•Consumption of formula reconstituted with fluoridated water can lead to excessive fluoride intake.•Breastfed infants receive very low intake of fluoride.•We compared IQ scores in 398 children who ...were formula-fed versus breastfed during infancy.•IQ scores were lower with higher levels of fluoride in tap water.•The effect was more pronounced among formula-fed children, especially for nonverbal skills.
Infant consumption of formula reconstituted with fluoridated water can lead to excessive fluoride intake. We examined the association between fluoride exposure in infancy and intellectual ability in children who lived in fluoridated or non-fluoridated cities in Canada.
We examined 398 mother-child dyads in the Maternal-Infant Research on Environmental Chemicals cohort who reported drinking tap water. We estimated water fluoride concentration using municipal water reports. We used linear regression to analyze the association between fluoride exposure and IQ scores, measured by the Wechsler Primary and Preschool Scale of Intelligence-III at 3–4 years. We examined whether feeding status (breast-fed versus formula-fed) modified the impact of water fluoride and if fluoride exposure during fetal development attenuated this effect. A second model estimated the association between fluoride intake from formula and child IQ.
Thirty-eight percent of mother-child dyads lived in fluoridated communities. An increase of 0.5 mg/L in water fluoride concentration (approximately equaling the difference between fluoridated and non-fluoridated regions) corresponded to a 9.3- and 6.2-point decrement in Performance IQ among formula-fed (95% CI: −13.77, −4.76) and breast-fed children (95% CI: −10.45, −1.94). The association between water fluoride concentration and Performance IQ remained significant after controlling for fetal fluoride exposure among formula-fed (B = −7.93, 95% CI: −12.84, −3.01) and breastfed children (B = −6.30, 95% CI: −10.92, −1.68). A 0.5 mg increase in fluoride intake from infant formula corresponded to an 8.8-point decrement in Performance IQ (95% CI: −14.18, −3.34) and this association remained significant after controlling for fetal fluoride exposure (B = −7.62, 95% CI: −13.64, −1.60).
Exposure to increasing levels of fluoride in tap water was associated with diminished non-verbal intellectual abilities; the effect was more pronounced among formula-fed children.
Display omitted
•Fluoride may disrupt thyroid function in pregnant women.•Fluoride exposure was associated with alterations in maternal thyroid hormone levels.•Urinary fluoride was associated with ...significantly higher TSH among those pregnant with females.•Adjustment for maternal iodine status did not change the results.
Fluoride exposure may increase the risk of hypothyroidism, but results from previous studies are inconsistent at low-level fluoride exposure (i.e., ≤0.7 mg/L). Human studies of fluoride and thyroid hormone levels in pregnancy are scarce.
We examined associations between fluoride exposure and maternal thyroid hormone levels in a Canadian pregnancy cohort, with consideration for fetal sex-specific effects.
We measured fluoride concentrations in drinking water and spot urine samples collected during each trimester from 1876 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. We also measured maternal thyroid stimulating hormone (TSH), free thyroxine (FT4), and total thyroxine (TT4) levels during the first trimester of pregnancy. We used linear and non-linear regression models to estimate associations between fluoride exposure and levels of TSH, FT4, and TT4. We explored effect modification by fetal sex and considered maternal iodine status as a potential confounder.
A 1 mg/L increase in urinary fluoride was associated with a 0.30 (95 %CI: 0.08, 0.51) logarithmic unit (i.e., 35.0 %) increase in TSH among women pregnant with females, but not males (B = 0.02; 95 %CI: −0.16, 0.19). Relative to women with urinary fluoride concentrations in the first quartile (0.05–0.32 mg/L), those with levels in the third quartile (0.49–0.75 mg/L) had higher FT4 and TT4 (i.e., inverted J-shaped associations), but the association was not statistically significant after adjustment for covariates (p = 0.06). Water fluoride concentration showed a U-shaped association with maternal FT4, whereby women with water fluoride concentrations in the second (0.13–0.52 mg/L) and third (0.52–0.62 mg/L) quartiles had significantly lower FT4 compared to those with levels in the first quartile (0.04–0.13 mg/L). Adjustment for maternal iodine status did not change the results.
