Prenatal alcohol exposure is associated with early motor, but not language development in a South African cohort.

OBJECTIVE: To investigate the association of prenatal alcohol exposure (PAE) and early neurodevelopment in the first 2 years of life, adjusting for maternal socio-demographic and psychosocial factors, in the Drakenstein Child Health Study (DCHS), a South African birth cohort study. METHODS: The DCHS comprises a population-based birth cohort of 1143 children, of which a subsample completed the Bayley Scales of Infant Development-III (BSID-III) at 6 (n = 260) and 24 months of age (n = 734). A subset of alcohol-exposed and -unexposed children was included in this analysis at age 6 (n = 52 exposed; n = 104 unexposed) and 24 months (n = 92 exposed; n = 184 unexposed). Multiple hierarchical regression was used to explore the associations of PAE with motor and language development. RESULTS: PAE was significantly associated with decreased gross motor [odds ratio (OR) = 0.16, 95% confidence interval (CI) = 0.06-0.44, p = 0.001] or fine motor (OR = 0.16, 95% CI = 0.06-0.46, p = 0.001) functioning after adjusting for maternal socio-demographic and psychosocial factors at 6 months of age only. No significant effects were found in either receptive or expressive communication and cognitive outcomes at either time points. CONCLUSION: PAE has potentially important consequences for motor development in the first 2 years of life, a period during which the most rapid growth and maturation occur. These findings highlight the importance of identifying high-risk families in order to provide preventive interventions, particularly in antenatal clinics and early intervention services.

Who is most affected by prenatal alcohol exposure: Boys or girls?

OBJECTIVE: To examine outcomes among boys and girls that are associated with prenatal alcohol exposure. METHODS: Boys and girls with fetal alcohol spectrum disorders (FASD) and randomly-selected controls were compared on a variety of physical and neurobehavioral traits. RESULTS: Sex ratios indicated that heavy maternal binge drinking may have significantly diminished viability to birth and survival of boys postpartum more than girls by age seven. Case control comparisons of a variety of physical and neurobehavioral traits at age seven indicate that both sexes were affected similarly for a majority of variables. However, alcohol-exposed girls had significantly more dysmorphology overall than boys and performed significantly worse on non-verbal IQ tests than males. A three-step sequential regression analysis, controlling for multiple covariates, further indicated that dysmorphology among girls was significantly more associated with five maternal drinking variables and three distal maternal risk factors. However, the overall model, which included five associated neurobehavioral measures at step three, was not significant (p=0.09, two-tailed test). A separate sequential logistic regression analysis of predictors of a FASD diagnosis, however, indicated significantly more negative outcomes overall for girls than boys (Nagelkerke R2=0.42 for boys and 0.54 for girls, z=-2.9, p=0.004). CONCLUSION: Boys and girls had mostly similar outcomes when prenatal alcohol exposure was linked to poor physical and neurocognitive development. Nevertheless, sex ratios implicate lower viability and survival of males by first grade, and girls have more dysmorphology and neurocognitive impairment than boys resulting in a higher probability of a FASD diagnosis.

Replication of High Fetal Alcohol Spectrum Disorders Prevalence Rates, Child Characteristics, and Maternal Risk Factors in a Second Sample of Rural Communities in South Africa.

Background: Prevalence and characteristics of fetal alcohol syndrome (FAS) and total fetal alcohol spectrum disorders (FASD) were studied in a second sample of three South African rural communities to assess change. Methods: Active case ascertainment focused on children with height, weight and/or head circumference ≤25th centile and randomly-selected children. Final diagnoses were based on dysmorphology, neurobehavioral scores, and maternal risk interviews. Results: Cardinal facial features, head circumference, and total dysmorphology scores differentiated specific FASD diagnostic categories in a somewhat linear fashion but all FASD traits were significantly worse than those of randomly-selected controls. Neurodevelopmental delays were significantly worse for children with FASD than controls. Binge alcohol use was clearly documented as the proximal maternal risk factor for FASD, and significant distal risk factors were: low body mass, education, and income; high gravidity, parity, and age at birth of the index child. FAS rates continue to extremely high in these communities at 9-129 per 1000 children. Total FASD affect 196-276 per 1000 or 20-28% of the children in these communities. Conclusions: Very high rates of FASD persist in these general populations where regular, heavy drinking, often in a binge fashion, co-occurs with low socioeconomic conditions.

