Background Fluoride from dietary and environmental sources may concentrate in calcium-containing ... more Background Fluoride from dietary and environmental sources may concentrate in calcium-containing regions of the body such as the pineal gland. The pineal gland synthesizes melatonin, a hormone that regulates the sleep-wake cycle. We examined associations between fluoride exposure and sleep outcomes among older adolescents and adults in Canada. Methods We used population-based data from Cycle 3 (2012–2013) of the Canadian Health Measures Survey. Participants were aged 16 to 79 years and 32% lived in communities supplied with fluoridated municipal water. Urinary fluoride concentrations were measured in spot samples and adjusted for specific gravity (UFSG; n = 1303) and water fluoride concentrations were measured in tap water samples among those who reported drinking tap water (n = 1016). We used multinomial and ordered logistic regression analyses (using both unweighted and survey-weighted data) to examine associations of fluoride exposure with self-reported sleep outcomes, including ...
INTRODUCTION Myelin oligodendrocyte glycoprotein antibodies are identified in approximately 30-50... more INTRODUCTION Myelin oligodendrocyte glycoprotein antibodies are identified in approximately 30-50% of youth with pediatric-onset acquired demyelinating syndromes. Little is known about the cognitive sequelae of relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with onset in childhood or adolescence.Overall, adults had 41% more risk than children to relapse over the whole disease course Overall, adults had 41% more risk than children to relapse over the whole disease course OBJECTIVE: To compare cognitive performance in participants with pediatric-onset relapsing MOGAD, pediatric-onset multiple sclerosis (POMS), and age-matched healthy controls. METHODS The Penn Computerized Neurocognitive Battery (PCNB) was administered to 12 individuals with relapsing MOGAD (age = 16.3 ± 4.8 years; 75% female; disease duration = 8.1 ± 2.7 years), 68 individuals with POMS (age = 18.3 ± 4.0 years; 72% female; disease duration = 3.8 ± 3.9 years), and 108 healthy controls (age = 17.0 ± 4.9 years; 68.5% female). Accuracy was assessed on four domains: Executive Function, Episodic Memory, Complex Cognition, Social Cognition; and overall response time (RT) and RT across three factors (i.e., Time Constrained, Open-Window, Memory). Global performance was determined by a composite score. Multiple linear regression was used to examine group differences on PCNB domain and factor z-scores, controlling for age and sex. We also covaried disease duration for relapsing MOGAD vs. POMS analyses. RESULTS Relative to healthy controls, relapsing MOGAD participants were less accurate on the Complex Cognition domain (B=-0.28, SE=0.11, p=.02), and had slower overall response time (B=-0.16, SE=0.07, p=.02). Relative to POMS, relapsing MOGAD participants were more accurate on the Executive Function domain (B = 0.70, SE=0.30, p=.02) and on the battery overall (B = 0.41, SE=0.18, p=.02). Relative to controls, overall PCNB score was significantly lower in the POMS group (B=-0.28, SE=0.06, p<.001) whereas the relapsing MOGAD participants did not differ from controls (p=.06) on the overall PCNB score. CONCLUSIONS The relapsing MOGAD group demonstrated reduced reasoning skills and slower overall response time, relative to controls. A broad pattern of deficits was observed among POMS participants relative to controls. Overall, cognitive difficulties in the MOGAD group were milder relative to the POMS group.
