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Background Previous studies using the California Verbal Learning Test-Children's Version ( CVLT-C) to examine effects of heavy prenatal alcohol exposure on verbal learning and memory have reported impaired information acquisition (i.e., encoding), rather than retrieval, as the primary mechanism underlying learning and memory impairment. We administered the CVLT-C to 2 independent cohorts to determine whether (i) effects on encoding are also seen at moderate exposure levels, using both categorical (diagnostic/exposure group) and continuous exposure measures; (ii) these deficits are specific or secondary to alcohol-related impairment in IQ; (iii) effects on retrieval can be detected over and above effects on initial encoding; and (iv) effects on learning are attributable to less efficient learning strategy use. Methods We administered the CVLT-C and Wechsler Intelligence Scale for Children to 151 Cape Town heavy and nonexposed children ( M = 10.3 years), and 291 Detroit adolescents recruited to over-represent moderate-to-heavy prenatal alcohol exposure ( M = 14.4 years). Results Effects on encoding in the heavily exposed Cape Town cohort and on retrieval in both cohorts were significant after adjustment for IQ. Although effects on retrieval were no longer significant in Cape Town after control for initial encoding, effects on recognition memory continued to be evident in Detroit. Children with full or partial fetal alcohol syndrome were less able to use the semantic cluster encoding strategy implicit in the CVLT-C. Conclusions Effects on verbal learning were seen primarily in the more heavily exposed Cape Town cohort; effects on recall and recognition memory were also seen at moderate exposure levels in Detroit. These effects were not attributable to alcohol-related impairment in overall intellectual competence. The finding that effects on retention continued to be evident after statistical adjustment for initial encoding in Detroit suggests that a fetal alcohol-related deficit in retrieval is not secondary to a failure to encode the initial information. These data confirm that this impairment in initial learning is mediated, in part, by failure to use the semantic cluster learning strategy. [ABSTRACT FROM AUTHOR]

Objectives. We examined the relation of household crowding to food insecurity among Inuit families with school-aged children in Arctic Quebec. Methods. We analyzed data collected between October 2005 and February 2010 from 292 primary caregiver--child dyads from 14 Inuit communities. We collected information about household conditions, food security, and family socioeconomic characteristics by interviews. We used logistic regression models to examine the association between household crowding and food insecurity. Results. Nearly 62% of Inuit families in the Canadian Arctic resided in more crowded households, placing them at risk for food insecurity. About 27% of the families reported reducing the size of their children’s meals because of lack of money. The likelihood of reducing the size of children’s meals was greater in crowded households (odds ratio = 3.73; 95% confidence interval = 1.96, 7.12). After we adjusted for different socioeconomic characteristics, results remained statistically significant. Conclusions. Interventions operating across different levels (community, regional, national) are needed to ensure food security in the region. Targeting families living in crowded conditions as part of social and public health policies aiming to reduce food insecurity in the Arctic could be beneficial. [ABSTRACT FROM AUTHOR]

Prenatal alcohol exposure (PAE) is known to have severe, long-term consequences for brain and behavioral development already detectable in infancy and childhood. Resulting features of fetal alcohol spectrum disorders include cognitive and behavioral effects, as well as facial anomalies and growth deficits. Diffusion tensor imaging (DTI) and tractography were used to analyze white matter (WM) development in 11 newborns (age since conception <45 weeks) whose mothers were recruited during pregnancy. Comparisons were made with nine age-matched controls born to abstainers or light drinkers from the same Cape Coloured (mixed ancestry) community near Cape Town, South Africa. DTI parameters, T1 relaxation time, proton density and volumes were used to quantify and investigate group differences in WM in the newborn brains. Probabilistic tractography was used to estimate and to delineate similar tract locations among the subjects for transcallosal pathways, cortico-spinal projection fibers, and cortico-cortical association fibers. In each of these WM networks, the axial diffusivity was the parameter that showed the strongest association with maternal drinking. The strongest relations were observed in medial and inferior WM, regions in which the myelination process typically begins. In contrast to studies of older individuals with PAE, fractional anisotropy did not exhibit a consistent and significant relation with alcohol exposure. To our knowledge, this is the first DTI-tractography study of prenatally alcohol exposed newborns. Hum Brain Mapp, 36:170-186, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background Because of their geographical location and traditional lifestyle, Canadian Inuit children are highly exposed to polychlorinated biphenyls (PCBs) and lead (Pb), environmental contaminants that are thought to affect fetal and child growth. We examined the associations of these exposures with the fetal and postnatal growth of Inuit children. Methods We conducted a prospective cohort study among Inuit from Nunavik (Arctic Québec). Mothers were recruited at their first prenatal visit; children ( n =290) were evaluated at birth and at 8–14 years of age. Concentrations of PCB 153 and Pb were determined in umbilical cord and child blood. Weight, height and head circumference were measured at birth and during childhood. Results Cord blood PCB 153 concentrations were not associated with anthropometric measurements at birth or school age, but child blood PCB 153 concentrations were associated with reduced weight, height and head circumference during childhood. There was no association between cord Pb levels and anthropometric outcomes at birth, but cord blood Pb was related to smaller height and shows a tendency of a smaller head circumference during childhood. Interpretation Our results suggest that chronic exposure to PCBs during childhood is negatively associated with skeletal growth and weight, while prenatal Pb exposure is related to reduced growth during childhood. This study is the first to link prenatal Pb exposure to poorer growth in school-age children. [ABSTRACT FROM AUTHOR]

