Fish is a valuable source of nutrition, and many people would benefit from eating fish regularly. But some people eat a lot of fish, every day or several meals per week, and thus can run a significant risk of overexposure to methylmercury. Current advice regarding methylmercury from fish consumption is targeted to protect the developing brain and nervous system but adverse health effects are increasingly associated with adult chronic low-level methylmercury exposure. Manifestations of methylmercury poisoning are variable and may be difficult to detect unless one considers this specific diagnosis and does an appropriate test (blood or hair analysis). We provide information to physicians to recognize and prevent overexposure to methylmercury from fish and seafood consumption. Physicians are urged to ask patients if they eat fish: how often, how much, and what kinds. People who eat fish frequently (once a week or more often) and pregnant women are advised to choose low mercury fish.

BACKGROUND Exposure to organochlorine compounds (OCs) can alter thyroid function in humans, and hypothyroidism during early life can adversely affect a child's neurodevelopment. OBJECTIVES In this study we aimed to assess the relationship between developmental organochlorine exposures and thyroid function and the relationship between thyroid function and subsequent neurodevelopment. METHODS A population-based birth cohort of 182 children was followed annually up to 5.5 years of age. The assessments included OC concentrations in maternal pregnancy serum and milk, clinical thyroid parameters in maternal and cord serum, and subsequent neuropsychological outcomes of the child, along with sociodemographic cofactors. Resin triiodothyronine uptake ratio (T3RU) was also assessed as an estimate of the amount of thyroxine-binding globulin (TBG) sites unsaturated by thyroxine. The T3RU is high in hyperthyroidism and low in hypothyroidism. RESULTS The findings showed consistent inverse and monotonic associations between organochlorine exposure and T3RU after covariate adjustments. We observed no associations with other thyroid parameters. T3RU was positively associated with improved performance on most of the neuropsychological tests. For other thyroid parameters, the findings were less consistent. CONCLUSIONS The results suggest that OC exposures may decrease the T3RU during early life, which is a proxy measure of the binding capacity of TBG. In addition, minor decreases of the thyroid function may be inversely associated with a child's neurodevelopment.

Lead exposure remains a public health concern due to its serious adverse effects, such as cognitive and behavioral impairment: children younger than six years of age being the most vulnerable population. In Europe, the lead-related economic impacts have not been examined in detail. We estimate the annual costs in France due to childhood exposure and, through a cost benefit analysis (CBA), aim to assess the expected social and economic benefits of exposure abatement. Monetary benefits were assessed in terms of avoided national costs. We used results from a 2008 survey on blood-lead (B-Pb) concentrations in French children aged one to six years old. Given the absence of a threshold concentration being established, we performed a sensitivity analysis assuming different hypothetical threshold values for toxicity above 15 μg/L, 24 μg/L and 100 μg/L. Adverse health outcomes of lead exposure were translated into social burden and economic costs based on literature data from literature. Direct health benefits, social benefits and intangible avoided costs were included. Costs of pollutant exposure control were partially estimated in regard to homes lead-based paint decontamination, investments aiming at reducing industrial lead emissions and removal of all lead drinking water pipes. The following overall annual benefits for the three hypothetical thresholds values in 2008 are: €22.72 billion, €10.72 billion and €0.44 billion, respectively. Costs from abatement ranged from €0.9 billion to 2.95 billion/year. Finally, from a partial CBA of lead control in soils and dust the estimates of total net benefits were € 3.78 billion, € 1.88 billion and €0.25 billion respectively for the three hypothesized B-Pb effect values. Prevention of childhood lead exposure has a high social benefit, due to reduction of B-Pb concentrations to levels below 15 μg/L or 24 μg/L, respectively. Reducing only exposures above 100 μg/L B-Pb has little economic impact due to the small number of children who now exhibit such high exposure levels. Prudent public policies would help avoiding future medical interventions, limit the need for special education and increase future productivity, and hence lifetime income for children exposed to lead.

