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Item Blood levels of lead and dental caries in permanent teeth(Wiley, 2020) Yepes, Juan F.; McCormick-Norris, Jayme; Vinson, LaQuia A.; Eckert, George J.; Hu, Howard; Wu, Yue; Jansen, Erica C.; Peterson, Karen E.; Téllez-Rojo, Martha M.; Martinez Mier, Esperanza Angeles; Pediatric Dentistry, School of DentistryObjectives: The purpose of this study was to determine whether there is an association between lead exposure within the ages of 1-4 years and dental caries in the permanent dentition between ages 9-17 among Mexican youth. Methods: Data were collected for the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort from a group of 490 children born and reared in Mexico City. Among ages 1-4 years, blood lead levels were measured in micrograms of lead per deciliter of blood (μg/dL) and the presence of caries in adolescence was determined using the International Caries and Detection and Assessment System (ICDAS). The relationship between blood levels of lead and decayed, missing, or filled surfaces (DMFS) was examined using negative binomial regression. Covariates were selected based on previous studies and included age, gender, socioeconomic status, oral hygiene, body mass index, and diet. The nonlinear relationship between lead and DMFS was examined using smoothing splines. Results: The mean overall blood lead level (BLL) was 4.83 μg/dL (S.D. of 2.2). The mean overall caries level (DMFS) was 4.1. No statistically significant association was found between early childhood blood lead levels and dental caries in adolescence. Conclusion: This study shows a lack of association between exposure to lead between the ages of 1-4 years of age and dental caries in permanent dentition later in life. Other covariates, such as age and sugar consumption, appeared to play a more prominent role in caries development.Item Dietary Fluoride Intake Over the Course of Pregnancy in Mexican Women(Cambridge, 2021-06) Castiblanco-Rubio, Gina A.; Muñoz-Rocha, Teresa V.; Cantoral, Alejandra; Téllez-Rojo, Martha M.; Ettinger, Adrienne S.; Téllez-Rojo, Adriana; Peterson, Karen E.; Hu, Howard; Martínez-Mier, E. Angeles; Cariology, Operative Dentistry and Dental Public Health, School of DentistryObjective: To estimate dietary fluoride intake (F) over the course of pregnancy and the overall adjusted difference in dietary F intake by pregnancy stages and levels of compliance with dietary recommendations. Design: Secondary data analysis from a longitudinal pregnancy cohort study in a population exposed to fluoridated salt. Women were followed during the early, middle and late stages of their pregnancy (n 568). The dietary intake of recommended prenatal nutrients according to Mexican dietary guidelines and F intake (mg/d) was estimated with a validated FFQ. Data were summarised with descriptive statistics. Levels of F intake were compared with the USA’s Institute of Medicine adequate intake (AI) of 3 mg/d for pregnancy. Adjusted differences in F intake by pregnancy stages and levels of compliance with recommendations were estimated using random effects models. Setting: Mexico City. Participants: Women participating in the Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) project, from 2001 to 2003. Results: Median dietary F intake throughout pregnancy ranged from 0·64 (interquartile range (IQR) 0·38) in the early to 0·70 (IQR 0·42) in the middle, and 0·72 (IQR 0·44) mg/d in the late stage (0·01 mg F/kg per d). Corresponding adjusted intakes of F were 0·72 (95 % CI 0·70, 0·74), 0·76 (95 % CI 0·74, 0·77) and 0·80 (95 % CI 0·78, 0·82) mg/d. Women who were moderately and highly compliant with Mexican dietary recommendations ingested, on average, 0·04 and 0·14 mg F/d more than non-compliant women (P < 0·005). Conclusions: Dietary F intake was below current AI, was greater with the progression of pregnancy and in women who were moderately and highly compliant with dietary recommendations.