Effectiveness of soil remediation intervention in abandoned used lead acid battery (ULAB) recycling sites to reduce lead exposure among the children.

Lead (Pb) is a neurotoxin, and children are vulnerable due to their evolving physiology and high-risk behaviours. Soil remediation interventions have proven effective in reducing Pb exposure. The primary objective is to measure the effectiveness of soil remediation at abandoned used lead acid battery (ULAB) recycling sites, nearby household cleaning, and community awareness in reducing blood lead levels (BLLs) in children. Additionally, this study aims to examine associations of Pb exposure with hematological, cardiovascular, renal, immunological, and endocrinological parameters in children aged 0-12 years. This study employs a quasi-experimental design, with abandoned ULAB sites as intervention sites and two control sites in Bangladesh. The intervention includes soil remediation coupled with community education. Data will be collected prior to the intervention and at a 12-month follow-up, including a comprehensive Pb exposure survey and collect environmental, turmeric samples, and blood from the child. Pb concentrations in environmental samples and turmeric samples will be determined using XRF analyser. Child BLL will be measured using Graphite Furnace Atomic Absorption Spectrometry (GF-AAS) and proposed biochemical parameters will be analysed using routine laboratory methods. This study could provide valuable insights for designing targeted interventions in similar settings and mitigating exposure to Pb.

Urinary iodine concentrations in preschoolers and cognitive development at 4 and 6 years of age, the Rhea mother-child cohort on Crete, Greece.

BACKGROUND: Evidence regarding child iodine intake and neurodevelopment is scarce. METHODS: We aimed to assess the impact of child iodine intake at 4 years of age on cognitive and motor development at 4 and 6 years among 304 children from the Rhea cohort on Crete, Greece. Child iodine intake was assessed via urinary iodine concentrations (UIC) measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and adjusted for specific gravity. Child cognitive and motor development was assessed using the McCarthy Scales of Children's Abilities (MSCA) at 4 years of age and Raven's Coloured Progressive Matrices (RCPM), Finger Tapping Test (FTT), and Trail Making Test (TMT) at 6 years. Associations were explored using multivariable-adjusted linear regression analyses with UIC categorized according to WHO criteria [insufficient intake <100 µg/L, adequate 100-299 µg/L (reference group), excessive ≥300 µg/L]. RESULTS: The children's median UIC was 249 µg/L (25-75th percentile: 181-344 µg/L). Children with UIC <100 µg/L had lower scores in the motor scale at 4 years (MSCA-motor scale: B=-10.3; 95 %CI -19.9, -0.6; n=10) and in intelligence at 6 years (RCPM-total score: B=-3.6, 95 %CI -6.8, -0.5; n=9) than children in the reference group. No associations were found with the general cognitive scale at 4 years or with TMT and FTT scales at 6 years. Children with UIC ≥300 µg/L had lower cognitive scores both at 4 (MSCA; B= -3.5; 95 %CI -6.9, -0.1; n =101) and 6 years of age (RCPM-total score; B= -1.2; 95 %CI -2.3, -0.0; n =98) than children in the reference group. No associations were observed with the motor scale at 4 years or with TMT and FTT scales at 6 years. CONCLUSION: Our findings indicate that both low and excessive iodine intake at preschool age may adversely affect child cognitive abilities. Additionally, low iodine intake may also impact motor abilities.

Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy and timing of pubertal onset in a longitudinal mother-child cohort in rural Bangladesh.

BACKGROUND: In experimental studies, several polycyclic aromatic hydrocarbons (PAHs) have shown endocrine disrupting properties, but very few epidemiological studies have examined their impact on pubertal development and results have been heterogenous. OBJECTIVE: To explore if maternal PAH exposure during pregnancy was associated with the offspring's timing of pubertal onset. METHODS: We studied 582 mother-daughter dyads originating from a population-based cohort in a rural setting in Bangladesh. Maternal urinary samples, collected in early pregnancy (on average, gestational week 8), were analyzed for monohydroxylated metabolites of phenanthrene (1-OH-Phe, Σ2-,3-OH-Phe, and 4-OH-Phe), fluorene (Σ2-,3-OH-Flu), and pyrene (1-OH-Pyr) using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The girls were interviewed on two separate occasions concerning date of menarche, as well as breast and pubic hair development according to Tanner. Associations were assessed using Kaplan-Meier analysis and multivariable-adjusted Cox proportional hazards regression or ordered logistic regression. RESULTS: In early pregnancy, the mothers' median urinary concentrations of Σ1-,2-,3-,4-OH-Phe, Σ2-,3-OH-Flu, and 1-OH-Pyr were 3.25 ng/mL, 2.0 ng/mL, and 2.3 ng/mL respectively. At the second follow-up, 78 % of the girls had reached menarche, and the median age of menarche was 12.7 ± 0.81 years. Girls whose mothers belonged to the second and third quintiles of ΣOH-Phe metabolites had a higher rate of menarche, indicating a younger menarcheal age (HR 1.39; 95 % CI 1.04, 1.86, and HR 1.41; 95 % CI 1.05, 1.88, respectively), than girls of mothers in the lowest quintile. This trend was not observed in relation to either breast or pubic hair development. None of the other maternal urinary PAH metabolites or the sum of all thereof in early pregnancy were associated with age at menarche or pubertal stage. CONCLUSIONS: Indications of non-monotonic associations of prenatal phenanthrene exposure with the daughters' age of menarche were found, warranting further investigation.

