Maternal Urinary Fluoride and Child Neurobehavior at Age 36 Months.

Importance: Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown. Objective: To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US. Design, Setting, and Participants: This prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks' gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024. Exposure: Specific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure. Main Outcomes and Measures: Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted. Results: A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02). Conclusions and Relevance: In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.

The Potential Systemic Role of Diet in Dental Caries Development and Arrest: A Narrative Review.

Current conceptualizations of dental caries etiology center primarily on the local role of sugar, starch, or other fermentable carbohydrates on tooth enamel demineralization-a well-established and empirically supported mechanism. However, in addition to this mechanism, studies dating back to the early 1900s point to an important systemic role of diet and nutrition, particularly from pasture-raised animal-source foods (ASF), in dental caries etiology and arrest. Findings from animal and human studies suggest that adherence to a diet high in calcium, phosphorus, fat-soluble vitamins A and D, and antioxidant vitamin C, as well as low in phytates, may contribute to arrest and reversal of dental caries, particularly among children. Furthermore, findings from observational and experimental studies of humans across the life-course suggest that fat-soluble vitamins A, D, and K2 may interact to protect against dental caries progression, even within a diet that regularly contains sugar. While these historic studies have not been revisited in decades, we emphasize the need for them to be reinvestigated and contextualized in the 21st century. Specifically, methodologically rigorous studies are needed to reinvestigate whether historical knowledge of systemic impacts of nutrition on dental health can help to inform current conceptualizations of dental caries etiology, prevention, and arrest.

Urinary fluoride levels and metal co-exposures among pregnant women in Los Angeles, California.

BACKGROUND: 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.

My nutrition index: a method for measuring optimal daily nutrient intake.

BACKGROUND: Adequate nutrition is essential for individual and population level health. However, determining adequacy of daily nutrient intake in research studies is often challenging given the unique nutritional needs of individuals. Herein, we examine construct, predictive, criterion, content, and concurrent validity of a dietary analytic tool - My Nutrition Index (MNI) for measuring nutrient intake in relation to personalized daily nutrient intake guidelines. MNI gauges adequacy of an individual's daily nutrient intake based on his or her unique demographic and lifestyle characteristics. MNI accounts for potential adverse effects of inadequate and excess nutrient consumption. METHODS: MNI, calculated based on 34 nutrients, provides an overall index score ranging from 0 to 100, with higher scores reflecting a more nutritious diet. We calculated MNI scores for 7154 participants ages 18-65 in the National Health and Nutrition Examination Surveys (2007-2014) by using average nutrient intakes from two 24-h dietary recalls. Survey-weighted binary logistic regression models were used to assess associations between MNI scores and obesity, depression, health perceptions, and past or present cardiovascular disease. RESULTS: Higher MNI scores were associated with lower prevalence of self-reported cardiovascular disease (OR = 0.69, CI: 0.52, 0.92, p = 0.012), depression (OR = 0.76, CI: 0.65, 0.90, p < 0.001), and obesity (OR = 0.92, CI: 0.87, 0.99, p = 0.016), as well as more favorable health perceptions (OR = 1.24, CI: 1.13, 1.37, p < 0.001). CONCLUSIONS: MNI provides an individualized approach for measuring adequacy/sufficiency of daily nutrient intake that can validly be employed to assess relationships between nutrition and health outcomes in research studies.

Early childhood fluoride exposure and preadolescent kidney function.

BACKGROUND: Early-life renal maturation is susceptible to nephrotoxic environmental chemicals. Given the widespread consumption of fluoride and the global obesity epidemic, our main aim was to determine whether childhood fluoride exposure adversely affects kidney function in preadolescence, and if adiposity status modifies this association. METHODS: Our study included 438 children from the PROGRESS cohort. Urinary fluoride (uF) was assessed at age 4 by diffusion analysis; outcomes studied included estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), selected kidney proteins and blood pressure measured at age 8-12 years. We modeled the relationship between uF and outcomes, and adjusted for body mass index (BMI), age, sex, and socioeconomic status. RESULTS: The median uF concentration was 0.67 µg/mL. We observed null associations between 4-year uF and preadolescent eGFR, although effect estimates were in the expected inverse direction. A single unit increase in ln-transformed uF was associated with a 2.2 mL/min decrease in cystatin C-based eGFR (95% CI: 5.8, 1.4; p = 0.23). We observed no evidence of sex-specific effects or effect modification by BMI status. Although uF was not associated with BMI, among children with obesity, we observed an inverse association (ß: 4.8; 95% CI: 10.2, 0.6; p = 0.08) between uF and eGFR. CONCLUSIONS: Low-level fluoride exposure in early childhood was not associated with renal function in preadolescence. However, given the adverse outcomes of chronic fluoride consumption it is possible that the preadolescent age was too young to observe any effects. Longitudinal follow-up in this cohort and others is an important next step.