To provide family physicians with a practical, evidence-based approach to counseling women about healthy fish eating. MEDLINE was searched for articles published between 1999 and 2008. Most studies described in this article provide level II or III evidence. Fish is an important component of a healthy diet for women in their reproductive years owing to the beneficial effects of omega-3 fatty acids on the neurologic development of the fetus. However, some fish species contain considerable methylmercury, which crosses the placenta and has harmful effects on neurobehavioural development. As many jurisdictions have issued fish consumption advisories, which can be confusing, women would benefit from individualized assistance from a trusted source, their family physicians, to clarify the risks and benefits of eating fish. We recommend that family physicians counsel women in their reproductive years about healthy choices regarding fish in their diet, and provide appropriate resources.

Methylmercury is now recognized as an important developmental neurotoxicant, though this insight developed slowly over many decades. Developmental neurotoxicity was first reported in a Swedish case report in 1952, and from a serious outbreak in Minamata, Japan, a few years later. Whereas the infant suffered congenital poisoning, the mother was barely harmed, thus reflecting a unique vulnerability of the developing nervous system. Nonetheless, exposure limits for this environmental chemical were based solely on adult toxicity until 50 years after the first report on developmental neurotoxicity. Even current evidence is affected by uncertainty, most importantly by imprecision of the exposure assessment in epidemiological studies. Detailed calculations suggest that the relative imprecision may be as much as 50%, or greater, thereby substantially biasing the results toward the null. In addition, as methylmercury exposure usually originates from fish and seafood that also contains essential nutrients, so-called negative confounding may occur. Thus, the beneficial effects of the nutrients may appear to dampen the toxicity, unless proper adjustment is included in the analysis to reveal the true extent of adverse effects. These problems delayed the recognition of low-level methylmercury neurotoxicity. However, such problems are not unique, and many other industrial compounds are thought to cause developmental neurotoxicity, mostly with less epidemiological support than methylmercury. The experience obtained with methylmercury should therefore be taken into account when evaluating the evidence for other substances suspected of being neurotoxic.

Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cognitive processing and focused attention, and finally sustained attention as the dominant demand. Prenatal methylmercury exposure is associated with increased reaction time (RT) latencies. We therefore examined the association of methylmercury exposure with the average HRT at age 14 years at three different time intervals after test initiation. A total of 878 adolescents (87% of birth cohort members) completed the CPT. The RT latencies were recorded for 10 min, with visual targets presented at 1000 ms intervals. After confounder adjustment, regression coefficients showed that CPT-RT outcomes differed in their associations with exposure biomarkers of prenatal methylmercury exposure: During the first 2 min, the average HRT was weakly associated with methylmercury (beta (SE) for a ten-fold increase in exposure,(3.41 (2.06)), was strongly for the 3-to-6 min interval (6.10 (2.18)), and the strongest during 7-10 min after test initiation (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger tapping speed were included in the models as covariates. Postnatal methylmercury exposures did not affect the outcomes. Thus, these findings suggest that sustained attention as a neuropsychological domain is particularly vulnerable to developmental methylmercury exposure, indicating probable underlying dysfunction of the frontal lobes. When using CPT data as a possible measure of neurotoxicity, test results should therefore be analyzed in regard to time from test initiation and not as overall average reaction times.

The relative contributions of proximity to mercury sources and trophic ecology to realized axial muscle mercury concentrations were explored for three deep-water chondrichthyans (Etmopterus princeps, Centroscymnus coelolepis, and Hydrolagus affinis), two species of which are harvested for human consumption. Samples were taken at three North Atlantic Ocean locations: the Azores, the Charlie Gibbs Fracture Zone, and the Bear Seamount. Despite the long distances between anthropogenic sources and the sampling locations, all species from all locations had muscle mercury concentrations exceeding the United States human health screening value of 0.3 mg/kg wet weight. Proximity to anthropogenic sources was not an obvious determinant of these elevated concentrations. Generally, mercury concentrations appeared to increase with increased dependence on benthic versus pelagic food sources (as indicated by interspecies differences in δ(13)C), and with higher position in the trophic web (as indicated by differences in δ(15)N).

