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.
Our aim was to estimate the association of prenatal exposure to fluoride with offspring neurocognitive development.
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.
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.
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.
Background: Rates of preterm birth have been rising over the past several decades. Factors contributing to this trend remain largely unclear, and exposure to environmental contaminants may play a ...role. Objective: We investigated the relationship between phthalate exposure and preterm birth. Methods: Within a large Mexican birth cohort study, we compared third-trimester urinary phthalate metabolite concentrations in 30 women who delivered preterm (< 37 weeks of gestation) with those of 30 controls (≥37 weeks of gestation). Results: Concentrations of most of the metabolites were similar to those reported among U.S. females, although in the present study mono-n-butyl phthalate (MBP) concentrations were higher and monobenzyl phthalate (MBzP) concentrations lower. In a crude comparison before correcting for urinary dilution, geometric mean urinary concentrations were higher for the phthalate metabolites MBP, MBzP, mono(3-carboxylpropyl) phthalate, and four metabolites of di(2-ethylhexyl) phthalate among women who subsequently delivered preterm. These differences remained, but were somewhat lessened, after correction by specific gravity or creatinine. In multivariate logistic regression analysis adjusted for potential confounders, elevated odds of having phthalate metabolite concentrations above the median level were found. Conclusions: We found that phthalate exposure is prevalent among this group of pregnant women in Mexico and that some phthalates may be associated with preterm birth.
Background: Fetal lead exposure is associated with adverse pregnancy outcomes and developmental and cognitive déficits; however, the mechanism(s) by which lead-induced toxicity occurs remains ...unknown. Epigenetic fetal programming via DNA methylation may provide a pathway by which environmental lead exposure can influence disease susceptibility. Objective: This study was designed to determine whether prenatal lead exposure is associated with alterations in genomic methylation of leukocyte DNA levels from umbilical cord samples. Methods: We measured genomic DNA methylation, as assessed by Alu and LINE-1 (long interspersed nuclear element-1) methylation via pyrosequencing, on 103 umbilical cord blood samples from the biorepository of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study group. Prenatal lead exposure had been assessed by measuring maternal bone lead levels at the mid-tibial shaft and the patella using a spot-source ¹⁰⁹Cd K-shell X-ray fluorescence instrument. Results: We found an inverse dose-response relationship in which quartiles of patella lead correlated with cord LINE-1 methylation (p for trend = 0.01) and and tibia lead correlated with Alu methylation (p for trend = 0.05). In mixed effects regression models, maternal tibia lead was negatively associated with umbilical cord genomic DNA methylation of Alu (β = -0.027; p -0.01). We found no associations between cord blood lead and cord genomic DNA methylation. Conclusions: Prenatal lead exposure is inversely associated with genomic DNA methylation in cord blood. These data suggest that the epigenome of the developing fetus can be influenced by maternal cumulative lead burden, which may influence long-term epigenetic programming and disease susceptibility throughout the life course.
Background: Identifying windows of vulnerability to environmental toxicants is an important area in children's health research. Objective: We compared and contrasted statistical approaches that may ...help identify windows of vulnerability by formally testing differences in exposure effects across time of exposure, incorporating continuous time metrics for timing of exposure, and efficiently incorporating incomplete cases. Methods: We considered four methods: 1) window-specific and simultaneously adjusted regression; 2) multiple informant models; 3) using features of individual exposure patterns to predict outcomes; and 4) models of population exposure patterns depending on the outcome. We illustrate them using a study of prenatal vulnerability to lead in relation to Bayley's Mental Development Index at 24 months of age (MDI24). Results: The estimated change in MDI24 score with a 1-loge-unit increase in blood lead during the first trimester was -2.74 95% confidence interval (CI), -5.78 to 0.29 based on a window-specific regression. The corresponding change in MDI24 was — 4.13 (95% CI, — 7.54 to — 0.72) based on a multiple informant model; estimated effects were similar across trimesters (p = 0.23). Results from method 3 suggested that blood lead levels in early pregnancy were significantly associated with reduced MDI24, but decreasing blood leads over the course of pregnancy were not. Method 4 results indicated that blood lead levels before 17 weeks of gestation were lower among children with MDI24 scores in the 90th versus the 10th percentile (p = 0.08). Conclusions: Method 2 is preferred over method 1 because it enables formal testing of differences in effects across a priori-denned windows (e.g., trimesters of pregnancy). Methods 3 and 4 are preferred over method 2 when there is large variability in the timing of exposure assessments among participants. Methods 3 and 4 yielded smaller/rvalues for tests of the hypothesis that not only level but also timing of lead exposure are relevant predictors of MDI24; systematic power comparisons are warranted.