Fetal alcohol spectrum disorder in Africa.

PURPOSE OF REVIEW: This review aims to summarize data published in the scientific literature and available on official websites on fetal alcohol spectrum disorder (FASD) in Africa. RECENT FINDINGS: There is a paucity of published literature and evidence-based information on prenatal exposure to alcohol in the African continent and the majority of the continent's literature on FASD emanates from South Africa. A small number of scientific publications document FASD and drinking in pregnancy in other Sub-Saharan African countries and these findings provide evidence that FASD occurs across the continent. Further evidence shows that the world's highest reported rates of FASD occur in South Africa and that this confers a significant public health and neurodevelopmental disability burden on the region. There is an established body of epidemiological, diagnostic, neurobehavioral and neuroscientific knowledge from studies in South Africa. Universal and indicated case method preventions are effective in reducing maternal alcohol consumption in high-risk areas. Throughout Africa, a policy and service implementation gap exists that impedes translation of generated knowledge into effective prevention and intervention strategies. SUMMARY: FASD is likely a widely occurring and largely unrecognized neurodevelopmental disability in Africa. A key future direction for global agencies and research partnerships is to collaboratively address evidence gaps and knowledge translation through scalable approaches and strategies that aim to ameliorate the burden of FASD in African and other countries.

The continuum of fetal alcohol spectrum disorders in a community in South Africa: Prevalence and characteristics in a fifth sample.

BACKGROUND: The prevalence and characteristics of the continuum of diagnoses within fetal alcohol spectrum disorders (FASD) were researched in a fifth sample in a South African community. METHODS: An active case ascertainment approach was employed among all first grade learners in this community (n=862). Following individual examination by clinical geneticists/dysmorphologists, cognitive/behavioral testing, and maternal interviews, final diagnoses were made in multidisciplinary case conferences. RESULTS: Physical measurements, cardinal facial features of FAS, and total dysmorphology scores clearly differentiated diagnostic categories in a consistent, linear fashion, from severe to mild. Neurodevelopmental delays and behavioral problems were significantly worse for each of the FASD diagnostic categories, although not as consistently linear across diagnostic groups. Alcohol use was documented by direct report from the mother in 71% to 100% of cases in specific diagnostic groups. Significant distal maternal risk factors in this population are: advanced maternal age at pregnancy; low height, weight, and body mass index (BMI); small head circumference; low education; low income; and rural residence. Even when controlling for socioeconomic status, prenatal drinking correlates significantly with total dysmorphology score, head circumference, and five cognitive and behavioral measures. In this community, FAS occurs in 59-79 per 1,000 children, and total FASD in 170-233 per 1,000 children, or 17% to 23%. CONCLUSIONS: Very high rates of FASD continue in this community where entrenched practices of regular binge drinking co-exist with challenging conditions for childbearing and child development in a significant portion of the population.

The Effects of Prenatal Alcohol Exposure on Episodic Memory Functioning: A Systematic Review.

OBJECTIVE: This paper systematically reviews the literature on the effects of prenatal alcohol exposure (PAE) on episodic memory. Specifically, the review focuses on recurring questions of whether memory deficits are consistent across memory domains, whether the impairments are consistent across the stages of episodic memory, and whether the impairments are primary episodic memory impairments or secondary to a global performance deficit or a higher order deficit. METHOD: In total, 33 relevant studies were identified through searches on electronic databases. Journal articles were limited to those that included human subjects and that were published in English-language journals. RESULTS: The vast majority of reviewed studies examined memory in school-aged children and adolescents. Twenty-three studies examined verbal memory and 19 studies examined visual-spatial memory. Although all of the reviewed studies examined encoding of new material, only 10 studies examined retention of the learned material over time. Ten studies controlled for IQ, either statistically or with matched controls, when analyzing memory task performance. CONCLUSION: In general, studies show that PAE results in impaired verbal and visual-spatial episodic memory performance in affected individuals and these impairments are unlikely to be secondary to a global impairment. However, impairments on some memory tests are specific to the encoding stage, whereas retention is relatively spared; suggesting that the episodic memory deficit might be influenced, at least in part, by higher order cognitive processes.

Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders.