Due to their geographic location and traditional diet, rich in seafood and marine mammals, the Inuit living in Arctic Quebec are exposed to high amounts of pollutants, including organochlorine pesticides (OCPs). While the adverse developmental effects of these pesticides on child cognitive functions are well known, the effects of developmental exposure to OP on sensory processes have not been investigated. The aim of this longitudinal study was to assess the effects of prenatal and childhood exposure to 1,1,1-trichloro-2,2-bis( p -chlorophenyl)ethane ( p , p ′-DDT) and its major metabolite 1,1,-dichloro-2,2-bis( p -chlorophenyl)ethylene ( p,p ′-DDE), on visual processing in Inuit children in Nunavik (Arctic Québec). p,p ′-DDT and p , p ′-DDE concentrations were determined from umbilical cord and 5- and 11-year plasma samples. Visual evoked potentials (VEPs) were successfully recorded in 150 children at 4 contrast levels (95%, 30%, 12%, and 4%). Hierarchical multiple regressions were conducted to determine the association between p , p ′-DDT, or p,p ′-DDE, exposure and VEPs while controlling for the effects of various confounders, including fish nutrients and other contaminants. p,p ′-DDE measured in umbilical cord plasma was significantly related to the amplitude of the N150 response at the lowest contrast (4%). In addition, 5-year p,p ′-DDE plasma concentration was significantly associated with decreased N75 amplitude. These findings indicate that p,p ′-DDE exposure, both pre- and postnatally, during early childhood is associated with visual processing impairment later in life. [ABSTRACT FROM AUTHOR]

Prenatal alcohol exposure is responsible for a broad range of brain structural malformations, which can be studied using magnetic resonance imaging (MRI). Advanced MRI methods have emerged to characterize brain abnormalities, but the teratogenic effects of alcohol on cortical morphology have received little attention to date. Twenty-four 9-year-old children with fetal alcohol spectrum disorders (9 with fetal alcohol syndrome, 15 heavy exposed nonsyndromal children) and 16 age-matched controls were studied to assess the effect of alcohol consumption during pregnancy on cortical morphology. An automated method was applied to 3D T1-weighted images to assess cortical gyrification using global and regional sulcal indices and two region-based morphological measurements, mean sulcal depth and fold opening. Increasing levels of alcohol exposure were related to reduced cortical folding complexity, even among children with normal brain size, indicating a reduction of buried cortical surface. Fold opening was the strongest anatomical correlate of prenatal alcohol intake, indicating a widening of sulci in all regions that were examined. These data identify cortical morphology as a suitable marker for further investigation of brain damage associated with prenatal alcohol exposure. Hum Brain Mapp 35:2285-2296, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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 35:1390-1403, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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 T2 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 35:659-672, 2014. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Background: Smoking during pregnancy is common among Inuit women from the Canadian Arctic. Yet prenatal cigarette smoke exposure (PCSE) is seen as a major risk factor for childhood behavior problems. Recent data also suggest that co-exposure to neurotoxic environmental contaminants can exacerbate the effects of PCSE on behavior. This study examined the association between PCSE and behavior at school age in a sample of Inuit children from Nunavik, Québec, where co-exposure to environmental contaminants is also an important issue. Interactions with lead (Pb) and mercury (Hg), two contaminants associated with behavioral problems, were also explored. Methods: Participants were 271 children (mean age=11.3years) involved in a prospective birth-cohort study. PCSE was assessed through maternal recall. Assessment of child behavior was obtained from the child's classroom teacher on the Teacher Report Form (TRF) and the Disruptive Behavior Disorders Rating Scale (DBD). Exposure to contaminants was assessed from umbilical cord and child blood samples. Other confounders were documented by maternal interview. Results: After control for contaminants and confounders, PCSE was associated with increased externalizing behaviors and attention problems on the TRF and higher prevalence of attention deficit hyperactivity disorder (ADHD) assessed on the DBD. No interactions were found with contaminants. Interpretation: This study extends the existing empirical evidence linking PCSE to behavioral problems in school-aged children by reporting these effects in a population where tobacco use is normative rather than marginal. Co-exposure to Pb and Hg do not appear to exacerbate tobacco effects, suggesting that these substances act independently. [Copyright &y& Elsevier]

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, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Despite several decades of research and prevention efforts, fetal alcohol spectrum disorders (FASD) remain the most common preventable cause of neurodevelopmental disabilities worldwide. Animal and human studies have implicated fetal alcohol-induced alterations in epigenetic programming as a chief mechanism in FASD. Several studies have demonstrated fetal alcohol-related alterations in methylation and expression of imprinted genes in placental, brain, and embryonic tissue. Imprinted genes are epigenetically regulated in a parent-of-origin-specific manner, in which only the maternal or paternal allele is expressed, and the other allele is silenced. The chief functions of imprinted genes are in placental development, somatic growth, and neurobehavior—three domains characteristically affected in FASD. In this review, we summarize the growing body of literature characterizing prenatal alcohol-related alterations in imprinted gene methylation and/or expression and discuss potential mechanistic roles for these alterations in the teratogenic effects of prenatal alcohol exposure. Future research is needed to examine potential physiologic mechanisms by which alterations in imprinted genes disrupt development in FASD, which may, in turn, elucidate novel targets for intervention. Furthermore, mechanistic alterations in imprinted gene expression and/or methylation in FASD may inform screening assays that identify individuals with FASD neurobehavioral deficits who may benefit from early interventions. [ABSTRACT FROM AUTHOR]

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±0.6years) 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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

Abstract: Background: 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. Objective: To assess the impact of mercury on HRV and BP among Nunavik Inuit children. Methods: 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 2h-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. Results: Median cord blood mercury and blood mercury levels at 11 years old were 81.5nmoL/L (IQR: 45.0–140.0) and 14.5nmol/L (IQR: 7.5–28.0), respectively. After adjusting for the covariates, child blood mercury was associated with low frequency (LF) (β =−0.21, p =0.05), the standard deviation of R–R intervals (SDNN) (β =−0.26, p =0.02), the standard deviation of R–R intervals measured over 5min periods (SDANN) (β =−0.31, p =0.01) and the coefficient of variation of R–R intervals (CVRR) (β =−0.06, p =0.02). No significant association was observed with BP. Conclusion: Mercury exposure during childhood seems to affect HRV among Nunavik Inuit children at school age. [Copyright &y& Elsevier]

Background: Prenatal exposure to methyl mercury (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. [ABSTRACT FROM AUTHOR]

Background: Prenatal exposure to methyl mercury (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [Copyright &y& Elsevier]

Background: Lead (Pb) and polychlorinated biphenyls (PCBs) are neurotoxic contaminants that have been related to impairment in response inhibition. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