Methylmercury (MeHg) is highly toxic, and its principal target tissue in humans is the nervous system, which has made MeHg intoxication a public health concern for many decades. The general population is primarily exposed to MeHg through consumption of contaminated fish and marine mammals, but recent studies have reported high levels of MeHg in rice and confirmed that in China the main human exposure to MeHg is related to frequent rice consumption in mercury (Hg) polluted areas. This article reviews the progress in the research on MeHg accumulation in rice, human exposure and health effects, and nutrient and co-contaminant interactions. Compared with fish, rice is of poor nutritional quality and lacks specific micronutrients identified as having health benefits (e.g., n-3 long chain polyunsaturated fatty acid, selenium, essential amino acids). The effects of these nutrients on the toxicity of MeHg should be better addressed in future epidemiologic and clinical studies. More emphasis should be given to assessing the health effects of low level MeHg exposure in the long term, with appropriate recommendations, as needed, to reduce MeHg exposure in the rice-eating population.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for neuronal survival and differentiation. We examined the concentration of BDNF in cord serum from newborns exposed to methylmercury (MeHg) and polychlorinated biphenyls (PCB) in utero by maternal consumption of whale meat. The cohort consisted of 395 singleton births (206 boys and 189 girls), gestational age ranging from 38 to 42 weeks. Serum BDNF was measured by sandwich ELISA. Maternal smoking habits and other relevant factors were obtained by interviewing the mothers. The exposure to MeHg was estimated from Hg concentrations in cord blood, whereas exposure to PCB was estimated based on maternal serum concentrations. Only MeHg exposure affected the serum BDNF, which decreased in a concentration-dependent manner in girls born to nonsmoking mothers. Maternal smoking significantly increased BNDF in girls but not in boys. For further statistical analyses, we used the serum BDNF concentration as a continuous outcome variable in supervised regression models. Serum BDNF concentration increased with gestational age, increased by maternal smoking, decreased slightly with MeHg exposure, and maternal smoking enhanced the decrease in serum BDNF induced by MeHg exposure. Cord blood BDNF has been reported to increase in association with perinatal brain injuries and has been proposed as a possible predictive marker of neurodevelopmental outcomes. The negative effect that MeHg seems to exert on cord blood BDNF concentration could endanger compensatory responses to an adverse impact and therefore deserves attention.

We developed a probabilistic model to characterize the plausible distribution of health and economic benefits that would accrue to the U.S. population following reduction of methyl mercury (MeHg) exposure. MeHg, a known human developmental neurotoxicant, may increase fatal heart attack risks. Model parameters reflect current understanding of the relationships between MeHg intake, health risks, and societal valuation of these risks. The expected monetary value of the annual health benefits generated by a 10% reduction in U.S. population exposure to MeHg for one year is $860 million; 80% of this is associated with reductions in fatal heart attacks and the remainder with IQ gains. The plausible distribution of the benefits is quite broad with 5th and 95th percentile estimates of approximately $50 million and $3.5 billion, respectively. The largest source of uncertainty is whether epidemiological associations between MeHg exposure and fatal heart attacks reflect causality. The next largest sources of uncertainty concern the slope of the relationship between maternal MeHg exposure and reduced intelligence among children and whether this relationship exhibits a threshold. Our analysis suggests that the possible causal relationship between MeHg exposure and fatal heart attacks should be better characterized, using additional epidemiological studies and formally elicited expert judgment.

Methylmercury poisoning may cause constriction of visual fields and deafness, especially if exposure occurs prenatally. However, the risks associated with exposure from contaminated seafood is unclear. We examined 149 children attending first grade in a Madeiran fishing community. As maternal dietary habits were relatively unchanged, current maternal hair concentrations were used as indicator of the child's prenatal exposure to methylmercury (geometric average, 9.64 microg/g [48.2 nmol/g]). After adjustment for age and sex, the mean (+/-SD) latency of peak III of the brainstem auditory evoked potentials at 40 Hz was increased by 0.128+/-0.047 ms when maternal hair-mercury concentrations exceeded 10 microg/g (50 nmol/g)(p for association, 0.002), and the increase of the N145 pattern-reversal visual evoked potential latency at 15 minutes of arc was 3.16+/-1.57 ms (p for association, 0.002). No such relationships were seen with the child's own hair-mercury concentration, and other clinical examinations revealed no mercury-associated deficits. Neurophysiological evidence of adverse effects on brain function are relatively independent of confounders, and should be considered in the risk assessment of this seafood pollutant.

