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Dominic T Cheng,
Ernesta M Meintjes,
Mark E Stanton,
John E Desmond,
Mariska Pienaar,
Neil C Dodge,
John M Power,
Christopher D Molteno,
John F Disterhoft, Joseph L Jacobson,
Sandra W Jacobson
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ABSTRACT: This study characterized human cerebellar activity during eyeblink classical conditioning (EBC) in children and adults using functional magnetic resonance imaging (fMRI). During fMRI, participants were administered delay conditioning trials, in which the conditioned stimulus (a tone) precedes, overlaps, and coterminates with the unconditioned stimulus (a corneal airpuff). Behavioral eyeblink responses and brain activation were measured concurrently during two phases: pseudoconditioning, involving presentations of tone alone and airpuff alone, and conditioning, during which the tone and airpuff were paired. Although all participants demonstrated significant conditioning, the adults produced more conditioned responses (CRs) than the children. When brain activations during pseudoconditioning were subtracted from those elicited during conditioning, significant activity was distributed throughout the cerebellar cortex (Crus I-II, lateral lobules IV-IX, and vermis IV-VI) in all participants, suggesting multiple sites of associative learning-related plasticity. Despite their less optimal behavioral performance, the children showed greater responding in the pons, lateral lobules VIII, IX, and Crus I, and vermis VI, suggesting that they may require greater activation and/or the recruitment of supplementary structures to achieve successful conditioning. Correlation analyses relating brain activations to behavioral CRs showed a positive association of activity in cerebellar deep nuclei (including dentate, fastigial, and interposed nuclei) and vermis VI with CRs in the children. This is the first study to compare cerebellar cortical and deep nuclei activations in children versus adults during EBC. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
Human Brain Mapping 05/2013; · 5.88 Impact Factor
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ABSTRACT: Visual evoked potentials (VEPs) are known to be influenced by several biological variables, including sex. In adult populations studies using conventional high-contrast checkerboard have shown that females display larger amplitudes and shorter latencies than males. To date, few studies have been conducted in children; the available data suggests that girls display significantly larger amplitudes than boys but the effect on latency is absent or negligible. We investigated sex-related VEP differences in 149 school-age (11.3 ± 0.6 years) children from Northern Quebec using several VEP protocols: achromatic pattern-reversal VEPs at high (95%) and low contrast (30%, 12% and 4%), as well as motion-onset VEPs and isoluminant pattern-reversal VEPs. Girls showed significantly larger amplitudes in achromatic VEPs for most of the contrast levels as well as in N2 response to motion-onset. No significant difference was found regarding the amplitude of isoluminant VEPs. In addition, girls showed shorter latencies for the achromatic N75 and a trend (p < 0.1) for the P100, regardless of the contrast level. Interestingly, this latency effect appeared mostly due to head size, not sex. No differences in latency were found for motion or isoluminant responses. Overall, these findings show that sex-related differences are present in children mostly in VEP amplitude not only for high contrast achromatic pattern-reversal but also for low contrast levels and motion-onset VEPs, suggesting that sex affects VEP responses in a general fashion.
International journal of psychophysiology: official journal of the International Organization of Psychophysiology 03/2013; · 3.05 Impact Factor
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Michael Suttie,
Tatiana Foroud,
Leah Wetherill, Joseph L Jacobson,
Christopher D Molteno,
Ernesta M Meintjes,
H Eugene Hoyme,
Nathaniel Khaole,
Luther K Robinson,
Edward P Riley,
Sandra W Jacobson,
Peter Hammond
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ABSTRACT: Classic facial characteristics of fetal alcohol syndrome (FAS) are shortened palpebral fissures, smooth philtrum, and thin upper vermillion. We aim to help pediatricians detect facial dysmorphism across the fetal alcohol spectrum, especially among nonsyndromal heavily exposed (HE) individuals without classic facial characteristics.
Of 192 Cape Coloured children recruited, 69 were born to women who reported abstaining from alcohol during pregnancy. According to multifaceted criteria, the remainder were allocated clinically to the FAS (n = 22), partial FAS (n = 26) or nonsyndromal HE (n = 75) categories. We used dense surface modeling and signature analyses of 3-dimensional facial photographs to determine agreement between clinical categorization and classifications induced from face shape alone, to visualize facial differences, and to consider predictive links between face shape and neurobehavior.