Background: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Alcohol consumption during pregnancy, a known teratogen often associated with drug use and smoking is a well-known public health concern. This study provides prevalence data for alcohol, smoking, and illicit drug use before, during, and after pregnancy among Inuit. Factors associated with alcohol use are also identified. Two hundred and eight Inuit women from Arctic Quebec were interviewed at mid-pregnancy, and at 1 and 11 months postpartum to provide descriptive data on smoking, alcohol, and drug use during pregnancy, and the year before and after pregnancy. Sociodemographic and family characteristics potentially associated with alcohol use were documented. Ninety-two percent of the women reported smoking and 61% reported drinking during pregnancy. Episodes of binging during pregnancy were reported by 62% of the alcohol users, which correspond to 38% of pregnant women. Thirty-six percent of the participants reported using marijuana during pregnancy. Alcohol use and binge drinking during pregnancy were more likely to be reported by women who lived in less crowded houses, had a better knowledge of a second language, drank alcohol more often and in larger amounts prior to pregnancy, and used illicit drugs. Binge drinkers were more likely to be single women and to have had fewer previous pregnancies. Postpartum distress and violence were more likely to be experienced by women who used alcohol during pregnancy. Binge drinking during pregnancy was best predicted by drinking habits before pregnancy, maternal symptoms of depression, the use of illicit drugs during pregnancy, and the number of young children living with the mother. These results confirm that alcohol is a major risk factor to maternal and child health in this population, underscoring the need for culturally relevant and effective prevention programs. [ABSTRACT FROM AUTHOR]

We consider 3-D brain structures as continuous parameterized surfaces and present a metric for their comparisons that is invariant to the way they are parameterized. Past comparisons of such surfaces involve either volume deformations or nonrigid matching under fixed parameterizations of surfaces. We propose a new mathematical representation of surfaces, called q-maps, such that \BBL^2 distances between such maps are invariant to re-parameterizations. This property allows for removing the parameterization variability by optimizing over the re-parameterization group, resulting in a proper parameterization-invariant distance between shapes of surfaces. We demonstrate this method in shape analysis of multiple brain structures, for 34 subjects in the Detroit Fetal Alcohol and Drug Exposure Cohort study, which results in a 91% classification rate for attention deficit hyperactivity disorder cases and controls. This method outperforms some existing techniques such as spherical harmonic point distribution model (SPHARM-PDM) or iterative closest point (ICP). [ABSTRACT FROM AUTHOR]

Classical eyeblink conditioning (EBC) involves contingent temporal pairing of a conditioned stimulus (e.g., tone) with an unconditioned stimulus (e.g., air puff). Impairment of EBC has been demonstrated in studies of alcohol-exposed animals and in children exposed prenatally at heavy levels. Fetal alcohol syndrome (FAS) was diagnosed by expert dysmorphologists in a large sample of Cape Coloured, South African children. Delay EBC was examined in a new sample of 63 children at 11.3 years, and trace conditioning in 32 of the same children at 12.8 years. At each age, 2 sessions of 50 trials each were administered on the same day; 2 more sessions the next day, for children not meeting criterion for conditioning. Six of 34 (17.6%) children born to heavy drinkers were diagnosed with FAS, 28 were heavily exposed nonsyndromal (HE), and 29 were nonexposed controls. Only 33.3% with FAS and 42.9% of HE met criterion for delay conditioning, compared with 79.3% of controls. The more difficult trace conditioning task was also highly sensitive to fetal alcohol exposure. Only 16.7% of the FAS and 21.4% of HE met criterion for trace conditioning, compared with 66.7% of controls. The magnitude of the effect of diagnostic group on trace conditioning was not greater than the effect on short delay conditioning, findings consistent with recent rat studies. Longer latency to onset and peak eyeblink CR in exposed children indicated poor timing and failure to blink in anticipation of the puff. Extended training resulted in some but not all of the children reaching criterion. These data showing alcohol-related delay and trace conditioning deficits extend our earlier findings of impaired EBC in 5-year-olds to school-age. Alcohol-related impairment in the cerebellar circuitry required for both forms of conditioning may be sufficient to account for the deficit in both tasks. Extended training was beneficial for some exposed children. EBC provides a well-characterized model system for assessment of degree of cerebellar-related learning and memory dysfunction in fetal alcohol exposed children. [ABSTRACT FROM AUTHOR]

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

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

Abstract: Many previous attempts by fetal alcohol spectrum disorders researchers to compare data across multiple prospective and retrospective human studies have failed because of both structural differences in the collected data and difficulty in coming to agreement on the precise meaning of the terminology used to describe the collected data. Although some groups of researchers have an established track record of successfully integrating data, attempts to integrate data more broadly among different groups of researchers have generally faltered. Lack of tools to help researchers share and integrate data has also hampered data analysis. This situation has delayed improving diagnosis, intervention, and treatment before and after birth. We worked with various researchers and research programs in the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CI-FASD) to develop a set of common data dictionaries to describe the data to be collected, including definitions of terms and specification of allowable values. The resulting data dictionaries were the basis for creating a central data repository (CI-FASD Central Repository) and software tools to input and query data. Data entry restrictions ensure that only data that conform to the data dictionaries reach the CI-FASD Central Repository. The result is an effective system for centralized and unified management of the data collected and analyzed by the initiative, including a secure, long-term data repository. CI-FASD researchers are able to integrate and analyze data of different types, using multiple methods, and collected from multiple populations, and data are retained for future reuse in a secure, robust repository. [Copyright &y& Elsevier]