Prenatal exposure to polychlorinated biphenyls (PCBs) was examined by analysis of cord tissue from 435 children from a Faroese birth cohort. Analysis of 50 paired cord blood samples showed excellent correlation with the cord tissue concentration (r=.90). Among 17 neuropsychological outcomes determined at age 7 years, the cord PCB concentration was associated with deficits on the Boston Naming Test (without cues, two-tailed P=.09 not adjusted for mercury; with cues, P=.03), the Continuous Performance Test reaction time (P=.03), and, possibly, on long-term recall on the California Verbal Learning Test (P=.15). The association between cord PCB and cord-blood mercury (r=.42) suggested possible confounding. While no PCB effects were apparent in children with low mercury exposure, PCB-associated deficits within the highest tertile of mercury exposure indicated a possible interaction between the two neurotoxicants. PCB-associated increased thresholds were seen at two of eight frequencies on audiometry, but only on the left side, and no deficits occurred on evoked potentials or contrast sensitivity. The limited PCB-related neurotoxicity in this cohort appears to be affected by concomitant methylmercury exposure.

Presentation of neuropsychological tests on a computer screen may involve a visual challenge to the examinee. The possible need for adjustment for visual contrast sensitivity on test performance was therefore determined from data on 917 mercury-exposed children who were examined at age 7 years. Contrast sensitivity was found to be associated with performance on the computer-assisted Continuous Performance Test. However, it showed similar associations with performance on traditional pencil-and-paper tests, especially Bender Visual Motor Gestalt Test and Wechsler Intelligence Scale for Children-Revised (WISC-R) Block Designs. Contrast sensitivity was not associated with prenatal mercury exposure, and adjustment for visual function had only a negligible effect on the regression coefficients for mercury as predictor of neuropsychological deficits. The mercury-associated neurobehavioral deficits are therefore unlikely to be due to mercury-induced visual system dysfunction causing secondary deficits in cognitive domain testing. Visuospatial processing appears to be a determinant in contrast sensitivity performance, and careful consideration of whether to control for contrast sensitivity in future studies of neurotoxicant effects is therefore recommended.

The mercury concentration in blood or scalp hair has been widely used as a biomarker for methylmercury exposure. Because of the increased risks associated with exposures during prenatal and early postnatal development, biomarker results must be interpreted with regard to the age-dependent susceptibility. The authors compared regression coefficients for five sets of exposure biomarkers in 917 children from the Faroe Islands examined at birth, 1 year, and 7 years. Outcome variables were the results of neuropsychologic examination carried out in 1993-1994 at age 7 years. After adjustment for covariates, the cord-blood concentration showed the clearest associations with deficits in language, attention, and memory. Fine-motor function deficits were particularly associated with the maternal hair mercury at parturition. Mercury concentrations in the child's blood and hair at age 7 years were significant predictors only of performance on memory for visuospatial information. These findings emphasize the usefulness of the cord-blood mercury concentration as a main risk indicator. They also support the notion that the greatest susceptibility to methylmercury neurotoxicity occurs during late gestation, while early postnatal vulnerability is less, and they suggest that the time-dependent susceptibility may vary for different brain functions.

Three tests from the computerized Neurobehavioral Examination System (NES) were administered to a group of 917 Faroese children at approximately 7 years of age. The NES Continuous Performance Test (CPT) was modified to use animal silhouettes as stimuli instead of letters. Almost all children completed Finger Tapping (FT), the modified CPT, and Hand-Eye Coordination (HE). However, 18% of the children missed at least 25% of the stimuli on the CPT (full test period), and 37% of the children did not improve their HE performance by at least 10%, as compared to the first trial. Boys obtained better results than girls, and older children performed better than younger ones. However, both factors were confounded by acquaintance with computer games. Children who used glasses, who had strabismus, or who had decreased contrast sensitivity obtained less satisfactory scores, especially on CPT and HE. The NES performance was significantly associated with functional neurological performance, including catching a ball, diadochokinesia, and finger agnosia. Slight, though statistically significant, decrements were seen with increased levels of prenatal exposure to neurotoxicants, as indicated by the mercury concentrations in cord blood obtained at the time of birth. In conclusion, the tests were feasible in this age group after slight modifications, and the test results showed meaningful associations with major predictors, thus supporting the validity of the data.