Long-term cognitive deficits have been observed in some children who experience an acquired demye... more Long-term cognitive deficits have been observed in some children who experience an acquired demyelinating syndrome (ADS). We examined changes in cognitive functioning over the first two years following incident ADS andtested whether normalized brain and thalamic volume accounted for decline over time. Twenty-five youth (mean age 12.8 years) with ADS, 9 of whom were diagnosed with multiple sclerosis (MS) and 16 of whom experienced monophasic ADS (monoADS), underwent two neuropsychological evaluationsand MRI scans at approximately6- and 24-months post ADS-onset. We examined changes in cognitive outcomes over time and between patient groups. Generalized linear mixed-effect regression models were used to examine the association of normalized brain and thalamic volumesbetween the two timepointswith cognitive z-scores. Cognitive performance was within the age-expected range for both groups and remained stable over time on 15 measures. In the combined sample of monoADS and MS patients, declines (p < .05) were noted on the Symbol Digit Modalities Test (SDMT), the Auditory Working Memory (AWM), and the WJ-III Visual Matching (VisMat)tests, but did not survive FDR correction. Clinically significant declines, as measured by the Reliable Change Index, were observed on the SDMT,AWM, and VisMattests by 19, 42, and 32%, respectively. Lower normalized brain volume at 6-months predicted a negative change in SDMT (B = 0.45, 95%CI: 0.07,0.83) and AWM (B = 0.30, 95%CI: 0.13, 0.47). Chronicity of demyelination is not required for cognitive decline nor for reduced brain volume, suggesting that even a single demyelinating event may negatively impact cognitive potential in children.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
INTRODUCTION: Epidemiologic and animal-based studies have raised concerns about the potential neu... more INTRODUCTION: Epidemiologic and animal-based studies have raised concerns about the potential neurotoxicity of fluoride exposure as manifested by deficits in IQ and problems with attention. To date...
OBJECTIVE We evaluated performance on the Penn Computerized Neurocognitive Battery (PCNB), a tool... more OBJECTIVE We evaluated performance on the Penn Computerized Neurocognitive Battery (PCNB), a tool assessing accuracy and response time across four cognitive domains, alongside the Symbol Digit Modalities Test (SDMT), a measure of processing speed commonly used in MS. We determined whether performance decrements are more likely to be detected on measures of accuracy versus response time in pediatric-onset multiple sclerosis (POMS). METHODS Performance on the SDMT, accuracy on PCNB tests belonging to four domains (executive function, episodic memory, complex cognition, social cognition), and response time on the PCNB were compared for 65 POMS patients (age range: 8-29 years) and 76 healthy controls (HCs) by ANCOVA. Associations between the Overall PCNB score and SDMT were examined for both groups, and their agreement in classifying impairment was assessed using Cohen's kappa. RESULTS POMS patients (age at testing = 18.3 ± 4.0 years; age at POMS onset = 14.9 ± 2.3 years) demonstrated reduced accuracy relative to HCs on tests of working memory, attention/inhibition, verbal memory, and visuospatial processing, after adjusting for response time (p ≤ .002). Patients demonstrated slower overall response time on the PCNB (p = .003), while group differences on the SDMT did not meet significance (p = .03). Performance on the PCNB and SDMT were correlated (MS: r = 0.43, HC: r = 0.50, both p < .001), however, the degree of agreement for impairment was minimal (k = 0.22, p = .14). CONCLUSION Specific cognitive deficits exist independently of slowed information processing speed in POMS, and may represent more significant areas of dysfunction. Delineation of accuracy and response time in neuropsychological assessment is important to identify areas of cognitive deficit in POMS. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Purpose of Review-A growing body of evidence suggests adverse neurodevelopmental effects of early... more Purpose of Review-A growing body of evidence suggests adverse neurodevelopmental effects of early-life exposure to fluoride that may differ depending on timing of exposure and sex of the exposed. We conducted a literature search to identify the animal and human epidemiologic studies that examined sex-specific neurodevelopmental differences in response to prenatal and postnatal exposure to fluoride. Recent Findings-Six of 138 animal studies and 15 of 106 human epidemiologic studies tested for sex-specific effects. Prenatal exposure to fluoride was associated with a male susceptibility to adverse behavioural effects in four of six animal studies and lower IQ in one of three prospective cohort studies. The body of evidence examining sex-effects associated with postnatal fluoride exposure was scarce, and many animal and cross-sectional human studies were considered to have a high risk of bias. Summary-Compared to females, male offspring appear to be more sensitive to prenatal, but not postnatal, exposure to fluoride. We discuss several sex-specific mechanisms and emphasize the need for future research.