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 Fluoride Content in Foods and Beverages From Mexico City Markets and Supermarkets(Sage, 2019-12) Cantoral, Alejandra; Luna-Villa, Lynda Cristina; Mantilla-Rodriguez, Andres A.; Mercado, Adriana; Lippert, Frank; Liu, Yun; Peterson, Karen E.; Hu, Howard; Téllez-Rojo, Martha M.; Martinez-Mier, Esperanza A.; Cariology, Operative Dentistry and Dental Public Health, School of DentistryBackground: Sources of fluoride exposure for Mexicans include foods, beverages, fluoridated salt, and naturally fluoridated water. There are no available data describing fluoride content of foods and beverages consumed in Mexico. Objective: To measure the content of fluoride in foods and beverages typically consumed and to compare their content to that of those from the United States and the United Kingdom. Methods: Foods and beverages reported as part of the Mexican Health and Nutrition Survey (n = 182) were purchased in the largest supermarket chains and local markets in Mexico City. Samples were analyzed for fluoride, at least in duplicate, using a modification of the hexamethyldisiloxane microdiffusion method. Value contents were compared to those from the US Department of Agriculture and UK fluoride content tables. Results: The food groups with the lowest and highest fluoride content were eggs (2.32 µg/100 g) and seafood (371 µg/100 g), respectively. When estimating the amount of fluoride per portion size, the lowest content corresponded to eggs and the highest to fast foods. Meats and sausages, cereals, fast food, sweets and cakes, fruits, dairy products, legumes, and seafood from Mexico presented higher fluoride contents than similar foods from the United States or the United Kingdom. Drinks and eggs from the United States exhibited the highest contents, while this was the case for pasta, soups, and vegetables from the United Kingdom. Conclusion: The majority of items analyzed contained higher fluoride contents than their US and UK counterparts. Data generated provide the first and largest table on fluoride content, which will be useful for future comparisons and estimations.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.Item Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6–12 Years of Age in Mexico(2017) Bashash, Morteza; Thomas, Deena; Hu, Howard; Martinez-Mier, E. Angeles; Sanchez, Brisa N.; Basu, Niladri; Peterson, Karen E.; Ettinger, Adrienne S.; Wright, Robert; Zhang, Zhenzhen; Liu, Yun; Schnaas, Lourdes; Mercado-García, Adriana; Téllez-Rojo, Martha María; Hernández-Avila, Mauricio; Cariology, Operative Dentistry and Dental Public Health, School of DentistryBACKGROUND: Some evidence suggests that fluoride may be neurotoxic to children. Few of the epidemiologic studies have been longitudinal, had individual measures of fluoride exposure, addressed the impact of prenatal exposures or involved more than 100 participants. OBJECTIVE: Our aim was to estimate the association of prenatal exposure to fluoride with offspring neurocognitive development. METHODS: We studied participants from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) project. An ion-selective electrode technique was used to measure fluoride in archived urine samples taken from mothers during pregnancy and from their children when 6–12 y old, adjusted for urinary creatinine and specific gravity, respectively. Child intelligence was measured by the General Cognitive Index (GCI) of the McCarthy Scales of Children’s Abilities at age 4 and full scale intelligence quotient (IQ) from the Wechsler Abbreviated Scale of Intelligence (WASI) at age 6–12. RESULTS: We had complete data on 299 mother–child pairs, of whom 287 and 211 had data for the GCI and IQ analyses, respectively. Mean (SD) values for urinary fluoride in all of the mothers (n=299) and children with available urine samples (n=211) were 0.90 (0.35) mg/L and 0.82 (0.38) mg/L, respectively. In multivariate models we found that an increase in maternal urine fluoride of 0.5mg/L (approximately the IQR) predicted 3.15 (95% CI: −5.42, −0.87) and 2.50 (95% CI −4.12, −0.59) lower offspring GCI and IQ scores, respectively. CONCLUSIONS: In this study, higher prenatal fluoride exposure, in the general range of exposures reported for other general population samples of pregnant women and nonpregnant adults, was associated with lower scores on tests of cognitive function in the offspring at age 4 and 6–12 y.Item Urinary and Plasma Fluoride Levels in Pregnant Women from Mexico City(Elsevier, 2016-10) Thomas, Deena B.; Basu, Niladri; Martinez-Mier, E. Angeles; Sánchez, Brisa N.; Zhang, Zhenzhen; Liu, Yun; Parajuli, Rajendra; Peterson, Karen; Mercado-Garcia, Adriana; Bashash, Morteza; Hernández-Avila, Mauricio; Hu, Howard; Téllez-Rojo, Martha Maria; Department of Cariology, Operative Dentistry and Dental Public Health, School of DentistryBackground There is