Prenatal Fluoride Exposure and Neurodevelopmental Outcomes in a National Birth Cohort

Background: The potential neurotoxicity of exposure to fluoride, which has sparked controversy about community water fluoridation, is poorly understood. Objective: To test the association between prenatal fluoride exposure and childhood IQ in 512 Canadian mother-child pairs. Methods: We measured fetal exposure to fluoride using: (a) maternal urinary fluoride (MUF) during pregnancy; (b) fluoride concentration in water; and (c) fluoride intake estimated from beverage consumption. We evaluated childrens IQ using the Wechsler Primary and Preschool Scale of Intelligence-III. Multiple linear regression analyses examined covariate-adjusted associations between fluoride predictors and IQ. Results: Higher MUF levels predicted lower IQ in males (B=-4.49, p=.02) but not females. Higher levels of water fluoride and fluoride intake predicted a main effect of diminished IQ. Conclusion: Exposure to fluoride during fetal development is associated with lower IQ scores. These findings, which suggest that fluoride is neurotoxic, underscore the need to critically evaluate the practice of water fluoridation

Using History in Public Policy Development

This thesis addresses two key problems: that historical practice in the academy is largely disengaged from politics as a domain of public purpose and that policymaking remains fixed on a very narrow (and quantitative) definition of evidence, although the “policy-relevant” disciplines have not proved able to solve long-standing policy issues. It inspects both phenomena with the aim of describing the space in which the two problems can be brought into a workable accommodation. The argument is made that public policy should be regarded as an important concern of academic history, and policymakers themselves as people with legitimate interests that historians should take seriously. Public history provides a helpful framework and set of concerns to work with in this respect. Given that the social and natural sciences have not been able to solve the pressing policy problems with which governments are faced, a certain obligation may be claimed for historians to reconsider their stance. The re-connection of history and policy – the nineteenth-century discipline clearly discerned a public-political purpose for history – requires attention to be given to articulating and demonstrating the distinctive cognitive tools of the historian and their distinctive value to the policymaking process. The thesis addresses two primary fields, whose interests and professional practices appear divergent such that both the principles and the terms of collaboration are difficult to imagine: academic history and government policymaking. The primary material on which the research draws is accordingly the products of these constituencies: works of historiography and policy documents of various kinds. Also of relevance are commentaries and analyses that address these domains, whether from other disciplines with an interest in political decision-making, from the media or from other organisations with a professional stake, such as think tanks. The originality of the research lies in conceiving of the question of the uses of history for public policy as one of integration of “supply” and “demand” perspectives. It seeks clarity on the distinctive value of historical skills and approaches, but not as an end in itself. Rather, the case is assembled for the affinities between history and policy as processes and hence that the two can be brought into a productive alignment. So, instead of history providing pre-packaged accounts for policy, it can be embedded as a way of thinking and reasoning in policy

Incidence of Anxiety in Patients with Multiple Sclerosis (MS)

Objective: To investigate the (1) incidence of anxiety and (2) association of anxiety with disease duration, depression, and age in an outpatient Multiple Sclerosis (MS) Center. Background: The incidence of anxiety varies in the literature but is estimated to affect 44.5% of people with MS. Anxiety can be a predictor of poor Quality of Life, especially relevant in progressive illnesses, such as MS. Though research has shown that patients newly diagnosed experience higher anxiety levels, the relationship between anxiety and disease duration is unclear. Since anxiety can be comorbid with depression in MS populations, it is relevant to establish its association in this setting. Finally, though anxiety usually increases in older age, research for this relationship in MS populations is inconclusive. Design/Methods: The commonly used Hospital Anxiety and Depression Scale, was distributed once to patients with MS over a 3 month period to assess anxiety and depression scores. MS disease duration and age were confirmed by neurologists. Results: Out of 160 patients with MS who completed the HADS, 19% reported abnormal anxiety, 14% reported borderline cases of anxiety, and 67% did not report anxiety. After following up on significant correlations, depression and younger age were related to higher anxiety levels, (R2=.35, F(4,144)=19.26, p<0.001). The standardized partial regression coefficients indicated 2 statistically significant predictors, depression (β=.55, p=<.001) and age (β=-.25, p=<.001). Discussion: 33% of patients reported symptoms of anxiety, emphasizing the need to focus on treating anxiety, specifically, early in their disease course. Clinicians may also want to recognize that elevated depression scores predicted anxiety. Lastly, in our cohort, the younger population reported higher anxiety, demonstrating that progressive illnesses may affect anxiety levels in younger populations more. Since approximately one third of patients with MS expressed anxiety symptoms, it is important to incorporate this into treatment plans

Prenatal fluoride exposure and attention deficit hyperactivity disorder (ADHD) symptoms in children at 6–12 years of age in Mexico City