A study of 7-year-old children from a fishing village on Madeira has suggested that latencies of evoked potentials may be delayed because of increased exposures to methylmercury during development. Data from a previously published prospective study in the Faroe Islands have therefore been reexamined. Because of changes in instrumentation, results obtained during the second year of examination were excluded. After this restriction, the results show significant mercury-associated delays of the peak III latency and the I-III interpeak latency of the auditory brainstem evoked potentials. Mercury concentrations in both maternal hair at parturition and in cord blood indicated this association, whereas no such relationship was apparent with the child's current hair-mercury concentration. Thus, in agreement with the findings from Madeira, a delay of the peak III latency of the brainstem auditory evoked potentials appears to serve as a marker of prenatal methylmercury toxicity from contaminated seafood.

Blood pressure in childhood is an important determinant of hypertension risk later in life, and methylmercury exposure is a potential environmental risk factor. A birth cohort of 1,000 children from the Faroe Islands was examined for prenatal exposure to methylmercury, and at age 7 years, blood pressure, heart rate, and heart rate variability were determined. After adjustment for body weight, diastolic and systolic blood pressure increased by 13.9 mmHg [95% confidence limits (CL)= 7.4, 20.4] and 14.6 mmHg (95% CL = 8.3, 20.8), respectively, when cord blood mercury concentrations increased from 1 to 10 microg/liter cord blood. Above this level, which corresponds to a current exposure limit, no further increase was seen. Birth weight acted as a modifier, with the mercury effect being stronger in children with lower birth weights. In boys, heart rate variability decreased with increasing mercury exposures, particularly from 1 to 10 microg/liter cord blood, at which the variability was reduced by 47%(95% CL = 14%, 68%). These findings suggest that prenatal exposure to methylmercury may affect the development of cardiovascular homeostasis.

Chronic neurobehavioral effects of acute sarin poisoning were evaluated in 9 male and 9 female patients who were exposed to sarin poisoning in the Tokyo subway incident in Japan. The investigators used nine neurobehavioral tests, as well as a posttraumatic stress disorder checklist, 6-8 mo after the poisoning occurred. Serum cholinesterase activity in patients on the day of poisoning (i.e., March 20, 1995) ranged from 13 to 131 IU/l (mean=72.1 IU/l). The results of analysis covariance, in which age, education level, alcohol consumption, and smoking status (covariates) were controlled in 18 sarin cases and in 18 controls, showed that the score on the digit symbol (psychomotor performance) test was significantly lower in the sarin cases than in controls. Nonetheless, the scores for the General Health Questionnaires, fatigue of Profile of Mood States, and posttraumatic stress disorder checklist were significantly higher in the sarin cases than controls. The investigators added posttraumatic stress disorder to the covariates, and only the score on the digit symbol test was significantly lower in sarin cases. In addition, the results of stepwise multiple regression analysis in 18 sarin cases revealed that scores for the General Health Questionnaires, fatigue of Profile of Mood States (i.e., fatigue, tension-anxiety, depression, and anger-hostility)-together with the paired-associate learning test-were associated significantly with posttraumatic stress disorder. The association did not remain significant for the digit symbol test score. Perhaps a chronic effect on psychomotor performance was caused directly by acute sarin poisoning; on the other hand, the effects on psychiatric symptoms (General Health Questionnaire) and fatigue (Profile of Mood States) appeared to result from posttraumatic stress disorder induced by exposure to sarin.

Within a cohort of 1022 consecutive singleton births in the Faroe Islands, we assessed prenatal methylmercury exposure from the maternal hair mercury concentration. At approximately 7 years of age, 917 of the children underwent detailed neurobehavioral examination. Little risk is thought to occur as long as the hair mercury concentration in pregnant women is kept below 10-20 microg/g (50-100 nmol/l). A case group of 112 children whose mothers had a hair mercury concentration of 10-20 microg/g was therefore matched to children with exposure below 3 microg/g, using age, sex, time of examination, and the mother's score on Raven's Progressive Matrices as matching criteria. The two groups were almost identical with regard to other factors that might affect neurobehavioral performance in this community. On six neuropsychological test measures, the case group showed mild decrements, relative to controls, especially in the domains of motor function, language, and memory. Subtle effects on brain function therefore seem to be detectable at prenatal methylmercury exposure levels currently considered to be safe.

