Dietary Influences on Urinary Fluoride over the Course of Pregnancy and at One-Year Postpartum.

Dietary factors are known to influence urinary fluoride (UF) levels in nonpregnant people. Maternal UF is used as a biomarker of fluoride exposure; however, dietary influences on UF during pregnancy are unknown. We compared UF levels and assessed the associations between UF and five select dietary influences in pregnancy vs. one-year postpartum: dietary fluoride (F), calcium intake from diet (Ca-diet), calcium intake from supplements (Ca-sup), dietary acid load (AL), and table salt use (TS) in 421 women exposed to fluoridated salt in the Mexican diet. Spot UF (mg/L) was measured by microdiffusion/fluoride-specific electrode and dilution-corrected with specific gravity (SG). Dietary variables were estimated from a validated Food Frequency Questionnaire. Comparisons among UF in pregnancy vs. one-year postpartum were performed with non-parametric tests. Associations between dietary variables and UF were assessed using random effect models (for pregnancy) and linear regression (for one-year postpartum). SG-corrected UF (median, range) during pregnancy (0.77, 0.01-4.73 mg/L) did not significantly differ from one-year postpartum (0.75, 0.15-2.62 mg/L) but did increase every 10 gestational weeks, ß = 0.05 (CI: 0.00-0.10). Different dietary influences on UF were identified at each state. Although Ca-diet and AL were not associated with UF in either state, Ca-sup decreased UF only during pregnancy, ß = - 0.012 mg/L (CI: - 0.023-0.00). Reporting TS use was associated with 12% increase in UF only at one-year postpartum (p = 0.026). These results suggest different dietary influences on UF in the pregnant state, which need consideration when using UF as a biomarker of fluoride exposure.

Association between cumulative childhood blood lead exposure and hepatic steatosis in young Mexican adults.

BACKGROUND: Exposure to environmental toxicants may play a role in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD). Cumulative exposure to lead (Pb) has chronic and permanent effects on liver function. Pediatric populations are vulnerable to the toxic effects of Pb, even at low exposure levels. The purpose of the study was to estimate the association between cumulative Pb exposure during childhood and hepatic steatosis biomarkers in young Mexican adults. METHODS: A subsample of 93 participants from the ELEMENT cohort were included in this study. Childhood blood samples were collected annually from ages 1-4 years and were used to calculate the Cumulative Childhood Blood Lead Levels (CCBLL). Hepatic steatosis during adulthood was defined as an excessive accumulation of hepatic triglycerides (>5%) determined using Magnetic Resonance Imaging (MRI). Liver enzymes were also measured at this time, and elevated liver enzyme levels were defined as ALT (≥30 IU/L), AST (≥30 IU/L), and GGT (≥40 IU/L). Adjusted linear regression models were fit to examine the association between CCBLL (quartiles) and the hepatic steatosis in young adulthood. RESULTS: In adulthood, the mean age was 21.4 years, 55% were male. The overall prevalence of hepatic steatosis by MRI was 19%. Elevate levels of the enzymes ALT, AST, and GGT were present in 25%, 15%, and 17% of the sample, respectively. We found a positive association between the highest quartile of CCBLL with the steatosis biomarkers of hepatic triglycerides (Q4 vs. Q1: ß = 6.07, 95% CI: 1.91-10.21), elevated ALT (Q4 vs. Q1: ß = 14.5, 95% CI: 1.39-27.61) and elevated AST (Q4 vs. Q1: ß = 7.23, 95% CI: 0.64-13.82). No significant associations were found with GGT. CONCLUSIONS: Chronic Pb exposure during early childhood is associated with a higher levels of hepatic steatosis biomarkers and hepatocellular injury in young adulthood. More actions should be taken to eliminate sources of Pb during the first years of life.

Dietary fluoride intake over the course of pregnancy in Mexican women.

