ADDENDUM: Critical windows of fluoride neurotoxicity in Canadian Children.
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ABSTRACT:
SUBMITTER: Farmus L
PROVIDER: S-EPMC10229144 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
ADDENDUM: Critical windows of fluoride neurotoxicity in Canadian Children.
Farmus Linda L Till Christine C Green Rivka R Hornung Richard R Martinez Mier E Angeles EA Ayotte Pierre P Muckle Gina G Lanphear Bruce P BP Flora David B DB
Environmental research 20221201 Pt. 3
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Project description:BackgroundFluoride has been associated with IQ deficits during early brain development, but the period in which children are most sensitive is unknown.ObjectiveWe assessed effects of fluoride on IQ scores across prenatal and postnatal exposure windows.MethodsWe 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.ResultsThe 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.ConclusionAssociations 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.
| S-EPMC9884092 | biostudies-literature
Project description:BackgroundMaternal prenatal exposure to air pollution has been associated with adverse birth outcomes. However, previous studies focused on a priori time intervals such as trimesters reported inconsistent associations.ObjectivesWe investigated time-varying vulnerability of birth weight to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) using flexible time intervals.MethodsWe analyzed 1,300 live, full-term births from Maternal-Infant Research on Environmental Chemicals, a Canadian prospective pregnancy cohort spanning 10 cities (2008-2011). Daily PM2.5 and NO2 concentrations were estimated from ground-level monitoring, satellite models, and land-use regression, and assigned to participants from pre-pregnancy through delivery. We developed a flexible two-stage modeling method-using a Bayesian Metropolis-Hastings algorithm and empirical density threshold-to identify time-dependent vulnerability to air pollution without specifying exposure periods a priori. This approach identified critical windows with varying lengths (2-363 days) and critical windows that fell within, or straddled, predetermined time periods (i.e., trimesters). We adjusted the models for detailed infant and maternal covariates.ResultsCritical windows associated with reduced birth weight were identified during mid- to late-pregnancy for both PM2.5 and NO2: -6 g (95% credible interval: -11, -1 g) and -5 g (-10, -0.1 g) per µg/m3 PM2.5 during gestational days 91-139 and 249-272, respectively; and -3 g (-5, -1 g) per ppb NO2 during days 55-145.DiscussionWe used a novel, flexible selection method to identify critical windows when maternal exposures to air pollution were associated with decrements in birth weight. Our results suggest that air pollution impacts on fetal development may not be adequately captured by trimester-based analyses.
| S-EPMC8614564 | biostudies-literature
Project description:Recently, epidemiological studies have suggested that fluoride is a human developmental neurotoxicant that reduces measures of intelligence in children, placing it into the same category as toxic metals (lead, methylmercury, arsenic) and polychlorinated biphenyls. If true, this assessment would be highly relevant considering the widespread fluoridation of drinking water and the worldwide use of fluoride in oral hygiene products such as toothpaste. To gain a deeper understanding of these assertions, we reviewed the levels of human exposure, as well as results from animal experiments, particularly focusing on developmental toxicity, and the molecular mechanisms by which fluoride can cause adverse effects. Moreover, in vitro studies investigating fluoride in neuronal cells and precursor/stem cells were analyzed, and 23 epidemiological studies published since 2012 were considered. The results show that the margin of exposure (MoE) between no observed adverse effect levels (NOAELs) in animal studies and the current adequate intake (AI) of fluoride (50 µg/kg b.w./day) in humans ranges between 50 and 210, depending on the specific animal experiment used as reference. Even for unusually high fluoride exposure levels, an MoE of at least ten was obtained. Furthermore, concentrations of fluoride in human plasma are much lower than fluoride concentrations, causing effects in cell cultures. In contrast, 21 of 23 recent epidemiological studies report an association between high fluoride exposure and reduced intelligence. The discrepancy between experimental and epidemiological evidence may be reconciled with deficiencies inherent in most of these epidemiological studies on a putative association between fluoride and intelligence, especially with respect to adequate consideration of potential confounding factors, e.g., socioeconomic status, residence, breast feeding, low birth weight, maternal intelligence, and exposure to other neurotoxic chemicals. In conclusion, based on the totality of currently available scientific evidence, the present review does not support the presumption that fluoride should be assessed as a human developmental neurotoxicant at the current exposure levels in Europe.
