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Background The aim of this study was to analyze whether late-onset fetal growth restriction (FGR) alters regulatory capability in infants, and whether this can be detected using both the neonatal behavior assessment scale (NBAS) and brainstem auditory-evoked potentials (BAEP). Methods The diagnosis of FGR was made on Doppler examination in the third trimester of pregnancy. NBAS and BAEP measurement were performed at 1 month of corrected postnatal age. Results The group with late-onset FGR was integrated with 17 infants and the control group consisted of 14 subjects. The NBAS range of state score, which reflects organization of behavioral state, was low in infants with late-onset FGR. No differences were found in BAEP between groups. No association between NBAS and BAEP was detected. Conclusion Late-onset FGR has a deleterious effect on NBAS range of state, but possibly does not alter BAEP response. It is proposed that regulatory capabilities in the neonatal period play a primary role in subtle cognitive difficulties in infants with late-onset FGR in the long term. [ABSTRACT FROM AUTHOR]

Background: The results of previous studies suggest that prenatal exposure to bis[p-chlorophenyl]-1,1,1-trichloroethane (DDT) and to its main metabolite, 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), impairs psychomotor development during the first year of life. However, information about the persistence of this association at later ages is limited. Objectives: We assessed the association of prenatal DDE exposure with child neurodevelopment at 42-60 months of age. Methods: Since 2001 we have been monitoring the neurodevelopment in children who were recruited at birth into a perinatal cohort exposed to DDT, in the state of Morelos, Mexico. We report McCarthy Scales of Children's Abilities for 203 children at 42, 48, 54, and 60 months of age. Maternal DDE serum levels were available for at least one trimester of pregnancy. The Home Observation for Measurement of the Environment scale and other covariables of interest were also available. Results: After adjustment, a doubling of DDE during the third trimester of pregnancy was associated with statistically significant reductions of -1.37, -0.88, -0.84, and -0.80 points in the general cognitive index, quantitative, verbal, and memory components respectively. The association between prenatal DDE and the quantitative component was weaker at 42 months than at older ages. No significant statistical interactions with sex or breastfeeding were observed. Conclusions: These findings support the hypothesis that prenatal DDE impairs early child neurodevelopment; the potential for adverse effects on development should be considered when using DDT for malaria control. [ABSTRACT FROM AUTHOR]

Most toxicologic studies focus on a single agent, although this does not reflect real-world scenarios in which humans are exposed to multiple chemicals. Objectives: We prospectively studied manganese-lead interactions in early childhood to examine whether manganese-lead coexposure is associated with neurodevelopmental deficiencies that are more severe than expected based on effects of exposure to each metal alone. Methods: Four hundred fifty-five children were enrolled at birth in an longitudinal cohort study in Mexico City, provided blood samples, and were followed until 36 months of age. We measured lead and manganese at 12 and 24 months and assessed neurodevelopment at 6-month intervals from 12 to 36 months of age using Bayley Scales of Infant Development-II. Results: Mean (± SD) blood concentrations at 12 and 24 months were, respectively, 24.7 ± 5.9 µg/L and 21.5 ± 7.4 µg/L for manganese and 5.1 ± 2.6 µg/dL and 5.0 ± 2.9 µg/dL for lead. Mixed-effects models, including Bayley scores at five time points, showed a significant interaction over time: highest manganese quintile x continuous lead; mental development score, â = -1.27 [95% confidence interval (CI): -2.18, -0.37]; psychomotor development score, β = -0.92 (95% CI: -1.76, -0.09). Slopes for the estimated 12-month lead effect on 18-month mental development and 24- through 36-month psychomotor development scores were steeper for children with high manganese than for children with midrange manganese levels. Conclusions: We observed evidence of synergism between lead and manganese, whereby lead toxicity was increased among children with high manganese coexposure. Findings highlight the importance of understanding health effects of mixed exposures, particularly during potentially sensitive developmental stages such as early childhood. [ABSTRACT FROM AUTHOR]