OBJECTIVE: To estimate dietary fluoride intake (F) over the course of pregnancy and the overall adjusted difference in dietary F intake by pregnancy stages and levels of compliance with dietary recommendations. DESIGN: Secondary data analysis from a longitudinal pregnancy cohort study in a population exposed to fluoridated salt. Women were followed during the early, middle and late stages of their pregnancy (n 568). The dietary intake of recommended prenatal nutrients according to Mexican dietary guidelines and F intake (mg/d) was estimated with a validated FFQ. Data were summarised with descriptive statistics. Levels of F intake were compared with the USA's Institute of Medicine adequate intake (AI) of 3 mg/d for pregnancy. Adjusted differences in F intake by pregnancy stages and levels of compliance with recommendations were estimated using random effects models. SETTING: Mexico City. PARTICIPANTS: Women participating in the Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) project, from 2001 to 2003. RESULTS: Median dietary F intake throughout pregnancy ranged from 0·64 (interquartile range (IQR) 0·38) in the early to 0·70 (IQR 0·42) in the middle, and 0·72 (IQR 0·44) mg/d in the late stage (0·01 mg F/kg per d). Corresponding adjusted intakes of F were 0·72 (95 % CI 0·70, 0·74), 0·76 (95 % CI 0·74, 0·77) and 0·80 (95 % CI 0·78, 0·82) mg/d. Women who were moderately and highly compliant with Mexican dietary recommendations ingested, on average, 0·04 and 0·14 mg F/d more than non-compliant women (P < 0·005). CONCLUSIONS: Dietary F intake was below current AI, was greater with the progression of pregnancy and in women who were moderately and highly compliant with dietary recommendations.

Prenatal Lead Exposure, Type 2 Diabetes, and Cardiometabolic Risk Factors in Mexican Children at Age 10-18 Years.

CONTEXT: Several cross-sectional studies have assessed the association of lead exposure with type 2 diabetes and cardiometabolic risk factors in adults; however, studies of such associations in childhood are rare. OBJECTIVE: We assessed the prospective associations of prenatal exposure to lead with type 2 diabetes and cardiometabolic risk factors in children. DESIGN: The Early Life Exposure in Mexico to Environmental Toxicants is a birth cohort study of pregnant women and their offspring. SETTING: Public hospitals in Mexico City. PATIENTS OR OTHER PARTICIPANTS: Women were recruited during pregnancy; their offspring were recruited for a follow-up visit at age 10 to 18 years (n = 369). MAIN OUTCOME MEASURES: We measured fasting serum markers of type 2 diabetes and cardiometabolic risk factors in children, including fasting glucose, insulin, and lipids. The index of insulin resistance was calculated. RESULTS: The geometric mean of maternal blood lead levels (BLLs) during pregnancy was 4.3 µg/dL (95% confidence interval [CI]): 4.0-4.6 µg/dL) in the entire sample. In boys, those with maternal BLLs ≥ 5 µg/dL (compared with those with BLLs < 5 µg/dL) had significantly lower z scores for total cholesterol (ß = -0.41, 95% CI: -0.71, -0.12), high-density lipoprotein cholesterol (ß = -0.32, 95% CI: -0.59, -0.05), and low-density lipoprotein cholesterol (ß = -0.52, 95% CI: -0.81, -0.22), adjusting for covariates. No associations were detected in girls. CONCLUSIONS: In our study, we found that higher prenatal exposure to lead was associated with lower levels of cholesterol in children following a sex-specific pattern. Further studies with a larger sample size that examine whether sex is a potential modifier are needed to confirm our findings.

Association between fluoride exposure and cardiometabolic risk in peripubertal Mexican children.