| S-EPMC7261729 | biostudies-literature
Project description:BackgroundAlthough fluoride may cause neurotoxicity in animal models and acute fluoride poisoning causes neurotoxicity in adults, very little is known of its effects on children's neurodevelopment.ObjectiveWe performed a systematic review and meta-analysis of published studies to investigate the effects of increased fluoride exposure and delayed neurobehavioral development.MethodsWe searched the MEDLINE, EMBASE, Water Resources Abstracts, and TOXNET databases through 2011 for eligible studies. We also searched the China National Knowledge Infrastructure (CNKI) database, because many studies on fluoride neurotoxicity have been published in Chinese journals only. In total, we identified 27 eligible epidemiological studies with high and reference exposures, end points of IQ scores, or related cognitive function measures with means and variances for the two exposure groups. Using random-effects models, we estimated the standardized mean difference between exposed and reference groups across all studies. We conducted sensitivity analyses restricted to studies using the same outcome assessment and having drinking-water fluoride as the only exposure. We performed the Cochran test for heterogeneity between studies, Begg's funnel plot, and Egger test to assess publication bias, and conducted meta-regressions to explore sources of variation in mean differences among the studies.ResultsThe standardized weighted mean difference in IQ score between exposed and reference populations was -0.45 (95% confidence interval: -0.56, -0.35) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas. Subgroup and sensitivity analyses also indicated inverse associations, although the substantial heterogeneity did not appear to decrease.ConclusionsThe results support the possibility of an adverse effect of high fluoride exposure on children's neurodevelopment. Future research should include detailed individual-level information on prenatal exposure, neurobehavioral performance, and covariates for adjustment.
| S-EPMC3491930 | biostudies-literature
Project description:An analysis of early growth patterns in children from 54 resource-poor countries in Africa and Southeast Asia shows a rapid falloff in the height-for-age z score during the first 2 y of life and no recovery until ≥5 y of age. This finding has focused attention on the period -9 to 24 mo as a window of opportunity for interventions against stunting and has garnered considerable political backing for investment targeted at the first 1000 d. These important initiatives should not be undermined, but the objective of this study was to counteract the growing impression that interventions outside of this period cannot be effective. We illustrate our arguments using longitudinal data from the Consortium of Health Oriented Research in Transitioning collaboration (Brazil, Guatemala, India, Philippines, and South Africa) and our own cross-sectional and longitudinal growth data from rural Gambia. We show that substantial height catch-up occurs between 24 mo and midchildhood and again between midchildhood and adulthood, even in the absence of any interventions. Longitudinal growth data from rural Gambia also illustrate that an extended pubertal growth phase allows very considerable height recovery, especially in girls during adolescence. In light of the critical importance of maternal stature to her children's health, our arguments are a reminder of the importance of the more comprehensive UNICEF/Sub-Committee on Nutrition Through the Life-Cycle approach. In particular, we argue that adolescence represents an additional window of opportunity during which substantial life cycle and intergenerational effects can be accrued. The regulation of such growth is complex and may be affected by nutritional interventions imposed many years previously.