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.

Urinary Fluoride Levels among Canadians with and without Community Water Fluoridation.

Drinking water is a major source of dietary fluoride intake in communities with water fluoridation. We examined the association between urinary fluoride adjusted for specific gravity (UFSG) and tap water fluoride levels, by age and sex, among individuals living in Canada. Participants included 1629 individuals aged 3 to 79 years from Cycle 3 (2012-2013) of the Canadian Health Measures Survey. We used multiple linear regression to estimate unique associations of tap water fluoride levels, age, sex, ethnicity, body mass index (BMI), use of fluoride-containing dental products, smoking in the home, and tea consumption with UFSG. UFSG concentration was significantly higher among participants who received fluoridated drinking water (mean = 1.06 mg/L, standard deviation = 0.83) than among those who did not (M = 0.58 mg/L, SD = 0.47), p < 0.01. UFSG increased over adulthood (ages 19 to 79). Higher UFSG concentration was associated with being female, tea drinking, and smoking in the home. In conclusion, community water fluoridation is a major source of contemporary fluoride exposure for Canadians. Lifestyle factors including tea consumption, as well as demographic variables such as age and sex, also predict urinary fluoride level, and are therefore important factors when interpreting population-based fluoride biomonitoring data.

Early Adverse Experiences and Repeated Wheezing From 6 to 30 Months of Age: Investigating the Roles of Hypothalamic-Pituitary-Adrenal Axis Functioning, Child Sex, and Caregiving Sensitivity.

This study examined associations among early adversity, diurnal cortisol, child sex, and caregiver sensitivity at age 6 months in relation to wheezing in children (47% male) followed to 30 months. Analyses included 676 mother-child dyads, 393 of whom completed an observational caregiver sensitivity measure. Participants were primarily ethnic minorities (42.7% Black, 25.4% Hispanic); 22.1% of children had ≥ 1 wheezing episode. Higher adversity was associated with increased wheeze frequency and blunted diurnal cortisol slope. The indirect effect of adversity on wheezing through cortisol slope was significant for females, but not males. Higher caregiver sensitivity was protective against wheezing for males, but not females, with high cortisol. Findings suggest complex associations among adversity, cortisol, child sex, and caregiver sensitivity in predicting wheezing.

Fluoride exposure and duration and quality of sleep in a Canadian population-based sample.

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 sleep duration, frequency of sleep problems, and daytime sleepiness. Covariates included age, sex, ethnicity, body mass index, chronic health conditions, and household income. RESULTS: Median (IQR) UFSG concentration was 0.67 (0.63) mg/L. Median (IQR) water fluoride concentration was 0.58 (0.27) mg/L among participants living in communities supplied with fluoridated municipal water and 0.01 (0.06) mg/L among those living in non-fluoridated communities. A 0.5 mg/L higher water fluoride level was associated with 34% higher relative risk of reporting sleeping less than the recommended duration for age [unweighted: RRR = 1.34, 95% CI: 1.03, 1.73; p = .026]; the relative risk was higher, though less precise, using survey-weighted data [RRR = 1.96, 95% CI: 0.99, 3.87; p = .05]. UFSG was not significantly associated with sleep duration. Water fluoride and UFSG concentration were not significantly associated with frequency of sleep problems or daytime sleepiness. CONCLUSIONS: Fluoride exposure may contribute to sleeping less than the recommended duration among older adolescents and adults in Canada.

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.

Fluoride exposure and sleep patterns among older adolescents in the United States: a cross-sectional study of NHANES 2015-2016.