need to assess the developmental neurotoxicity of fluoride. Our knowledge of prenatal fluoride exposure is challenged as few population-based studies have been conducted and these generally date back several decades, provide incomplete data on sociodemographic variables, and have methodological limitations. Objective To measure urinary and plasma fluoride levels across three time points in pregnant mothers who were enrolled in the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) birth cohort study. Methods Fluoride levels were characterized in archived urine and plasma from 872 pregnant mothers sampled from the ELEMENT cohort. Various statistical methods were used to analyze the fluoride data with particular consideration for changes across three stages of pregnancy and against sociodemographic variables. Results All samples had detectable levels of fluoride. The mean urinary and plasma fluoride levels were 0.91 and 0.0221 mg/L respectively, and these were not statistically different across three stages of pregnancy. Fluoride levels correlated across the stages of pregnancy studied, with stronger correlations between neighboring stages. Urinary fluoride changed as pregnancy progressed with levels increasing until ~23 weeks and then decreasing until the end of pregnancy. For plasma fluoride, there was a decreasing trend but this was not of statistical significance. Creatinine-adjusted urinary fluoride levels did not associate consistently with any of the sociodemographic variables studied. Conclusions This study provides the most extensive characterization to date of fluoride exposure throughout pregnancy. These results provide the foundation to explore exposure-related health outcomes in the ELEMENT cohort and other studies.Item Urinary fluoride levels and metal co-exposures among pregnant women in Los Angeles, California(BMC, 2023-10-26) Malin, Ashley J.; Hu, Howard; Martínez‑Mier, E. Angeles; Eckel, Sandrah P.; Farzan, Shohreh F.; Howe, Caitlin G.; Funk, William; Meeker, John D.; Habre, Rima; Bastain, Theresa M.; Breton, Carrie V.; Cariology, Operative Dentistry and Dental Public Health, School of DentistryBackground: Fluoride is ubiquitous in the United States (US); however, data on biomarkers and patterns of fluoride exposure among US pregnant women are scarce. We examined specific gravity adjusted maternal urinary fluoride (MUFsg) in relation to sociodemographic variables and metal co-exposures among pregnant women in Los Angeles, California. Methods: Participants were from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort. There were 293 and 490 women with MUFsg measured during first and third trimesters, respectively. An intra-class correlation coefficient examined consistency of MUFsg between trimesters. Kruskal-Wallis and Mann-Whitney U tests examined associations of MUFsg with sociodemographic variables. Covariate adjusted linear regression examined associations of MUFsg with blood metals and specific gravity adjusted urine metals among a subsample of participants within and between trimesters. A False Discovery Rate (FDR) correction accounted for multiple comparisons. Results: Median (IQR) MUFsg was 0.65 (0.5) mg/L and 0.8 (0.59) mg/L, during trimesters one and three respectively. During both trimesters, MUFsg was higher among older participants, those with higher income, and White, non-Hispanic participants than Hispanic participants. MUFsg was also higher for White, non-Hispanic participants than for Black, non-Hispanic participants in trimester three, and for those with graduate training in trimester one. MUFsg was negatively associated with blood mercury in trimester one and positively associated with blood lead in trimester three. MUFsg was positively associated with various urinary metals, including antimony, barium, cadmium, cobalt, copper, lead, nickel, tin, and zinc in trimesters one and/or three. Conclusions: MUFsg levels observed were comparable to those found in pregnant women in Mexico and Canada that have been associated with poorer neurodevelopmental outcomes. Lower urinary fluoride levels among Hispanic and non-Hispanic Black participants in MADRES compared to non-Hispanic White participants may reflect lower tap water consumption or lower fluoride exposure from other sources. Additional research is needed to examine whether MUFsg levels observed among pregnant women in the US are associated with neurodevelopmental outcomes.