Background Epidemiologic and animal-based studies have raised concern over the potential impact of fluoride exposure on neurobehavioral development as manifested by lower IQ and deficits in attention. To date, no prospective epidemiologic studies have examined the effects of prenatal fluoride exposure on behavioral outcomes using fluoride biomarkers and sensitive measures of attention. Objective We aimed to examine the association between prenatal fluoride exposure and symptoms associated with attention-deficit/hyperactivity disorder (ADHD). Method 213 Mexican mother-children pairs of the Early Life Exposures to Environmental Toxicants (ELEMENT) birth cohort study had available maternal urinary samples during pregnancy and child assessments of ADHD-like behaviors at age 6–12. We measured urinary fluoride levels adjusted for creatinine (MUFcr) in spot urine samples collected during pregnancy. The Conners' Rating Scales-Revised (CRS-R) was completed by mothers, and the Conners' Continuous Performance Test (CPT-II) was administered to the children. Results Mean MUFcr was 0.85 mg/L (SD = 0.33) and the Interquartile Range (IQR) was 0.46 mg/L. In multivariable adjusted models using gamma regression, a 0.5 mg/L higher MUFcr (approximately one IQR higher) corresponded with significantly higher scores on the CRS-R for DSM-IV Inattention (2.84 points, 95% CI: 0.84, 4.84) and DSM-IV ADHD Total Index (2.38 points, 95% CI: 0.42, 4.34), as well as the following symptom scales: Cognitive Problems and Inattention (2.54 points, 95% CI: 0.44, 4.63) and ADHD Index (2.47 points; 95% CI: 0.43, 4.50). The shape of the associations suggested a possible celling effect of the exposure. No significant associations were found with outcomes on the CPT-II or on symptom scales assessing hyperactivity. Conclusion Higher levels of fluoride exposure during pregnancy were associated with global measures of ADHD and more symptoms of inattention as measured by the CRS-R in the offspring

Associations between Urinary, Dietary, and Water Fluoride Concentrations among Children in Mexico and Canada

Fluoride, which may be toxic to the developing brain, is added to salt in Mexico and drinking water in Canada to prevent dental caries. We compared childhood urinary fluoride (CUF) concentrations in Mexico City and Canada to characterize patterns of fluoride exposure in these two populations. We also examined associations of CUF with dietary and water fluoride levels in Mexico City and Canada respectively. We included 561 children (ages 4–6; mean age 4.8 years) from the Programming Research in Obesity, Growth, Environment, and Social Stress (PROGRESS) cohort in Mexico City, and 645 children (ages 2–6; mean age 3.7 years) from the Maternal–Infant Research on Environmental Chemicals (MIREC) cohort in Canada. We applied Spearman correlations, T-tests, ANOVA or covariate-adjusted linear regression to examine associations of CUF (mg/L; adjusted for specific gravity) with demographics and dietary or water fluoride concentrations. We used Welch equivalence testing to compare means across cohorts. Mean (SD) CUF was equivalent (t = 4.26, p < 0.001) in PROGRESS: 0.74 (0.42) and fluoridated Canadian communities: 0.66 (0.47), but lower in non-fluoridated Canadian communities: 0.42 (0.31) (t = −6.37, p < 0.001). Water fluoride concentrations were significantly associated with CUF after covariate adjustment for age and sex in MIREC (B = 0.44, 95% CI: 0.30, 0.59, p < 0.001). In contrast, daily food and beverage fluoride intake was not associated with CUF in PROGRESS (p = 0.82). We found that CUF levels are comparable among children in Mexico City and fluoridated Canadian communities, despite distinct sources of exposure. Community water fluoridation is a major source of fluoride exposure for Canadian children

Education effects on cognitive function in a healthy aged Arab population

Abstract Background-The Minimental State Examination (MMSE) has not been validated in Arabic speaking populations. The Brookdale Cognitive Screening Test (BCST) has been developed for use in low schooling populations. We investigated the influence of gender, education and occupation in a cognitively normal community sample assessed with an Arabic translation of the MMSE and the BCST