Abstract: In order to evaluate the persistency of the association between DDE and infant neurodevelopment we assessed mental and psychomotor development between 12 and 30 months of age in an ongoing cohort in Mexico. A total of 270 singleton children without perinatal asphyxia diagnosis, with a birth weight ≥2kg, mothers>15 years of age with organochlorine maternal serum levels measured at least in one trimester of pregnancy, and who were evaluated at least in two of the four visits at 12, 18, 24 and 30 months of age, were included in this report. The Spanish version of Bayley Scales of Infant Development II (BSID_II; ) was administered to the children and Psychomotor Development Index (PDI) and Mental Development Index (MDI) were calculated. Information about stimulation at home was measured using the Home Observation of Measurement of the Environment (HOME) at 6 months, and breastfeeding history was obtained through direct interviews with the mothers. Maternal serum DDE levels were determined during pregnancy by means of electron capture gas–liquid chromatography. The association between DDE prenatal exposure and neurodevelopment was estimated using separate generalized mixed effects models. Our results suggest that the association between prenatal DDE and infant neurodevelopment does not persist beyond 12 months of age even after adjusting for known risk factors for neurodevelopment. In addition, we observed an interaction between early home stimulation and mental improvement at 24 and 30 months of age (p <0.001). The association of DDE with infant neurodevelopment seems to be reversible. However, we cannot rule out that other DDT metabolites may play a role in neurodevelopment. [Copyright &y& Elsevier]

Abstract: The notion that maternal personality characteristics influence cognitive development in their children has been grounded in stress moderation theory. Maternal personality traits, such as self-esteem, may buffer maternal stressors or lead to improved maternal–child interactions that directly impact neurodevelopment. This can be extended to suggest that maternal personality may serve to attenuate or exacerbate the effects of other neurotoxicants, although this has not been studied directly. We examined whether mothers’ self-esteem had a direct or main effect on their children''s cognitive outcomes. We also explored the modifying effects of maternal self-esteem on the association between exposure to lead and neurodevelopment in these children. Study participants included 379 mother–child pairs from Mexico City. Data included the Coopersmith Self-Esteem Scale in mothers, children''s Bayley''s Scale of Infant Development (BSID) scores, and sociodemographic information. Linear regression was used to model the relationship between maternal self-esteem and the Bayley''s Mental Development Index (MDI) and Psychomotor Development Index (PDI) scores at age 24 months using models stratified by levels of maternal self-esteem. In adjusted models, each point increase in maternal self-esteem was associated with children having 0.2 higher score on the Bayley''s MDI (p =0.04). Similar results were observed using the PDI outcome. Moreover, there was evidence that maternal self-esteem attenuated the negative effects of lead exposure, although the interaction fell short of conventional levels of statistical significance. [Copyright &y& Elsevier]

OBJECTIVE: Low-level postnatal lead exposure is associated with poor intellectual development in children, although effects of prenatal exposure are less well studied. We hypothesized that prenatal lead exposure would have a more powerful and lasting impact on child development than postnatal exposure. DESIGN: We used generalized linear mixed models with random intercept and slope to analyze the pattern of lead effect of the cohort from pregnancy through 10 years of age on child IQ from 6 to 10 years. We statistically evaluated dose-response nonlinearity. PARTICIPANTS: A cohort of 175 children, 150 of whom had complete data for all included covariates, attended the National Institute of Perinatology in Mexico City from 1987 through 2002. EVALUATIONS/MEASUREMENTS: We used the Wechsler Intelligence Scale for Children-Revised, Spanish version, to measure IQ. Blood lead (BPb) was measured by a reference laboratory of the Centers for Disease Control and Prevention (CDC) quality assurance program for BPb. RESULTS: Geometric mean BPb during pregnancy was 8.0 µg/dL (range, 1-33 µg/dL), from 1 through 5 years was 9.8 µg/dL (2.8-36.4 µg/dL), and from 6 through 10 years was 6.2 µg/dL (2.2-18.6 µg/dL). IQ at 6-10 years decreased significantly only with increasing natural-log third-trimester BPb (β = -3.90; 95% confidence interval, -6.45 to -1.36), controlling for other BPb and covariates. The dose-response BPb-IQ function was log-linear, not linear-linear. CONCLUSIONS: Lead exposure around 28 weeks gestation is a critical period for later child intellectual development, with lasting and possibly permanent effects. There was no evidence of a threshold; the strongest lead effects on IQ occurred within the first few micrograms of BPb. RELEVANCE TO CLINICAL PRACTICE: Current CDC action limits for children applied to pregnant women permit most lead-associated child IQ decreases measured over the studied BPb range. [ABSTRACT FROM AUTHOR]