The adverse effects of prenatal alcohol exposure constitute a continuum of disabilities (fetal alcohol spectrum disorders [FASD]). In 1996, the Institute of Medicine established diagnostic categories delineating the spectrum but not specifying clinical criteria by which diagnoses could be assigned. In 2005, the authors published practical guidelines operationalizing the Institute of Medicine categories, allowing for standardization of FASD diagnoses in clinical settings. The purpose of the current report is to present updated diagnostic guidelines based on a thorough review of the literature and the authors' combined expertise based on the evaluation of >10 000 children for potential FASD in clinical settings and in epidemiologic studies in conjunction with National Institute on Alcohol Abuse and Alcoholism-funded studies, the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, and the Collaboration on FASD Prevalence. The guidelines were formulated through conference calls and meetings held at National Institute on Alcohol Abuse and Alcoholism offices in Rockville, MD. Specific areas addressed include the following: precise definition of documented prenatal alcohol exposure; neurobehavioral criteria for diagnosis of fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder; revised diagnostic criteria for alcohol-related birth defects; an updated comprehensive research dysmorphology scoring system; and a new lip/philtrum guide for the white population, incorporating a 45-degree view. The guidelines reflect consensus among a large and experienced cadre of FASD investigators in the fields of dysmorphology, epidemiology, neurology, psychology, developmental/behavioral pediatrics, and educational diagnostics. Their improved clarity and specificity will guide clinicians in accurate diagnosis of infants and children prenatally exposed to alcohol.

Breastfeeding and maternal alcohol use: Prevalence and effects on child outcomes and fetal alcohol spectrum disorders.

OBJECTIVE: Determine any effects that maternal alcohol consumption during the breastfeeding period has on child outcomes. METHODS: Population-based samples of children with fetal alcohol spectrum disorders (FASD), normally-developing children, and their mothers were analyzed for differences in child outcomes. RESULTS: Ninety percent (90%) of mothers breastfed for an average of 19.9 months. Of mothers who drank postpartum and breastfed (MDPB), 47% breastfed for 12 months or more. In case control analyses, children of MDPB were significantly lighter, had lower verbal IQ scores, and more anomalies in comparisons controlling for prenatal alcohol exposure and final FASD diagnosis. Utilizing a stepwise logistic regression model adjusting for nine confounders of prenatal drinking and other maternal risks, MDPB were 6.4 times more likely to have a child with FASD than breastfeeding mothers who abstained from alcohol while breastfeeding. CONCLUSIONS: Alcohol use during the period of breastfeeding was found to significantly compromise a child's development.

The continuum of fetal alcohol spectrum disorders in four rural communities in South Africa: Prevalence and characteristics.

BACKGROUND: Prevalence and characteristics of the continuum of diagnoses within fetal alcohol spectrum disorders (FASD) were researched in previously unstudied rural, agricultural, lower socioeconomic populations in South Africa (ZA). METHODS: Using an active case ascertainment approach among first grade learners, 1354 (72.6%) were consented into the study via: height, weight, and/or head circumference ≤ 25th centile and/or random selection as normal control candidates. Final diagnoses were made following: examination by pediatric dysmorphologists/geneticists, cognitive/behavioral testing, and maternal risk factor interviews. RESULTS: FASD children were significantly growth deficient and dysmorphic: physical measurements, cardinal facial features of FAS, and total dysmorphology scores clearly differentiated diagnostic categories from severe to mild to normal in a consistent, linear fashion. Neurodevelopmental delays were also significantly worse for each of the FASD diagnostic categories, although not as consistently linear across groups. Alcohol use is well documented as the proximal maternal risk factor for each diagnostic group. Significant distal maternal risk factors in this population are: low body weight, body mass, education, and income; and high gravidity, parity, and age at birth of the index child. In this low SES, highly rural region, FAS occurs in 93-128 per 1000 children, PFAS in 58-86, and, ARND in 32-46 per 1000. Total FASD affect 182-259 per 1000 children or 18-26%. CONCLUSIONS: Very high rates of FASD exist in these rural areas and isolated towns where entrenched practices of regular binge drinking co-exist with challenging conditions for childbearing and child development.

Volume changes and brain-behavior relationships in white matter and subcortical gray matter in children with prenatal alcohol exposure.