Metal mixture exposures and serum lipid levels in childhood: the Rhea mother-child cohort in Greece.

BACKGROUND: Growing evidence suggests that cardiovascular disease develops over the lifetime, often beginning in childhood. Metal exposures have been associated with cardiovascular disease and important risk factors, including dyslipidemia, but prior studies have largely focused on adult populations and single metal exposures. OBJECTIVE: To investigate the individual and joint impacts of multiple metal exposures on lipid levels during childhood. METHODS: This cross-sectional study included 291 4-year-old children from the Rhea Cohort Study in Heraklion, Greece. Seven metals (manganese, cobalt, selenium, molybdenum, cadmium, mercury, and lead) were measured in whole blood using inductively coupled plasma mass spectrometry. Serum lipid levels included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. To determine the joint and individual impacts of child metal exposures (log2-transformed) on lipid levels, Bayesian kernel machine regression (BKMR) was employed as the primary multi-pollutant approach. Potential effect modification by child sex and childhood environmental tobacco smoke exposure was also evaluated. RESULTS: BKMR identified a positive association between the metal mixture and both total and LDL cholesterol. Of the seven metals examined, selenium (median 90.6 [IQR = 83.6, 96.5] µg/L) was assigned the highest posterior inclusion probability for both total and LDL cholesterol. A difference in LDL cholesterol of 8.22 mg/dL (95% CI = 1.85, 14.59) was observed when blood selenium was set to its 75th versus 25th percentile, holding all other metals at their median values. In stratified analyses, the positive association between selenium and LDL cholesterol was only observed among boys or among children exposed to environmental tobacco smoke during childhood. IMPACT STATEMENT: Growing evidence indicates that cardiovascular events in adulthood are the consequence of the lifelong atherosclerotic process that begins in childhood. Therefore, public health interventions targeting childhood cardiovascular risk factors may have a particularly profound impact on reducing the burden of cardiovascular disease. Although growing evidence supports that both essential and nonessential metals contribute to cardiovascular disease and risk factors, such as dyslipidemia, prior studies have mainly focused on single metal exposures in adult populations. To address this research gap, the current study investigated the joint impacts of multiple metal exposures on lipid concentrations in early childhood.

Accelerometer-Measured Physical Activity, Fitness and Indicators of Cardiometabolic Risk among Rural Adolescents: A Cross-Sectional Study at 15-Year Follow-up of the MINIMat Cohort.

BACKGROUND: Little is known about the relationship of physical activity (PA) and fitness with cardiometabolic risk among rural adolescents in low- and middle-income countries. Thus, we examined the associations of PA and fitness with selected cardiometabolic indicators along with potential gender-based differences in a birth cohort of rural adolescents from southeast Bangladesh. METHODS: We utilized data from the 15-year follow-up of Maternal and Infant Nutrition Interventions in Matlab (MINIMat) cohort (n = 2253). Wrist-worn ActiGraph wGT3x-BT accelerometers were used to estimate sedentary time (ST) and PA. Fitness was assessed using: handgrip strength, standing long jump, and Chester Step Test. Anthropometric parameters, systolic blood pressure (SBP), and fasting lipid, insulin and glucose levels were measured. We calculated insulin resistance using the Homeostasis Model Assessment equation (HOMA-IR). Linear regression and isotemporal substitution models were fitted. RESULTS: The adolescents spent 64 min/day (inter-quartile range: 50-81) in moderate-to-vigorous physical activity (MVPA). A 10-minute-per-day higher vigorous PA (VPA) was associated with: 4.9% (95% confidence interval (CI): 2.9-6.8%) lower waist circumference (WC), 3.2 mmHg (95% CI: 1.5-4.8) lower SBP, 10.4% (95% CI: 2.9-17.3%) lower TG, and 24.4% (95% CI: 11.3-34.9%) lower HOMA-IR. MVPA showed similar associations of notably smaller magnitude. Except for WC, the associations were more pronounced among the boys. Substituting ST with VPA of equal duration was associated with lower WC, SBP, triglyceride and HOMA-IR. Grip strength was favorably associated with all indicators, displaying considerably large effect sizes. CONCLUSION: Our findings indicated beneficial roles of PA- particularly VPA- and muscular fitness in shaping cardiometabolic profile in mid-adolescence. VPA and grip strength may represent potential targets for preventive strategies tailored to adolescents in resource-limited settings.