BACKGROUND: Several animal studies have suggested that fluoride exposure may increase the levels of cardiometabolic risk factors, but little is known about whether fluoride exposure is associated with such risk in humans. OBJECTIVES: We examined the cross-sectional association between peripubertal exposure to fluoride and markers of cardiometabolic risk in 280 girls and 256 boys at age 10-18 years living in Mexico City. METHODS: We measured plasma fluoride concentration using a microdiffusion method. We collected data on anthropometry including BMI, waist circumference (WC) and trunk fat percentage. We measured serum markers of cardiometabolic risk, including fasting glucose, insulin and lipids. All the indicators of outcome were converted to age- and sex-specific z-scores. We also calculated a summary cardiometabolic risk score for each participant. Multivariable linear regression models were used to examine these associations. RESULTS: The geometric mean (95% confidence interval (CI)) of plasma fluoride was 0.21 µmol/L (0.20, 0.23 µmol/L) in the total sample. In girls, plasma fluoride concentrations were associated with higher z-scores for all the individual markers (except for lipids) and for the combined cardiometabolic risk score (risk score: ß = 1.28, 95% CI: 0.57-2.00, p-sex interaction = 0.02)), adjusting for covariates. No associations were found in boys. CONCLUSIONS: We found that higher peripubertal fluoride exposure at the levels observed in this study population was significantly associated with increased levels of cardiometabolic risk factors in Mexican girls but not boys. Future studies with a longitudinal design are needed to confirm our findings and further elucidate the role of fluoride in cardiometabolic risk.

Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project.

PURPOSE: The Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project is a mother-child pregnancy and birth cohort originally initiated in the mid-1990s to explore: (1) whether enhanced mobilisation of lead from maternal bone stores during pregnancy poses a risk to fetal and subsequent offspring neurodevelopment; and (2) whether maternal calcium supplementation during pregnancy and lactation can suppress bone lead mobilisation and mitigate the adverse effects of lead exposure on offspring health and development. Through utilisation of carefully archived biospecimens to measure other prenatal exposures, banking of DNA and rigorous measurement of a diverse array of outcomes, ELEMENT has since evolved into a major resource for research on early life exposures and developmental outcomes. PARTICIPANTS: n=1643 mother-child pairs sequentially recruited (between 1994 and 2003) during pregnancy or at delivery from maternity hospitals in Mexico City, Mexico. FINDINGS TO DATE: Maternal bone (eg, patella, tibia) is an endogenous source for fetal lead exposure due to mobilisation of stored lead into circulation during pregnancy and lactation, leading to increased risk of miscarriage, low birth weight and smaller head circumference, and transfer of lead into breastmilk. Daily supplementation with 1200 mg of elemental calcium during pregnancy and lactation reduces lead resorption from maternal bone and thereby, levels of circulating lead. Beyond perinatal outcomes, early life exposure to lead is associated with neurocognitive deficits, behavioural disorders, higher blood pressure and lower weight in offspring during childhood. Some of these relationships were modified by dietary factors; genetic polymorphisms specific for iron, folate and lipid metabolism; and timing of exposure. Research has also expanded to include findings published on other toxicants such as those associated with personal care products and plastics (eg, phthalates, bisphenol A), other metals (eg, mercury, manganese, cadmium), pesticides (organophosphates) and fluoride; other biomarkers (eg, toxicant levels in plasma, hair and teeth); other outcomes (eg, sexual maturation, metabolic syndrome, dental caries); and identification of novel mechanisms via epigenetic and metabolomics profiling. FUTURE PLANS: As the ELEMENT mothers and children age, we plan to (1) continue studying the long-term consequences of toxicant exposure during the perinatal period on adolescent and young adult outcomes as well as outcomes related to the original ELEMENT mothers, such as their metabolic and bone health during perimenopause; and (2) follow the third generation of participants (children of the children) to study intergenerational effects of in utero exposures. TRIAL REGISTRATION NUMBER: NCT00558623.

Dietary Intake of Selenium in Relation to Pubertal Development in Mexican Children.

