Dietary fluoride intake during pregnancy and neurodevelopment in toddlers: A prospective study in the progress cohort.

Foods and beverages provide a source of fluoride exposure in Mexico. While high fluoride concentrations are neurotoxic, recent research suggests that exposures within the optimal range may also pose a risk to the developing brain. This prospective study examined whether dietary fluoride intake during pregnancy is associated with toddlers' neurodevelopment in 103 mother-child pairs from the PROGRESS cohort in Mexico City. Food and beverage fluoride intake was assessed in trimesters 2 and 3 using a food frequency questionnaire and Mexican tables of fluoride content. We used the Bayley-III to evaluate cognitive, motor, and language outcomes at 12 and 24 months of age. Adjusted linear regression models were generated for each neurodevelopment assessment time point (12 and 24 months). Mixed-effects models were used to consider a repeated measurement approach. Interactions between maternal fluoride intake and child sex on neurodevelopmental outcomes were tested. Median (IQR) dietary fluoride intake during pregnancy was 1.01 mg/d (0.73, 1.32). Maternal fluoride intake was not associated with cognitive, language, or motor outcomes collapsing across boys and girls. However, child sex modified the association between maternal fluoride intake and cognitive outcome (p interaction term = 0.06). A 0.5 mg/day increase in overall dietary fluoride intake was associated with a 3.50-point lower cognitive outcome in 24-month old boys (95 % CI: -6.58, -0.42); there was no statistical association with girls (ß = 0.07, 95 % CI: -2.37, 2.51), nor on the cognitive outcome at 12-months of age. Averaging across the 12- and 24-month cognitive outcomes using mixed-effects models revealed a similar association: a 0.5 mg/day increase in overall dietary fluoride intake was associated with a 3.46-point lower cognitive outcome in boys (95 % CI: -6.23, -0.70). These findings suggest that the development of nonverbal abilities in males may be more vulnerable to prenatal fluoride exposure than language or motor abilities, even at levels within the recommended intake range.

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 4­6; 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 2­6; mean age 3.7 years) from the Maternal­Infant 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.

Association of water fluoride and urinary fluoride concentrations with attention deficit hyperactivity disorder in Canadian youth.

BACKGROUND: Exposure to fluoride has been linked with increased prevalence of attention deficit hyperactivity disorder (ADHD) in the United States and symptoms of inattention in Mexican children. We examined the association between fluoride exposure and attention outcomes among youth living in Canada. METHOD: We used cross-sectional data collected from youth 6 to 17 years of age from the Canadian Health Measures Survey (Cycles 2 and 3). Urinary fluoride concentration adjusted for specific gravity (UFSG) was available for 1877 participants. Water fluoride concentration measured in tap water samples was available for 980 participants. Community water fluoridation (CWF) status was determined by viewing reports on each city's website or contacting the water treatment plant. We used logistic regression to test the association between the three measures of fluoride exposure and ADHD diagnosis. Linear regression was used to examine the relationship between the three measures of fluoride exposure and the hyperactivity/inattention score on the Strengths and Difficulties Questionnaire (SDQ). RESULTS: UFSG did not significantly predict ADHD diagnosis or hyperactive/inattentive symptoms. A 1 mg/L increase in tap water fluoride level was associated with a 6.1 times higher odds of an ADHD diagnosis (95% CI = 1.60, 22.8). A significant interaction between age and tap water fluoride level (p = .03) indicated a stronger association between tap water fluoride and hyperactivity/inattention symptoms among older youth. A 1 mg/L increase in water fluoride level was associated with a 1.5 SDQ score increase (95% CI: 0.23, 2.68, p = .02) for youth at the 75th percentile of age (14 years old). Similarly, there was a significant interaction between age and CWF. At the 75th percentile of age (14 years old), those living in a fluoridated region had a 0.7-point higher SDQ score (95% CI = 0.34, 1.06, p < .01) and the predicted odds of an ADHD diagnosis was 2.8 times greater compared with youth in a non-fluoridated region (aOR = 2.84, 95% CI: 1.40, 5.76, p < .01). DISCUSSION: Exposure to higher levels of fluoride in tap water is associated with an increased risk of ADHD symptoms and diagnosis of ADHD among Canadian youth, particularly among adolescents. Prospective studies are needed to confirm these results.

Caregiving and infants' neurodevelopment in rural Costa Rica: Results from the Infants' Environmental Health Study (ISA).