Manganese - a scoping review for Nordic Nutrition Recommendations 2023.

Manganese is an essential trace element that is required for multiple enzymes in the human body. The general population is mainly exposed to manganese via food intake, in particular plant foods. In areas with elevated concentrations of manganese in groundwater, drinking water can also be an important source of exposure. The gastrointestinal absorption of manganese is below 10%, and it appears to be influenced by the amount of manganese in the diet and by the nutritional status of the individual, especially the iron status. In blood, most of the manganese is found in the cellular fractions. Manganese is primarily eliminated via the bile followed by excretion via faeces. To date, no specific biomarkers of manganese intake have been identified. The dietary intake of manganese in the Nordic countries has been reported to be within the range that has been reported for other European countries (2-6 mg/day). Since manganese is found in nutritionally adequate amounts in food, deficiency is not of public health concern. On the other hand, there is emerging epidemiological evidence that various suggested manganese biomarkers may be negatively associated with children's neurodevelopment. However, the limited number of prospective studies, the lack of appropriate exposure biomarkers, and validated neurodevelopmental outcomes render data uncertain and inconclusive. In 2013, the European Food Safety Authority considered the evidence to be insufficient to derive an average requirement or a population reference intake, and instead an adequate intake for adults was set at 3.0 mg/day.

Toxic metals and essential trace elements in placenta and their relation to placental function.

INTRODUCTION: Placental function is essential for fetal development, but it may be susceptible to malnutrition and environmental stressors. OBJECTIVE: To assess the impact of toxic and essential trace elements in placenta on placental function. METHODS: Toxic metals (cadmium, lead, mercury, cobalt) and essential elements (copper, manganese, zinc, selenium) were measured in placenta of 406 pregnant women in northern Sweden using ICP-MS. Placental weight and birth weight were obtained from hospital records and fetoplacental weight ratio was used to estimate placental efficiency. Placental relative telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) were determined by quantitative PCR (n = 285). Single exposure-outcome associations were evaluated using linear or spline regression, and joint associations and interactions with Bayesian kernel machine regression (BKMR), all adjusted for sex, maternal smoking, and age or BMI. RESULTS: Median cadmium, mercury, lead, cobalt, copper, manganese, zinc, and selenium concentrations in placenta were 3.2, 1.8, 4.3, 2.3, 1058, 66, 10626, and 166 µg/kg, respectively. In the adjusted regression, selenium (>147 µg/kg) was inversely associated with placental weight (B: -158; 95 % CI: -246, -71, per doubling), as was lead at low selenium (B: -23.6; 95 % CI: -43.2, -4.0, per doubling). Manganese was positively associated with placental weight (B: 41; 95 % CI: 5.9, 77, per doubling) and inversely associated with placental efficiency (B: -0.01; 95 % CI: -0.019, -0.004, per doubling). Cobalt was inversely associated with mtDNAcn (B: -11; 95 % CI: -20, -0.018, per doubling), whereas all essential elements were positively associated with mtDNAcn, individually and joint. CONCLUSION: Among the toxic metals, lead appeared to negatively impact placental weight and cobalt decreased placental mtDNAcn. Joint essential element concentrations increased placental mtDNAcn. Manganese also appeared to increase placental weight, but not birth weight. The inverse association of selenium with placental weight may reflect increased transport of selenium to the fetus in late gestation.

Arsenic exposure and increased C-reactive protein are independently associated with lower erythrocyte glutathione peroxidase activity in Bangladeshi children.