Alterations in pubertal timing have been associated with long-term health outcomes. While a few reports have shown that dietary intake of selenium is associated with fertility and testosterone levels in men, no human studies have considered the association between selenium and pubertal development in children. We examined the cross-sectional association of childhood dietary intake of selenium with pubertal development among 274 girls and 245 boys aged 10-18 years in Mexico City. Multiple logistic and ordinal regression models were used to capture the association between energy-adjusted selenium intake (below Recommended Dietary Allowance (RDA) vs. above RDA) and stages of sexual maturity in children, adjusted for covariates. We found that boys with consumption of selenium below the RDA had lower odds of a higher stage for pubic hair growth (odds ratio (OR) = 0.51, 95% confidence interval (95% CI): 0.27-0.97) and genital development (OR = 0.53, 95% CI: 0.28-0.99) as well as a lower probability of having matured testicular volume (OR = 0.37, 95% CI: 0.15-0.88) compared with boys who had adequate daily dietary intake of selenium (above RDA). No associations were found in girls. According to our results, it is possible that inadequate consumption of selenium may be associated with later pubertal development in boys, suggesting a sex-specific pattern. Future work with a larger sample size and measures of selenium biomarkers is needed to confirm our findings and improve understanding of the role of this mineral in children's sexual development.

Early lead exposure and childhood adiposity in Mexico city.

BACKGROUND: Prenatal and early childhood lead exposures have been associated with reduced weight in infants and young children, while studies that have examined such associations in children during peripubescence are rare. OBJECTIVES: We investigated the associations of prenatal and early-life exposure to lead with indices of adiposity in peripubertal children living in Mexico City. METHODS: Maternal bone lead (as a proxy for cumulative fetal exposure) was assessed at 1 month postpartum. Blood samples were obtained from children annually from 1 to 4 years. Multivariable linear regression models were used to examine the association between each lead biomarker and BMI z-score, waist circumference, sum of skinfolds and body fat percentage in 248 children aged 8-16 years. RESULTS: After adjusting for covariates, maternal patella lead was associated with lower child BMI z-score (ß = -0.02, 95% CI: 0.03, -0.01, p = 0.004), waist circumference (ß = -0.12 cm, 95% CI: 0.22, -0.03, p = 0.01), sum of skinfolds (ß = -0.29 mm, 95% CI: 0.50, -0.08, p = 0.007) and body fat percentage (ß = -0.09%, 95% CI: 0.17, -0.01, p = 0.03). No significant associations were detected from the postnatal exposure period. CONCLUSIONS: We observed a significant and inverse association of prenatal lead exposure with body composition in Mexican children, suggesting the potential role of early lead exposure in the fetal programming of child growth. Further research on the biological mechanisms underlying these associations is needed.

Dietary Sources of Fructose and Its Association with Fatty Liver in Mexican Young Adults.

Fructose intake has been associated with non-alcoholic fatty liver disease (NAFLD). The objective of this study was to assess the consumption of dietary fructose according to: 1) classification of hepatic steatosis by two indexes and 2) diagnosis of NAFLD by MRI. We conducted a cross-sectional analysis among 100 young adults from Mexico City. The Hepatic Steatosis Index (HSI) and the Fatty Liver Index (FLI) were estimated using Body Mass Index (BMI), waist circumference, and fasting concentrations of glucose, triglycerides, and hepatic enzymes (ALT, AST, GGT). A semi-quantitative food frequency questionnaire was administered to obtain dietary sources of fructose. We estimated the concordance between the hepatic indices and NAFLD and the correlation between the index scores and the percentage of liver fat. Eighteen percent presented NAFLD; 44% and 46% were classified with hepatic steatosis according to HSI and FLI, respectively. We compared dietary intake of fructose by each outcome: HSI, FLI, and NAFLD. Sugar-sweetened beverages (SSB) and juices were consumed significantly more by those with steatosis by FLI and NAFLD suggesting that SSB intake is linked to metabolic alterations that predict the risk of having NAFLD at a young age.

Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6-12 Years of Age in Mexico.