Abstract: Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are seafood contaminants known for their adverse effects on neurodevelopment. This study examines the relation of developmental exposure to these contaminants to information processing assessed with event-related potentials (ERPs) in school-aged Inuit children from Nunavik (Arctic Québec). In a prospective longitudinal study on child development, exposure to contaminants was measured at birth and 11 years of age. An auditory oddball protocol was administered at 11 years to measure ERP components N1 and P3b. Multiple regression analyses were performed to examine the associations of levels of the contaminants to auditory oddball performance (mean reaction time, omission errors and false alarms) and ERP parameters (latency and amplitude) after control for potential confounding variables. A total of 118 children provided useable ERP data. Prenatal MeHg exposure was associated with slower reaction times and fewer false alarms during the oddball task. Analyses of the ERP parameters revealed that prenatal MeHg exposure was related to greater amplitude and delayed latency of the N1 wave in the target condition but not to the P3b component. MeHg effects on the N1 were stronger after control for seafood nutrients. Prenatal PCB exposure was not related to any endpoint for sample as a whole but was associated with a decrease in P3b amplitude in the subgroup of children who had been breast-fed for less than 3 months. Body burdens of MeHg and PCBs at 11 years were not related to any of the behavioural or ERP measures. These data suggest that prenatal MeHg exposure alters attentional mechanisms modulating early processing of sensory information. By contrast, prenatal PCB exposure appears to affect information processing at later stages, when the information is being consciously evaluated. These effects seem to be mitigated in children who are breast-fed for a more extended period. [Copyright &y& Elsevier]

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 (≤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. [ABSTRACT FROM AUTHOR]

Abstract: By contrast to the adult literature, in which a consistent parietofrontal network for number processing has been identified, the data from studies of number processing in children have been less consistent, probably due to differences in study design and control conditions. Number processing was examined using functional magnetic resonance imaging in 18 right-handed children (8–12 years) from the Cape Coloured community in Cape Town, South Africa, using Proximity Judgment and Exact Addition (EA) tasks. The findings were consistent with the hypothesis that, as in adults, the anterior horizontal intraparietal sulcus (HIPS) plays a major role in the representation and manipulation of quantity in children. The posterior medial frontal cortex, believed to be involved in performance monitoring in more complex arithmetic manipulations in adults, was extensively activated even for relatively simple symbolic number processing in the children. Other areas activated to a greater degree in the children included the left precentral sulcus, which may mediate number knowledge and, for EA, the head of the caudate nucleus, which is part of a fronto-subcortical circuit involved in the behavioral execution of sequences. Two regions that have been linked to number processing in adults — the angular gyrus and posterior superior parietal lobule — were not activated in the children. The data are consistent with the inference that although the functional specialization of the anterior HIPS may increase as symbolic number processing becomes increasingly automatic, this region and other elements of the parietofrontal network identified in adults are already reliably and robustly activated by middle childhood. [Copyright &y& Elsevier]

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

Abstract: The event-related potential (ERP) P3b, a cognitive electrophysiological measure that has been linked to working memory processing in many experimental paradigms, was measured in Inuit children from Nunavik (Arctic Québec, Canada) to assess lead (Pb) neurotoxicity. Visual and auditory oddball paradigms were administered at 5 (N =27) and 11 (N =110) years of age, respectively, to elicit this ERP component. Pearson correlations and multiple regression analyses were performed to examine the associations between Pb levels and P3b parameters (peak latency and amplitude). Greater prenatal Pb exposure was related to a decrease in P3b amplitude at 5 years of age, and early childhood Pb exposure was associated with delayed P3b latency at 5 years. No significant association was observed at 11 years. These results, in line with those from previous neurobehavioral studies, suggest that Pb exposure affects cognitive processing in children even though the Pb levels measured in a large majority of our sample were below the threshold value for public health intervention used by federal agencies. This study strengthens the arguments for reducing sources of Pb exposure in Nunavik and for lowering the blood Pb concentrations considered “acceptable” in governmental policies. [Copyright &y& Elsevier]

BACKGROUND: An increasing number of studies have shown that several ubiquitous environmental contaminants possess thyroid hormone-disrupting capacities. Prenatal exposure to some of them, such as polychlorinated biphenyls (PCBs), has also been associated with adverse neurodevelopmental effects in infants. OBJECTIVES: In this study we examined the relationship between exposure to potential thyroid hormone-disrupting toxicants and thyroid hormone status in pregnant Inuit women from Nunavik and their infants within the first year of life. METHODS: We measured thyroid hormone parameters [thyroid stimulating hormone (TSH), free thyroxine (fT4), total triiodothyronine (T3), thyroxine-binding globulin (TBG)] and concentrations of several contaminants [PCB-153, hydroxylated metabolites of PCBs (HO-PCBs), pentachlorophenol (PCP) and hexachlorobenzene (HCB)] in maternal plasma at delivery (n = 120), in umbilical cord plasma (n = 95), and in infant plasma at 7 months postpartum (n = 130). RESULTS: In pregnant women, we found a positive association between HO-PCBs and T3 concentrations (β = 0.57, p = 0.02). In umbilical cord blood, PCB-153 concentrations were negatively associated with TBG levels (β = -0.26, p = 0.01). In a subsample analysis, a negative relationship was also found between maternal PCP levels and cord fT4 concentrations in neonates (β = -0.59, p = 0.02). No association was observed between contaminants and thyroid hormones at 7 months of age. CONCLUSION: Overall, there is little evidence that the environmental contaminants analyzed in this study affect thyroid hormone status in Inuit mothers and their infants. The possibility that PCP may decrease thyroxine levels in neonates requires further investigation. [ABSTRACT FROM AUTHOR]

Background: Eyeblink conditioning (EBC) is a Pavlovian paradigm that involves contingent temporal pairing of a conditioned stimulus (e.g., tone) with an unconditioned stimulus (e.g., air puff). Animal studies have shown that binge consumption of alcohol during pregnancy impairs EBC and that this impairment is likely mediated by a loss of neurons in the inferior olive and the cerebellar cortex and deep nuclei, as well as by a reduction in neural plasticity in the cerebellar deep nuclei. Methods: Short delay EBC was examined in 98 5-year-old children born to women from the Coloured (mixed ancestry) community in Cape Town, South Africa, who were recruited prenatally and are participating in the first prospective longitudinal study of children with fetal alcohol syndrome (FAS). FAS status was assessed at 5 years by expert dysmorphologists. Two sessions of 50 trials each were administered to the children; a third session was administered the following day to those children who did not meet criterion of 40% conditioned responses in session 2. Results: Not a single child with FAS met criterion for conditioning as contrasted with 75.0% of the controls. Whereas 86.7% of the controls who were conditioned met criterion by the end of Session 2, a large proportion of the relatively few alcohol-exposed nonsyndromal children who conditioned did not do so until Session 3. These alcohol effects on EBC persisted after controlling for IQ. Three of 4 microcephalic children who were not exposed to alcohol were successfully conditioned. Conclusions: This is the first prospective study to demonstrate impaired EBC in children diagnosed with FAS. Successful EBC in a microcephalic group supports the inference that the EBC deficit is specific to prenatal alcohol exposure and a potential biomarker for diagnosis of exposed children lacking the distinctive FAS dysmorphology. Delay EBC has a high sensitivity for identifying individuals with a diagnosis of probable FAS. [ABSTRACT FROM AUTHOR]