BACKGROUND: Fluoride from environmental sources accumulates preferentially in the pineal gland which produces melatonin, the hormone that regulates the sleep-wake cycle. However, the effects of fluoride on sleep regulation remain unknown. This population-based study examined whether chronic low-level fluoride exposure is associated with sleep patterns and daytime sleepiness among older adolescents in the United States (US). METHOD: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (2015-2016). We analyzed data from adolescents who had plasma fluoride (n = 473) and water fluoride (n = 419) measures and were not prescribed medication for sleep disorders. Relationships between fluoride exposure and self-reported sleep patterns or daytime sleepiness were examined using survey-weighted linear, binomial logistic or multinomial logistic regression after covariate adjustment. A Holm-Bonferroni correction accounted for multiple comparisons. RESULTS: The average age of adolescents was 17 years (range = 16-19). Median (IQR) water and plasma fluoride concentrations were 0.27 (0.52) mg/L and 0.29 (0.19) µmol/L respectively. An IQR increase in water fluoride was associated with 1.97 times higher odds of reporting symptoms suggestive of sleep apnea (95% CI: 1.27, 3.05; p = 0.02), a 24 min later bedtime (B = 0.40, 95% CI: 0.10, 0.70; p = 0.05), a 26 min later morning wake time (B = 0.43, 95% CI: 0.13, 0.73; p = 0.04), and among males, a 38% reduction in the odds of reporting snoring (95% CI: 0.45, 0.87, p = 0.03). CONCLUSIONS: Fluoride exposure may contribute to changes in sleep cycle regulation and sleep behaviors among older adolescents in the US. Additional prospective studies are warranted to examine the effects of fluoride on sleep patterns and determine critical windows of vulnerability for potential effects.

Prenatal Exposure to PM2.5 and Cardiac Vagal Tone during Infancy: Findings from a Multiethnic Birth Cohort.

BACKGROUND: The autonomic nervous system plays a key role in maintaining homeostasis and responding to external stimuli. In adults, exposure to fine particulate matter (PM2.5) has been associated with reduced heart rate variability (HRV), an indicator of cardiac autonomic control. OBJECTIVES: Our goal was to investigate the associations of exposure to fine particulate matter (PM2.5) with HRV as an indicator of cardiac autonomic control during early development. METHODS: We studied 237 maternal-infant pairs in a Boston-based birth cohort. We estimated daily residential PM2.5 using satellite data in combination with land-use regression predictors. In infants at 6 months of age, we measured parasympathetic nervous system (PNS) activity using continuous electrocardiogram monitoring during the Repeated Still-Face Paradigm, an experimental protocol designed to elicit autonomic reactivity in response to maternal interaction and disengagement. We used multivariable linear regression to examine average PM2.5 exposure across pregnancy in relation to PNS withdrawal and activation, indexed by changes in respiration-corrected respiratory sinus arrhythmia (RSAc)-an established metric of HRV that reflects cardiac vagal tone. We examined interactions with infant sex using cross-product terms. RESULTS: In adjusted models we found that a 1-unit increase in PM2.5 (in micrograms per cubic meter) was associated with a 3.53% decrease in baseline RSAc (95% CI: -6.96, 0.02). In models examining RSAc change between episodes, higher PM2.5 was generally associated with reduced PNS withdrawal during stress and reduced PNS activation during recovery; however, these associations were not statistically significant. We did not observe a significant interaction between PM2.5 and sex. DISCUSSION: Prenatal exposure to PM2.5 may disrupt cardiac vagal tone during infancy. Future research is needed to replicate these preliminary findings. https://doi.org/10.1289/EHP4434.

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.

Fluoride exposure and kidney and liver function among adolescents in the United States: NHANES, 2013-2016.

BACKGROUND: Hepato- and nephrotoxicity of fluoride have been demonstrated in animals, but few studies have examined potential effects in humans. This population-based study examines the relationship between chronic low-level fluoride exposure and kidney and liver function among United States (U.S.) adolescents. This study aimed to evaluate whether greater fluoride exposure is associated with altered kidney and liver parameters among U.S. youth. METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (2013-2016). We analyzed data from 1983 and 1742 adolescents who had plasma and water fluoride measures respectively and did not have kidney disease. Fluoride was measured in plasma and household tap water. Kidney parameters included estimated glomerular filtration rate (calculated by the original Schwartz formula), serum uric acid, and the urinary albumin to creatinine ratio. Liver parameters were assessed in serum and included alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen, gamma-glutamyl transferase, and albumin. Survey-weighted linear regression examined relationships between fluoride exposure and kidney and liver parameters after covariate adjustment. A Holm-Bonferroni correction accounted for multiple comparisons. RESULTS: The average age of adolescents was 15.4 years. Median water and plasma fluoride concentrations were 0.48 mg/L and 0.33 µmol/L respectively. A 1 µmol/L increase in plasma fluoride was associated with a 10.36 mL/min/1.73 m2 lower estimated glomerular filtration rate (95% CI: -17.50, -3.22; p = 0.05), a 0.29 mg/dL higher serum uric acid concentration (95% CI: 0.09, 0.50; p = 0.05), and a 1.29 mg/dL lower blood urea nitrogen concentration (95%CI: -1.87, -0.70; p < 0.001). A 1 mg/L increase in water fluoride was associated with a 0.93 mg/dL lower blood urea nitrogen concentration (95% CI: -1.44, -0.42; p = 0.007). CONCLUSIONS: Fluoride exposure may contribute to complex changes in kidney and liver related parameters among U.S. adolescents. As the study is cross-sectional, reverse causality cannot be ruled out; therefore, altered kidney and/or liver function may impact bodily fluoride absorption and metabolic processes.