Toxic metal contaminants present in food and water have widespread effects on health and disease. Chalcophiles, such as arsenic, cadmium, and mercury, show a high affinity to selenium and exposure to these metals could have a modulating effect on enzymes dependent on selenocysteine in their active sites. The aim of this study was to assess the influence of these metals on the activity of the selenoprotein glutathione peroxidase 1 (GPX1) in erythrocytes of 100 children residing in rural Bangladesh, where drinking water often contains arsenic. GPX1 expression, as measured using high-throughput immunoblotting, showed little correlation with GPX activity (rs = 0.02, p = 0.87) in blood samples. Toxic metals and selenium measured in erythrocytes using inductively coupled plasma mass spectrometry (ICP-MS) and C-reactive protein (CRP) measured in plasma, were all considered as effectors of this divergence in GPX enzymatic activity. Arsenic concentrations in erythrocytes were most influential for GPX1 activity (rs = -0.395, p < 0.0001), and CRP levels also negatively impacted GPX1 activity (rs = -0.443, p < 0.0001). These effects appear independent of each other as arsenic concentrations and CRP showed no correlation (rs = 0.124, p = 0.2204). Erythrocyte selenium, cadmium, and mercury did not show any correlation with GPX1 activity, nor with CRP or arsenic. Our findings suggest that childhood exposure to inorganic arsenic, as well as inflammation triggering the release of CRP, may negatively affect GPX1 activity in erythrocytes.

Prediagnostic Blood Metal Levels and the Risk of Parkinson's Disease: A Large European Prospective Cohort.

BACKGROUND: Metals have been postulated as environmental concerns in the etiology of Parkinson's disease (PD), but metal levels are typically measured after diagnosis, which might be subject to reverse causality. OBJECTIVE: The aim of this study was to investigate the association between prediagnostic blood metal levels and PD risk. METHODS: A case-control study was nested in a prospective European cohort, using erythrocyte samples collected before PD diagnosis. RESULTS: Most assessed metals were not associated with PD risk. Cadmium has a suggestive negative association with PD (odds ratio [95% confidence interval] for the highest quartile, 0.70 [0.42-1.17]), which diminished among never smokers. Among current smokers only, lead was associated with decreased PD risk (0.06 [0.01-0.35]), whereas arsenic showed associations toward an increased PD risk (1.85 [0.45-7.93]). CONCLUSIONS: We observe no strong evidence to support a role of metals in the development of PD. In particular, smoking may confound the association with tobacco-derived metals. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Associations of gestational and early-life exposure to toxic metals and fluoride with a diagnosis of food allergy or atopic eczema at 1 year of age.

Studies have indicated that early-life exposure to toxic metals and fluoride affects the immune system, but evidence regarding their role in allergic disease development is scarce. We aimed to evaluate the relations of exposure to such compounds in 482 pregnant women and their infants (4 months of age) with food allergy and atopic eczema diagnosed by a paediatric allergologist at 1 year of age within the Swedish birth-cohort NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment). Urinary cadmium and erythrocyte cadmium, lead, and mercury concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS), urinary inorganic arsenic metabolites by ICP-MS after separation by ion exchange chromatography, and urinary fluoride by an ion-selective electrode. The prevalence of food allergy and atopic eczema was 8 and 7%, respectively. Gestational urinary cadmium, reflecting chronic exposure, was associated with increased odds of infant food allergy (OR [95% CI]: 1.34 [1.09, 1.66] per IQR [0.08 µg/L]). Both gestational and infant urinary fluoride were associated, albeit at a statistically non-significant level, with increased atopic eczema odds (1.48 [0.98, 2.25], 1.36 [0.95, 1.95], per doubling, respectively). By contrast, gestational and infant erythrocyte lead was associated with decreased odds of atopic eczema (0.48 [0.26, 0.87] per IQR [6.6 µg/kg] and 0.38 [0.16, 0.91] per IQR [5.94 µg/kg], respectively), and infant lead with decreased odds of food allergy (0.39 [0.16, 0.93] per IQR [5.94 µg/kg]). Multivariable adjustment had marginal impact on the estimates above. After additional adjustment for fish intake biomarkers, the methylmercury associated atopic-eczema odds were considerably increased (1.29 [0.80, 2.06] per IQR [1.36 µg/kg]). In conclusion, our results indicate that gestational cadmium exposure might be associated with food allergy at 1 year of age and, possibly, early-life exposure to fluoride with atopic eczema. Further prospective and mechanistic studies are needed to establish causality.

Urinary phosphate is associated with cardiovascular disease incidence.