OBJECTIVES. Our goals were to determine whether prenatal alcohol exposure is associated with an increased incidence of iron-deficiency anemia in infancy and to compare effects of fetal alcohol exposure and iron-deficiency anemia on infant growth. We also tested whether effects of fetal alcohol exposure on growth are mediated or moderated by iron-deficiency anemia. METHODS. A total of 96 infants born to mothers from the Coloured (mixed ancestry) community in Cape Town, South Africa, were recruited prenatally; 42 mothers drank heavily during pregnancy, and 54 abstained or drank small amounts of alcohol. Growth was assessed at birth and 6.5 and i2 months, and iron-deficiency anemia was assessed at 6.5 or 12 months. RESULTS. Infants whose mothers binge drank during pregnancy (≥4 drinks per occasion) were 3.6 times more likely to be diagnosed with iron-deficiency anemia at 12 months than were infants whose mothers did not binge drink. Prenatal alcohol exposure was associated with reduced weight at birth, 6.5 months, and 12 months and with shorter length at 6.5 and 12 months. Iron-deficiency anemia was related to reduced 12-month weight and head circumference and to slower growth velocity between 6 and 12 months. The effects of prenatal alcohol on weight were not mediated by iron-deficiency anemia; however, they were seen primarily in infants with iron-deficiency anemia. CONCLUSIONS. The association of maternal binge drinking with an increased incidence of iron-deficiency anemia may reflect disruption of accumulation of fetal iron stores or postnatal deficiencies in iron uptake, absorption, or intake. Moreover, iron deficiency seems to exacerbate the prenatal alcohol effects on growth. [ABSTRACT FROM AUTHOR]

Background: Rates of preterm delivery, a major proximate cause of perinatal morbidity and mortality, have been increasing. Prenatal alcohol exposure has been implicated in preterm delivery, although results have been inconsistent due to inadequate control for confounding factors, insufficient power, unreliable and inaccurate assessment of both exposure and gestational age, and lack of stratification of prematurity into severity levels. The purpose of this study was to examine the relation between maternal alcohol, cocaine and cigarette use during pregnancy, and extreme and mild preterm birth. Methods: Three thousand one hundred thirty consecutive gravidas were followed prospectively for antenatal substance use and had ultrasound confirmed pregnancy dating. Results: Alcohol and cocaine, but not cigarette use, were associated with increased risk of extreme preterm delivery after control for potential confounders. For every unit increase in alcohol exposure, risk of extreme preterm delivery increased significantly [odds ratio (OR) 34.8]. Furthermore, in women aged 30+, alcohol exposure was associated with mild prematurity. Abstention from alcohol while continuing to use cocaine and tobacco was related to a decrease in extreme prematurity of 41%. Conclusions: The risk of extreme preterm delivery associated with alcohol use is substantial and similar in magnitude to other well-recognized risks. Increased accuracy in identifying exposure and the use of ultrasound to confirm gestational age dating likely contributed to the findings of the current study. These findings suggest that eliminating pregnancy alcohol use might substantially reduce the risk of preterm delivery. [ABSTRACT FROM AUTHOR]

The Inuit population of Nunavik (Canada) is exposed to immunotoxic organochlorines (OCs) mainly through the consumption of fish and marine mammal fat. We investigated the effect of perinatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) on the incidence of acute infections in Inuit infants. We reviewed the medical charts of a cohort of 199 Inuit infants during the first 12 months of life and evaluated the incidence rates of upper and lower respiratory tract infections (URTI and LRTIs, respectively), otitis media, and gastrointestinal (CI) infections. Maternal plasma during delivery and infant plasma at 7 months of age were sampled and assayed for PCBs and DDE. Compared to rates kr infants in the first quartile of exposure to PCBs (least exposed), adjusted rate ratios kr infants in higher quartiles ranged between 1.09 and 1.32 kr URTIs, 0.99 and 1.39 for otitis, 1.52 and 1.89 for CI infections, and 1.16 and 1.68 for LRTIs during the first 6 months of follow-up. For all infections combined, the rate ratios ranged from 1.17 to 1.27. The effect size was similar for DDE exposure but was lower kr the full 12-month follow-up. Globally, most rate ratios were> 1.0, but few were statistically significant (p c 0.05). No association was found when postnatal exposure was considered. These results show a possible association between prenatal exposure to OCs and acute infections early in life in this Inuit population. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain, and detectable amounts are in the blood of almost every person in most populations that have been examined. Extensive evidence from animal studies shows that PCBs are neurotoxins, even at low doses. Interpretation of human data regarding low-level, early-life PCB exposure and subsequent neurodevelopment is problematic because levels of exposure were not similarly quantified across studies. We expressed the exposure levels from l0 studies of PCB and neurodevelopment in a uniform manner using a combination of data from original investigators, laboratory reanalyses, calculations based on published data, and expert opinion. The mainstay of our comparison was the median level of PCB 153 in maternal pregnancy serum. The median concentration of PCB 153 in the 10 studies ranged from 30 to 450 ng/g serum lipid, and the median of the 10 medians was 110 ng/g. We found that a) the distribution of PCB 153 exposure in most studies overlapped substantially, b) exposure levels in the Faroe Islands study were about 3-4-fold higher than in most other studies, and c) the exposure levels in the two recent U.S. studies were about one-third of those in the four earlier U.S. studies or recent Dutch, German, and northern Quebec studies. Our results will facilitate a direct comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies. [ABSTRACT FROM AUTHOR]