BACKGROUND: Some evidence suggests that fluoride may be neurotoxic to children. Few of the epidemiologic studies have been longitudinal, had individual measures of fluoride exposure, addressed the impact of prenatal exposures or involved more than 100 participants. OBJECTIVE: Our aim was to estimate the association of prenatal exposure to fluoride with offspring neurocognitive development. METHODS: We studied participants from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) project. An ion-selective electrode technique was used to measure fluoride in archived urine samples taken from mothers during pregnancy and from their children when 6-12 y old, adjusted for urinary creatinine and specific gravity, respectively. Child intelligence was measured by the General Cognitive Index (GCI) of the McCarthy Scales of Children's Abilities at age 4 and full scale intelligence quotient (IQ) from the Wechsler Abbreviated Scale of Intelligence (WASI) at age 6-12. RESULTS: We had complete data on 299 mother-child pairs, of whom 287 and 211 had data for the GCI and IQ analyses, respectively. Mean (SD) values for urinary fluoride in all of the mothers (n=299) and children with available urine samples (n=211) were 0.90 (0.35) mg/L and 0.82 (0.38) mg/L, respectively. In multivariate models we found that an increase in maternal urine fluoride of 0.5mg/L (approximately the IQR) predicted 3.15 (95% CI: -5.42, -0.87) and 2.50 (95% CI -4.12, -0.59) lower offspring GCI and IQ scores, respectively. CONCLUSIONS: In this study, higher prenatal fluoride exposure, in the general range of exposures reported for other general population samples of pregnant women and nonpregnant adults, was associated with lower scores on tests of cognitive function in the offspring at age 4 and 6-12 y. https://doi.org/10.1289/EHP655.

Association of Bisphenol A Exposure with Breastfeeding and Perceived Insufficient Milk Supply in Mexican Women.

Introduction Estrogen inhibits lactation and bisphenol A (BPA) is a high production environmental estrogen. We hypothesize an inhibitory effect of BPA on lactation and aim to analyze the association between third trimester pregnancy urinary BPA and breastfeeding rates 1 month postpartum. Methods Odds ratios (OR) and 95 % confidence intervals (95 % CI) of breastfeeding and perceived insufficient milk supply (PIM) in relation to maternal peripartum urinary BPA concentrations were calculated in 216 mothers. Results 97.2 % of mothers in the lowest BPA tertile were breastfeeding at 1 month postpartum, compared to 89.9 % in highest (p = 0.01). Adjusted ORs (95 % CI) for not breastfeeding at 1 month were 1.9 (0.3, 10.7) and 4.3 (0.8, 21.6) for second and third BPA tertiles, respectively, compared to the lowest (p = 0.06, trend). 4.2 % reported PIM in the lowest BPA tertile, compared to 8.7 % in the highest (p = 0.03). Adjusted ORs (95 % CI) for PIM were 1.8 (0.4, 7.7) and 2.2 (0.5, 9.5), for the second and third BPA tertiles, respectively, compared to the lowest (p = 0.29, trend). Discussion These results suggest an association between maternal BPA exposure and decreased breastfeeding.

Urinary 3-phenoxybenzoic acid (3-PBA) levels among pregnant women in Mexico City: Distribution and relationships with child neurodevelopment.

BACKGROUND: In recent years, pyrethroid pesticide use has increased in Mexico, the United States, and elsewhere, resulting in extensive human exposure. There is growing concern that pregnant women may be a particularly vulnerable population, as in utero fetal exposure during critical periods of development could adversely affect long-term neurobehavioral function. METHODS: We measured maternal urinary 3-phenoxybenzoic acid (3-PBA) concentrations during the third trimester of pregnancy as a measure of in utero pyrethroid exposure to the fetus among participants in an established Mexico City birth cohort (n=187). In a subset of mothers, we measured 3-PBA during the first, second, and third trimester (n=21) to assess variability across pregnancy. We examined associations between third trimester 3-PBA concentrations and children's scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) from the Bayley Scales for Infant Development (BSID-IIS) at 24 and 36 months of age. RESULTS: 3-PBA was detected in 46% of all urine samples, with similar detection rates and geometric mean concentrations across pregnancy among the 21 participants who provided repeat samples. Participants in the medium and high 3-PBA categories (≥LOD) had lower MDI scores at 24 months compared to those in the low 3-PBA category (

Childhood Blood Lead Levels and Symptoms of Attention Deficit Hyperactivity Disorder (ADHD): A Cross-Sectional Study of Mexican Children.