Changes in mitochondrial DNA (mtDNA) can serve as a marker of cumulative oxidative stress (OS) due to the mitochondria's unique genome and relative lack of repair systems. In utero particulate matter ...≤2.5μm (PM2.5) exposure can enhance oxidative stress. Our objective was to identify sensitive windows to predict mtDNA damage experienced in the prenatal period due to PM2.5 exposure using mtDNA content measured in cord blood.
Women affiliated with the Mexican social security system were recruited during pregnancy in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study. Mothers with cord blood collected at delivery and complete covariate data were included (n=456). Mothers' prenatal daily exposure to PM2.5 was estimated using a satellite-based spatio-temporally resolved prediction model and place of residence during pregnancy. DNA was extracted from umbilical cord leukocytes. Quantitative real-time polymerase chain reaction (qPCR) was used to determine mtDNA content. A distributive lag regression model (DLM) incorporating weekly averages of daily PM2.5 predictions was constructed to plot the association between exposure and OS over the length of pregnancy.
In models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, birth year, maternal education, and assay batch, we found significant associations between higher PM2.5 exposure during late pregnancy (35–40weeks) and lower mtDNA content in cord blood.
Increased PM2.5 during a specific prenatal window in the third trimester was associated with decreased mtDNA content suggesting heightened sensitivity to PM-induced OS during this life stage.
•Examined sensitive windows of prenatal PM2.5 exposure on mtDNA in cord blood•Sensitive window identified at gestational weeks 35–40•Higher PM2.5 during sensitive window associated with lower mtDNA content•Findings suggest sex-specific associations.
Mercury is a global contaminant of concern though little is known about exposures in México.
To characterize mercury levels in pregnant women, children, and commonly consumed seafood samples.
Use ...resources of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) birth cohorts to measure total mercury levels in archived samples from 348 pregnant women (blood from three trimesters and cord blood), 825 offspring (blood, hair, and urine) and their mothers (hair), and 91 seafood and canned tuna samples from Mexico City.
Maternal blood mercury levels correlated across three trimesters and averaged 3.4μg/L. Cord blood mercury averaged 4.7μg/L and correlated with maternal blood from trimester 3 (but not trimesters 1 and 2). In children, blood, hair and urine mercury levels correlated and averaged 1.8μg/L, 0.6μg/g, and 0.9μg/L, respectively. Hair mercury was 0.5μg/g in mothers and correlated with child׳s hair. Mean consumption of canned tuna, fresh fish, canned sardine, and shellfish was 3.1, 2.2, 0.5, and 1.0 times per month respectively in pregnant women. Mean mercury content in 7 of 23 seafood species and 5 of 9 canned tuna brands purchased exceeded the U.S. EPA guidance value of 0.3 μg/g.
Mercury exposures in pregnant women and children from Mexico City, via biomarker studies, are generally 3–5 times greater than values reported in population surveys from the U.S., Canada, and elsewhere. In particular, mercury levels in 29–39% of the maternal participants exceeded the biomonitoring guideline associated with the U.S. EPA reference dose for mercury.
•Mercury measured in 348 pregnant women, 825 offspring, and 91 seafood from Mexico.•Exposures to organic and inorganic mercury are widespread.•Exposures are 3–5 times higher than populations surveys elsewhere.
Many analytical methods used in gut microbiome research focus on either single bacterial taxa or the whole microbiome, ignoring multibacteria relationships (microbial cliques). We present a novel ...analytical approach to identify microbial cliques within the gut microbiome of children at 9–11 years associated with prenatal lead (Pb) exposure. Data came from a subset of participants (n = 123) in the Programming Research in Obesity, Growth, Environment and Social Stressors cohort. Pb concentrations were measured in maternal whole blood from the second and third trimesters of pregnancy. Stool samples collected at 9–11 years old underwent metagenomic sequencing to assess the gut microbiome. Using a novel analytical approach, Microbial Co-occurrence Analysis (MiCA), we paired a machine learning algorithm with randomization-based inference to first identify microbial cliques that were predictive of prenatal Pb exposure and then estimate the association between prenatal Pb exposure and microbial clique abundance. With second-trimester Pb exposure, we identified a two-taxa microbial clique that included Bifidobacterium adolescentis and Ruminococcus callidus and a three-taxa clique that also included Prevotella clara. Increasing second-trimester Pb exposure was associated with significantly increased odds of having the two-taxa microbial clique below the median relative abundance (odds ratio (OR) = 1.03, 95% confidence interval (CI) 1.01–1.05). Using a novel combination of machine learning and causal inference, MiCA identified a significant association between second-trimester Pb exposure and the reduced abundance of a probiotic microbial clique within the gut microbiome in late childhood.
Background
Studies report associations between maternal mental health and adverse respiratory outcomes in children; however, the impact of timing and duration of maternal distress remains ...understudied. We sought to longitudinally examine associations between maternal depression and childhood asthma and wheeze, and explore sex differences.