ABSTRACT. Objective. Evidence that mothers report higher levels of drinking retrospectively than during pregnancy has led some investigators to suggest that women systematically underreport alcohol antenatally and that alcohol-related deficits may actually reflect heavier prenatal exposure. This study is the first to compare the validity of antenatal and retrospective reports of pregnancy drinking, drug use, and smoking in relation to effects on infant neurobehavioral outcomes. Methodology. Three hundred fifty-four inner-city mothers were interviewed regarding their alcohol, drug use, and smoking during pregnancy and retrospectively at 13 months' postpartum. Their infants were assessed at 6.5, 12, and 13 months on a large battery of neurobehavioral assessments. Results. Although higher levels of alcohol were reported retrospectively, the correlations of prenatal alcohol exposure with infant outcome were as strong or stronger for the antenatal measures and only the antenatal reports predicted poorer cognitive performance on the Bayley Scales and symbolic play, slower processing speed on the Fagan Test of Infant Intelligence and cross-modal transfer, and slower infant reaction time. Women also reported higher levels of cocaine and marijuana but not cigarette smoking retrospectively. Relations between cocaine use and smoking on birth size and gestational age were as strong for either report. No effects were detected in relation to either report of marijuana use during pregnancy. Conclusions. These findings suggest that antenatal alcohol interviews provide the most valid information and demonstrate the importance of assessing prenatal alcohol use during pregnancy to minimize the risk of failing to detect neurobehavioral deficits. Adverse effects were consistently seen at levels as low as 0.5 oz absolute alcohol/day (the equivalent of 7 drinks per week) based on maternal antenatal report. These data suggest that alcohol-related deficits do not reflect heavier... [ABSTRACT FROM AUTHOR]

The Inuit population residing in Nunavik (northern Québec, Canada) relies on species from the marine food web for subsistence and is therefore exposed to high doses of environmental contaminants such as polychlorinated biphenyls and methylmercury and to a lesser extent lead. In view of the neurotoxic properties of these substances following developmental exposure, we initiated a study on infant development in this remote coastal population. Here we report the magnitude of prenatal exposure to these contaminants and to selective nutrients in Inuit mothers and their newborns who were recruited on the Hudson Bay coast. We conducted interviews during the women's pregnancies and at 1 and 11 months postpartum and collected biological samples for mercury, lead, polychlorinated biphenyls (PCBs), and chlorinated pesticides analyses as well as selenium and N-3 polyunsaturated fatty acids (n3-PUFA). Cord blood, maternal blood, and maternal hair mercury concentrations averaged 18.5 µg/L, 10.4 µg/L, and 3.7 µg/g, respectively, and are similar to those found in the Faroe Islands but lower than those documented in the Seychelles Islands and New Zealand cohorts. Concentrations of PCB congener 153 averaged 86.9, 105.3, and 131.6 µg/kg (lipids) in cord plasma, maternal plasma, and maternal milk, respectively; prenatal exposure to PCBs in the Nunavik cohort is similar to that reported in the Dutch but much lower than those in other Arctic cohorts. Levels of n3-PUFA in plasma phospholipids and selenium in blood are relatively high. The relatively low correlations observed between organochlorine and methylmercury concentrations may make it easier to identify the specific developmental deficits attributable to each toxicant. Similarly, the weak correlations noted between environmental contaminants and nutrients will facilitate the documentation of possible protective effects afforded by either n3-PUFA or selenium against neurotoxic contaminants. Key... [ABSTRACT FROM AUTHOR]

The objectives of this study were to to identify maternal characteristics associated with traditional food consumption and to examine food items associated with polychlorinated biphenyls (PCBs) and mercury body burden in pregnant Inuit women from Northern Québec. We interviewed women from three communities at mid-pregnancy and at 1 and 11 months postpartum. We measured PCBs, Hg, and selenium in maternal blood; Hg was also measured in maternal hair. The women reported eating significant amounts of fish, beluga muktuk/fat, seal meat, and seal fat. Although consumption of fish and seal was associated with lower socioeconomic status, consumption of beluga whale was uniform across strata. Fish and seal meat consumption was associated with increased Hg concentrations in hair. Traditional food intake during pregnancy was unrelated to PCB body burden, which is more a function of lifetime consumption. This study corroborated previous findings relating marine mammal and fish consumption to increased Hg and selenium body burden. Despite widespread knowledge regarding the presence of these contaminants in traditional foods, a large proportion of Inuit women increased their consumption of these foods during pregnancy, primarily because of pregnancy-related changes in food preferences and the belief that these foods are beneficial during pregnancy. Key words: Canada, Inuit, methylmercury, polychlorinated biphenyls. Environ Health Perspect 109:957-963 (2001). [Online 12 September 2001] http://ehpnet1.niehs.nih.gov/docs/200l/109p957-963muckle/abstr act.html [ABSTRACT FROM AUTHOR]

Background: Although many studies have examined the development of children of male alcoholics, few studies have considered substance use by the female caregiver. This study evaluated the relationship between substance use by female caregivers and factors that affect the child-rearing environment. Methods: A total of 480 inner-city African-American women were recruited during pregnancy for a longitudinal study of the effects of prenatal alcohol use and substance use by caregivers on the development of their children. All women were screened for alcohol consumption at their first prenatal visit to a large urban maternity hospital. Those who averaged seven or more drinks per week (0.5 oz absolute alcohol per day) at the time of conception were invited to participate in the study, as was a 5% random sample of lighter drinkers and abstainers. At the 7.5-year follow-up assessment, the quantity and frequency of alcohol consumption and drug use, as well as several measures of the child-rearing environment, were assessed for 231 of the caregivers. Results: Current alcohol use was uncorrelated with standard demographic factors, such as socioeconomic status, but was related to poorer family functioning, lower quality of parental intellectual stimulation, and higher levels of domestic violence. There were independent effects of illicit drug use on family environment, domestic violence, and caregiver depression. History of drinking during pregnancy, however, was not related to the current child-rearing environment. Poorer parental functioning generally was found only among the caregivers who currently drank both heavily (six or more drinks/occasion) and frequently (three or more days/week). After controlling for lifetime alcohol problems, current drinking still predicted a less cohesive and organized family environment and higher levels of domestic violence. Conclusions: Current heavy, frequent drinking in this relatively homogenous, economically disadvantaged sample was unrelated to demographics and seemed to have an important negative impact on the quality of the child-rearing environment, whereas drinking during pregnancy was unrelated to the current child-rearing environment. [ABSTRACT FROM AUTHOR]