Children with prenatal alcohol exposure (PAE) may have cognitive, behavioral and brain abnormalities. Here, we compare rates of white matter and subcortical gray matter volume change in PAE and control children, and examine relationships between annual volume change and arithmetic ability, behavior, and executive function. Participants (n = 75 PAE/64 control; age: 7.1-15.9 years) each received two structural magnetic resonance scans, ~2 years apart. Assessments included Wechsler Intelligence Scale for Children (WISC-IV), the Child Behavior Checklist and the Behavior Rating Inventory of Executive Function. Subcortical white and gray volumes were extracted for each hemisphere. Group volume differences were tested using false discovery rate (q < 0.05). Analyses examined group-by-age interactions and group-score interactions for correlations between change in volume and raw behavioral scores. Results showed that subjects with PAE had smaller volumes than control subjects across the brain. Significant group-score interactions were found in temporal and parietal regions for WISC arithmetic scores and in frontal and parietal regions for behavioral measures. Poorer cognitive/ behavioral outcomes were associated with larger volume increases in PAE, while control subjects generally showed no significant correlations. In contrast with previous results demonstrating different trajectories of cortical volume change in PAE, our results show similar rates of subcortical volume growth in subjects with PAE and control subjects. We also demonstrate abnormal brain-behavior relationships in subjects with PAE, suggesting different use of brain resources. Our results are encouraging in that, due to the stable volume differences, there may be an extended window of opportunity for intervention in children with PAE.

Maternal alcohol consumption producing fetal alcohol spectrum disorders (FASD): quantity, frequency, and timing of drinking.

BACKGROUND: Concise, accurate measures of maternal prenatal alcohol use are needed to better understand fetal alcohol spectrum disorders (FASD). METHODS: Measures of drinking by mothers of children with specific FASD diagnoses and mothers of randomly-selected controls are compared and also correlated with physical and cognitive/behavioral outcomes. RESULTS: Measures of maternal alcohol use can differentiate maternal drinking associated with FASD from that of controls and some from mothers of alcohol-exposed normals. Six variables that combine quantity and frequency concepts distinguish mothers of FASD children from normal controls. Alcohol use variables, when applied to each trimester and three months prior to pregnancy, provide insight on critical timing of exposure as well. Measures of drinking, especially bingeing, correlate significantly with increased child dysmorphology and negative cognitive/behavioral outcomes in children, especially low non-verbal IQ, poor attention, and behavioral problems. Logistic regression links (p<.001) first trimester drinking (vs. no drinking) with FASD, elevating FASD likelihood 12 times; first and second trimester drinking increases FASD outcomes 61 times; and drinking in all trimesters 65 times. Conversely, a similar regression (p=.008) indicates that drinking only in the first trimester makes the birth of a child with an FASD 5 times less likely than drinking in all trimesters. CONCLUSIONS: There is significant variation in alcohol consumption both within and between diagnostic groupings of mothers bearing children diagnosed within the FASD continuum. Drinking measures are empirically identified and correlated with specific child outcomes. Alcohol use, especially heavy use, should be avoided throughout pregnancy.

Maternal factors predicting cognitive and behavioral characteristics of children with fetal alcohol spectrum disorders.

OBJECTIVE: To provide an analysis of multiple predictors of cognitive and behavioral traits for children with fetal alcohol spectrum disorders (FASDs). METHOD: Multivariate correlation techniques were used with maternal and child data from epidemiologic studies in a community in South Africa. Data on 561 first-grade children with fetal alcohol syndrome (FAS), partial FAS (PFAS), and not FASD and their mothers were analyzed by grouping 19 maternal variables into categories (physical, demographic, childbearing, and drinking) and used in structural equation models (SEMs) to assess correlates of child intelligence (verbal and nonverbal) and behavior. RESULTS: A first SEM using only 7 maternal alcohol use variables to predict cognitive/behavioral traits was statistically significant (B = 3.10, p < .05) but explained only 17.3% of the variance. The second model incorporated multiple maternal variables and was statistically significant explaining 55.3% of the variance. Significantly correlated with low intelligence and problem behavior were demographic (B = 3.83, p < .05) (low maternal education, low socioeconomic status [SES], and rural residence) and maternal physical characteristics (B = 2.70, p < .05) (short stature, small head circumference, and low weight). Childbearing history and alcohol use composites were not statistically significant in the final complex model and were overpowered by SES and maternal physical traits. CONCLUSIONS: Although other analytic techniques have amply demonstrated the negative effects of maternal drinking on intelligence and behavior, this highly controlled analysis of multiple maternal influences reveals that maternal demographics and physical traits make a significant enabling or disabling contribution to child functioning in FASD.