Face classification achieved significant agreement with clinical categories for discrimination of nonexposed from FAS alone (face: 0.97-1.00; profile: 0.92) or with the addition of partial FAS (face: 0.90; profile: 0.92). Visualizations of face signatures delineated dysmorphism across the fetal alcohol spectrum and in half of the nonsyndromal HE category face signature graphs detected facial characteristics consistent with prenatal alcohol exposure. This subgroup performed less well on IQ and learning tests than did nonsyndromal subjects without classic facial characteristics.
Heat maps and morphing visualizations of face signatures may help clinicians detect facial dysmorphism across the fetal alcohol spectrum. Face signature graphs show potential for identifying nonsyndromal heavily exposed children who lack the classic facial phenotype but have cognitive impairment.
PEDIATRICS 03/2013; 131(3):e779-88. · 4.47 Impact Factor
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ABSTRACT: BACKGROUND: Several studies have reported negative associations of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB) and mercury (Hg) with duration of gestation and fetal growth in fish eating populations. Docosahexaenoic acid (DHA) from fish, seafood and marine mammal intake has been reported to be positively related with pregnancy duration and fetal growth. So far, it remains unclear, however, if the associations of environmental contaminants (ECs) with growth are direct or mediated through their relation with the duration of gestation and the degree to which DHA intake during pregnancy attenuates the negative association of ECs with fetal growth. OBJECTIVES: To investigate direct and indirect associations of in utero exposure to ECs with fetal growth and pregnancy duration while taking into account the possible positive effects of DHA. METHODS: Pregnant Inuit women (N=248) from Arctic Quebec were recruited and cord blood samples were analyzed for PCBs, HCB, Hg and DHA. Anthropometric measurements were assessed at birth. Path models were used to evaluate direct and indirect associations. RESULTS: Cord concentrations of PCB 153, HCB and Hg were significantly associated with shorter duration of pregnancy (β varying from -0.17 to -0.20, p<0.05). Path models indicated that the associations of PCBs, HCB and Hg with reduced fetal growth (β varying from -0.09 to -0.13, p<0.05) were mediated through their relations with shorter gestation duration. Cord DHA was indirectly related to greater growth parameters (β varying from 0.17 to 0.20, p<0.05) through its positive association with gestation duration. CONCLUSION: Prenatal exposure to ECs was associated with reduced gestation duration, which is a recognized determinant of fetal growth. DHA intake during pregnancy appeared to have independent positive association with fetal growth by prolonging gestation. Whether these associations are causal remains to be elucidated.
Environment international 02/2013; 54C:85-91. · 4.79 Impact Factor
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Dominic T. Cheng,
Ernesta M. Meintjes,
Mark E. Stanton,
John E. Desmond,
Mariska Pienaar,
Neil C. Dodge,
John M. Power,
Christopher D. Molteno,
John F. Disterhoft, Joseph L. Jacobson,
Sandra W. Jacobson
[show abstract]
[hide abstract]
ABSTRACT: This study characterized human cerebellar activity during eyeblink classical conditioning (EBC)
in children and adults using functional magnetic resonance imaging (fMRI). During fMRI, participants
were administered delay conditioning trials, in which the conditioned stimulus (a tone) precedes, overlaps,
and coterminates with the unconditioned stimulus (a corneal airpuff). Behavioral eyeblink responses and
brain activation were measured concurrently during two phases: pseudoconditioning, involving presentations
of tone alone and airpuff alone, and conditioning, during which the tone and airpuff were paired.
Although all participants demonstrated significant conditioning, the adults produced more conditioned
responses (CRs) than the children. When brain activations during pseudoconditioning were subtracted
from those elicited during conditioning, significant activity was distributed throughout the cerebellar cortex
(Crus I-II, lateral lobules IV-IX, and vermis IV–VI) in all participants, suggesting multiple sites of associative
learning-related plasticity. Despite their less optimal behavioral performance, the children showed
greater responding in the pons, lateral lobules VIII, IX, and Crus I, and vermis VI, suggesting that they may
require greater activation and/or the recruitment of supplementary structures to achieve successful conditioning.