We determined the secular trend in blood lead levels in a cohort of 321 children born in Mexico City between 1987 and 1992. Blood lead level was measured every 6 months during a 10-year period. We modeled the effect of yearly air lead concentration nested within the calendar year in which the child was born, family use of lead-glazed pottery, socioeconomic status, year in which the child was born, age of the child at the time of blood lead measurement, place of residence, and an indicator variable for subjects with complete or incomplete blood lead values. The yearly mean of air lead of the Valley of Mexico decreased from its highest level of 2.80 µg/m³ in 1987 to 0.07 µg/m³ in 2002. The contribution of air lead to blood lead according to year of birth was strongest for subjects born in 1987 and fell to nearly zero for children born in 1992. The geometric mean of the entire cohort rose from 8.4 µg/dL in the first year of life to 10.1 µg/dL in the second and decreased thereafter until it reached 6.4 µg/dL at 10 years of age. Children of families who used lead-glazed ceramics had blood lead levels 18.5% higher than did children of nonusing families. Children who belonged to the lowest socioeconomic levels had blood lead levels 32.2% higher than did those of highest socioeconomic levels. Children who lived in the northeast part of the city had blood lead levels 10.9% higher compared with those who lived in the southwest. [ABSTRACT FROM AUTHOR]

ABSTRACT. The authors determined the secular trend in blood lead levels in a cohort of 91 children born in Mexico City between 1987 and the beginning of 1993. The authors grouped children by calendar year in which they reached 36 mo of age (i.e., 1990-1995), and their blood lead levels were measured every 6 mo during a 66-mo period. The overall geometric mean blood lead level was 8.6 mg/dl (range = 1.0-61.0 Mu g/dl). A repeated measures analysis of variance revealed a significant downward linear trend in blood lead levels by year (p < .001)--from an estimated marginal geometric mean of 14.2 Mu g/dl in 1990 to 6.3 mg/dl in 1995. There was also a significant linear age effect (p < .001); blood lead levels generally fell during the 36th-66th mo. Family use of lead-glazed pottery significantly elevated blood lead levels (p = .006), and the effect magnified as age increased (Age x Pottery Interaction [p = .014]). Although the overall downward trend in blood lead levels during the time period described corresponded to a reduction in various sources of lead exposure, there was no alteration in production, distribution, or use of leaded pottery. Currently, use of lead-glazed ceramic pottery is one of the most profound sources of lead exposure in the Mexican population. [ABSTRACT FROM AUTHOR]

Discusses a study which determined the secular trend in blood lead levels in children born in Mexico City, Mexico between 1987 and 1993. Methods of the study; Effects of age on elevated blood lead levels (PbB); Effect of family use of lead-glazed ceramic pottery on PbB.

Assessing the status and determinants of early child development (ECD) requires accurate and regularly updated measurements. Yet, little information has been published on the subject in low- and middle-income countries, particularly regarding the proximal determinants of childhood development in contexts of high social marginalization. This article analyzes the factors that favor or mitigate suboptimal ECD outcomes in Mexico. A cross-sectional study was conducted using recently collected data for 918 children aged 0–38 months from socially marginalized communities in 23 Mexican municipalities. The ECD outcomes of the children were estimated based on indicators of chronic undernutrition and neurodevelopment (normal, lagging and at risk of delay). The distribution of outcomes was described across the ECD proximal determinants analyzed, including the co-occurrence of chronic undernutrition and suboptimal neurodevelopment. Covariate-adjusted prevalence of the ECD outcomes and co-occurrences were calculated as post-estimations from a multiple multinomial logistic regression. The prevalence of chronic undernutrition was 23.5%; 45.9% of children were classified with neurodevelopmental lag, and 11% at risk of neurodevelopmental delay. The prevalence of stunting co-occurring with suboptimal neurodevelopment came to 15.4%. The results of the multinomial logistic regression model indicated that early gestational age, low birth weight, a low household socioeconomic level, being male and having numerous siblings were all associated with the co-occurrence of chronic undernutrition and suboptimal child neurodevelopment. This study identified important predictors of child development in the first three years of life, specifically in two of its principal indicators: nutritional and neurodevelopmental status. Most of the predictors observed can be improved by means of social programs and interventions. Trial registration: ClinicalTrials.gov ID: NCT04210362. [ABSTRACT FROM AUTHOR]

