g) or placebo on gestational day 8. On day 40, male mice exposed to alcohol in utero were treated daily for 10 days with D-NAPVSIPQ and D-SALLRSIPA (n=20) or placebo (n=13); and control offspring were treated with placebo (n=46), with the treatment blinded. Learning evaluation began after 3 days using the Morris watermaze and the T-maze. The hippocampus, cortex, and cerebellum were isolated. Expression of NR2A, NR2B, GABAAbeta3, GABAAalpha5, vasoactive intestinal peptide (VIP), activity-dependent neuroprotective protein, and glial fibrillary acidic protein was measured using calibrator-normalized relative real-time polymerase chain reaction. Statistical analysis included analysis of variance and Fisher's protected least significant difference. RESULTS: Treatment with D-NAPVSIPQ and D-SALLRSIPA reversed the alcohol-induced learning deficit in both learning tests as well as the NR2A and NR2B down-regulation in the hippocampus and the up-regulation of NR2A in the cortex and NR2B in the cortex and cerebellum (all P<.05). No significant differences were found in GABAA expression. Moreover, the peptides changed activity-dependent neuroprotective protein expression in the cortex (P=.016) but not the down-regulation of VIP (P=.883), probably because the peptides are downstream from VIP. CONCLUSION: Alcohol-induced learning deficit was reversed and expression of NR2A and NR2B was restored in the hippocampus and cortex of young adult mice treated with D-NAPVSIPQ and D-SALLRSIPA. Given the role of NMDA receptors in learning, this may explain in part the mechanism of prevention of alcohol-induced learning deficits by D-NAPVSIPQ and D-SALLRSIPA.

Maternal smoking in pregnancy and externalizing behavior in 18-month-old children: results from a population-based prospective study.

OBJECTIVE: The relation between prenatal smoking and child behavioral problems has been investigated in children of school age and older, but prospective studies in younger children are lacking. Using the population-based prospective Norwegian Mother and Child Cohort Study, we examined the risk for externalizing behaviors among 18-month-old children after exposure to maternal smoking during pregnancy. METHOD: Participants were 22,545 mothers and their 18-month-old children. Mothers reported their smoking habits at the 17th week of gestation and their child's externalizing behavior at 18 months of age by means of standardized questionnaires. Data were analyzed using logistic regression, with scores of externalizing behavior above the 88.6th percentile as the dependent variable and self-reported smoking as the independent variable. We examined the child's sex as a possible moderator. RESULTS: We documented a threshold effect of smoking 10 cigarettes or more per day during pregnancy on subsequent externalizing behaviors among 18-month-old children, even after adjusting for relevant confounders (odds ratio 1.32, 95% confidence interval 1.03-1.70). The child's sex did not moderate these effects (odds ratio 0.98, 95% confidence interval 0.83-1.16). CONCLUSIONS: Maternal smoking during pregnancy increases offspring's subsequent risk for externalizing behavior problems at 18 months of age. The pattern of risk does not differ between boys and girls. Our findings suggest a population attributable risk of 1.75% [corrected] (i.e., the proportion of externalizing cases that could potentially be avoided if prenatal smoking was eliminated or reduced to fewer than 10 cigarettes per day).

A exposição pré-natal ao álcool como fator de risco para comportamentos disfuncionais: o papel do pediatra: [revisão] / Prenatal alcohol exposure as a risk factor for dysfunctional behaviors: the role of the pediatrician: [review]

OBJETIVO: Ainda que as características clássicas da síndrome fetal alcoólica tenham sido descritas desde 1968, a pesquisa sobre a teratogênese do álcool apenas recentemente demonstrou que o cérebro é o órgão do corpo mais vulnerável aos efeitos da exposição pré-natal ao álcool. No presente artigo, fazemos uma revisão da literatura focalizando principalmente os distúrbios comportamentais relacionados à exposição pré-natal ao álcool. FONTES DOS DADOS: Foi realizada uma pesquisa com base no PubMed sobre a literatura publicada entre 1968 e 2006, com as palavras-chave etanol, gestação e comportamento. Foram estabelecidos limites a estudos em humanos. SÍNTESE DOS DADOS: Os dados apresentados nesta revisão sugerem que jovens com efeitos do espectro do álcool fetal estão sob risco maior de terem comportamento social disruptivo, entre outros problemas neurocomportamentais. CONCLUSÕES: Ainda que seja impossível separar completamente a teratogênese sobre o cérebro decorrente da exposição ao álcool de influências ambientais pós-natais como a causa definitiva desses resultados, o pediatra deve ser estimulado ao diagnóstico precoce de crianças afetadas pela síndrome fetal alcoólica e efeitos do espectro do álcool fetal. Isso permite iniciar o manejo e cuidados apropriados para evitar as conseqüências em longo prazo no comportamento e assegurar uma adaptação social e escolar melhor e mais produtiva.

OBJECTIVE: Although the classic features of fetal alcohol syndrome have been recognized since 1968, research on alcohol teratogenesis has only recently demonstrated that the brain is the organ in the body most vulnerable to the effects of prenatal alcohol exposure. In this present article, we reviewed the literature focusing mainly on behavioral disturbances related to prenatal ethanol exposure. SOURCES: We performed a PubMed search on the literature published between 1968 and 2006 using the terms ethanol, pregnancy and behavior. We limited our search to studies on humans. SUMMARY OF THE FINDINGS: The data presented in this review suggested that youths with fetal alcohol spectrum disorder are at risk of disruptive social behavior, among other neurobehavioral abnormalities. CONCLUSIONS: Although it is still impossible to completely separate brain teratogenesis secondary to alcohol exposure from environmental postnatal influences as the definite cause for these outcomes, the pediatrician should be encouraged to early diagnose children affected by fetal alcohol syndrome and fetal alcohol spectrum disorder. This provides proper management and care and avoids long-term consequences on their behavior, besides ensuring better and productive school and social adaptation.

Effects of alcohol exposure during development on play behavior and c-Fos expression in response to play behavior.

Developmental exposure to alcohol can produce characteristic physiological and cognitive deficits, often termed Fetal Alcohol Spectrum Disorder (FASD). More recently, social deficits have been shown to occur both in FASD and animal models of FASD; the behavioral and neural bases of these deficits remain to be determined. It was hypothesized that changes in sensory processing may in part underlie the social deficits seen in FASD. This study used a rat model of FASD and social play, a behavior critical to adult social functioning, to begin to examine this hypothesis. Somatosensory cues from dorsal contact to the nape of the neck, critical to the initiation of pinning, were systematically degraded by administration of different doses of xylocaine, a topical anesthetic. Neuronal activity after 1h of play was assessed by measurement of c-Fos immunoreactivity (IR) in different brain regions. Ethanol-exposed rats showed an increased frequency of pinning during social play and were more sensitive to the degradation of somatosensory cues compared to the control groups, suggesting difficulties in processing somatosensory cues. Neuronal activity in the somatosensory cortex induced by play was significantly decreased in the ethanol-exposed group compared to the non-treated group. The c-Fos IR in the nucleus accumbens was altered in a sexually dimorphic manner in the ethanol-exposed group. Thus, the behavioral and brain measures are consistent with the hypothesis that ethanol exposure during development induces alterations in social play via deficits in processing somatosensory cues that are important to social play.