Correlation analyses relating brain activations to behavioral CRs showed a positive association of
activity in cerebellar deep nuclei (including dentate, fastigial, and interposed nuclei) and vermis VI with
CRs in the children. This is the first study to compare cerebellar cortical and deep nuclei activations in children
versus adults during EBC.
Human Brain Mapping 01/2013; · 5.88 Impact Factor
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Evidence-based mental health 11/2012;
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ABSTRACT: Surface deformation-based analysis was used to assess local shape variations in the hippocampi and caudate nuclei of children with fetal alcohol spectrum disorders. High-resolution structural magnetic resonance imaging images were acquired for 31 children (19 controls and 12 children diagnosed with fetal alcohol syndrome/partial FAS). Hippocampi and caudate nuclei were manually segmented, and surface meshes were reconstructed. An iterative closest point algorithm was used to register the template of one control subject to all other shapes in order to capture the true geometry of the shape with a fixed number of landmark points. A point distribution model was used to quantify the shape variations in terms of a change in co-ordinate positions. Using the localized Hotelling T(2) method, regions of significant shape variations between the control and exposed subjects were identified and mapped onto the mean shapes. Binary masks of hippocampi and caudate nuclei were generated from the segmented volumes of each brain. These were used to compute the volumes and for further statistical analysis. The Mann-Whitney test was performed to predict volume differences between the groups. Although the exposed and control subjects did not differ significantly in their volumes, the shape analysis showed the hippocampus to be more deformed at the head and tail regions in the alcohol-exposed children. Between-group differences in caudate nucleus morphology were dispersed across the tail and head regions. Correlation analysis showed associations between the degree of compression and the level of alcohol exposure. These findings demonstrate that shape analysis using three-dimensional surface measures is sensitive to fetal alcohol exposure and provides additional information than volumetric measures alone. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
Human Brain Mapping 11/2012; · 5.88 Impact Factor
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ABSTRACT: Studies conducted in the Faeroe Islands and Japan suggest a negative impact of mercury on heart rate variability (HRV) among children while the results regarding blood pressure (BP) are less consistent.
To assess the impact of mercury on HRV and BP among Nunavik Inuit children.
A cohort of 226 children was followed from birth to 11 years old. Mercury concentration in cord blood and in blood and hair at 11 years old were used as markers of prenatal and childhood exposure, respectively. HRV was measured using ambulatory 2 h-Holter monitoring while BP was measured through a standardized protocol. Simple regression was used to assess the relationship of mercury to BP and HRV parameters. Multiple linear regressions were performed adjusting for covariates such as age, sex, birth weight, body mass index (BMI), height, total n-3 fatty acids, polychlorinated biphenyls (PCB 153), lead, selenium and maternal smoking during pregnancy.
Median cord blood mercury and blood mercury levels at 11 years old were 81.5 nmoL/L (IQR:45.0–140.0) and 14.5 nmol/L (IQR: 7.5–28.0), respectively. After adjusting for the covariates, child blood mercury was associated with low frequency (LF) (b = 0.21, p = 0.05), the standard deviation of R–R intervals (SDNN) (b = 0.26, p = 0.02), the standard deviation of R–R intervals measured over 5 min periods (SDANN) (b = 0.31, p = 0.01) and the coefficient of variation of R–R intervals (CVRR) (b = 0.06,p = 0.02). No significant association was observed with BP.
Mercury exposure during childhood seems to affect HRV among Nunavik Inuit children at school age.
NeuroToxicology 10/2012; 33(5):1067-74. · 3.10 Impact Factor
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ABSTRACT: Background: Prenatal exposure to methylmercury (MeHg) and polychlorinated biphenyls (PCBs)
has been associated with impaired performance on attention tasks in previous studies, but the extent
to which these cognitive deficits translate into behavioral problems in the classroom and attention
deficit/hyperactivity disorder (ADHD) remains unknown. By contrast, lead (Pb) exposure in childhood
has been associated with ADHD and disruptive behaviors in several studies.