The Impact of Toxic Chemicals on Neurodevelopment: A Turn Towards Prevention

Exposure to toxic chemicals can adversely impact children’s neurodevelopment. Yet, remarkably few resources are dedicated to preventing these adverse effects. We developed a developmental neurotoxicological knowledge translation (KT) tool, the PRevention of Toxic Chemicals in the Environment for Children Tool (PRoTECT), and evaluated the efficacy of a KT video, Little Things Matter: The Impact of Toxins on the Developing Brain. In study one, PRoTECT was refined via focus groups and implemented with 190 participants of childbearing age for development via exploratory factor analysis. We found evidence for a four-factor model, of which 16 of the 18 items had adequate loadings > 0.40 on a derived factor. In study two, we evaluated responses of 15,594 international participants to validate PRoTECT’s conceptual dimensionality and general response patterns across various demographic characteristics. Seventeen items fit into a three-factor model with factors, or subscales, representing (1) preferences to lower exposure and increase prevention, (2) knowledge of the regulation of toxic chemicals by government and industry, and (3) knowledge of developmental neurotoxicology. Scores on subscales 1 and 3 tended to be higher among participants from India, participants with higher education, and parents and pregnant women, indicating stronger preferences to lower exposure and increase prevention and greater knowledge of developmental neurotoxicology, whereas scores on subscale 2 tended to be higher among participants from the United States, indicating less trust in government and industry. In study three, a randomized controlled trial was conducted, whereby participants were assigned to either watch the KT video (experimental group) or serve in the control group. Scores on PRoTECT and other behavioural items were examined at baseline and six-week follow-up. At baseline, participants in the experimental group showed greater changes in scores on PRoTECT and a greater intent to reduce exposure than the control group, but the differences were much smaller at six-week follow up; no meaningful changes in behaviour were noted. This dissertation addresses KT gaps in developmental neurotoxicology. While we wait for legislation to reduce exposure to toxic chemicals, we must find ways to effectively communicate these risks with the hope of advocating for stricter regulations

Efficacy and tolerability of dimethyl fumarate in White-, African- and Hispanic- Americans with multiple sclerosis

Background: Dimethyl fumarate (DMF) was approved by the US Food and Drug Administration (FDA) for treatment of relapsing–remitting multiple sclerosis (RRMS) based on two phase III randomized clinical trials (RCTs). There were not enough non-White patients enrolled in these RCTs to allow for subgroup analysis based on race. Efficacy and tolerability of DMF therapy across various racial groups is unknown. Methods: Retrospective chart review was performed on all patients with RRMS who were started on DMF in two tertiary multiple sclerosis (MS) clinics. Efficacy and tolerability of DMF was compared across three self-identified racial groups: White-American (WA), African-American (AA) and Hispanic-American (HA). Results: A total of 390 RRMS patients were included in the study: 261 (66.9%) WA, 69 (17.7%) AA and 52 (13.3%) HA. When comparing ‘pre-DMF’ (1 year) and ‘on DMF’ (mean follow up of 14 months) periods, statistically significant reduction in rates of annualized relapses (WA from 0.44 to 0.19, AA from 0.39 to 0.15, and HA from 0.39 to 0.14; no differences between groups), new T2 lesions (WA from 45% to 23%, AA from 39% to 23%, HA from 52% to 26%; no difference between groups), and Gd+ lesions (WA from 25% to 13%, AA from 24% to 7%, HA from 23% to 12%; no difference between groups) were seen. DMF was relatively well tolerated across all groups, with an overall discontinuation rate of 20% (no difference between the three groups). Conclusion: Efficacy of DMF in our clinic population did not differ across three major ethnic groups, WA, AA and HA, and was comparable with results observed in the pivotal studies. These ‘real-life’ data suggest that race is not a factor that needs to be taken into account when initiating DMF

Prenatal fluoride exposure, offspring visual acuity and autonomic nervous system function in 6-month-old infants

Background: Prenatal fluoride exposure can have adverse effects on children’s development; however, associations with visual and cardiac autonomic nervous system functioning are unknown. We examined associations between prenatal fluoride exposure and visual acuity and heart rate variability (HRV) in 6-month-old infants. Methods: We used data from Canadian mother-infant pairs participating in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort. We estimated prenatal fluoride exposure using: i) fluoride concentration in drinking water (mg/L), ii) maternal urinary fluoride adjusted for specific gravity (MUFSG; mg/L) and averaged across pregnancy, and iii) maternal fluoride intake (µg/kg/day) from consumption of water, tea, and coffee, adjusted for maternal body weight (kg). We used multivariable linear regression to examine associations between each measure of fluoride exposure and Teller Acuity Card visual acuity scores (n = 435) and assessed HRV (n = 400) using two measures: root mean square of successive differences (RMSSD) and the standard deviation of N-N intervals (SDNN) measured at 6-months of age. Results: Median (IQR) values for water fluoride, MUFSG, and daily fluoride intake were 0.20 (IQR: 0.13–0.56) mg/L; 0.44 (0.28–0.70) mg/L and 4.82 (2.58–10.83) µg/kg/day, respectively. After adjustment for confounding variables, water fluoride concentration was associated with poorer infant visual acuity (B = -1.51; 95 % CI: −2.14,-0.88) and HRV as indicated by lower RMSSD (B = -1.60; 95 % CI: −2.74,-0.46) but not SDNN. Maternal fluoride intake was also associated with poorer visual acuity (B = -0.82; 95 % CI: −1.35,-0.29) and lower RMSSD (B = -1.22; 95 % CI: −2.15,-0.30). No significant associations were observed between MUFSG and visual acuity or HRV. Conclusion: Fluoride in drinking water was associated with reduced visual acuity and alterations in cardiac autonomic function in infancy, adding to the growing body of evidence suggesting fluoride's developmental neurotoxicity