Exposure to mercury, lead and polychlorinated biphenyls (PCBs) have been associated with emotional dysregulation, but their neuronal correlates have yet to be examined. Inuit from Nunavik (Northern Quebec, Canada) face internalizing problems and are among the most exposed individuals to these environmental contaminants in the world. The aim of this study was to examine the link between pre- and postnatal exposure to these contaminants and brain fear-circuitry in Inuit adolescents. Facial expression stimuli were presented to participants (mean age = 18.3 years) in a magnetic resonance imaging (MRI) scanner. Fear conditioning and extinction tasks included neutral faces as the conditioned threat and safety cues and a fearful face paired with a shrieking scream as the unconditioned stimulus. Functional MRI data were gathered at the conditioning phase (n = 71) and at the extinction phase (n = 62). Mercury, lead and PCB 153 concentrations were measured in blood samples at birth (cord blood) and at the time of the adolescent testing to estimate pre- and postnatal exposure, respectively. For each time point, exposures were categorized in tertiles (low, moderate and high exposed groups). Mixed analyses of variance were conducted for each contaminant of interest controlling for sex, age, socioeconomic status, drug/alcohol use, food insecurity and contaminant co-exposure. Results revealed greater differential activation during the conditioning phase in the right orbitofrontal cortex in participants with moderate and high concentrations of cord blood PCB 153 compared to those in the low exposure group. During the extinction phase, the high prenatal mercury exposed group showed a lower differential activation in the right and left anterior cingulate cortex compared to those in the low-exposed group; whereas there was a higher differential activation in right dorsolateral prefrontal cortex in the high postnatal lead exposed group compared to the moderate- and low-exposed groups. Our study is the first to show alterations in the prefrontal brain areas in fear conditioning and extinction tasks in relation to environmental contaminant exposures. The observed brain correlates may advance our understanding of the emotional problems associated with environmental chemical toxicity. • Exposure to environmental contaminants (mercury, lead and PCB) is associated with emotional dysregulation • Brain fear-circuitry was examined in exposed Inuit adolescents from Nunavik using fMRI • Orbitofrontal cortex activation to discriminative fear learning was affected in association with prenatal PCB exposure • Prenatal exposure to Hg and current Pb exposure were associated with dysfunctions of fear extinction brain responses. [ABSTRACT FROM AUTHOR]

Given that their traditional lifestyle and diet still relies on fish and other marine species for sustenance, the Inuit are highly exposed to polychlorinated biphenyls (PCBs) and PCBs are increasingly linked to obesity. However, evidence is not consistent regarding which periods of exposure are most relevant. In this study, we examine whether in utero, childhood, and adolescent exposure to PCBs are related to physical growth at adolescence. Inuit adolescents from Canada (N=212) enrolled in a prospective longitudinal cohort study since birth were assessed for height, weight, body mass index (BMI), fat mass index (FMI) and fat free mass index (FFMI) at 18 years of age. PCB 153 concentrations were quantified in blood samples obtained at birth (umbilical cord), 11, and 18 years of age. Maternal anthropometrics were measured and those for the newborns collected from medical records. Data on biological mothers and participants' sociodemographic characteristics and food security were collected using interviews. Multiple linear regression analyses were used to test associations between PCB 153 concentrations and adolescent anthropometric measures. Cord PCB 153 was not related to height or FFMI at adolescence. By contrast, analyses showed that cord PCB 153 was related to higher BMI, FMI and marginally to weight in girls but not boys. Child PCB 153 was not related to height, weight or FFMI in adolescence. Child PCB 153 was related to lower BMI and FMI at adolescence in both sexes, particularly among those considered overweight or obese during childhood. Adolescent PCB 153 was not associated with any outcome. This study suggests that prenatal exposure to PCBs may have a long-term effect on growth in early adulthood among girls and identifies the peri-pubertal period as another window of sensitivity for the action of PCBs. Our findings also suggest that exposure to PCBs and body size be documented in multiple time periods from infancy to adulthood. • Prenatal exposure to PCBs may have a long-term effect on growth among girls. • Peri-pubertal period identified as a window of sensitivity for PCBs. • Exposure to PCBs and body size be documented in multiple time periods. [ABSTRACT FROM AUTHOR]

This study aimed to examine the relation between anxiety among the at-risk population of Inuit adolescents and diverse developmental risk factors including exposure to environmental chemicals, a subject of concern in Nunavik. Anxiety was assessed in 89 Inuit participants (mean age = 18.4 years; range = 16.2–21.9) with the Screen for Child Anxiety Related Emotional Disorders (SCARED) and the State-Trait Anxiety Inventory (STAI). Potential risk factors for anxiety were documented at birth, 11 years of age and 18 years of age, including blood levels of chemicals (mercury, lead, PCBs) and nutrients, as well as age, sex, estimated IQ, drug and alcohol use, bullying, exposure to domestic violence, food insecurity, crowding and socio-economic status. Results showed that participants scored high on both measures of anxiety, particularly the SCARED, for which the mean score was above the clinical threshold. Multiple regression results show that significant risk predictors obtained from the SCARED scores were female sex (β = 0.32), higher current blood mercury concentration (β = 0.26), food insecurity (β = 0.26) and bullying experiences in the last year (β = 0.21). The significant predictors for the STAI trait anxiety were food insecurity (β = 0.25) and lower estimated IQ (β = −0.31), whereas food insecurity (β = 0.21), lower blood levels of vitamin E (β = −0.25) and higher cord blood mercury concentrations (β = 0.25) were found for STAI situational anxiety. Further regression analyses suggested that the adolescent-related variables were the most important risk factors. Our findings show that Inuit adolescents are at risk for anxiety via multiple contributing factors, particularly current exposure to mercury, food insecurity and female sex. • High anxiety levels were observed in Inuit adolescents from Nunavik • Current exposure to mercury, food insecurity and female sex were found to be strong risk factors of anxiety • The identified modifiable risk factors may help to improve prevention of anxiety disorders among the Nunavik Inuit [ABSTRACT FROM AUTHOR]