BACKGROUND: Previous studies suggest that blood lead levels are positively associated with attention deficit/hyperactivity disorder (ADHD) and ADHD-symptoms in children. However, the associations between lead exposure and ADHD subtypes are inconsistent and understudied. OBJECTIVE: The objective of this study was to explore the association of low-level concurrent lead exposure with subtypes of ADHD symptoms in 578 Mexican children 6-13 years of age. METHODS: We measured concurrent blood lead levels using inductively coupled plasma mass spectrometry (ICPMS). We administered the Conners' Rating Scales-Revised (CRS-R) to mothers to evaluate their children's ADHD symptoms. We used imputation to fill missing values in blood lead levels and used segmented regression models adjusted for relevant covariates to model the nonlinear relationship between blood lead and ADHD symptoms. RESULTS: Mean ± SD blood lead levels were 3.4 ± 2.9 µg/dL. In adjusted models, a 1-µg/dL increase in blood lead was positively associated with Hyperactivity and Restless-Impulsivity scores on the CRS-R scale and Hyperactivity-Impulsivity scores on the CRS-R scale of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, but only in children with blood lead level ≤ 5 µg/dL. Blood lead was not associated with Inattentive symptoms or overall ADHD behavior. CONCLUSIONS: In this population of Mexican children, current blood lead level among children with low exposure (≤ 5 µg/dL) was positively associated with hyperactive/impulsive behaviors, but not with inattentiveness. These results add to the existing evidence of lead-associated neurodevelopmental deficits at low levels of exposure. CITATION: Huang S, Hu H, Sánchez BN, Peterson KE, Ettinger AS, Lamadrid-Figueroa H, Schnaas L, Mercado-García A, Wright RO, Basu N, Cantonwine DE, Hernández-Avila M, Téllez-Rojo MM. 2016. Childhood blood lead levels and symptoms of attention deficit hyperactivity disorder (ADHD): a cross-sectional study of Mexican children. Environ Health Perspect 124:868-874; http://dx.doi.org/10.1289/ehp.1510067.

Differential association of lead on length by zinc status in two-year old Mexican children.

BACKGROUND: Blood lead levels have decreased in Mexico since leaded fuel was banned in 1997, but other sources remain, including the use of lead-glazed ceramics for food storage and preparation. Zinc deficiency is present in almost 30% of children aged 1-2 years. Previous studies have documented negative associations of both lead exposure and zinc deficiency with stature, but have not considered the joint effects. Given that the prevalence of stunting in pre-school aged children was 13.6% in 2012, the aim of this study was to evaluate if the relationship between blood lead and child stature was modified by zinc status. METHODS: Anthropometry, dietary energy intake, serum zinc and blood lead were measured in 291 children aged 24 months from an ongoing birth cohort study in Mexico City. Child stature was represented by recumbent length as appropriate for this age group. The association between blood lead (BPb) and length-for-age Z score (LAZ) was evaluated using a model stratified by zinc status measured by standard criteria and adjusted for: birth length, breastfeeding practices, energy intake, maternal height and education. RESULTS: Median (IQR) BPb was: 0.17 (0.12-0.26) µmol/L and 17% of the sample had zinc deficiency (<9.9 µmol/L). BPb was inversely associated with LAZ in the overall sample (ß = -0.19, p = 0.02). In stratified models, this negative association was more than three times higher and statistically significant only in the zinc deficient group (ß = -0.43, p = 0.04) compared to the zinc replete group (ß = -0.12, p = 0.22) (BPb*zinc status, p-for-interaction = 0.04). CONCLUSIONS: Zinc adequacy is a key factor that may attenuate the negative association of lead on stature in young children.