Objectives: In this study we examined the relation of developmental exposure to MeHg, PCBs,
and Pb to behavioral problems at school age in Inuit children exposed through their traditional diet.
Methods: In a prospective longitudinal study conducted in the Canadian Arctic, exposure to contaminants
was measured at birth and at school age. An assessment of child behavior (n = 279; mean
age = 11.3 years) was obtained from the child’s classroom teacher on the Teacher Report Form (TRF)
from the Child Behavior Checklist, and the Disruptive Behavior Disorders Rating Scale (DBD).
Results: Cord blood mercury concentrations were associated with higher TRF symptom scores
for attention problems and DBD scores consistent with ADHD. Current blood Pb concentrations
were associated with higher TRF symptom scores for externalizing problems and with symptoms of
ADHD (hyperactive-impulsive type) based on the DBD.
Conclusions: To our knowledge, this study is the first to identify an association between prenatal
MeHg and ADHD symptomatology in childhood and the first to replicate previously reported
associations between low-level childhood Pb exposure and ADHD in a population exposed to Pb
primarily from dietary sources.
Environmental Health Perspectives 10/2012; 120(10):2-7. · 7.04 Impact Factor
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ABSTRACT: BACKGROUND: Fetal alcohol-related growth restriction persists through infancy, but its impact later in life is less clear. Animal studies have demonstrated important roles for maternal nutrition in fetal alcohol spectrum disorders, but the impact of prenatal maternal body composition has not been studied in humans. This study examined the effects of prenatal alcohol exposure on longitudinal growth from birth through young adulthood and the degree to which maternal weight and body mass index (BMI) moderate these effects. METHODS: Nearly 480 mothers were recruited at their first prenatal clinic visit to overrepresent moderate-to-heavy use of alcohol during pregnancy, including a 5% random sample of low-level drinkers and abstainers. They were interviewed at every prenatal visit about their alcohol consumption using a timeline follow-back approach. Their children were examined for weight, length/height, and head circumference at birth, 6.5 and 13 months, and 7.5, 14, and 19 years. RESULTS: In multiple regression models with repeated measures (adjusted for confounders), prenatal alcohol exposure was associated with longitudinal reductions in weight, height, and weight-for-length/BMI that were largely determined at birth. At low-to-moderate levels of exposure, these effects were more severe in infancy than in later childhood. By contrast, effects persisted among children whose mothers drank at least monthly and among those born to women with alcohol abuse and/or dependence who had consumed ≥ 4 drinks/occasion. In addition, effects on weight, height, and head circumference were markedly stronger among children born to mothers with lower prepregnancy weight. CONCLUSIONS: These findings confirm prior studies demonstrating alcohol-related reductions in weight, height, weight-for-height/BMI, and head circumference that persist through young adulthood. Stronger effects were seen among children born to mothers with smaller prepregnancy weight, which may have been because of attainment of higher blood alcohol concentrations in smaller mothers for a given amount of alcohol intake or to increased vulnerability in infants born to women with poorer nutrition.
Alcoholism Clinical and Experimental Research 09/2012; · 3.34 Impact Factor
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ABSTRACT: Background: Prenatal exposure to methylmercury (MeHg) and polychlorinated biphenyls (PCBs) has been associated with impaired performance on attention tasks in previous studies, but the extent to which these cognitive deficits translate into behavioral problems in the classroom and attention deficit/hyperactivity disorder (ADHD) remains unknown. By contrast, lead (Pb) exposure in childhood has been associated with ADHD and disruptive behaviors in several studies.Objectives: In this study we examined the relation of developmental exposure to MeHg, PCBs, and Pb to behavioral problems at school age in Inuit children exposed through their traditional diet.Methods: In a prospective longitudinal study conducted in the Canadian Arctic, exposure to contaminants was measured at birth and at school age. An assessment of child behavior (n = 279; mean age = 11.3 years) was obtained from the child's classroom teacher on the Teacher Report Form (TRF) from the Child Behavior Checklist, and the Disruptive Behavior Disorders Rating Scale (DBD).Results: Cord blood mercury concentrations were associated with higher TRF symptom scores for attention problems and DBD scores consistent with ADHD. Current blood Pb concentrations were associated with higher TRF symptom scores for externalizing problems and with symptoms of ADHD (hyperactive-impulsive type) based on the DBD.Conclusions: To our knowledge, this study is the first to identify an association between prenatal MeHg and ADHD symptomatology in childhood and the first to replicate previously reported associations between low-level childhood Pb exposure and ADHD in a population exposed to Pb primarily from dietary sources.