INTRODUCTION: Elevated phosphate (P) in urine may reflect a high intake of inorganic P salts from food additives. Elevated P in plasma is linked to vascular dysfunction and calcification. OBJECTIVE: To explore associations between P in urine as well as in plasma and questionnaire-estimated P intake, and incidence of cardiovascular disease (CVD). METHODS: We used the Swedish Mammography Cohort-Clinical, a population-based cohort study. At baseline (2004-2009), P was measured in urine and plasma in 1625 women. Dietary P was estimated via a food-frequency questionnaire. Incident CVD was ascertained via register-linkage. Associations were assessed using Cox proportional hazards regression. RESULTS: After a median follow-up of 9.4 years, 164 composite CVD cases occurred (63 myocardial infarctions [MIs] and 101 strokes). Median P (percentiles 5-95) in urine and plasma were 2.4 (1.40-3.79) mmol/mmol creatinine and 1.13 (0.92-1.36) mmol/L, respectively, whereas dietary P intake was 1510 (1148-1918) mg/day. No correlations were observed between urinary and plasma P (r = -0.07) or dietary P (r = 0.10). Urinary P was associated with composite CVD and MI. The hazard ratio of CVD comparing extreme tertiles was 1.57 (95% confidence interval 1.05, 2.35; P trend 0.037)-independently of sodium excretion, the estimated glomerular filtration rate, both P and calcium in plasma, and diuretic use. Association with CVD for plasma P was 1.41 (0.96, 2.07; P trend 0.077). CONCLUSION: Higher level of urinary P, likely reflecting a high consumption of highly processed foods, was linked to CVD. Further investigation is needed to evaluate the potential cardiovascular toxicity associated with excessive intake of P beyond nutritional requirements.

Polycyclic aromatic hydrocarbon (PAH) exposure during pregnancy and child anthropometry from birth to 10 years of age: Sex-specific evidence from a cohort study in rural Bangladesh.

Polycyclic aromatic hydrocarbons (PAHs) have endocrine disrupting properties and they cross the placental barrier, but studies on gestational exposure and child anthropometry are inconclusive. We aimed to elucidate the impact of early gestational PAH exposure on anthropometry from birth to 10 years of age in 1295 mother-child pairs from a nested sub-cohort of the MINIMat trial in Bangladesh. Several PAH metabolites [1-hydroxyphenanthrene (1-OH-Phe), Σ2-,3-hydroxyphenanthrene (Σ2-,3-OH-Phe), 4-hydroxyphenanthrene (4-OH-Phe), 1-hydroxypyrene (1-OH-Pyr), Σ2-,3-hydroxyfluorene (Σ2-,3-OH-Flu)] were quantified in spot urine collected around gestational week 8 using LC-MS/MS. Child weight and height were measured at 19 occasions from birth to 10 years. Multivariable-adjusted regression models were used to assess associations of maternal PAH metabolites (log2-transformed) with child anthropometry. The median concentration of 1-OH-Phe, Σ2-,3-OH-Phe, 4-OH-Phe, 1-OH-Pyr and Σ2-,3-OH-Flu was 1.5, 1.9, 0.14, 2.5, and 2.0 ng/mL, respectively. All maternal urinary PAH metabolites were positively associated with newborn weight and length and all associations were more pronounced in boys than in girls (p interaction for all <0.14). In boys, the strongest associations were observed with Σ2-,3-OH-Phe and Σ2-,3-OH-Flu for which each doubling increased mean birth weight by 41 g (95% CI: 13; 69 and 12; 70) and length by 0.23 cm (0.075; 0.39) and 0.21 cm (0.045; 0.37), respectively. Maternal urinary PAH metabolites were not associated with child anthropometry at 10 years. In longitudinal analysis, however, maternal urinary PAH metabolites were positively associated with boys' weight-for-age (WAZ) and height-for-age Z-scores (HAZ) from birth to 10 years, but only the association of 4-OH-Phe with HAZ was significant (B: 0.080 Z-scores; 95% CI 0.013, 0.15). No associations were observed with girls' WAZ or HAZ. In conclusion, gestational PAH exposure was positively associated with fetal and early childhood growth, especially in boys. Further studies are needed to confirm causality and to explore long-term health effects.

Biomarkers of seafood intake during pregnancy - Pollutants versus fatty acids and micronutrients.