As a safe exposure level for fluoride in pregnancy has not been established, we used data from tw... more As a safe exposure level for fluoride in pregnancy has not been established, we used data from two prospective studies for benchmark dose modeling. We included mother-child pairs from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort in Mexico and the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort in Canada. Children were assessed for IQ at age 4 (n=211) and between 6 and 12 years (n=287) in the ELEMENT cohort and between ages 3 and 4 years (n=512) in the MIREC cohort. We calculated covariate-adjusted regression coefficients and their standard errors to explore the concentration-effect function for maternal urinary fluoride with children’s IQ, including possible sex-dependence. Assuming a benchmark response of 1 IQ point, we derived benchmark concentrations (BMCs) of maternal urinary fluoride and benchmark concentration levels (BMCLs). No deviation from linearity was detected from the results of the two studies. Using a linear slope, ...
Many women of childbearing age are exposed to reproductive toxicants in the workplace. This artic... more Many women of childbearing age are exposed to reproductive toxicants in the workplace. This article highlights the need for an evaluation of current occupational exposure guidelines for pregnant women working with hazardous agents that have the potential of being reproductive toxins. Limited information regarding reproductive risks associated with many chemicals in the workplace presents challenges in the establishment of standards that are 'safe' for vulnerable populations, such as the fetus. The management of these risks must take into consideration the limitations of available knowledge as well as individual risk factors that may amplify the likelihood of adverse outcomes. In 1981, Quebec adopted a policy that provides "precautionary leave" or reassignment of pregnant workers to other jobs if they are exposed to a factor suspected to compromise their health or that of their fetus during pregnancy. The advantages and disadvantages of this approach to managing reproductive hazards are discussed. The existence of a regulatory safety net at the level of the workplace for minimizing the impact of toxicant exposure on reproductive health outcomes is stressed. Management options that can be implemented early to provide added protection when a hazard cannot be reduced or eliminated are recommended.
IMPORTANCE The potential neurotoxicity associated with exposure to fluoride, which has generated ... more IMPORTANCE The potential neurotoxicity associated with exposure to fluoride, which has generated controversy about community water fluoridation, remains unclear. OBJECTIVE To examine the association between fluoride exposure during pregnancy and IQ scores in a prospective birth cohort. DESIGN, SETTING, AND PARTICIPANTS This prospective, multicenter birth cohort study used information from the Maternal-Infant Research on Environmental Chemicals cohort. Children were born between 2008 and 2012; 41% lived in communities supplied with fluoridated municipal water. The study sample included 601 mother-child pairs recruited from 6 major cities in Canada; children were between ages 3 and 4 years at testing. Data were analyzed between March 2017 and January 2019. EXPOSURES Maternal urinary fluoride (MUF SG), adjusted for specific gravity and averaged across 3 trimesters available for 512 pregnant women, as well as self-reported maternal daily fluoride intake from water and beverage consumption available for 400 pregnant women. MAIN OUTCOMES AND MEASURES Children's IQ was assessed at ages 3 to 4 years using the Wechsler Primary and Preschool Scale of Intelligence-III. Multiple linear regression analyses were used to examine covariate-adjusted associations between each fluoride exposure measure and IQ score. RESULTS Of 512 mother-child pairs, the mean (SD) age for enrollment for mothers was 32.3 (5.1) years, 463 (90%) were white, and 264 children (52%) were female. Data on MUF SG concentrations, IQ scores, and complete covariates were available for 512 mother-child pairs; data on maternal fluoride intake and children's IQ were available for 400 of 601 mother-child pairs. Women living in areas with fluoridated tap water (n = 141) compared with nonfluoridated water (n = 228) had significantly higher mean (SD) MUF SG concentrations (0.69 [0.42] mg/L vs 0.40 [0.27] mg/L; P = .001; to convert to millimoles per liter, multiply by 0.05263) and fluoride intake levels (0.93 [0.43] vs 0.30 [0.26] mg of fluoride per day; P = .001). Children had mean (SD) Full Scale IQ scores of 107.16 (13.26), range 52-143, with girls showing significantly higher mean (SD) scores than boys: 109.56 (11.96) vs 104.61 (14.09); P = .001. There was a significant interaction (P = .02) between child sex and MUF SG (6.89; 95% CI, 0.96-12.82) indicating a differential association between boys and girls. A 1-mg/L increase in MUF SG was associated with a 4.49-point lower IQ score (95% CI, −8.38 to −0.60) in boys, but there was no statistically significant association with IQ scores in girls (B = 2.40; 95% CI, −2.53 to 7.33). A 1-mg higher daily intake of fluoride among pregnant women was associated with a 3.66 lower IQ score (95% CI, −7.16 to −0.14) in boys and girls. CONCLUSIONS AND RELEVANCE In this study, maternal exposure to higher levels of fluoride during pregnancy was associated with lower IQ scores in children aged 3 to 4 years. These findings indicate the possible need to reduce fluoride intake during pregnancy.