Six to eight months after the Tokyo subway attack in March 1995, the neurophysiological effects of acute sarin poisoning were investigated in 18 passengers exposed to sarin (sarin cases) in the subways to ascertain the focal or functional brain deficits induced by sarin. The event-related and visual evoked potentials (P300 and VEP), brainstem auditory evoked potential, and electrocardiographic R-R interval variability (CVRR), together with the score on the posttraumatic stress disorder (PTSD) checklist, were measured in the sarin cases and the same number of control subjects matched for sex and age. None of the sarin cases had any obvious clinical abnormalities at the time of testing. The P300 and VEP (P100) latencies in the sarin cases were significantly prolonged compared with the matched controls. In the sarin cases, the CVRR was significantly related to serum cholinesterase (ChE) levels determined immediately after exposure; the PTSD score was not significantly associated with any neurophysiological data despite the high PTSD score in the sarin cases. These findings suggest that asymptomatic sequelae to sarin exposure, rather than PTSD, persist in the higher and visual nervous systems beyond the turnover period of ChE; sarin may have neurotoxic actions in addition to the inhibitory action on brain ChE.

This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on children's cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age.

PURPOSE This study aimed to explore cognitive functions in patients with childhood epilepsy with occipital paroxysms (CEOP) and to compare the performance of these patients with that of patients with symptomatic occipital epilepsy (SOE) and healthy control subjects. METHOD Twenty-eight patients with epilepsy (17 CEOP, 11 SOE) were enrolled. The control group had similar demographical characteristics. Cognitive functions evaluated with Wechsler Intelligence Scale for Children-revised edition (WISC-R), The Visual Aural Digit Span (VADS) and Bender Visual Motor Gestalt Test (BVMG). RESULTS The WISC-R showed lower performance IQ with WISC-R in patients with occipital epilepsy than in healthy controls. The VADS test only showed lower scores in children with symptomatic occipital epilepsy. Mean BVMG test scores were significantly abnormal in both subgroups of childhood epilepsy with occipital paroxysms (early-onset CEOP/late-onset CEOP) and the group with SOE. CONCLUSION Patients with CEOP, especially the late-onset form, have significant problems in the domains of visuomotor coordination, memory and attention. The academic performance of these patients should be monitored carefully in follow-up and appropriate educational support should be given as necessary.

In Nepal, antenatal iron-folic acid supplementation improved aspects of intellectual, executive, and fine motor function among school-age children. We examined the impact of added zinc to the maternal antenatal supplement (M-IFAZn) and preschool supplementation from 12 to 36 mo with iron-folic acid (C-IFA) ± zinc (C-IFAZn) on cognitive outcomes compared to maternal iron-folic acid (M-IFA) alone. Children 7-9 y old (n = 780) who participated in early childhood micronutrient supplementation trial during 2001-2004 and whose mothers participated in an antenatal micronutrient supplementation between 1999 and 2001 were followed for cognitive assessments in 2007-2009. Using multivariate analysis of variance and adjusting for confounders, M-IFA with child supplementation (either C-IFA or C-IFAZn) did not impact scores on the tests of general intelligence (Universal Nonverbal Intelligence Test), and executive function (Stroop and go/no go tests) relative to the M-IFA alone. However, children in the C-IFAZn group had slightly lower scores on the backward digit span (-0.29, 95% CI:-0.55,-0.04) and Movement Assessment Battery for Children (1.33, 95% CI: 0.26, 2.40) relative to the referent group, whereas both C-IFA (-1.92, 95% CI:-3.12,-0.71) and C-IFAZn (-1.78, 95% CI:-2.63,-0.92) produced somewhat lower finger tapping test scores (fine motor skills). The combination of M-IFAZn and C-IFA or C-IFAZn did not lead to any outcome differences relative to M-IFA alone. Preschool iron-folic acid ± zinc to children exposed to iron-folic acid in utero or addition of zinc to maternal iron-folic acid conferred no additional benefit to cognitive outcomes assessed in early school age. The late timing of supplementation during preschool may explain the lack of impact of iron and/or zinc.