Combined exposure to lead, cadmium, mercury, and arsenic and kidney health in adolescents age 12-19 in NHANES 2009-2014.

BACKGROUND: Occupational and environmental exposures to toxic metals are established risk factors for the development of hypertension and kidney disease in adults. There is some evidence of developmental metal nephrotoxicity in children and from animal studies; however, to our knowledge no previous studies have examined associations between co-exposure to nephrotoxic environmental metals and children's kidney health. OBJECTIVE: The objective of this study was to assess the association between co-exposure to lead (Pb), cadmium (Cd), mercury (Hg), and arsenic (As), measured in urine and blood, and kidney parameters in US adolescents. METHODS: We performed a cross-sectional analysis of a subsample of 2709 children aged 12-19 participating in the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2014. We analyzed urine levels of 4 nephrotoxic metals selected a priori (As, Cd, Pb and Hg), Umix, and 3 nephrotoxic metals in blood (Cd, Pb, and Hg), Bmix, using a weighted quantile sum (WQS) approach. We applied WQS regression to analyze the association of Bmix and Umix with estimated glomerular filtration rate (eGFR), serum uric acid (SUA), urine albumin, blood urea nitrogen (BUN), and systolic blood pressure (SBP), adjusting for sex, race/ethnicity, age, head of household's education level, height, BMI, serum cotinine, and NHANES cohort year. Umix and urine albumin models were also adjusted for urine creatinine, and Bmix models were also adjusted for fish consumption. Subanalyses included stratification by sex and an arsenic-only model including six speciated forms of As measured in urine. RESULTS: In WQS regression models, each decile increase of Umix was associated with 1.6% (95% CI: 0.5, 2.8) higher BUN, 1.4% (95% CI: 0.7, 2.0) higher eGFR, and 7.6% (95% CI: 2.4, 13.1) higher urine albumin. The association between Umix and BUN was primarily driven by As (72%), while the association with eGFR was driven by Hg (61%), and Cd (17%), and the association with urine albumin was driven by Cd (37%), Hg (33%), and Pb (25%). There was no significant relationship between Umix and SUA or SBP. In WQS models using the combined blood metals, Bmix, each decile increase of Bmix was associated with 0.6% (95% CI: 0.0, 1.3) higher SUA; this association was driven by Pb (43%), Hg (33%), and Cd (24%) and was marginally significant (p = 0.05). No associations were observed between Bmix and urine albumin, eGFR, BUN, or SBP. CONCLUSIONS: The findings suggest metals including As, Pb, Hg, Cd and their combinations may affect renal parameters, although potential reverse causation cannot be ruled out due to the cross-sectional study design. Implications of early life low-level exposure to multiple metals on kidney function may have far-reaching consequences later in life in the development of hypertension, kidney disease, and renal dysfunction. Longitudinal studies should further evaluate these relationships.

Fluoride exposure and thyroid function among adults living in Canada: Effect modification by iodine status.

BACKGROUND: Fluoride exposure has the potential to disrupt thyroid functioning, though adequate iodine intake may mitigate this effect. This is the first population-based study to examine the impact of chronic low-level fluoride exposure on thyroid function, while considering iodine status. The objective of this study was to determine whether urinary iodine status modifies the effect of fluoride exposure on thyroid stimulating hormone (TSH) levels. METHODS: This cross-sectional study utilized weighted population-based data from Cycle 3 (2012-2013) of the Canadian Health Measures Survey (CHMS). Information was collected via a home interview and a visit to a mobile examination centre. The weighted sample represented 6,914,124 adults in Canada aged 18-79 who were not taking any thyroid-related medication. Urinary fluoride concentrations were measured in spot samples using an ion selective electrode and adjusted for specific gravity (UFSG). Serum TSH levels provided a measure of thyroid function. Multivariable regression analyses examined the relationship between UFSG and TSH, controlling for covariates. RESULTS: Approximately 17.8% of participants fell in the moderately-to-severely iodine deficient range. The mean (SD) age of the sample was 46.5 (15.6) years and the median UFSG concentration was 0.74 mg/L. Among iodine deficient adults, a 1 mg/L increase in UFSG was associated with a 0.35 mIU/L increase in TSH [95% CI: 0.06, 0.64; p = 0.01, one-tailed]. CONCLUSIONS: Adults living in Canada who have moderate-to-severe iodine deficiencies and higher levels of urinary fluoride may be at an increased risk for underactive thyroid gland activity.