Fluoride exposure was associated with alterations in maternal thyroid hormone levels, the magnitude of which appeared to vary by fetal sex. Given the importance of maternal thyroid hormones for fetal neurodevelopment, replication of findings is warranted.
Although prenatal methylmercury exposure has been linked to poorer intellectual function in several studies, data from two major prospective, longitudinal studies yielded contradictory results. ...Associations with cognitive deficits were reported in a Faroe Islands cohort, but few were found in a study in the Seychelles Islands. It has been suggested that co-exposure to another contaminant, polychlorinated biphenyls (PCBs), may be responsible for the positive findings in the former study and that co-exposure to nutrients in methylmercury-contaminated fish may have obscured and/or protected against adverse effects in the latter.
We aimed to determine the degree to which co-exposure to PCBs may account for the adverse effects of methylmercury and the degree to which co-exposure to docosahexaenoic acid (DHA) may obscure these effects in a sample of Inuit children in Arctic Québec.
IQ was estimated in 282 school-age children from whom umbilical cord blood samples had been obtained and analyzed for mercury and other environmental exposures.
Prenatal mercury exposure was related to poorer estimated IQ after adjustment for potential confounding variables. The entry of DHA into the model significantly strengthened the association with mercury, supporting the hypothesis that beneficial effects from DHA intake can obscure adverse effects of mercury exposure. Children with cord mercury ≥ 7.5 μg/L were four times as likely to have an IQ score < 80, the clinical cut-off for borderline intellectual disability. Co-exposure to PCBs did not alter the association of mercury with IQ.
To our knowledge, this is the first study to document an association of prenatal mercury exposure with poorer performance on a school-age assessment of IQ, a measure whose relevance for occupational success in adulthood is well established. This association was seen at levels in the range within which many U.S. children of Asian-American background are exposed.
Selenium (Se) is a trace mineral essential to human health, and is especially abundant in marine foods consumed by Inuit populations in Nunavik (northern Quebec, Canada), leading to exceptionally ...high whole blood Se levels. While most epidemiological studies to date examine plasma or whole blood Se, little is known about the health implications of specific Se biomarkers (e.g. selenoproteins and small Se compounds). Selenoneine, a novel Se compound, is found in high concentrations in marine foods (and particularly beluga mattaaq) and the red blood cells (RBCs) of populations that consume them. We report here RBC selenoneine concentrations in a population of Inuit adults (n = 885) who participated in the Qanuippitaa? 2004 survey. Simple associations between RBC selenoneine and other Se and mercury (Hg) biomarkers were assessed using Spearman correlations and linear regressions. Wilcoxon ranksum tests were used to examine differences in biomarkers and characteristics between tertiles of RBC selenoneine concentration. A multiple linear regression analysis was used to determine factors (sociodemographic, lifestyle, and dietary) associated with RBC selenoneine concentrations. Selenoneine comprised a large proportion of whole blood Se and RBC Se in this population. Age and sex-adjusted geometric mean RBC selenoneine concentration was 118 μg/L (range: 1–3226 μg/L) and was much higher (p = 0.001) among women (150.3 μg/L) than men (87.6 μg/L) across all regions of Nunavik after controlling for age, region, and diet. RBC selenoneine was highly correlated with RBC Se (rs = 0.96, p < 0.001) and whole blood Se (rs = 0.89, p < 0.001), but only weakly correlated with plasma Se (rs = 0.13, p < 0.001). Overall, increasing age (standardized β = 0.24), higher body-mass index (BMI; β = 0.08), female sex (β = 0.10), living in a Hudson Strait community (compared to Hudson Bay and Ungava Bay; β = 0.38), and consuming beluga mattaaq (g/day; β = 0.19) were positively associated with RBC selenoneine. Meanwhile, consumption of market meats (g/day; β = −0.07) was negatively associated with RBC selenoneine. RBC selenoneine is an important biomarker of Se dietary intake from local marine foods in Inuit populations. Further studies are needed to examine the health effects of selenoneine intake and the underlying mechanisms for sex differences among Inuit populations.