Prediction of Serum Zinc Levels in Mexican Children at 2 Years of Age Using a Food Frequency Questionnaire and Different Zinc Bioavailability Criteria.

BACKGROUND: The 2006 Mexican National Health and Nutrition Survey documented a prevalence of zinc deficiency of almost 30% in children under 2 years of age. OBJECTIVE: We sought to validate a food frequency questionnaire (FFQ) for quantifying dietary bioavailable zinc intake in 2-year-old Mexican children accounting for phytic acid intake and using serum zinc as a reference. METHODS: This cross-sectional study was nested within a longitudinal birth cohort of 333 young children in Mexico City. Nonfasting serum zinc concentration was measured and dietary zinc intake was calculated on the basis of a semiquantitative FFQ administered to their mothers. The relationship between dietary zinc intake and serum zinc was assessed using linear regression, adjusting for phytic acid intake, and analyzed according to two distinct international criteria to estimate bioavailable zinc. Models were stratified by zinc deficiency status. RESULTS: Dietary zinc, adjusted for phytic acid intake, explained the greatest proportion of the variance of serum zinc. For each milligram of dietary zinc intake, serum zinc increased on average by 0.95 µg/dL (0.15 µmol/L) (p = .06). When stratified by zinc status, this increase was 0.74 µg/dL (p = .12) for each milligram of zinc consumed among children with adequate serum zinc (n = 276), whereas among those children with zinc deficiency (n = 57), serum zinc increased by only 0.11 µg/dL (p = .82). CONCLUSIONS: A semiquantitative FFQ can be used for predicting serum zinc in relation to dietary intake in young children, particularly among those who are zinc-replete, and when phytic acid or phytate intake is considered. Future studies should be conducted accounting for both zinc status and dietary zinc inhibitors to further elucidate and validate these findings.

Patterns of exposure to multiple metals and associations with neurodevelopment of preschool children from Montevideo, Uruguay.

While it is known that toxic metals contribute individually to child cognitive and behavioral deficits, we still know little about the effects of exposure to multiple metals, particularly when exposures are low. We studied the association between children's blood lead and hair arsenic, cadmium, and manganese and their performance on the Bayley Scales of Infant Development III. Ninety-two preschool children (age 13-42 months) from Montevideo, Uruguay, provided a hair sample and 78 had a blood lead level (BLL) measurement. Using latent class analysis (LCA), we identified four groups of exposure based on metal concentrations: (1) low metals, (2) low-to-moderate metals, (3) high lead and cadmium, and (4) high metals. Using the four-group exposure variable as the main predictor, and fitting raw scores on the cognitive, receptive vocabulary, and expressive vocabulary scales as dependent variables, both complete-case and multiple imputation (MI) analyses were conducted. We found no association between multiple-metal exposures and neurodevelopment in covariate-adjusted models. This study demonstrates the use of LCA together with MI to determine patterns of exposure to multiple toxic metals and relate these to child neurodevelopment. However, because the overall study population was small, other studies with larger sample sizes are needed to investigate these associations.

Effect of calcium supplementation on bone resorption in pregnancy and the early postpartum: a randomized controlled trial in Mexican women.