Further development of a neurobehavioral profile of fetal alcohol spectrum disorders.

BACKGROUND: Heavy prenatal alcohol exposure (AE) results in a broad array of neurobehavioral deficits. Recent research has focused on identification of a neurobehavioral profile or profiles that will improve the identification of children affected by AE. This study aimed to build on our preliminary neurobehavioral profile to improve classification accuracy and test the specificity of the resulting profile in an alternate clinical group. METHODS: A standardized neuropsychological test battery was administered to 3 groups of children: subjects with AE (n = 209), typically developing controls (CON, n = 185), and subjects with attention-deficit/hyperactivity disorder (ADHD, n = 74). We assessed a large sample from 6 sites in the United States and South Africa, using standardized methodology. Data were analyzed using 3 latent profile analyses including (i) subjects with fetal alcohol syndrome (FAS) and controls, (ii) subjects with AE without FAS and controls, and (iii) subjects with AE (with or without FAS) and subjects with ADHD. RESULTS: Classification accuracy was moderate but significant across the 3 analyses. In analysis 1, overall classification accuracy was 76.1% (77.2% FAS, 75.7% CON). In the second analysis, overall classification accuracy was 71.5% (70.1% AE/non-FAS, 72.4% CON). In the third analysis, overall classification accuracy was 73.9% (59.8% AE, 75.7% ADHD). Subjects that were misclassified were examined for systematic differences from those that were correctly classified. CONCLUSIONS: The results of this study indicate that the neuropsychological effects of AE are clinically meaningful and can be used to accurately distinguish alcohol-affected children from both typically developing children and children with ADHD. Further, in combination with other recent studies, these data suggest that approximately 70% of children with heavy prenatal alcohol exposure are neurobehaviorally affected, while the remaining 30% are spared these often-devastating consequences, at least those in the domains under study. Refining the neurobehavioral profile will allow improved identification and treatment development for children affected by prenatal alcohol exposure.

Approaching the prevalence of the full spectrum of fetal alcohol spectrum disorders in a South African population-based study.

BACKGROUND: The prevalence and characteristics of fetal alcohol spectrum disorders (FASD) were determined in this fourth study of first-grade children in a South African community. METHODS: Active case ascertainment methods were employed among 747 first-grade pupils. The detailed characteristics of children within the continuum of FASD are contrasted with randomly selected, normal controls on (i) physical growth and dysmorphology; (ii) cognitive/behavioral characteristics; and (iii) maternal risk factors. RESULTS: The rates of specific diagnoses within the FASD spectrum continue to be among the highest reported in any community in the world. The prevalence (per 1,000) is as follows: fetal alcohol syndrome (FAS)-59.3 to 91.0; partial fetal alcohol syndrome (PFAS)-45.3 to 69.6; and alcohol-related neurodevelopmental disorder (ARND)-30.5 to 46.8. The overall rate of FASD is therefore 135.1 to 207.5 per 1,000 (or 13.6 to 20.9%). Clinical profiles of the physical and cognitive/behavioral traits of children with a specific FASD diagnosis and controls are provided for understanding the full spectrum of FASD in a community. The spectral effect is evident in the characteristics of the diagnostic groups and summarized by the total (mean) dysmorphology scores of the children: FAS = 18.9; PFAS = 14.3; ARND = 12.2; and normal controls, alcohol exposed = 8.2 and unexposed = 7.1. Documented drinking during pregnancy is significantly correlated with verbal (r = -0.253) and nonverbal ability (r = -0.265), negative behaviors (r = 0.203), and total dysmorphology score (r = 0.431). Other measures of drinking during pregnancy are significantly associated with FASD, including binge drinking as low as 3 drinks per episode on 2 days of the week. CONCLUSIONS: High rates of specific diagnoses within FASD were well documented in this new cohort of children. FASD persists in this community. The data reflect an increased ability to provide accurate and discriminating diagnoses throughout the continuum of FASD.

