Browsing by Author "Till, Christine"
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Item ADDENDUM: Critical windows of fluoride neurotoxicity in Canadian Children(Elsevier, 2022) Farmus, Linda; Till, Christine; Green, Rivka; Hornung, Richard; Martinez Mier, E. Angeles; Ayotte, Pierre; Muckle, Gina; Lanphear, Bruce P.; Flora, David B.; Dental Public Health and Dental Informatics, School of DentistryItem Associations between Urinary, Dietary, and Water Fluoride Concentrations among Children in Mexico and Canada(MDPI, 2020-11-08) Green, Rivka; Till, Christine; Cantoral, Alejandra; Lanphear, Bruce; Martinez-Mier, E. Angeles; Ayotte, Pierre; Wright, Robert O.; Tellez-Rojo, Martha M.; Malin, Ashley J.; Cariology, Operative Dentistry and Dental Public Health, School of DentistryFluoride, 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.Item Critical windows of fluoride neurotoxicity in Canadian children(Elsevier, 2021) Farmus, Linda; Till, Christine; Green, Rivka; Hornung, Richard; Martinez Mier, E. Angeles; Ayotte, Pierre; Muckle, Gina; Lanphear, Bruce P.; Flora, David B.; Dental Public Health and Dental Informatics, School of DentistryBackground: Fluoride has been associated with IQ deficits during early brain development, but the period in which children are most sensitive is unknown. Objective: We assessed effects of fluoride on IQ scores across prenatal and postnatal exposure windows. Methods: We used repeated exposures from 596 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals pregnancy and birth cohort. Fluoride was measured in urine (mg/L) collected from women during pregnancy and in their children between 1.9 and 4.4 years; urinary fluoride was adjusted for specific gravity. We estimated infant fluoride exposure (mg/day) using water fluoride concentration and duration of formula-feeding over the first year of life. Intelligence was assessed at 3-4 years using the Wechsler Preschool and Primary Scale of Intelligence-III. We used generalized estimating equations to examine the associations between fluoride exposures and IQ, adjusting for covariates. We report results based on standardized exposures given their varying units of measurement. Results: The association between fluoride and performance IQ (PIQ) significantly differed across prenatal, infancy, and childhood exposure windows collapsing across child sex (p = .001). The strongest association between fluoride and PIQ was during the prenatal window, B = -2.36, 95% CI: -3.63, -1.08; the association was also significant during infancy, B = -2.11, 95% CI: -3.45, -0.76, but weaker in childhood, B = -1.51, 95% CI: -2.90, -0.12. Within sex, the association between fluoride and PIQ significantly differed across the three exposure windows (boys: p = .01; girls: p = .01); among boys, the strongest association was during the prenatal window, B = -3.01, 95% CI: -4.60, -1.42, whereas among girls, the strongest association was during infancy, B = -2.71, 95% CI: -4.59, -0.83. Full-scale IQ estimates were weaker than PIQ estimates for every window. Fluoride was not significantly associated with Verbal IQ across any exposure window. Conclusion: Associations between fluoride exposure and PIQ differed based on timing of exposure. The prenatal window may be critical for boys, whereas infancy may be a critical window for girls.Item Dietary Fluoride Intake during Pregnancy and Neurodevelopment in Toddlers: A Prospective Study in the PROGRESS Cohort(Elsevier, 2021) Cantoral, Alejandra; Téllez-Rojo, Martha M.; Malin, Ashley J.; Schnaas, Lourdes; Osorio-Valencia, Erika; Mercado, Adriana; Martínez-Mier, E. Ángeles; Wright, Robert O.; Till, Christine; Cariology, Operative Dentistry and Dental Public Health, School of DentistryFoods 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 (β = 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.Item Domain-specific effects of prenatal fluoride exposure on child IQ at 4, 5, and 6–12 years in the ELEMENT cohort(Elsevier, 2022) Goodman, Carly V.; Bashash, Morteza; Green, Rivka; Song, Peter; Peterson, Karen E.; Schnaas, Lourdes; Mercado-García, Adriana; Martínez-Medina, Sandra; Hernández-Avila, Mauricio; Martinez-Mier, Angeles; Téllez-Rojo, Martha M.; Hu, Howard; Till, Christine; Dental Public Health and Dental Informatics, School of DentistryObjective: Prenatal exposure to fluoride has been associated with adverse neurodevelopmental outcomes. However, the neuropsychological profile of fluoride's developmental neurotoxicity at low levels and the stability of this relationship across childhood has not been characterized. We investigated the longitudinal and domain specific effect of prenatal fluoride exposure on IQ among children ages 4, 5, and 6-12 years in the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort. Methods: We measured the average of maternal urinary fluoride at each trimester of pregnancy adjusted for creatinine (MUFCRE). Children were administered the McCarthy Scales of Children's Abilities at ages 4 (N = 386) and 5 (N = 308), and the Wechsler Abbreviated Scale of Intelligence at age 6-12 (N = 278). We used generalized estimating equation (GEE) models to estimate the population averaged effect of MUFCRE concentration on longitudinal General Cognitive Index (GCI)/Full-Scale IQ (FSIQ), Verbal IQ (VIQ), and Performance IQ (PIQ) scores (N = 348). We tested for possible interactions between MUFCRE and child sex as well as for MUFCRE and time point on children's IQ. All models controlled for relevant available covariates. Results: The mean/median MUFCRE concentration was 0.90/0.83 mg/L (SD = 0.39; IQR, 0.64-1.11 mg/L). A 0.5 mg/L increase in MUFCRE predicted an average 2.12-point decrease in GCI/FSIQ (95% CI: -3.49, -0.75) and 2.63-point decrease in PIQ (95% CI: -3.87, -1.40). MUFCRE was marginally associated with VIQ across time (B = -1.29, 95% CI: -2.60, 0.01). No interactions between MUFCRE and child sex or MUFCRE and time were observed. Conclusion: The negative association between prenatal fluoride exposure and longitudinal IQ was driven by decrements in non-verbal intelligence (i.e. PIQ), suggesting that visual-spatial and perceptual reasoning abilities may be more impacted by prenatal fluoride exposure as compared to verbal abilities.Item Iodine Status Modifies the Association between Fluoride Exposure in Pregnancy and Preschool Boys' Intelligence(MDPI, 2022-07-16) Goodman, Carly V.; Hall, Meaghan; Green, Rivka; Chevrier, Jonathan; Ayotte, Pierre; Martinez-Mier, Esperanza Angeles; McGuckin, Taylor; Krzeczkowski, John; Flora, David; Hornung, Richard; Lanphear, Bruce; Till, Christine; Cariology, Operative Dentistry and Dental Public Health, School of DentistryIn animal studies, the combination of in utero fluoride exposure and low iodine has greater negative effects on offspring learning and memory than either alone, but this has not been studied in children. We evaluated whether the maternal urinary iodine concentration (MUIC) modifies the association between maternal urinary fluoride (MUF) and boys' and girls' intelligence. We used data from 366 mother-child dyads in the Maternal-Infant Research on Environmental Chemicals Study. We corrected trimester-specific MUF and MUIC for creatinine, and averaged them to yield our exposure variables (MUFCRE, mg/g; MUICCRE, µg/g). We assessed children's full-scale intelligence (FSIQ) at 3 to 4 years. Using multiple linear regression, we estimated a three-way interaction between MUFCRE, MUICCRE, and child sex on FSIQ, controlling for covariates. The MUICCRE by MUFCRE interaction was significant for boys (p = 0.042), but not girls (p = 0.190). For boys whose mothers had low iodine, a 0.5 mg/g increase in MUFCRE was associated with a 4.65-point lower FSIQ score (95% CI: -7.67, -1.62). For boys whose mothers had adequate iodine, a 0.5 mg/g increase in MUFCRE was associated with a 2.95-point lower FSIQ score (95% CI: -4.77, -1.13). These results suggest adequate iodine intake during pregnancy may minimize fluoride's neurotoxicity in boys.Item Maternal fluoride exposure, fertility and birth outcomes: The MIREC cohort(Elsevier, 2022-04) Goodman , Carly; Hall , Meaghan; Green , Rivka; Hornung , Richard; Martinez-Mier , Esperanza Angeles; Lanphear , Bruce; Till, Christine; Dental Public Health and Dental Informatics, School of DentistryObjective Fluoride exposure >1.5 mg/L from water has been associated with adverse pregnancy and birth outcomes. Little is known, however, about the effect of fluoride at levels consistent with water fluoridation (i.e., 0.7 mg/L) on pregnancy and birth outcomes. We examined the relationship between maternal fluoride exposure, fertility, and birth outcomes in a Canadian pregnancy cohort living in areas where municipal drinking water fluoride concentrations ranged from 0.04 to 0.87 mg/L. Methods Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, we estimated fluoride exposure during pregnancy using three different metrics: (1) maternal urinary fluoride concentrations standardized for specific gravity (MUFSG) and averaged across all three trimesters (N = 1566), (2) water fluoride concentration (N = 1370), and (3) fluoride intake based on self-reported consumption of water, coffee, and tea, adjusted for body weight (N = 1192). Data on fertility, birth weight, gestational age, preterm birth, and small-for-gestational age (SGA) were assessed. We used multiple linear regression to examine associations between fluoride exposure, birth weight and gestational age, and logistic regression to examine associations with fertility, preterm birth, and SGA, adjusted for relevant covariates. Results Median (IQR) MUFSG was 0.50 (0.33–0.76) mg/L, median water fluoride was 0.52 (0.17–0.64) mg/L, and median fluoride intake was 0.008 (0.003–0.013) mg/kg/day. MUFSG, water fluoride concentrations, and fluoride intake were not significantly associated with fertility, birth weight, gestational age, preterm birth, or SGA. Fetal sex did not modify any of the associations. Conclusion Fluoride exposure during pregnancy was not associated with fertility or birth outcomes in this Canadian cohort.Item Prenatal fluoride exposure and attention deficit hyperactivity disorder (ADHD) symptoms in children at 6–12 years of age in Mexico City(Elsevier, 2018-12-01) Bashash, Morteza; Marchand, Maelle; Hu, Howard; Till, Christine; Martinez-Mier, E. Angeles; Sanchez, Brisa N.; Basu, Niladri; Peterson, Karen E.; Green, Rivka; Schnaas, Lourdes; Mercado-García, Adriana; Hernández-Avila, Mauricio; Téllez-Rojo, Martha María; Cariology, Operative Dentistry and Dental Public Health, School of DentistryBackground 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.