| S-EPMC3628381 | biostudies-literature
Project description:The absence of microbial exposure early in life leaves individuals vulnerable to immune overreaction later in life, manifesting as immunopathology, autoimmunity, or allergies. A key factor is thought to be a "critical window" during which the host's immune system can "learn" tolerance, and beyond which learning is no longer possible. Animal models indicate that many mechanisms have evolved to enable critical windows, and that their time limits are distinct and consistent. Such a variety of mechanisms, and precision in their manifestation suggest the outcome of strong evolutionary selection. To strengthen our understanding of critical windows, we explore their underlying evolutionary ecology using models encompassing demographic and epidemiological transitions, identifying the length of the critical window that would maximize fitness in different environments. We characterize how direct effects of microbes on host mortality, but also indirect effects via microbial ecology, will drive the optimal length of the critical window. We find that indirect effects such as magnitude of transmission, duration of infection, rates of reinfection, vertical transmission, host demography, and seasonality in transmission all have the effect of redistributing the timing and/or likelihood of encounters with microbial taxa across age, and thus increasing or decreasing the optimal length of the critical window. Declining microbial population abundance and diversity are predicted to result in increases in immune dysfunction later in life. We also make predictions for the length of the critical window across different taxa and environments. Overall, our modeling efforts demonstrate how critical windows will be impacted over evolution as a function of both host-microbiome/pathogen interactions and dispersal, raising central questions about potential mismatches between these evolved systems and the current loss of microbial diversity and/or increases in infectious disease.
| S-EPMC9783423 | biostudies-literature
Project description:The brain acquires certain skills-from visual perception to language-during critical windows, specific times in early life when the brain is actively shaped by environmental input. Scientists like Takao K. Hensch are now discovering pathways in animal models through which these windows might be re-opened in adults, thus re-awakening a brain's youth-like plasticity. Such research has implications for brain injury repair, sensory recovery, and neurodevelopmental disorder treatment. In addition, what we know today about these critical windows of development already has enormous implications for social and educational policy.
| S-EPMC3574806 | biostudies-other
Project description:BackgroundWhile fluoride can have thyroid-disrupting effects, associations between low-level fluoride exposure and thyroid conditions remain unclear, especially during pregnancy when insufficient thyroid hormones can adversely impact offspring development.ObjectivesWe evaluated associations between fluoride exposure and hypothyroidism in a Canadian pregnancy cohort.MethodsWe measured fluoride concentrations in drinking water and three dilution-corrected urine samples and estimated fluoride intake based on self-reported beverage consumption. We classified women enrolled in the Maternal-Infant Research on Environmental Chemicals Study as euthyroid (n = 1301), subclinical hypothyroid (n = 100) or primary hypothyroid (n = 107) based on their thyroid hormone levels in trimester one. We used multinomial logistic regression to estimate the association between fluoride exposure and classification of either subclinical or primary hypothyroidism and considered maternal thyroid peroxidase antibody (TPOAb) status, a marker of autoimmune hypothyroidism, as an effect modifier. In a subsample of 466 mother-child pairs, we used linear regression to explore the association between maternal hypothyroidism and child Full-Scale IQ (FSIQ) at ages 3-to-4 years and tested for effect modification by child sex.ResultsA 0.5 mg/L increase in drinking water fluoride concentration was associated with a 1.65 (95 % confidence interval [CI]: 1.04, 2.60) increased odds of primary hypothyroidism. In contrast, we did not find a significant association between urinary fluoride (adjusted odds ratio [aOR]: 1.00; 95%CI: 0.73, 1.39) or fluoride intake (aOR: 1.25; 95%CI: 0.99, 1.57) and hypothyroidism. Among women with normal TPOAb levels, the risk of primary hypothyroidism increased with both increasing water fluoride and fluoride intake (aOR water fluoride concentration: 2.85; 95%CI: 1.25, 6.50; aOR fluoride intake: 1.75; 95%CI: 1.27, 2.41). Children born to women with primary hypothyroidism had lower FSIQ scores compared to children of euthyroid women, especially among boys (B coefficient: -8.42; 95 % CI: -15.33, -1.50).DiscussionFluoride in drinking water was associated with increased risk of hypothyroidism in pregnant women. Thyroid disruption may contribute to developmental neurotoxicity of fluoride.
| S-EPMC9992168 | biostudies-literature
Project description: Not available
| S-EPMC11906732 | biostudies-literature