Prevalence and patterns of medication use in children and adolescents with autism spectrum disorders in the Western Cape, South Africa.

OBJECTIVE: This study was conducted to investigate the prevalence and patterns of medication use amongst a sample of school going children and adolescents with autism spectrum disorders (ASD) in the Western Cape, South Africa. METHOD: This was a descriptive, quantitative, analytic study. A survey questionnaire and the Nisonger Child Behaviour Rating Form (NCBRF) were administered to parents of children and adolescents recruited from two schools for children with ASD in Cape Town and from the Autism Action database. RESULTS: A total of 24.6% of the 65 children used psychotropic medications. Antipsychotics were the most common reportedly used psychotropics followed by stimulants, antidepressants and mood stabilisers. Complementary and alternative medications were also commonly used with 40% of children using over the counter medications (OTC) and 15.4% being on a special diet for autism. Children of black African or coloured ethnicity were less likely to use OTC medication than children in the white/ Asian ethnic group. CONCLUSIONS: In keeping with international studies this sample of children with ASD was a highly medicated group. The findings of this pilot study were limited by the response rates and sample size, but provide valuable insight into medication use in the South African ASD population.

A Practical Testing Battery to Measure Neurobehavioral Ability among Children with FASD.

AIMS: To determine a brief, practical battery of tests that discriminate between children with a fetal alcohol spectrum disorder (FASD) and unexposed controls. DESIGN: Children received dysmorphology exams, a targeted battery of cognitive and behavioral tests, and their mothers were interviewed about maternal risk factors. Children diagnosed with an FASD and children unexposed to alcohol prenatally were compared on cognitive/behavioral test results. SETTING: A community in The Western Cape Province of South Africa. PARTICIPANTS: Sixty-one, first grade children with FASD and 52 matched normal controls. MEASURES: Statistical analyses of maternal drinking behavior and their child's test performance. FINDINGS: Self-reported maternal drinking patterns before during and after pregnancy were used to confirm prenatal exposures to alcohol in the group of children diagnosed with FASD. With this sample of children diagnosed with FASD and completely unexposed controls, the adverse effects of maternal drinking on children's performance are reported. Results of the battery of standardized cognitive and behavioral tests indicate highly significant differences (p ≤ .001) between groups on: intelligence, perceptual motor, planning, and logical, spatial, short term, long term, and working memory abilities. Furthermore, a binary logistical regression model of only 3 specific cognitive and behavioral tests, including Digit Span A+B (Wald = 4.10), Absurd Situation (Wald = 3.57), and Word Association (Wald = 4.30) correctly classified 79.1% of the child participants as FASD or controls. CONCLUSIONS: A brief, practical set of tests can discriminate children with and without FASD and provide useful information for interventions for affected children.

A longitudinal study of the long-term consequences of drinking during pregnancy: heavy in utero alcohol exposure disrupts the normal processes of brain development.

Exposure to alcohol in utero can cause birth defects, including face and brain abnormalities, and is the most common preventable cause of intellectual disabilities. Here we use structural magnetic resonance imaging to measure cortical volume change longitudinally in a cohort of human children and youth with prenatal alcohol exposure (PAE) and a group of unexposed control subjects, demonstrating that the normal processes of brain maturation are disrupted in individuals whose mothers drank heavily during pregnancy. Trajectories of cortical volume change within children and youth with PAE differed from those of unexposed control subjects in posterior brain regions, particularly in the parietal cortex. In these areas, control children appear to show a particularly plastic cortex with a prolonged pattern of cortical volume increases followed by equally vigorous volume loss during adolescence, while the alcohol-exposed participants showed primarily volume loss, demonstrating decreased plasticity. Furthermore, smaller volume changes between scans were associated with lower intelligence and worse facial morphology in both groups, and were related to the amount of PAE during each trimester of pregnancy in the exposed group. This demonstrates that measures of IQ and facial dysmorphology predict, to some degree, the structural brain development that occurs in subsequent years. These results are encouraging in that interventions aimed at altering "experience" over time may improve brain trajectories in individuals with heavy PAE and possibly other neurodevelopmental disorders.

1H-MRS in autism spectrum disorders: a systematic meta-analysis.