OBJECTIVES: Occupational manganese (Mn) exposure has been associated with motor deficits in adult workers, but data on the potential effects of environmental exposure to Mn on the developing motor function for a children population is scarce. The aim of this study was to evaluate the association between exposure to Mn and motor function of school aged children. METHODS: We conducted a cross-sectional study selecting 195 children (100 exposed and 95 unexposed) between 7 and 11 years old. The following tests were used to evaluate the motor function: Grooved pegboard, finger tapping, and Santa Ana test. Mn exposure was assessed by blood (MnB) and hair concentrations (MnH). We constructed linear regression models to evaluate the association between exposure to Mn and the different test scores adjusting for age, sex, maternal education, hemoglobin and blood lead. RESULTS: The median concentration of MnH and MnB was significantly higher in exposed (12.6μg/g and 9.5μg/L) compared to unexposed children (0.6μg/g and 8.0μg/L). The exposed children on average performed the grooved pegboard test faster, but made more errors, although these results did not reach statistical significance with neither one of the Mn exposure biomarkers. MnB showed an inverse association on the execution of the finger tapping test (average in 5 trials β -0.4, p=0.02), but no association was observed with MnH. CONCLUSIONS: A subtle negative association of Mn exposure on motor speed and coordination was shown. In adults, the main effect of environmental Mn exposure has been associated with motor skills, but these results suggest that such alterations are not the main effect on children.

Methamphetamine/polysubstance abuse in women of childbearing age is a major concern because of the potential long-term detrimental effects on the brain function of the fetus following in utero exposure. A battery of established tests, including the Wechsler Abbreviated Scale of Intelligence, Conners' Continuous Performance Test II, Behavioral Rating Inventory of Executive Function, the CMS Family Pictures and Dot Location tests, the Spatial Span test from the WISC-IV-Integrated, and a recently developed spatial learning and memory measure (Memory Island), was used to assess the effects of prenatal drug exposure on neurobehavioral performance. Participants were 7 to 9 year old children from similar socioeconomic backgrounds who either had (N=31) or had not (N=35) been exposed to methamphetamine/polysubstance during pregnancy. Compared to unexposed children, exposed children showed pronounced elevations (i.e. more problems) in parental ratings of executive function, including behavioral regulation and metacognition. Exposed children also exhibited subtle reductions in spatial performance in the Memory Island test. In contrast, IQ, Spatial Span, Family Pictures, Dot Location, and vigilance performance were unaffected by prenatal drug exposure history. Thus, children of women who reported using methamphetamine and other recreational drugs during pregnancy showed a selective profile of abnormalities in parentally rated executive function.

Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cognitive processing and focused attention, and finally sustained attention as the dominant demand. Prenatal methylmercury exposure is associated with increased reaction time (RT) latencies. We therefore examined the association of methylmercury exposure with the average HRT at age 14 years at three different time intervals after test initiation. A total of 878 adolescents (87% of birth cohort members) completed the CPT. The RT latencies were recorded for 10 min, with visual targets presented at 1000 ms intervals. After confounder adjustment, regression coefficients showed that CPT-RT outcomes differed in their associations with exposure biomarkers of prenatal methylmercury exposure: During the first 2 min, the average HRT was weakly associated with methylmercury (beta (SE) for a ten-fold increase in exposure,(3.41 (2.06)), was strongly for the 3-to-6 min interval (6.10 (2.18)), and the strongest during 7-10 min after test initiation (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger tapping speed were included in the models as covariates. Postnatal methylmercury exposures did not affect the outcomes. Thus, these findings suggest that sustained attention as a neuropsychological domain is particularly vulnerable to developmental methylmercury exposure, indicating probable underlying dysfunction of the frontal lobes. When using CPT data as a possible measure of neurotoxicity, test results should therefore be analyzed in regard to time from test initiation and not as overall average reaction times.