Early caregiving is one of the strongest influences on children's development, and among the most significant modifiable environmental factor. The aim of this study was to explore the association between quality of caregiver-infant interactions and neurodevelopment of infants living in banana-growing communities in rural Costa Rica characterized as having environmental toxic exposures. Home visits were conducted with 94 caregiver-infant dyads from the Infants' Environmental Health Study (ISA), living within Matina county, Limón province. One-year infant neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development®, Third Edition (Bayley-III). Quality of caregiver-infant interaction was assessed with a standardized observational task: Nursing Child Assessment Satellite Training Teaching scale (NCATS) at around two years of age. Multiple regression analyses examined associations between components of caregiver-infant interactions and neurodevelopmental outcomes, adjusting for mancozeb and manganese exposure and other potential confounders. Compared to NCATS normative data for U.S. Hispanic mothers, 35% of the sample had overall caregiving interaction scores ≤10th percentile cut-off, indicating less than optimal interactions. Higher quality of caregiver-infant interaction was associated with higher expressive communication ability in infants [ß = 0.03 (95% CI: 0.01, 0.06)], controlling for pesticide exposure and confounders. Aspects of caregiving such as stimulation and growth-fostering of infants were most strongly associated with language outcomes. Results suggest an association between positive caregiving on language development for infants living in a rural agricultural area in Costa Rica, and highlight aspects of caregiving that could be targeted to improve resilience of these children who live in vulnerable conditions.

Assessment of neuropsychological performance in Mexico City youth using the Cambridge Neuropsychological Test Automated Battery (CANTAB).

BACKGROUND: The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a computerized tool used to measure cognitive function in diverse populations and is sensitive for assessing developmental changes in children. Although CANTAB has been used in several countries, its applicability in a Mexican child population is unknown. This study examined developmental trends on CANTAB in a large sample of urban Mexico City youth and tested the hypothesis that their performance would be similar to a large US normative sample. METHOD: As part of a birth cohort, Early Life Exposures in Mexico to Environmental Toxicants, 826 children, ages 5-15 years, completed CANTAB. Subtests measured planning (Stockings of Cambridge; SOC), short-term memory (Delayed Matching to Sample; DMS), sustained attention (Rapid Visual Information Processing; RVP), ability to match visual stimuli (Match to Sample Visual Search; MTS), flexibility (Intra-extra Dimensional Set Shift; IED), and response inhibition (Stop Signal Task; SST). Determinants of performance on the CANTAB, including age, maternal/child IQ, and sex, were analyzed using Spearman correlation and Welch t tests. Equivalence testing compared performance with existing norms. RESULTS: Performance improved with age on all measures. Child IQ was mildly associated with measures of memory and attention but not executive functioning, consistent with US norms. Maternal IQ was not associated with any outcomes, and males performed better on IED. Mexican norms were comparable to US norms on almost all outcomes, with the exception of a short-term visual recognition memory task (DMS). CONCLUSIONS: This study provides the largest normative data for CANTAB performance in a community sample of Mexican youth. Findings demonstrate the expected maturational effects of executive function, specifically in cognitive shifting and inhibition. Levels of executive function performance demonstrated by a Mexican sample were consistent with normative values reported in US youth. These findings, as well as expected associations with child IQ, indicate high applicability of CANTAB for Mexican youth in neurobehavioral studies.

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.

Physical Activity and Its Correlates in Youth with Multiple Sclerosis.

OBJECTIVES: To investigate physical activity levels in youth with multiple sclerosis and monophasic acquired demyelinating syndromes ([mono-ADS], ie, children without relapsing disease) compared with healthy controls and to determine factors that contribute to engagement in physical activity. We hypothesized that greater physical activity goal setting and physical activity self-efficacy would be associated with greater levels of vigorous physical activity in youth with multiple sclerosis. STUDY DESIGN: A total of 68 consecutive patients (27 multiple sclerosis, 41 mono-ADS) and 37 healthy controls completed fatigue, depression, Physical Activity Self-Efficacy Scale, perceived disability, Exercise Goal-Setting scale, and physical activity questionnaires, and wore an accelerometer for 7 days. All patients had no ambulatory limitations (Expanded Disability Status Scale, scores all <4). RESULTS: Youth with multiple sclerosis engaged in fewer minutes per day of vigorous (P = .009) and moderate and vigorous physical activity (P = .048) than did patients with mono-ADS and healthy controls. A lower proportion of the group with multiple sclerosis (63%) reported participating in any strenuous physical activity than the mono-ADS (85%) and healthy control (89%) groups (P = .020). When we adjusted for age and sex, the Physical Activity Self-Efficacy Scale and Exercise Goal-Setting scale were associated positively with vigorous physical activity in the group with multiple sclerosis. Fatigue and depression did not predict physical activity or accelerometry metrics. CONCLUSIONS: Youth with multiple sclerosis participate in less physical activity than their counterparts with mono-ADS and healthy controls. Physical activity self-efficacy and exercise goal setting serve as potentially modifiable correlates of physical activity, and are measures suited to future interventions aimed to increase physical activity in youth with multiple sclerosis.