Quality of Prenatal and Childhood Diet Predicts Neurodevelopmental Outcomes among Children in Mexico City.

Adequate nutrition is important for neurodevelopment. Although nutrients are ingested in combination, the impact of specific nutrients within the context of a nutrient mixture has not been studied with respect to health, such as neurodevelopment. Therefore, we examined the impact of prenatal and childhood nutrient mixtures on neurodevelopmental outcomes. Participants included mother⁻child pairs in the Programming Research in Obesity, Growth, Environment, and Social Stress (PROGRESS) prospective birth cohort in Mexico City. We assessed prenatal and child micro- and macronutrient profiles among 65 and 329 children, respectively, via food frequency questionnaires. Neurodevelopmental outcomes of 4⁻6-year-old children were measured using the McCarthy Scales of Children's Abilities (MSCA). We conducted weighted quantile sum (WQS) regression analyses to calculate indices reflecting "good" and "poor" prenatal and childhood nutrition. After adjusting for maternal education, socioeconomic status, the Home Observation for Measurement of the Environment (HOME) score, and total caloric intake, the good prenatal and childhood nutrition indices predicted more favorable neurodevelopment, while both poor nutrition indices predicted poorer neurodevelopment. These associations were stronger in prenatal than childhood models. Monounsaturated fats predicted various neurodevelopmental abilities relatively strongly in both models. Prenatal and childhood consumption of combinations of beneficial nutrients may contribute to more favorable neurodevelopment.

Exposure to fluoridated water and attention deficit hyperactivity disorder prevalence among children and adolescents in the United States: an ecological association.

BACKGROUND: Epidemiological and animal-based studies have suggested that prenatal and postnatal fluoride exposure has adverse effects on neurodevelopment. The aim of this study was to examine the relationship between exposure to fluoridated water and Attention-Deficit Hyperactivity Disorder (ADHD) prevalence among children and adolescents in the United States. METHODS: Data on ADHD prevalence among 4-17 year olds collected in 2003, 2007 and 2011 as part of the National Survey of Children's Health, and state water fluoridation prevalence from the Centers for Disease Control and Prevention (CDC) collected between 1992 and 2008 were utilized. RESULTS: State prevalence of artificial water fluoridation in 1992 significantly positively predicted state prevalence of ADHD in 2003, 2007 and 2011, even after controlling for socioeconomic status. A multivariate regression analysis showed that after socioeconomic status was controlled each 1% increase in artificial fluoridation prevalence in 1992 was associated with approximately 67,000 to 131,000 additional ADHD diagnoses from 2003 to 2011. Overall state water fluoridation prevalence (not distinguishing between fluoridation types) was also significantly positively correlated with state prevalence of ADHD for all but one year examined. CONCLUSIONS: Parents reported higher rates of medically-diagnosed ADHD in their children in states in which a greater proportion of people receive fluoridated water from public water supplies. The relationship between fluoride exposure and ADHD warrants future study.

The impact of early empathy on alliance building, emotional processing, and outcome during experiential treatment of depression.

OBJECTIVE: This study examined the relationships among the therapist process of expressed empathy during first sessions, clients' post-session one alliance reports, clients' later working phase emotional processing, and clients' final reductions in depressive symptoms for 30 clients receiving short-term experiential therapy for depression. METHOD: The therapist process of expressed empathy was assessed using a new observer-rated measure: the measure of expressed empathy, which was demonstrated to be valid and reliable. RESULTS: Results indicate that therapist expressed empathy in session one significantly affected the outcome, albeit indirectly. This indirect effect occurred through two direct effects on other important therapy processes that did directly predict client outcomes: (i) Therapist expressed empathy in first sessions directly and positively predicted client reports of first-session alliances; and (ii) therapist expressed empathy directly predicted observer-rated deepened client emotional processing in the working phase of therapy. CONCLUSIONS: Empirical support was provided for the theorized relationships in experiential theory amongst the variables examined.