OBJECTIVE: The present study examined how sleep duration and sleep quality are associated with cognitive performance in 8-year-old children using standardized neurocognitive tests. METHODS: Two hundred ninety children aged 7.4-8.8years participated in the study. Sleep duration and quality were measured using actigraphs and the Sleep Disturbance Scale for Parents. Cognitive performance was measured using four subtests of the Wechsler Intelligence Scale for Children III, the Beery Developmental Test of Visual-Motor Integration (VMI), and the Narrative memory subtest of the Developmental Neuropsychological Assessment for Children. RESULTS: When adjusting for age, sex, and maternal education, shorter sleep duration, but not sleep quality, was associated with lower visuospatial abilities (p-values 0.043). Sleep duration and quality were not associated with verbal abilities (p-values0.18). With regard to the individual test results, shorter sleep duration was associated with worse performance in Visual-Motor Integration (p=0.028), and when excluding children with high depression scores the same was also true with Block Design (p-values0.047). Moreover, poor sleep efficiency was associated with worse performance in Similarities (p=0.004). CONCLUSIONS: In a community sample of 8-year-old children, those who slept less or had poorer sleep quality had lower test scores in cognitive tasks, particularly those pertaining to visuospatial performance, although the association was not very strong.

Overexposure to glucocorticoids may link prenatal adversity with detrimental outcomes in later life. Glycyrrhiza, a natural constituent of licorice, inhibits placental 11-beta-hydroxysteroid dehydrogenase type 2, the feto-placental "barrier" to higher maternal levels of cortisol. The authors studied whether prenatal exposure to glycyrrhiza in licorice exerts detrimental effects on cognitive performance (subtests of the Wechsler Intelligence Scale for Children III as well as the Children's Developmental Neuropsychological Assessment and the Beery Developmental Test of Visual-Motor Integration) and psychiatric symptoms (Child Behavior Checklist) in 321 Finnish children 8.1 years of age born in 1998 as healthy singletons at 35-42 weeks of gestation. In comparison to the group with zero-low glycyrrhiza exposure (0-249 mg/week), those with high exposure (>/=500 mg/week) had significant decrements in verbal and visuospatial abilities and in narrative memory (range of mean differences in standard deviation units,-0.31 to -0.41; P < 0.05) and significant increases in externalizing symptoms and in attention, rule-breaking, and aggression problems (range of odds ratios, 2.15 to 3.43; P < 0.05). The effects on cognitive performance appeared dose related. Data are compatible with adverse fetal "programming" by overexposure to glucocorticoids and caution against excessive intake of licorice-containing foodstuffs during pregnancy.

Kyttälä, M., Aunio, P.& Hautamäki, J.(2009). Working memory resources in young children with mathematical difficulties. Scandinavian Journal of Psychology.Working memory (WM)(Baddeley, 1986, 1997) is argued to be one of the most important cognitive resources underlying mathematical competence (Geary, 2004). Research has established close links between WM deficits and mathematical difficulties. This study investigated the possible deficits in WM, language and fluid intelligence that seem to characterize 4- to 6-year-old children with poor early mathematical skills before formal mathematics education. Children with early mathematical difficulties showed poor performance in both verbal and visuospatial WM tasks as well as on language tests and a fluid intelligence test indicating a thoroughly lower cognitive base. Poor WM performance was not moderated by fluid intelligence, but the extent of WM deficits was related to language skills. The educational implications are discussed.

The aim of this study was to clarify which cognitive mechanisms underlie Trail Making Test (TMT) direct and derived scores. A comprehensive review of the literature on the topic was carried out to clarify which cognitive factors had been related to TMT performance. Following the review, we explored the relative contribution from working memory, inhibition/interference control, task-switching ability, and visuomotor speed to TMT performance. Forty-one healthy old subjects participated in the study and performed a battery of neuropsychological tests including the TMT, the Digit Symbol subtest [Wechsler Adult Intelligence Scale (Third Version)(WAIS-III)], a Finger Tapping Test, the Digits Forward and Backward subtests (WAIS-III), Stroop Test, and a task-switching paradigm inspired in the Wisconsin Card Sorting Test. Correlation and regression analyses were used in order to clarify the joint and unique contributions from different cognitive factors to the prediction of TMT scores. The results suggest that TMT-A requires mainly visuoperceptual abilities, TMT-B reflects primarily working memory and secondarily task-switching ability, while B-A minimizes visuoperceptual and working memory demands, providing a relatively pure indicator of executive control abilities.