Environmental Health Perspectives 08/2012; 120(10):1456-61. · 7.04 Impact Factor
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ABSTRACT: BACKGROUND: Prenatal alcohol exposure has been associated with pre- and postnatal growth restriction, but little is known about the natural history of this restriction throughout childhood or the effects of prenatal alcohol on body composition. The objective of this study was to examine the effects of heavy prenatal alcohol exposure on longitudinal growth and body composition. METHODS: Eighty-five heavy drinking pregnant women (≥2 drinks/d or ≥4 drinks/occasion) and 63 abstaining and light-drinking controls (<1 drink/d, no binging) were recruited at initiation of prenatal care in an urban obstetrical clinic in Cape Town, South Africa and prospectively interviewed during pregnancy about alcohol, smoking, drug use, and demographics. Among their children, length/height, weight, and head circumference were measured at 6.5 and 12 months and at 5 and 9 years. Percent body fat (BF) was estimated at age 9 years using bioelectric impedance analysis. RESULTS: In multiple regression models with repeated measures (adjusted for confounders), heavy alcohol exposure was associated with reductions in weight (0.6 SD), length/height (0.5 SD), and head circumference (0.9 cm) from 6.5 months to 9 years that were largely determined at birth. These effects were exacerbated by iron deficiency in infancy but were not modified by iron deficiency or measures of food security at 5 years. An alcohol-related postnatal delay in weight gain was seen at 12 months. Effects on head circumference were greater at age 9 than at other age points. Although heavy alcohol exposure was not associated with changes in body composition, children with fetal alcohol syndrome (FAS) and partial fetal alcohol syndrome (PFAS) had lower percent BF than heavy exposed nonsyndromal and control children. CONCLUSIONS: Heavy prenatal alcohol exposure is related to prenatal growth restriction that persists through age 9 years and an additional delay in weight gain during infancy. FAS and PFAS diagnoses are associated with leaner body composition in later childhood.
Alcoholism Clinical and Experimental Research 08/2012; · 3.34 Impact Factor
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ABSTRACT: The Inuit from Nunavik (Northern Québec) are one of the most highly exposed populations to environmental contaminants in North America mainly due to the bioaccumulation of contaminants in fish and marine mammals that constitute an important part of their diet. This follow-up study aimed to assess the impact of exposure to contaminants on visual brain development in school-age Inuit children (mean age=10.9 years). Concentrations of polychlorinated biphenyls (PCBs), mercury (Hg), and lead (Pb) were measured in umbilical cord blood and again in blood samples at the time of testing, reflecting pre- and current exposure, respectively. Pattern-reversal visual evoked potentials (VEPs) were scalp-recorded at the occipital cortex. Visual stimulation consisted of achromatic gratings presented at four visual contrast levels: 95%, 30%, 12% and 4%. The relation between environmental contaminant body burdens and VEPs was examined by regression analysis controlling for confounding variables, including fish nutrients and other toxicants. No significant association was found for PCB exposure after statistical adjustments. Cord blood mercury level was associated with a reduction of the N75 amplitude at the highest contrast level and with a delay of the N75 latency at the 12% contrast level. Prenatal exposure to lead was associated with a delay of the N150 latency at most contrast levels. This study suggests that heavy metal exposure, in particular during the gestational period, can impair the development of visual processing.