•Selenoneine is a major selenium compound in the red blood cells of Inuit adults•Selenoneine levels are higher among women, elderly individuals, and those consuming high amounts of beluga mattaaq•Further research is needed to assess the origin, kinetics, and health impacts of selenoneine
Persistent organic pollutants (POPs) bioaccumulate in the food chain and have been detected in human blood and adipose tissue. Experimental studies demonstrated that POPs can cause and promote growth ...of breast cancer. However, inconsistent results from epidemiological studies do not support a causal relationship between POPs and breast cancer in women. To identify individual POPs that are repeatedly found to be associated with both breast cancer incidence and progression, and to demystify the observed inconsistencies between epidemiological studies, we conducted a systematic review of 95 studies retrieved from three main electronic databases. While no clear pattern of associations between blood POPs and breast cancer incidence could be drawn, POPs measured in breast adipose tissue were more clearly associated with higher breast cancer incidence. POPs were more consistently associated with worse breast cancer prognosis whether measured in blood or breast adipose tissue. In contrast, POPs measured in adipose tissue other than breast were inversely associated with both breast cancer incidence and prognosis. Differences in biological tissues used for POPs measurement and methodological biases explain the discrepancies between studies results. Some individual compounds associated with both breast cancer incidence and progression, deserve further investigation.
Background: Several ubiquitous polyhalogenated compounds (PHCs) have been shown to alter thyroid function in animal and in vitro studies. So far, epidemiologic studies have focused on the potential ...effect of a small number of them, namely, polychlorinated biphenyls (PCBs) and some organochlorines (OCs), without paying attention to other important PHCs. Objectives: We investigated the relationship between exposure to several PHCs and thyroid hormone homeostasis in Inuit adults from Nunavik. Methods: We measured thyroid parameters thyroid-stimulating-hormone (TSH), free thyroxine (fT₄), total triiodothyronine (tT₃), and thyroxine-binding globulin (TBG) and concentrations of 41 contaminants, including PCBs and their metabolites, organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), perfluorooctanesulfonate (PFOS), and a measure of dioxinlike compounds, detected in plasma samples from Inuit adults (n = 623). Results: We found negative associations between tT₃ concentrations and levels of 14 PCBs, 7 hydroxylated PCBs (HO-PCBs), all methylsulfonyl metabolites of PCBs (MeSO₂-PCBs), and 2 OCPs. Moreover, we found negative associations between fT 4 levels and hexachlorobenzene concentrations. TBG concentrations were inversely related to 8 PCBs, 5 HO-PCBs, and 3 OCPs. Exposure to BDE-47 was positively related to tT₃, whereas PFOS concentrations were negatively associated with TSH, tT₃, and TBG and positively with fT₄ concentrations. Conclusion: Exposure to several PHCs was associated with modifications of the thyroid parameters in adult Inuit, mainly by reducing tT₃ and TBG circulating concentrations. The effects of PFOS and BDE-47 on thyroid homeostasis require further investigation because other human populations display similar or higher concentrations of these chemicals.
Bisphenol A (BPA) and triclosan (TCS) are two nonpersistent chemicals that have been frequently measured in spot urine samples from the general population but less so in pregnant women; however, data ...are limited on the free (bioactive) and conjugated forms of these phenols.
The Maternal-Infant Research on Environmental Chemicals (MIREC) Study addressed these data gaps by utilizing stored maternal urine samples from a large multicenter cohort study of Canadian pregnant women.
Concentrations of free and conjugated forms of BPA and TCS were measured in about 1,890 first-trimester urine samples by ultra performance liquid chromatography-tandem mass spectrometry using isotope dilution.