We conducted a systematic review and meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies comparing autism spectrum disorder (ASD) patients with healthy controls, with the aim of profiling ASD-associated changes in the metabolites N-acetyl-aspartate (NAA) and Creatine (Cr). Meta-regression models of NAA and Cr levels were employed, using data from 20 eligible studies (N = 852), to investigate age-dependent differences in both global brain and region-specific metabolite levels, while controlling for measurement method (Cr-ratio versus absolute concentrations). Decreased NAA concentrations that were specific to children were found for whole-brain grey and white matter. In addition, a significant decrease in NAA was evident across age categories in the parietal cortex, the cerebellum, and the anterior cingulate cortex. Higher levels of Cr were observed for ASD adults than children in global grey matter, with specific increases for adults in the temporal lobe and decreased Cr in the occipital lobe in children. No differences were found for either NAA or Cr in the frontal lobes. These data provide some evidence that ASD is characterized by age-dependent fluctuations in metabolite levels across the whole brain and at the level of specific regions thought to underlie ASD-associated behavioural and affective deficits. Differences in Cr as a function of age and brain region suggests caution in the interpretation of Cr-based ratio measures of metabolites. Despite efforts to control for sources of heterogeneity, considerable variability in metabolite levels was observed in frontal and temporal regions, warranting further investigation.

Regional brain volume reductions relate to facial dysmorphology and neurocognitive function in fetal alcohol spectrum disorders.

Individuals with heavy prenatal alcohol exposure can experience significant deficits in cognitive and psychosocial functioning and alterations in brain structure that persist into adulthood. In this report, data from 99 participants collected across three sites (Los Angeles and San Diego, California, and Cape Town, South Africa) were analyzed to examine relationships between brain structure, neurocognitive function, facial morphology, and maternal reports of quantities of alcohol consumption during the first trimester. Across study sites, we found highly significant volume reductions in the FASD group for all of the brain regions evaluated. After correcting for scan location, age, and total brain volume, these differences remained significant in some regions of the basal ganglia and diencephalon. In alcohol-exposed subjects, we found that smaller palpebral fissures were significantly associated with reduced volumes in the ventral diencephalon bilaterally, that greater dysmorphology of the philtrum predicted smaller volumes in basal ganglia and diencephalic structures, and that lower IQ scores were associated with both smaller basal ganglia volumes and greater facial dysmorphology. In subjects from South Africa, we found a significant negative correlation between intracranial volume and total number of drinks per week in the first trimester. These results corroborate previous reports that prenatal alcohol exposure is particularly toxic to basal ganglia and diencephalic structures. We extend previous findings by illustrating relationships between specific measures of facial dysmorphology and the volumes of particular subcortical structures, and for the first time show that continuous measures of maternal alcohol consumption during the first trimester relates to overall brain volume reduction.

Callosal thickness reductions relate to facial dysmorphology in fetal alcohol spectrum disorders.

BACKGROUND: Structural abnormalities of the corpus callosum (CC), such as reduced size and increased shape variability, have been documented in individuals with fetal alcohol spectrum disorders (FASD). However, the regional specificity of altered CC structure, which may point to the timing of neurodevelopmental disturbances and/or relate to specific functional impairments, remains unclear. Furthermore, associations between facial dysmorphology and callosal structure remain undetermined. METHODS: One hundred and fifty-three participants (age range 8 to 16) including 82 subjects with FASD and 71 nonexposed controls were included in this study. The structural magnetic resonance imaging data of these subjects was collected at 3 sites (Los Angeles and San Diego, California, and Cape Town, South Africa) and analyzed using classical parcellation schemes, as well as more refined surface-based geometrical modeling methods, to identify callosal morphological alterations in FASD at high spatial resolution. RESULTS: Reductions in callosal thickness and area, specifically in the anterior third and the splenium, were observed in FASD compared with nonexposed controls. In addition, reduced CC thickness and area significantly correlated with reduced palpebral fissure length. CONCLUSIONS: Consistent with previous reports, findings suggest an adverse effect of prenatal alcohol exposure on callosal growth and further indicate that fiber pathways connecting frontal and parieto-occipital regions in each hemisphere may be particularly affected. Significant associations between callosal and facial dysmorphology provide evidence for a concurrent insult to midline facial and brain structural development in FASD.