Early childhood development (ECD) is a critical stage in the intergenerational process of human development. Targeted interventions depend on accurate and up-to-date ECD measurements. This paper presents estimates for the nutritional and neurodevelopmental status of socially marginalized children in Mexico. We performed a cross-sectional study based on data collected in 2019–2020 during home visits to 1,176 children aged 0–38 months across 24 highly marginalized locations in Oaxaca. We assessed nutritional status according to the World Health Organization 2006 child-growth standards and ECD status using the Child Development Evaluation Test, 2nd Edition. We stratified results by sex. Prevalence of stunting was 5.3 percentage points (p.p.) higher (p = 0.023) in males (25.3%; 95% CI: 20.2%, 31.1%) compared to females (20.0%; 95% CI: 15.0%, 26.1%). Overall prevalence rates stood at 5.7% (95% CI: 4.0%, 8.1%) for underweight, 1.5% (95% CI: 0.9%, 2.7%) for wasting and 3.6% (95% CI: 2.3%, 5.7%) for overweight/obesity, with no significant differences by sex. Prevalence of normal development was 8.3 p.p. lower (p = 0.001) in males (39.3%; 95% CI: 34.5%, 44.4%) compared to females (47.6%; 95% CI: 41.6%, 53.6%). By development area, the highest prevalence of suboptimal outcomes among children with developmental lag or at risk of delay was observed in their gross motor and language skills: 24.1% (95% CI: 20.0%, 28.8%) and 38.6% (95% CI: 34.0%, 43.3%), respectively. The largest difference between the sexes was found in the language area. Our results show that childhood development strategies have been insufficient thus far in the studied population. Programs specifically designed to prevent ECD lags and bridge inequality gaps are urgently needed. Trial registration: ClinicalTrials.gov ID: NCT04210362. [ABSTRACT FROM AUTHOR]

Background: Early childhood development (ECD) is essential in human capacity building and a critical element in the intergenerational process of human development. In some countries, social programs targeted at improving ECD have proven to be successful. Oaxaca is one of the States with the greatest social inequities in Mexico. Therefore, children in Oaxaca are at a high risk of suboptimal ECD. In 2014, the non-governmental organization (NGO) Un Kilo de Ayuda started to implement the Neurological and Psycho-affective Early Childhood Development Program in eighty marginalized communities of Oaxaca. In this article, we present the impact evaluation design to estimate the effect of this program on ECD. Methods: We will use a cluster randomized stepped-wedge design with an allocation ratio of 1:1. Communities will be randomly assigned to each study group: four groups of twenty communities each. We expect that children from intervened communities will show better ECD outcomes. Discussion: This study is one of the few rigorous assessments of the effect of an ECD program on the neurodevelopment of Mexican children recruited in their first 3 years of life from communities of high social vulnerability. Our study design is recommended when the way in which outcomes are measured and assessed depends on age, self-selection is present, and assignment is performed at an aggregate level. Implementation research will be conducted prior to study launch and quality control measures will be in place to maximize the fidelity of study design implementation. Trial registration: ClinicalTrials.gov NCT04210362 [ABSTRACT FROM AUTHOR]

Background: Early childhood development (ECD) is essential in human capacity building and a critical element in the intergenerational process of human development. In some countries, social programs targeted at improving ECD have proven to be successful. Oaxaca is one of the States with the greatest social inequities in Mexico. Therefore, children in Oaxaca are at a high risk of suboptimal ECD. In 2014, the non-governmental organization (NGO) Un Kilo de Ayuda started to implement the Neurological and Psycho-affective Early Childhood Development Program in eighty marginalized communities of Oaxaca. In this article, we present the impact evaluation design to estimate the effect of this program on ECD.Methods: We will use a cluster randomized stepped-wedge design with an allocation ratio of 1:1. Communities will be randomly assigned to each study group: four groups of twenty communities each. We expect that children from intervened communities will show better ECD outcomes.Discussion: This study is one of the few rigorous assessments of the effect of an ECD program on the neurodevelopment of Mexican children recruited in their first 3 years of life from communities of high social vulnerability. Our study design is recommended when the way in which outcomes are measured and assessed depends on age, self-selection is present, and assignment is performed at an aggregate level. Implementation research will be conducted prior to study launch and quality control measures will be in place to maximize the fidelity of study design implementation.Trial Registration: ClinicalTrials.gov NCT04210362. [ABSTRACT FROM AUTHOR]