NeuroToxicology 06/2012; 33(5):1075-85. · 3.10 Impact Factor
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ABSTRACT: BACKGROUND: Many children with heavy exposure to alcohol in utero display characteristic alterations in brain size and structure. However, the long-term effects of low-to-moderate alcohol exposure on these outcomes are unknown. METHODS: Using voxel-based morphometry and region-of-interest analyses, we examined the influence of lower doses of alcohol on gray and white matter composition in a prospectively recruited, homogeneous, well-characterized cohort of alcohol-exposed (n = 11, age 19.5 ± 0.3 years) and control (n = 9, age 19.6 ± 0.5 years) young adults. A large proportion of the exposed individuals were born to mothers whose alcohol consumption during pregnancy was in the low-to-moderate range. RESULTS: There were no differences in total brain volume or total gray or white matter volume between the exposed and control groups. However, gray matter volume was reduced in alcohol-exposed individuals in several areas previously reported to be affected by high levels of exposure, including the left cingulate gyrus, bilateral middle frontal gyri, right middle temporal gyrus, and right caudate nucleus. Notably, this gray matter loss was dose dependent, with higher exposure producing more substantial losses. CONCLUSIONS: These results indicate that even at low doses, alcohol exposure during pregnancy impacts brain development and that these effects persist into young adulthood.
Alcoholism Clinical and Experimental Research 05/2012; · 3.34 Impact Factor
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ABSTRACT: Although children with heavy prenatal alcohol exposure may exhibit the distinctive facial dysmorphology seen in full or partial fetal alcohol syndrome (FAS/PFAS), many lack that dysmorphology. This study examined the functional organization of working memory in the brain in three groups of children-those meeting diagnostic criteria for FAS or PFAS, heavily exposed (HE) nonsyndromal children, and healthy controls. A verbal n-back task (1-back and 0-back) was administered to 47 children (17 with FAS/PFAS, 13 HE, and 17 controls) during fMRI. Intra-group one-sample t-tests were used to identify activity regions of interest central to verbal working memory including the dorsal prefrontal cortex (dPFC), inferior frontal gyrus, caudate/putamen, parietal cortex, and cerebellar Crus I/lobule VI and lobule VIIB-IX. Whereas groups did not differ in task sensitivity, fMRI analyses suggested different patterns of sub-network recruitment across groups. Controls primarily recruited left inferior frontal gyrus (Broca's area). By contrast, HE primarily recruited an extensive set of fronto-striatal regions, including left dPFC and left caudate, and the FAS/PFAS group relied primarily on two cerebellar subregions and parietal cortex. This study is, to our knowledge, the first to demonstrate differential recruitment of critical brain regions that subserve basic function in children with different fetal alcohol spectrum disorders compared to controls. The distinct activation patterns seen in the two exposed groups may be related to substantial differences in alcohol dose/occasion to which these groups were exposed in utero. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
Human Brain Mapping 03/2012; · 5.88 Impact Factor
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ABSTRACT: 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 Québec. 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).
Alcohol (Fayetteville, N.Y.) 03/2012; 46(3):277-83. · 2.41 Impact Factor
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Tatiana Foroud,
Leah Wetherill,
Sophia Vinci-Booher,
Elizabeth S Moore,
Richard E Ward,
H Eugene Hoyme,
Luther K Robinson,
Jeffrey Rogers,
Ernesta M Meintjes,
Christopher D Molteno, Joseph L Jacobson,
Sandra W Jacobson
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ABSTRACT: 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).
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.
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.
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.
Alcoholism Clinical and Experimental Research 03/2012; 36(9):1634-46. · 3.34 Impact Factor
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ABSTRACT: This study compared brain activation during unpaced rhythmic finger tapping in 12-year-old children with that of adults. Subjects pressed a button at a pace initially indicated by a metronome (12 consecutive tones), and then continued for 16 seconds of unpaced tapping to provide an assessment of their ability to maintain a steady rhythm. These analyses focused on the superior vermis of the cerebellum, which is known to play a key role in timing. Twelve adults and 12 children performed this rhythmic finger tapping task in a 3 T scanner. Whole-brain analyses were performed in Brain Voyager, with a random-effects analysis of variance using a general linear model. A dedicated cerebellar atlas was used to localize cerebellar activations. As in adults, unpaced rhythmic finger tapping in children demonstrated activations in the primary motor cortex, premotor cortex, and cerebellum. However, overall activation was different, in that adults demonstrated much more deactivation in response to the task, particularly in the occipital and frontal cortices. The other main differences involved the additional recruitment of motor and premotor areas in children compared with adults, and increased activity in the vermal region of the cerebellum. These findings suggest that the timing component of the unpaced rhythmic finger tapping task is less efficient and automatic in children, who need to recruit the superior vermis more intensively to maintain the rhythm, although they performed somewhat more poorly than adults.