Synopses are brief descriptions of original research articles and reviews such as those that appe... more Synopses are brief descriptions of original research articles and reviews such as those that appear in the evidence-based abstraction journals. Synopses may be evaluative, and are generally not written by the authors of the original work. Key messages This article adds to knowledge about the relationship between thyroid stimulating hormone (TSH) levels, urinary iodine and urinary fluoride as found in a representative sample of Canadians from the Canadian Health Measures Survey (CHMS). Public Health Ontario Public Health Ontario is a Crown corporation dedicated to protecting and promoting the health of all Ontarians and reducing inequities in health. Public Health Ontario links public health practitioners, frontline health workers and researchers to the best scientific intelligence and knowledge from around the world. For more information about PHO, visit publichealthontario.ca. Public Health Ontario acknowledges the financial support of the Ontario Government.
Huntington disease (HD) is associated with a variety of cognitive deficits, with prominent diffic... more Huntington disease (HD) is associated with a variety of cognitive deficits, with prominent difficulties in working memory (WM). WM deficits are notably compromised in early-onset and prodromal HD patients. This study aimed to determine the feasibility of a computerized WM training program (Cogmed QM), novel to the HD population. Nine patients, aged 26-62, with early stage HD underwent a 25-session (5 days/week for 5 weeks) WM training program (Cogmed QM). Training exercises involved the manipulation and storage of verbal and visuospatial information, with difficulty adapted as a function of individual performance. Neuropsychological testing was conducted before and after training, and performance on criterion WM measures (Digit Span and Spatial Span), near-transfer WM measures (Symbol Span and Auditory WM), and control measures were evaluated. Post-training interviews about patient experience were thematically analyzed using NVivo software. Seven of nine patients demonstrated adhere...
Journal of Neurology, Neurosurgery & Psychiatry, 2016
randomised. Three individuals in the intervention group were withdrawn within the first month due... more randomised. Three individuals in the intervention group were withdrawn within the first month due to concomitant medical conditions, resulting in 14 participants in intervention and 15 in control groups. There were two AEs in the intervention group, both related to previous medical conditions, and there were two SAEs, both in the control group. The intervention group had statistically significantly better fitness (predicted VO2 max difference: 493.3 ml.min-1, 95% CI: [97.1, 887.6]), lower UHDRS mMS (difference 2.9 points, 95% [À5.42, À0.32]) and lower weight at Week 13 (difference 2.25 kg, 95% CI: [À4.47, À0.03]). Conclusions This study demonstrates that a short-term exercise intervention is safe and feasible. Individuals with HD may benefit from structured exercise, and intensity, monitoring and support may be key factors in optimising response. Larger scale trials are now required to fully elucidate the extended clinical potential of exercise in HD. This trial was funded by The Jacques and Gloria Gossweiler Foundation.
Journal of the International Neuropsychological Society, 2016
Objectives:The aim of this study was to describe cognitive, academic, and psychosocial outcomes a... more Objectives:The aim of this study was to describe cognitive, academic, and psychosocial outcomes after an incident demyelinating event (acquired demyelinating syndromes, ADS) in childhood and to investigate the contribution of brain lesions and confirmed MS diagnosis on outcome.Methods:Thirty-six patients with ADS (mean age=12.2 years,SD=2.7, range: 7–16 years) underwent brain MRI scans at presentation and at 6-months follow-up. T2-weighted lesions on MRI were assessed using a binary classification. At 6-months follow-up, patients underwent neuropsychological evaluation and were compared with 42 healthy controls.Results:Cognitive, academic, and behavioral outcomes did not differ between the patients with ADS and controls. Three of 36 patients (8.3%) were identified with cognitive impairment, as determined by performance falling ≤1.5SDbelow normative values on more than four independent tests in the battery. Poor performance on a visuomotor integration task was most common, observed a...