Intake of fish and seafood during pregnancy may have certain beneficial effects on fetal development, but measurement of intake using questionnaires is unreliable. Here, we assessed several candidate biomarkers of seafood intake, including long-chain omega 3 fatty acids (n-3 LCPUFA), selenium, iodine, methylmercury, and different arsenic compounds, in 549 pregnant women (gestational week 29) in the prospective birth cohort NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment). Proportions of the fatty acids eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) in erythrocytes were measured using gas chromatography with flame ionization detector. Selenium was measured in blood plasma and erythrocytes, mercury and arsenic in erythrocytes, and iodine and several arsenic compounds in urine, using inductively coupled plasma mass spectrometry, arsenic compounds after first being separated by ion exchange high-performance liquid chromatography (HPLC). Each biomarker was related to intake of total seafood and to intake of fatty and lean fish, and shellfish in third trimester, estimated from a semi-quantitative food frequency questionnaire filled out in gestational week 34. The pregnant women reported a median total seafood intake of 184 g/week (5th-95th percentiles: 34-465 g/week). This intake correlated most strongly with erythrocyte mercury concentrations (rho = 0.49, p < 0.001), consisting essentially of methylmercury, followed by total arsenic in erythrocytes (rho = 0.34, p < 0.001), and arsenobetaine in urine (rho = 0.33, p < 0.001), the main form of urinary arsenic. These biomarkers correlated well with intake of both fatty fish, lean fish, and shellfish. Erythrocyte DHA and plasma selenium correlated, although weakly, mainly with fatty fish (rho = 0.25 and 0.22, respectively, both p < 0.001). In conclusion, elevated concentrations of erythrocyte mercury and urinary arsenobetaine can be useful indicators of seafood intake, more so than the n-3 LCPUFAs. However, the relative importance of the biomarkers may differ depending on the type and amount of seafood consumed.

Early Life Environmental Exposure to Cadmium, Lead, and Arsenic and Age at Menarche: A Longitudinal Mother-Child Cohort Study in Bangladesh.

BACKGROUND: Several metals act as endocrine disruptors, but there are few large longitudinal studies about associations with puberty onset. OBJECTIVES: We evaluated whether early life cadmium, lead, and arsenic exposure was associated with timing of menarche. METHODS: In a mother-child cohort in rural Bangladesh (n=935), the exposure was assessed by concentrations in maternal erythrocytes in early pregnancy and in girls' urine at 5 and 10 years of age using inductively coupled plasma mass spectrometry. The girls were interviewed twice, at average ages 13.3 [standard deviation (SD)=0.43] and 13.8 (SD=0.43) y, and the date of menarche, if present, was recorded. Associations were assessed using Kaplan-Meier analysis and multivariable-adjusted Cox regression. RESULTS: In total, 77% of the girls (n=717) had reached menarche by the second follow-up. The median age of menarche among all girls was 13.0 y (25th-75th percentiles: 12.4-13.7 y). At 10 years of age, median urinary cadmium was 0.25µg/L (5th-95th percentiles: 0.087-0.72µg/L), lead 1.6µg/L (0.70-4.2µg/L), and arsenic 54µg/L (19-395µg/L). Given the same age, girls in the highest quartile of urinary cadmium at 5 and 10 years of age had a lower rate of menarche than girls in the lowest quartile, with an adjusted hazard ratio of (HR) 0.80 (95% CI: 0.62, 1.01) at 5 years of age, and 0.77 (95% CI: 0.60, 0.98) at 10 years of age. This implies that girls in the highest cadmium exposure quartile during childhood had a higher age at menarche. Comparing girls in the highest to the lowest quartile of urinary lead at 10 years of age, the former had a higher rate of menarche [adjusted HR = 1.23 (95% CI: 0.97, 1.56)], implying lower age at menarche, whereas there was no association with urinary lead at 5 years of age. Girls born to mothers in the highest quartile of erythrocyte arsenic during pregnancy were less likely to have attained menarche than girls born to mothers in the lowest quartile [adjusted HR= 0.79 (95% CI: 0.62, 0.99)]. No association was found with girls' urinary arsenic exposure. DISCUSSION: Long-term childhood cadmium exposure was associated with later menarche, whereas the associations with child lead exposure were inconclusive. Maternal exposure to arsenic, but not cadmium or lead, was associated with later menarche. https://doi.org/10.1289/EHP11121.

Dietary patterns and indicators of cardiometabolic risk among rural adolescents: A cross-sectional study at 15-year follow-up of the MINIMat cohort.