Methods
Maternal depression (n = 601) was assessed using the Edinburgh Depression Scale questionnaire, dichotomized at a clinically relevant cutoff (>12) (a) during pregnancy, (b) postpartum, and (c) postpartum and subsequent time points postnatally (recurrent depression). Report of wheeze in the past 12 months (current wheeze) and asthma were obtained using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire at 48 and 72 months. Associations were analyzed using a modified Poisson regression adjusted for covariates, and in interaction models.
Results
Both postpartum and recurrent depression were associated with higher risk of current wheeze (relative risk RR: 1.87, 95% confidence interval CI: 1.21, 2.90; RR: 2.41, 95% CI: 1.53, 3.79) and asthma at 48 months (RR: 2.42, 95% CI: 1.01, 5.84; RR: 2.45, 95% CI: 1.02, 5.84). In interaction analyses, associations were stronger in females. Recurrent depression was associated with a higher risk of current wheeze at 48 months in females (RR: 4.34, 95% CI: 2.02, 9.32) when compared to males (RR: 1.89, 95% CI: 1.05, 3.39).
Conclusions
Postpartum and recurrent depression were associated with a higher risk of wheeze and asthma in children. Understanding the temporal‐ and sex‐specific effects of maternal depression may better inform prevention strategies.
Over the past several decades, the age of pubertal onset in girls has shifted downward worldwide. As early pubertal onset is associated with increased risky behavior and psychological issues during ...adolescence and cardiometabolic disease and cancer in adulthood, this is an important public health concern. Exposure to endocrine disrupting chemicals during critical windows of in utero development may play a role in this trend. Our objective was to investigate trimester-specific phthalate and BPA exposure in relation to pubertal development among girls in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort.
We measured maternal urinary phthalate metabolites and BPA in samples collected during the first, second, and third trimesters of pregnancy. To assess reproductive development among their female children, we measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation, including Tanner staging for breast and pubic hair development and menarche status, at age 8–13 years (n = 120). We used linear and logistic regression to examine measures of trimester-specific in utero exposure as predictors of peripubertal hormone levels and pubertal onset, respectively. In secondary analyses, we evaluated estimated exposure at the midpoint of the first trimester and rates of change in exposure across pregnancy in relation to outcomes.
Several phthalate metabolites measured throughout in utero development were associated with higher serum testosterone concentrations, while a number of metabolites measured in the third trimester were associated with higher DHEA-S. For example, an interquartile range (IQR) increase in mean monoethyl phthalate (MEP) levels across pregnancy was associated with 44% higher peripubertal testosterone (95% CI: 13–83%), while an IQR increase in di-2-ethylhexyl phthalate metabolites (ΣDEHP) specifically in the third trimester was associated with 25% higher DHEA-S (95%CI: 4.7–47%). In IQR increase in mean mono-2-ethylhexyl phthalate (MEHP) levels across pregnancy was associated with lower odds of having a Tanner Stage >1 for breast development (OR = 0.32, 95%CI: 0.11–0.95), while MEHP in the third trimester was associated with higher odds of having a Tanner Stage >1 for pubic hair development (OR = 3.76, 95%CI: 1.1–12.8). Results from secondary analyses were consistent with findings from our main analysis.
These findings suggest that female reproductive development may be more vulnerable to the effects of phthalate or BPA exposure during specific critical periods of in utero development. This highlights the need for comprehensive characterizations of in utero exposure and consideration of windows of susceptibility in developmental epidemiological studies. Future research should consider repeated measures of in utero phthalate and BPA exposure within each trimester and across pregnancy.
•Investigated exposure during in utero windows of development and female puberty.•In utero phthalate exposure was associated with higher peripubertal testosterone.•3rd trimester phthalate exposure was associated with higher peripubertal DHEA-S.•In utero MEHP was associated with lower odds of breast development.
Summary
Childhood obesity is a major public health challenge across Latin America and the United States. Addressing childhood obesity depends on valid, reliable, and culturally sensitive ...measurements. Such progress within and between countries of the Americas could be enhanced through better measurement across different age groups, different countries, and in sending and receiving communities. Additionally, better and more comparable measurements could accelerate cross‐border collaboration and learning. Here, we present (1) frameworks that influenced our perspectives on childhood obesity and measurement needs across the Americas; (2) a summary of resources and guidance available concerning measurement and adaptation of measures for childhood obesity research; and (3) three major areas that present challenges and opportunities for measurement advances related to childhood obesity, including parental behavior, acculturation, and the potential to incorporate ethnographic methods to identify critical factors related to economics and globalization. Progress to reduce childhood obesity across the Americas could be accelerated by further transnational collaboration aimed at improving measurement for better surveillance, intervention development and evaluation, implementation research, and evaluation of natural experiments. Additionally, there is a need to improve training related to measurement and for improving access to valid and reliable measures in Spanish and other languages common in the Americas.
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