The glucuronides of BPA and TCS were the predominant forms of these chemicals measured (detected in 95% and 99% of samples, respectively), whereas the free forms were detected in 43% and 80% of samples, respectively. The geometric mean urinary concentrations for glucuronides of BPA and TCS were 0.80 μg/L (95% CI: 0.75, 0.85) and 12.30 μg/L (95% CI: 11.08, 13.65), respectively. Significant predictors of BPA included maternal age < 25 vs. ≥ 35 years, current smoking, low vs. high household income, and low vs. high education. For TCS, urinary concentrations were significantly higher in women ≥ 25 years of age, never vs. current smokers, and women with high household income and high education.
The results from this study represent the largest national-level data on urinary concentrations of free and conjugated forms of BPA and TCS in pregnant women and suggest that maternal characteristics predicting elevated urinary concentrations of these phenols largely act in opposite directions.
•A PFAS mixture was examined in association with cardiometabolic health in Nunavik.•PFAS were associated with increases in lipoproteins and prediabetes.•No associations were observed with diabetes ...and high blood pressure.
The cardiometabolic health status of Inuit in Nunavik has worsened in the last thirty years. The high concentrations of perfluoroalkyl acids (PFAAs) may be contributing to this since PFAAs have been linked with hypercholesterolemia, diabetes, and high blood pressure. The aim of this study was to examine the association between a PFAAs mixture and lipid profiles, Type II diabetes, prediabetes, and high blood pressure in this Inuit population.
We included 1212 participants of the Qanuilirpitaa? 2017 survey aged 16–80 years. Two mixture models (quantile g-computation and Bayesian Kernel Machine Regression (BKMR)) were used to investigate the associations between six PFAAs (PFHxS, PFOS, PFOA and three long-chain PFAAs (PFNA, PFDA and PFUnDA)) with five lipid profiles and three cardiometabolic outcomes. Non-linearity and interaction between PFAAs were further assessed.
An IQR increase in all PFAAs congeners resulted in an increase in total cholesterol (β 0.15, 95% confidence interval (CI) 0.06, 0.24), low-density lipoprotein cholesterol (LDL) (β 0.08, 95% CI 0.01, 0.16), high-density lipoprotein cholesterol (HDL) (β 0.04, 95% CI 0.002, 0.08), apolipoprotein B-100 (β 0.03, 95% CI 0.004, 0.05), and prediabetes (OR 1.80, 95% CI 1.11, 2.91). There was no association between PFAAs and triglycerides, diabetes, or high blood pressure. Long-chain PFAAs congeners were the main contributors driving the associations. Associations were largely linear, and there was no evidence of interaction between the PFAAs congeners.
Our study provides further evidence of increasing circulating lipids with increased exposure to PFAAs. The increased risk of prediabetes points to the influence of PFAAs on potential clinical outcomes. International regulation of PFAAs is essential to curb PFAAs exposure and related health effects in Arctic communities.
Serum composition of PFAAs congeners in Nunavik pregnant women from the NQN study in 2016–2017 compared to women from the Canadian general population who participated in the Canadian Health Measure ...Survey (CHMS) cycle 5.
Display omitted
•In pregnant women from Nunavik, exposure to long-chain PFAAs is increasing.•Nunavimmiut women exposure to PFOS, PFNA, PFDA and PFuDA was higher than in the Canadian general population.•The results suggest that 8:2 FTOH contributes to the exposure profile in the Arctic.•Marine country food consumption is associated with higher exposure to PFAAs.
Perfluoroalkyl acids (PFAAs) are persistent and ubiquitous environmental contaminants that potentially disrupt endocrine system functions. While some PFAAs (perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA)) are regulated, currently used fluorotelomer alcohols (FTOHs) can be transported to the Arctic and are degraded in a number of PFAAs which biomagnify in Arctic wildlife (e.g. perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA)).
From 2004 to 2017, 279 pregnant Inuit women were recruited as part of biomonitoring projects in Nunavik. Our goal was to evaluate: (i) time-trends in plasma/serum PFAAs levels in pregnant Nunavimmiut women between 2004 and 2017; (ii) compare plasma/serum PFAAs levels in Nunavimmiut women in 2016–2017 to those measured in women of childbearing age in the Canadian Health Measure Survey (CHMS); and (iii) evaluate the associations of PFAAs levels with the consumption of country foods and pregnancy and maternal characteristics during pregnancy in the 97 participants recruited in 2016–2017.