Background Fluoride from dietary and environmental sources may concentrate in calcium-containing ... more Background Fluoride from dietary and environmental sources may concentrate in calcium-containing regions of the body such as the pineal gland. The pineal gland synthesizes melatonin, a hormone that regulates the sleep-wake cycle. We examined associations between fluoride exposure and sleep outcomes among older adolescents and adults in Canada. Methods We used population-based data from Cycle 3 (2012–2013) of the Canadian Health Measures Survey. Participants were aged 16 to 79 years and 32% lived in communities supplied with fluoridated municipal water. Urinary fluoride concentrations were measured in spot samples and adjusted for specific gravity (UFSG; n = 1303) and water fluoride concentrations were measured in tap water samples among those who reported drinking tap water (n = 1016). We used multinomial and ordered logistic regression analyses (using both unweighted and survey-weighted data) to examine associations of fluoride exposure with self-reported sleep outcomes, including ...
INTRODUCTION Myelin oligodendrocyte glycoprotein antibodies are identified in approximately 30-50... more INTRODUCTION Myelin oligodendrocyte glycoprotein antibodies are identified in approximately 30-50% of youth with pediatric-onset acquired demyelinating syndromes. Little is known about the cognitive sequelae of relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with onset in childhood or adolescence.Overall, adults had 41% more risk than children to relapse over the whole disease course Overall, adults had 41% more risk than children to relapse over the whole disease course OBJECTIVE: To compare cognitive performance in participants with pediatric-onset relapsing MOGAD, pediatric-onset multiple sclerosis (POMS), and age-matched healthy controls. METHODS The Penn Computerized Neurocognitive Battery (PCNB) was administered to 12 individuals with relapsing MOGAD (age = 16.3 ± 4.8 years; 75% female; disease duration = 8.1 ± 2.7 years), 68 individuals with POMS (age = 18.3 ± 4.0 years; 72% female; disease duration = 3.8 ± 3.9 years), and 108 healthy controls (age = 17.0 ± 4.9 years; 68.5% female). Accuracy was assessed on four domains: Executive Function, Episodic Memory, Complex Cognition, Social Cognition; and overall response time (RT) and RT across three factors (i.e., Time Constrained, Open-Window, Memory). Global performance was determined by a composite score. Multiple linear regression was used to examine group differences on PCNB domain and factor z-scores, controlling for age and sex. We also covaried disease duration for relapsing MOGAD vs. POMS analyses. RESULTS Relative to healthy controls, relapsing MOGAD participants were less accurate on the Complex Cognition domain (B=-0.28, SE=0.11, p=.02), and had slower overall response time (B=-0.16, SE=0.07, p=.02). Relative to POMS, relapsing MOGAD participants were more accurate on the Executive Function domain (B = 0.70, SE=0.30, p=.02) and on the battery overall (B = 0.41, SE=0.18, p=.02). Relative to controls, overall PCNB score was significantly lower in the POMS group (B=-0.28, SE=0.06, p<.001) whereas the relapsing MOGAD participants did not differ from controls (p=.06) on the overall PCNB score. CONCLUSIONS The relapsing MOGAD group demonstrated reduced reasoning skills and slower overall response time, relative to controls. A broad pattern of deficits was observed among POMS participants relative to controls. Overall, cognitive difficulties in the MOGAD group were milder relative to the POMS group.