Lead (Pb) exposure is associated with adverse neurological development. Most notably, it has been observed through externalizing behavior symptoms, as observed among Inuit children from northern Québec. Evidence for a persistent neurological impact of early Pb exposure later in life is however scarce. Pb exposure may initiate a developmental cascade that increases the risk of long-term behavior problems. Testing for direct associations between childhood Pb concentrations and adolescent externalizing symptoms and substance use, as well as indirect associations through childhood behavior assessments. The study sample is a longitudinal cohort of Inuit children (n = 212) followed since birth. Blood Pb concentrations were measured during childhood (median age = 11.4 years) and adolescence (median age = 18.5 years). Externalizing/inattentive behavior were teacher-assessed through the Teacher Report Form and the Disruptive Behavior Disorders Rating Scale for children. At the adolescence follow-up, behavior problems were self-reported by filling Achenbach's Youth Self-Report, the Barkley Adult ADHD-IV Rating Scale, and the Diagnostics Interview Schedule for Children. Adolescent substance use was also self-assessed through the DEP-ADO. Direct and indirect associations of child Pb concentrations with adolescent outcomes were tested through mediation models. Child blood Pb concentrations were not directly associated with any adolescent outcomes. On the contrary, childhood Pb exposure was indirectly associated, through childhood externalizing behavior assessments, with adolescent externalizing behaviors, binge drinking, and cannabis use. These indirect associations held after controlling for adolescents' concurrent Pb blood concentrations. Our results highlight the indirect but lasting effects of child Pb exposure on adolescent behavior problems, and the importance of childhood externalizing behavior in this relationship. Adverse early-life environment put children on a riskier developmental trajectory, increasing their likelihood of lifelong psychological, social and health problems. • Child Pb associated with adolescent externalizing behavior and substance use. • These associations mediated by child externalizing behaviors. • Early-life impairments may put children on a riskier developmental trajectory. [ABSTRACT FROM AUTHOR]

Background: Although animal and human studies have demonstrated interactions between dietary choline and fetal alcohol spectrum disorders, dietary choline deficiency in pregnancy is common in the US and worldwide. We sought to develop and validate a quantitative food frequency questionnaire (QFFQ) to estimate usual daily choline intake in pregnant mothers.Methods: A panel of nutrition experts developed a Choline-QFFQ food item list, including sources with high choline content and the most commonly consumed choline-containing foods in the target population. A data base for choline content of each item was compiled. For reliability and validity testing in a prospective longitudinal cohort, 123 heavy drinking Cape Coloured pregnant women and 83 abstaining/light-drinking controls were recruited at their first antenatal clinic visit. At 3 prenatal study visits, each gravida was interviewed about alcohol, smoking, and drug use, and administered a 24-hour recall interview and the Choline-QFFQ.Results: Across all visits and assessments, > 78% of heavy drinkers and controls reported choline intake below the Dietary Reference Intakes adequate intake level (450 mg/day). Women reported a decrease in choline intake over time on the QFFQ. Reliability of the QFFQ across visits was good-to-acceptable for 2 of 4 group-level tests and 4 of 5 individual-level tests for both drinkers and controls. When compared with 24-hr recall data, validity of the QFFQ was good-to-acceptable for 3 of 4 individual-level tests and 3 of 5 group-level tests. For controls, validity was good-to-acceptable for all 4 individual-level tests and all 5 group-level tests.Conclusions: To our knowledge, this is the first quantitative choline food frequency screening questionnaire to be developed and validated for use with both heavy and non-drinking pregnant women and the first to be used in the Cape Coloured community in South Africa. Given the high prevalence of inadequate choline intake and the growing evidence that maternal choline supplementation can mitigate some of the adverse effects of prenatal alcohol exposure, this tool may be useful for both research and future clinical outreach programs. [ABSTRACT FROM AUTHOR]

Introduction: Although performance deficits in place learning have been reported in fetal alcohol spectrum disorders (FASD), neural correlates of these deficits have not been investigated. This functional magnetic resonance imaging (fMRI) study of 57 children (41 alcohol‐exposed; 16 controls; mean age = 9.4 years; 29 boys) examined effects of prenatal alcohol exposure (PAE) on place learning in a virtual environment, the computer‐generated (CG) arena. Methods: Functional magnetic resonance imaging data were acquired while children passively viewed a recording of an experimenter completing the task. Visible‐target blocks involved navigation to a visible platform. During invisible‐target blocks, the platform appeared only when the experimenter moved over it. After the scan, all children performed a post‐test during which they had to navigate to the location of the invisible platform. Results: Although there were no group differences in post‐test performance for sex or FASD diagnosis, PAE in boys was associated with poorer performance and reduced activation in the parahippocampal gyrus (PHG), precuneus, posterior cingulate, frontal and temporal lobes, caudate, insula, claustrum, lentiform nucleus, and thalamus. By contrast, PAE was not associated with performance or activation in any regions in girls. Discussion and conclusion: Girls and boys are known to use different navigation strategies. Boys rely more on an allocentric navigational strategy and girls more on landmarks. Poorer recruitment of the PHG, a region known to mediate allocentric navigation, in more heavily exposed boys may explain the observed dose‐dependent place learning deficit. The absence of PAE effects in girls suggests that landmark‐based navigational strategies may be less affected by alcohol exposure. In boys, prenatal alcohol exposure (PAE) was associated with poorer place learning performance in a virtual environment and reduced fMRI activation in the parahippocampal gyrus, precuneus, posterior cingulate, frontal and temporal lobes, caudate, insula, claustrum, lentiform nucleus, and thalamus. By contrast, PAE was not associated with performance or activation in any regions in girls. This sex difference is possibly due to girls and boys using different navigation strategies, with boys using allocentric navigation, relying on regions affected by PAE, and girls using landmark strategies which are less affected by PAE. [ABSTRACT FROM AUTHOR]