Background: Diet being a modifiable factor, its relationship with cardiometabolic risk is of public health interest. The vast majority of studies on associations of dietary patterns with cardiometabolic risk indicators among adolescents are from high-income countries and urban settings. We sought to describe dietary patterns and examine their associations with selected cardiometabolic risk indicators-waist circumference (WC), systolic blood pressure, fasting lipid profile and insulin resistance-along with its gender stratification among adolescents in a low-income, rural setting. Methods: This cross-sectional study utilized data from the 15-year follow-up of the Maternal and Infant Nutrition Interventions in Matlab (MINIMat) cohort in southeast Bangladesh. The children who were born as singletons to the mothers randomized in the MINIMat trial and had valid birth anthropometrics were eligible for the follow-up. We employed a single, qualitative 24-hour recall to assess diet. Dietary patterns were derived from simple K-means cluster analysis, and calculation of dietary diversity score (DDS) using a validated instrument. Anthropometric parameters and systolic blood pressure were recorded. Fasting plasma triglyceride, total cholesterol, low- and high-density lipoproteins, insulin and glucose levels were measured. We calculated insulin resistance using the Homeostasis Model Assessment equation (HOMA-IR). Three right-skewed outcome variables were natural log (Ln) transformed: WC, triglyceride and HOMA-IR. Omnibus and gender-specific multiple linear regression models were fitted. Results: Among 2,253 adolescents (52.1% girls, 7.1% overweight/obese), we identified four diet clusters: Traditional, Fish-dominant, Meat-dominant, and High-variety. No significant associations were found between the clusters and indicators. On gender-stratification, triglyceride levels were lower among boys in the Fish-dominant (Ln-triglyceride ßadjusted: -0.09; 95% confidence interval (CI): -0.15, -0.02) and Meat-dominant (Ln-triglyceride ßadjusted: -0.08; 95% CI: -0.15, -0.004) clusters than among boys in the Traditional cluster. Compared to boys in the bottom quartile of DDS, boys in the top quartile had 2.1 mm of Hg (95% CI: 0.5, 3.6) higher systolic blood pressure and 1.9% (95% CI: 0.01-3.8%) higher WC. Conclusion: While statistically significant, the gender-specific differences in triglyceride, systolic blood pressure, and waist circumference across dietary patterns were small. Associations between dietary patterns and cardiometabolic risk indicators may require a time lag beyond mid-adolescence to manifest in a rural setting. Prospective studies are warranted to delineate the magnitude and direction of those associations.

Gestational and childhood urinary iodine concentrations and children's cognitive function in a longitudinal mother-child cohort in rural Bangladesh.

BACKGROUND: Severe iodine deficiency adversely affects neurodevelopment; however, evidence regarding the association of non-severe deficiency and child cognitive functioning is inconclusive. METHODS: This prospective mother-child cohort study was nested in a population-based nutritional supplementation trial in Bangladesh (Maternal and Infant Nutrition Interventions in Matlab [MINIMat]). Participants with data on cognitive abilities at 5 and 10 years of age (n = 1530) and at least one measurement of urinary iodine concentration (UIC) (gestational week 8, 5, and 10 years) were selected. Cognitive abilities were assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and Wechsler Intelligence Scale for Children (WISC-IV). UICs were measured with inductively coupled plasma mass spectrometry and thereafter adjusted for specific gravity. RESULTS: Median UICs in our population: (282 µg/L [pregnancy]; 406 µg/L [5 years]; 294 µg/L [10 years]) indicated that iodine intake corresponded to above 'adequate' or even 'excessive', according to the WHO classification. Maternal 'UIC <150 µg/L' was associated with lower full-scale and verbal scores at 5 and 10 years, although the associations were weakened in the fully adjusted models. A tendency of decreased verbal scores was also observed for maternal 'UIC ≥500 µg/L' but not for the corresponding child iodine category (≥300 µg/L). Child 'UIC <100 µg/L' was associated with lower processing speed (B=-3.1, 95% CI [-6.2, -0.1]; P-value = 0.041) compared with the reference group (100 µg/L≤ UIC <300 µg/L). CONCLUSIONS: Current findings add to the growing evidence of a causal association of early-life iodine intake with cognitive development, indicating that low iodine intake during childhood is associated with reduced processing speed and non-optimal gestational iodine intake is weakly associated with slightly poorer verbal development outcomes.

Fluoride - a scoping review for Nordic Nutrition Recommendations 2023.