Long-term cognitive deficits have been observed in some children who experience an acquired demye... more Long-term cognitive deficits have been observed in some children who experience an acquired demyelinating syndrome (ADS). We examined changes in cognitive functioning over the first two years following incident ADS andtested whether normalized brain and thalamic volume accounted for decline over time. Twenty-five youth (mean age 12.8 years) with ADS, 9 of whom were diagnosed with multiple sclerosis (MS) and 16 of whom experienced monophasic ADS (monoADS), underwent two neuropsychological evaluationsand MRI scans at approximately6- and 24-months post ADS-onset. We examined changes in cognitive outcomes over time and between patient groups. Generalized linear mixed-effect regression models were used to examine the association of normalized brain and thalamic volumesbetween the two timepointswith cognitive z-scores. Cognitive performance was within the age-expected range for both groups and remained stable over time on 15 measures. In the combined sample of monoADS and MS patients, declines (p < .05) were noted on the Symbol Digit Modalities Test (SDMT), the Auditory Working Memory (AWM), and the WJ-III Visual Matching (VisMat)tests, but did not survive FDR correction. Clinically significant declines, as measured by the Reliable Change Index, were observed on the SDMT,AWM, and VisMattests by 19, 42, and 32%, respectively. Lower normalized brain volume at 6-months predicted a negative change in SDMT (B = 0.45, 95%CI: 0.07,0.83) and AWM (B = 0.30, 95%CI: 0.13, 0.47). Chronicity of demyelination is not required for cognitive decline nor for reduced brain volume, suggesting that even a single demyelinating event may negatively impact cognitive potential in children.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
INTRODUCTION: Epidemiologic and animal-based studies have raised concerns about the potential neu... more INTRODUCTION: Epidemiologic and animal-based studies have raised concerns about the potential neurotoxicity of fluoride exposure as manifested by deficits in IQ and problems with attention. To date...
OBJECTIVE We evaluated performance on the Penn Computerized Neurocognitive Battery (PCNB), a tool... more OBJECTIVE We evaluated performance on the Penn Computerized Neurocognitive Battery (PCNB), a tool assessing accuracy and response time across four cognitive domains, alongside the Symbol Digit Modalities Test (SDMT), a measure of processing speed commonly used in MS. We determined whether performance decrements are more likely to be detected on measures of accuracy versus response time in pediatric-onset multiple sclerosis (POMS). METHODS Performance on the SDMT, accuracy on PCNB tests belonging to four domains (executive function, episodic memory, complex cognition, social cognition), and response time on the PCNB were compared for 65 POMS patients (age range: 8-29 years) and 76 healthy controls (HCs) by ANCOVA. Associations between the Overall PCNB score and SDMT were examined for both groups, and their agreement in classifying impairment was assessed using Cohen's kappa. RESULTS POMS patients (age at testing = 18.3 ± 4.0 years; age at POMS onset = 14.9 ± 2.3 years) demonstrated reduced accuracy relative to HCs on tests of working memory, attention/inhibition, verbal memory, and visuospatial processing, after adjusting for response time (p ≤ .002). Patients demonstrated slower overall response time on the PCNB (p = .003), while group differences on the SDMT did not meet significance (p = .03). Performance on the PCNB and SDMT were correlated (MS: r = 0.43, HC: r = 0.50, both p < .001), however, the degree of agreement for impairment was minimal (k = 0.22, p = .14). CONCLUSION Specific cognitive deficits exist independently of slowed information processing speed in POMS, and may represent more significant areas of dysfunction. Delineation of accuracy and response time in neuropsychological assessment is important to identify areas of cognitive deficit in POMS. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Purpose of Review-A growing body of evidence suggests adverse neurodevelopmental effects of early... more Purpose of Review-A growing body of evidence suggests adverse neurodevelopmental effects of early-life exposure to fluoride that may differ depending on timing of exposure and sex of the exposed. We conducted a literature search to identify the animal and human epidemiologic studies that examined sex-specific neurodevelopmental differences in response to prenatal and postnatal exposure to fluoride. Recent Findings-Six of 138 animal studies and 15 of 106 human epidemiologic studies tested for sex-specific effects. Prenatal exposure to fluoride was associated with a male susceptibility to adverse behavioural effects in four of six animal studies and lower IQ in one of three prospective cohort studies. The body of evidence examining sex-effects associated with postnatal fluoride exposure was scarce, and many animal and cross-sectional human studies were considered to have a high risk of bias. Summary-Compared to females, male offspring appear to be more sensitive to prenatal, but not postnatal, exposure to fluoride. We discuss several sex-specific mechanisms and emphasize the need for future research.
As a safe exposure level for fluoride in pregnancy has not been established, we used data from tw... more As a safe exposure level for fluoride in pregnancy has not been established, we used data from two prospective studies for benchmark dose modeling. We included mother-child pairs from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort in Mexico and the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort in Canada. Children were assessed for IQ at age 4 (n=211) and between 6 and 12 years (n=287) in the ELEMENT cohort and between ages 3 and 4 years (n=512) in the MIREC cohort. We calculated covariate-adjusted regression coefficients and their standard errors to explore the concentration-effect function for maternal urinary fluoride with children’s IQ, including possible sex-dependence. Assuming a benchmark response of 1 IQ point, we derived benchmark concentrations (BMCs) of maternal urinary fluoride and benchmark concentration levels (BMCLs). No deviation from linearity was detected from the results of the two studies. Using a linear slope, ...