Pediatric Neurology 02/2012; 46(2):94-100. · 1.52 Impact Factor
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ABSTRACT: Lead (Pb) and polychlorinated biphenyls (PCBs) are neurotoxic contaminants that have been related to impairment in response inhibition.
In this study we examined the neurophysiological correlates of the response inhibition deficits associated with these exposures, using event-related potentials (ERPs) in a sample of school-age Inuit children from Arctic Québec exposed through their traditional diet.
In a prospective longitudinal study, we assessed 196 children (mean age, 11.3 years) on a visual go/no-go response inhibition paradigm. Pb, PCB, and mercury (Hg) concentrations were analyzed in cord and current blood samples. Hierarchical multiple regression analyses were conducted to examine the associations of contaminant levels to go/no-go performance (mean reaction time, percent correct go, percent correct no-go) and five ERPs [N2, P3, error-related negativity, error positivity (Pe), and correct response positivity (Pc)] after control for confounding variables.
Current blood Pb concentrations were associated with higher rates of false alarms and with decreased P3 amplitudes to go and no-go trials. Current plasma PCB-153 concentrations were associated with slower reaction times and with reduced amplitudes of the Pe and Pc response-related potentials. Hg concentrations were not related to any outcome on this task but showed significant interactions with other contaminants on certain outcomes.
These results suggest that Pb exposure during childhood impairs the child's ability to allocate the cognitive resources needed to correctly inhibit a prepotent response, resulting in increased impulsivity. By contrast, postnatal PCB exposure appears to affect processes associated with error monitoring, an aspect of behavioral regulation required to adequately adapt to the changing demands of the environment, which results in reduced task efficiency.
Environmental Health Perspectives 12/2011; 120(4):608-15. · 7.04 Impact Factor
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ABSTRACT: Prenatal alcohol exposure is related to a wide range of neurocognitive effects. Eyeblink conditioning (EBC), which involves temporal pairing of a conditioned with an unconditioned stimulus, has been shown to be a potential biomarker of fetal alcohol exposure. A growing body of evidence suggests that white matter may be a specific target of alcohol teratogenesis, and the neural circuitry underlying EBC is known to involve the cerebellar peduncles. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that has proven useful for assessing central nervous system white matter integrity. This study used DTI to examine the degree to which the fetal alcohol-related deficit in EBC may be mediated by structural impairment in the cerebellar peduncles.
Thirteen children with fetal alcohol spectrum disorder (FASD) and 12 matched controls were scanned using DTI and structural MRI sequences. The DTI data were processed using a voxelwise technique, and the structural data were used for volumetric analyses. Prenatal alcohol exposure group and EBC performance were examined in relation to brain volumes and outputs from the DTI analysis.
Fractional anisotropy (FA) and perpendicular diffusivity group differences between alcohol-exposed and nonexposed children were identified in the left middle cerebellar peduncle. Alcohol exposure correlated with lower FA and greater perpendicular diffusivity in this region, and these correlations remained significant even after controlling for total brain and cerebellar volumes. Conversely, trace conditioning performance was related to higher FA and lower perpendicular diffusivity in the left middle peduncle. The effect of prenatal alcohol exposure on trace conditioning was partially mediated by lower FA in this region.
This study extends recent findings that have used DTI to reveal microstructural deficits in white matter in children with FASD. This is the first DTI study to demonstrate mediation of a fetal alcohol-related effect on neuropsychological function by deficits in white matter integrity.
Alcoholism Clinical and Experimental Research 07/2011; 35(12):2174-83. · 3.34 Impact Factor