Fluoride has a well-documented role in the prevention and treatment of dental caries, but the mechanism is attributed to local effects on the tooth enamel surface rather than systemic effects. Fluoride is not considered essential for humans, no deficiencies are known, and no optimal range, which will not result in moderate fluorosis in some individuals, can be set. Recently, research studies have shown evidence for a relationship between fluoride intake and cognitive outcomes and interaction with iodine nutrition, but the evidence is weak so more data are warranted. For performing longitudinal cohort studies in the Nordic and Baltic region, data on fluoride in food and beverages need to be implemented in food composition tables. As the preventive effects of fluoride are mainly from topical treatment, monitoring of fluoride intake and establishing reference values for fluoride in urine and plasma are warranted to establish safe intake values.

Molybdenum - a scoping review for Nordic Nutrition Recommendations 2023.

Molybdenum is an essential element in the form of the molybdenum cofactor (Moco). In humans, Moco is required for four enzymes: xanthine oxidase (XO), aldehyde oxidase, sulfite oxidase (SO), and mitochondrial amidoxime-reducing component (mARC). The enzymes are involved in the oxidation of purines to uric acid, metabolism of aromatic aldehydes and heterocyclic compounds, and in the catabolism of sulfur amino acids. Molybdenum cofactor deficiency is a rare autosomal recessive syndrome due to a defective synthesis of Moco, resulting in a deficiency of all the molybdoenzymes. There are no reports on clinical signs of dietary molybdenum deficiency in otherwise healthy humans. Water-soluble molybdate is efficiently absorbed from the digestive tract. The body retention is regulated by urinary excretion. Plasma molybdenum reflects long-term intake and 24-h urinary excretion is related to recent intake. There are no biochemical markers of molybdenum status. Cereal products are the main contributors to molybdenum dietary intake, estimated to 100-170 µg/day in Nordic studies. Little data are available on molybdenum toxicity in humans. A tolerable upper intake level of molybdenum has been based on reproductive toxicity in rats, but the effects have not been reproduced in more recent studies. The U.S. Institute of Medicine (IOM, present National Academy of Sciences, Engineering, and Medicine; NASEM) established a Recommended Dietary Allowance of 45 µg/day in adult men and women in 2001, based on a small study reporting urinary excretion in balance with intake at 22 µg/day. The European Food Safety Authority (EFSA) considered in 2013 the evidence to be insufficient to derive an Average Requirement and a Population Reference Intake, but proposed an Adequate Intake of 65 µg/day for adults.

Association of maternal urinary fluoride concentrations during pregnancy with size at birth and the potential mediation effect by maternal thyroid hormones: The Swedish NICE birth cohort.

BACKGROUND: Observational studies have indicated that elevated maternal fluoride exposure during pregnancy may impair child neurodevelopment but a potential impact on birth outcomes is understudied. OBJECTIVES: To evaluate the impact of gestational fluoride exposure on birth outcomes (birth size and gestational age at birth) and to assess the potential mediating role of maternal thyroid hormones. METHODS: We studied 583 mother-child dyads in the NICE cohort in northern Sweden. Maternal fluoride exposure was assessed by measuring urinary concentrations at late pregnancy (median: 29th gestational week) using an ion selective electrode. Plasma levels of free and total thyroxine (fT4, tT4) and triiodothyronine (fT3, tT3), and thyroid stimulating hormone (TSH) were measured with electrochemiluminescence immunoassays. The infant's weight, length, head circumference, and gestational age at birth were extracted from hospital records. RESULTS: Median urinary fluoride concentration was 0.71 mg/L (5th-95th percentile 0.31-1.9 mg/L; specific gravity adjusted). In multivariable-adjusted regression models, every 1 mg/L increase of maternal urinary fluoride was associated with a mean increase in birth weight by 84 g (95%CI: 30, 138), length by 0.41 cm (95%CI: 0.18, 0.65), head circumference by 0.3 cm (95%CI: 0.1, 0.4), and with increased odds of being born large for gestational age (OR = 1.39, 95%CI: 1.03, 1.89). Every 1 mg/L increase of maternal urinary fluoride was also associated with a mean increase of the plasma fT3:fT4 ratio (B = 0.007, 95%CI: 0.000, 0.014), but not with the hormones or TSH. In mediation analyses, the maternal fT3:fT4 ratio did not explain the urinary fluoride-birth size relationships. DISCUSSION: Gestational urinary fluoride concentrations were associated with increased size at birth and even with increased odds of being born large for gestational age. The fluoride-related associations with increased size at birth were not explained by changes in maternal thyroid hormone levels.