Many women of childbearing age are exposed to reproductive toxicants in the workplace. This artic... more Many women of childbearing age are exposed to reproductive toxicants in the workplace. This article highlights the need for an evaluation of current occupational exposure guidelines for pregnant women working with hazardous agents that have the potential of being reproductive toxins. Limited information regarding reproductive risks associated with many chemicals in the workplace presents challenges in the establishment of standards that are 'safe' for vulnerable populations, such as the fetus. The management of these risks must take into consideration the limitations of available knowledge as well as individual risk factors that may amplify the likelihood of adverse outcomes. In 1981, Quebec adopted a policy that provides "precautionary leave" or reassignment of pregnant workers to other jobs if they are exposed to a factor suspected to compromise their health or that of their fetus during pregnancy. The advantages and disadvantages of this approach to managing reproductive hazards are discussed. The existence of a regulatory safety net at the level of the workplace for minimizing the impact of toxicant exposure on reproductive health outcomes is stressed. Management options that can be implemented early to provide added protection when a hazard cannot be reduced or eliminated are recommended.
IMPORTANCE The potential neurotoxicity associated with exposure to fluoride, which has generated ... more IMPORTANCE The potential neurotoxicity associated with exposure to fluoride, which has generated controversy about community water fluoridation, remains unclear. OBJECTIVE To examine the association between fluoride exposure during pregnancy and IQ scores in a prospective birth cohort. DESIGN, SETTING, AND PARTICIPANTS This prospective, multicenter birth cohort study used information from the Maternal-Infant Research on Environmental Chemicals cohort. Children were born between 2008 and 2012; 41% lived in communities supplied with fluoridated municipal water. The study sample included 601 mother-child pairs recruited from 6 major cities in Canada; children were between ages 3 and 4 years at testing. Data were analyzed between March 2017 and January 2019. EXPOSURES Maternal urinary fluoride (MUF SG), adjusted for specific gravity and averaged across 3 trimesters available for 512 pregnant women, as well as self-reported maternal daily fluoride intake from water and beverage consumption available for 400 pregnant women. MAIN OUTCOMES AND MEASURES Children's IQ was assessed at ages 3 to 4 years using the Wechsler Primary and Preschool Scale of Intelligence-III. Multiple linear regression analyses were used to examine covariate-adjusted associations between each fluoride exposure measure and IQ score. RESULTS Of 512 mother-child pairs, the mean (SD) age for enrollment for mothers was 32.3 (5.1) years, 463 (90%) were white, and 264 children (52%) were female. Data on MUF SG concentrations, IQ scores, and complete covariates were available for 512 mother-child pairs; data on maternal fluoride intake and children's IQ were available for 400 of 601 mother-child pairs. Women living in areas with fluoridated tap water (n = 141) compared with nonfluoridated water (n = 228) had significantly higher mean (SD) MUF SG concentrations (0.69 [0.42] mg/L vs 0.40 [0.27] mg/L; P = .001; to convert to millimoles per liter, multiply by 0.05263) and fluoride intake levels (0.93 [0.43] vs 0.30 [0.26] mg of fluoride per day; P = .001). Children had mean (SD) Full Scale IQ scores of 107.16 (13.26), range 52-143, with girls showing significantly higher mean (SD) scores than boys: 109.56 (11.96) vs 104.61 (14.09); P = .001. There was a significant interaction (P = .02) between child sex and MUF SG (6.89; 95% CI, 0.96-12.82) indicating a differential association between boys and girls. A 1-mg/L increase in MUF SG was associated with a 4.49-point lower IQ score (95% CI, −8.38 to −0.60) in boys, but there was no statistically significant association with IQ scores in girls (B = 2.40; 95% CI, −2.53 to 7.33). A 1-mg higher daily intake of fluoride among pregnant women was associated with a 3.66 lower IQ score (95% CI, −7.16 to −0.14) in boys and girls. CONCLUSIONS AND RELEVANCE In this study, maternal exposure to higher levels of fluoride during pregnancy was associated with lower IQ scores in children aged 3 to 4 years. These findings indicate the possible need to reduce fluoride intake during pregnancy.