Individual blood sample were collected for serum or plasma PFAAs (PFOS, PFOA, pentafluorobenzoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorobutanesulfonic acid (PFBS), perfluorohexane-1-sulfonic acid (PFHxS), PFNA, PFDA, PFUdA) analyses. Socio-demographic data, pregnancy and maternal characteristics and country foods consumption were documented using a questionnaire. Omega-3 and −6 polyunsaturated fatty acids (PUFA) were measured in red blood cell membranes and their ratio used as a biomarker of marine country foods consumption. Time-trends in PFAAs levels were evaluated using ANCOVA models adjusted for relevant co-variables. Serum/plasma levels of PFAAs in the 97 pregnant women aged 16 to 40 years old and recruited in 2016–2017 were compared to those measured in women aged 18 to 40 years old from the CHMS cycle 5 (2016–2017) using the geometric means (GM) and 95% confidence intervals (95% CI). Multivariate regression analyses were performed to examine associations between concentrations of PFAAs and country foods consumption data.
Statistically-significant downward time trends were noted for concentrations of PFOS, PFOA and PFHxS in pregnant Nunavik women between 2004 and 2017. Conversely, between 2011 and 2016–2017, PFNA, PFDA and PFUdA maternal serum levels increased by 19, 13 and 21% respectively. Among participants in 2016–2017, mean concentrations for PFNA (GM: 2.4 μg/L), PFDA (0.53 μg/L) and PFUdA (0.61 μg/L) were higher than those measured in women aged 18–40 years old in the Cycle 5 (2016–2017) of the CHMS. PFOA (0.53 μg/L) and PFHxS (0.26 μg/L) were lower than in CHMS, whereas PFBA, PFHxA and PFBS were not detected in 2016–2017. Ratios of serum/plasma levels of PFNA/PFOA, PFNA/PFOS, PFNA/PFHxS and PFUdA/PFDA were significantly higher in the 97 pregnant women from Nunavik recruited in 2016–2017 compared to CHMS, highlighting their distinct exposure profile. In multivariate models, PFHxS, PFOS, PFNA, PFDA and PFUdA levels in 2016–2017 were strongly associated with the omega-3/omega-6 PUFA ratio, indicating a positive association between marine country foods consumption and higher exposure to PFAAs.
The exposure of pregnant women to long-chain PFAAs (PFNA, PFDA and PFUdA) increased from 2004 to 2017 in Nunavik. Associations noted between PFAAs levels and the omega-3/omega-6 ratio highlights the importance of implementing additional strict regulations on PFAAs and their precursors to protect the high nutritional quality and cultural importance of country foods in Nunavik.
Objectives To examine the relation of cord plasma docosahexaenoic acid (DHA) concentration to gestation length, birth size, growth, and infant visual acuity, cognitive, and motor development and the ...effects on growth and development associated with DHA intake from breast-feeding. Study design DHA, other polyunsaturated fatty acids, and 3 environmental contaminants (polychlorinated biphenyls, mercury, and lead) were assessed in cord plasma and maternal plasma and milk in 109 Inuit infants in Arctic Quebec. Multiple regression was used to examine the relation of cord DHA and DHA from breast-feeding on growth and development at 6 and 11 months, after controlling for contaminant exposure and other potential confounders. Results Higher cord DHA concentration was associated with longer gestation, better visual acuity and novelty preference on the Fagan Test at 6 months, and better Bayley Scale mental and psychomotor performance at 11 months. By contrast, DHA from breast-feeding was not related to any indicator of cognitive or motor development in this full-term sample. Conclusions The association of higher cord DHA concentration with more optimal visual, cognitive, and motor development is consistent with the need for substantial increases in this critically important fatty acid during the third trimester spurt of synaptogenesis in brain and photoreceptor development.