BACKGROUND: Calcium needs are physiologically upregulated during pregnancy and lactation to meet demands of the developing fetus and breastfeeding infant. Maternal calcium homeostasis is maintained by hormonal adaptive mechanisms, thus, the role of dietary calcium supplementation in altering maternal responses to fetal-infant demand for calcium is thought to be limited. However, increased calcium absorption is directly related to maternal calcium intake and dietary supplementation has been suggested to prevent transient bone loss associated with childbearing. METHODS: In a double-blind, randomized placebo-controlled trial, we randomly assigned 670 women in their first trimester of pregnancy to 1,200 mg/day calcium (N = 334) or placebo (N = 336). Subjects were followed through 1-month postpartum and the effect on urinary cross-linked N-telopeptides (NTx) of type I collagen, a specific marker of bone resorption, was evaluated using an intent-to-treat analysis. Women with a baseline and at least one follow-up measurement (N = 563; 84%) were included. Subsequent analyses were conducted stratifying subjects by compliance assessed using pill counts. In random subsets of participants, bone-specific alkaline phosphatase (BAP) (N = 100) and quantitative ultrasound (QUS) (N = 290) were also measured. RESULTS: Calcium was associated with an overall reduction of 15.8% in urinary NTx relative to placebo (p < 0.001). Among those who consumed ≥50%, ≥67%, and ≥75% of pills, respectively, the effect was associated with 17.3%, 21.3%, and 22.1% reductions in bone resorption (all p < 0.001). There was no significant effect of calcium on bone formation measured by BAP. However, by 1-month postpartum, those in the calcium group had significantly lower NTx/BAP ratios than those in the placebo group (p = 0.04) indicating a net reduction in bone loss in the supplement group by the end of follow-up. Among subjects who consumed ≥50% and ≥75% of pills, respectively, calcium was also associated with an increase of 26.3 m/s (p = 0.03) and 59.0 m/s (p = 0.009) in radial SOS relative to placebo by 1-month postpartum. CONCLUSIONS: Calcium administered during pregnancy and the early postpartum period, to women with intakes around adequacy, was associated with reduced bone resorption and, thus, may constitute a practical intervention to prevent transient skeletal loss associated with childbearing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00558623.

Distribution of metals exposure and associations with cardiometabolic risk factors in the "Modeling the Epidemiologic Transition Study".

BACKGROUND: Metals are known endocrine disruptors and have been linked to cardiometabolic diseases via multiple potential mechanisms, yet few human studies have both the exposure variability and biologically-relevant phenotype data available. We sought to examine the distribution of metals exposure and potential associations with cardiometabolic risk factors in the "Modeling the Epidemiologic Transition Study" (METS), a prospective cohort study designed to assess energy balance and change in body weight, diabetes and cardiovascular disease risk in five countries at different stages of social and economic development. METHODS: Young adults (25-45 years) of African descent were enrolled (N = 500 from each site) in: Ghana, South Africa, Seychelles, Jamaica and the U.S.A. We randomly selected 150 blood samples (N = 30 from each site) to determine concentrations of selected metals (arsenic, cadmium, lead, mercury) in a subset of participants at baseline and to examine associations with cardiometabolic risk factors. RESULTS: Median (interquartile range) metal concentrations (µg/L) were: arsenic 8.5 (7.7); cadmium 0.01 (0.8); lead 16.6 (16.1); and mercury 1.5 (5.0). There were significant differences in metals concentrations by: site location, paid employment status, education, marital status, smoking, alcohol use, and fish intake. After adjusting for these covariates plus age and sex, arsenic (OR 4.1, 95% C.I. 1.2, 14.6) and lead (OR 4.0, 95% C.I. 1.6, 9.6) above the median values were significantly associated with elevated fasting glucose. These associations increased when models were further adjusted for percent body fat: arsenic (OR 5.6, 95% C.I. 1.5, 21.2) and lead (OR 5.0, 95% C.I. 2.0, 12.7). Cadmium and mercury were also related with increased odds of elevated fasting glucose, but the associations were not statistically significant. Arsenic was significantly associated with increased odds of low HDL cholesterol both with (OR 8.0, 95% C.I. 1.8, 35.0) and without (OR 5.9, 95% C.I. 1.5, 23.1) adjustment for percent body fat. CONCLUSIONS: While not consistent for all cardiometabolic disease markers, these results are suggestive of potentially important associations between metals exposure and cardiometabolic risk. Future studies will examine these associations in the larger cohort over time.