Synopses are brief descriptions of original research articles and reviews such as those that appe... more Synopses are brief descriptions of original research articles and reviews such as those that appear in the evidence-based abstraction journals. Synopses may be evaluative, and are generally not written by the authors of the original work. Key messages This article adds to knowledge about the relationship between thyroid stimulating hormone (TSH) levels, urinary iodine and urinary fluoride as found in a representative sample of Canadians from the Canadian Health Measures Survey (CHMS). Public Health Ontario Public Health Ontario is a Crown corporation dedicated to protecting and promoting the health of all Ontarians and reducing inequities in health. Public Health Ontario links public health practitioners, frontline health workers and researchers to the best scientific intelligence and knowledge from around the world. For more information about PHO, visit publichealthontario.ca. Public Health Ontario acknowledges the financial support of the Ontario Government.
Huntington disease (HD) is associated with a variety of cognitive deficits, with prominent diffic... more Huntington disease (HD) is associated with a variety of cognitive deficits, with prominent difficulties in working memory (WM). WM deficits are notably compromised in early-onset and prodromal HD patients. This study aimed to determine the feasibility of a computerized WM training program (Cogmed QM), novel to the HD population. Nine patients, aged 26-62, with early stage HD underwent a 25-session (5 days/week for 5 weeks) WM training program (Cogmed QM). Training exercises involved the manipulation and storage of verbal and visuospatial information, with difficulty adapted as a function of individual performance. Neuropsychological testing was conducted before and after training, and performance on criterion WM measures (Digit Span and Spatial Span), near-transfer WM measures (Symbol Span and Auditory WM), and control measures were evaluated. Post-training interviews about patient experience were thematically analyzed using NVivo software. Seven of nine patients demonstrated adhere...
Journal of Neurology, Neurosurgery & Psychiatry, 2016
randomised. Three individuals in the intervention group were withdrawn within the first month due... more randomised. Three individuals in the intervention group were withdrawn within the first month due to concomitant medical conditions, resulting in 14 participants in intervention and 15 in control groups. There were two AEs in the intervention group, both related to previous medical conditions, and there were two SAEs, both in the control group. The intervention group had statistically significantly better fitness (predicted VO2 max difference: 493.3 ml.min-1, 95% CI: [97.1, 887.6]), lower UHDRS mMS (difference 2.9 points, 95% [À5.42, À0.32]) and lower weight at Week 13 (difference 2.25 kg, 95% CI: [À4.47, À0.03]). Conclusions This study demonstrates that a short-term exercise intervention is safe and feasible. Individuals with HD may benefit from structured exercise, and intensity, monitoring and support may be key factors in optimising response. Larger scale trials are now required to fully elucidate the extended clinical potential of exercise in HD. This trial was funded by The Jacques and Gloria Gossweiler Foundation.
Journal of the International Neuropsychological Society, 2016
Objectives:The aim of this study was to describe cognitive, academic, and psychosocial outcomes a... more Objectives:The aim of this study was to describe cognitive, academic, and psychosocial outcomes after an incident demyelinating event (acquired demyelinating syndromes, ADS) in childhood and to investigate the contribution of brain lesions and confirmed MS diagnosis on outcome.Methods:Thirty-six patients with ADS (mean age=12.2 years,SD=2.7, range: 7–16 years) underwent brain MRI scans at presentation and at 6-months follow-up. T2-weighted lesions on MRI were assessed using a binary classification. At 6-months follow-up, patients underwent neuropsychological evaluation and were compared with 42 healthy controls.Results:Cognitive, academic, and behavioral outcomes did not differ between the patients with ADS and controls. Three of 36 patients (8.3%) were identified with cognitive impairment, as determined by performance falling ≤1.5SDbelow normative values on more than four independent tests in the battery. Poor performance on a visuomotor integration task was most common, observed a...
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Papers by Christine Till