Prenatal exposure to dichlorodiphenyldichloroethylene (DDE) is associated with decreased motor development during the first year of life, though the effects of DDE in the neonatal stage are not conclusive. The main aim of this study was to evaluate the association between prenatal DDE exposure and neonatal neurodevelopment in a cohort from four municipalities in the state of Morelos, Mexico. The children (265), born from pregnancies with no perinatal complications, were evaluated at 1 month of age (±7 days) for the presence of abnormal reflexes with the Brazelton Scale (NBAS), neurological soft signs with the Graham-Rosenblith Scale, as well as mental and psychomotor development by the Bayley Scales of Infant Development. Maternal DDE concentrations during each trimester of the pregnancy were determined by gas chromatography. Multiple linear and ordinal logistic models assessed the association between DDE and the outcomes of interest. Prenatal exposure to DDE was associated with a non-significant increase in neurological soft signs (6-8%) and a decrease in psychomotor (β1T=−0.02) and mental (β2T=−0.03 and β3T=−0.19) development. Our results are consistent with previous studies and suggest that prenatal DDE exposure is not associated with neurological functions present in the neonatal stage. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence suggests that p,p'-dichlorodiphenyldichloroethene (DDE) affects neurodevelopment in infants, although a critical exposure window has not yet been identified. OBJECTIVES: Our goal was to assess the prenatal DDE exposure window and its effect on the psychomotor development index (PDI) and mental development index (MDI) during the first year of life. METHODS: We recruited 244 children whose pregnancies and deliveries were uncomplicated, and whose mothers were monitored throughout the pregnancy. Participating mothers were not occupationally exposed to DDT (dichlorodiphenyltrichloroethane) but were residents of a zone in Mexico with endemic malaria. We measured serum levels of DDE before pregnancy and during each trimester of the pregnancy. We evaluated PDI and MDI of the Bayley Scales for Infant Development (BSID-II), at 1, 3, 6, and 12 months of age. We adjusted for quality of the home environment and maternal intellectual coefficient (IQ). We used generalized mixed-effects models for statistical analysis. RESULTS: Third-trimester DDE level (7.8 ± 2.8 ppb) was significantly higher than the level at baseline, first, and second trimesters, but the differences never exceeded 20%. Only DDE levels during the first trimester of pregnancy were associated with a significant reduction in PDI (every doubled increase of DDE level reduced the PDI 0.5 points). DDE was not associated with MDI. CONCLUSIONS: A critical window of exposure to DDE in utero may be the first trimester of the pregnancy, and psychomotor development is a target of this compound. Residues of DDT metabolites may present a risk of developmental delay for years after termination of DDT use. [ABSTRACT FROM AUTHOR]

ABSTRACT. Although Mexico substantially reduced use of leaded gasoline during the 1990s, lead-glazed pottery remains a significant source of population exposure. Most previous studies of lead in nonoccupationally exposed groups in Mexico have been conducted in the Mexico City metropolitan area. Oaxaca, a poor southern state of Mexico, has a centuries-old tradition of use of low temperature lead-glazed ceramic ware manufactured mainly by small family businesses. We measured blood lead levels in 220 8-10-y-old children (i.e., not from pottery-making families) who were students in the innercity of Oaxaca and in the mothers of all children. The geometric mean blood lead level of the children was 10.5 Mug/dl (+7.0/-4.3 Mu g/dl standard deviation; range = 1.3-35.5 Mu g/dl). The corresponding mean value for the mothers was 13.4 (+9.0/-5.4 Mu g/dl standard deviation; range = 2.8-45.3 Mu g/dl). We used cutoffs that were greater than or equal to 10 Mu g/dl, 20 Mu g/dl, and 30 Mu g/dl, and we determined that 54.9%, 10.3%, and 3.0% of the children were at or above the respective criteria. We accounted for 25.2% of the variance in blood lead levels of the children, using maternal responses to a questionnaire that assessed possible lead sources in a linear multiple-regression model. The most important factors related to lead levels were family use of lead-glazed pottery, use of animal fat in cooking, and family income. The addition of maternal blood lead level to the model increased accounted variance in blood lead to 48.0%. In logistic-regression modeling of children's blood lead levels, we used a cutoff of greater than or equal to 10 Mu g/dl, and we found that use of lead-glazed pottery was the most important of all questionnaire items that were predictive of blood lead levels (odds ratio = 2.98). In Oaxaca, as is the case elsewhere in Mexico, lead-glazed ceramic ware remains a significant risk factor for elevated blood lead levels in children. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To evaluate whether childhood emotional and behavioral characteristics are associated with soda intake. Methods: The study population included 391 Mexico City adolescents enrolled in a birth cohort study. When children were between 6 and 12 years of age, the Behavioral Assessment System for Children (BASC)‐2 was administered. Nondiet soda intake was measured concurrently and again when participants were of peripubertal ages via food frequency questionnaire. Linear regression models were run with soda mL/day (cross‐sectional and change in soda over time) as the outcome and BASC composite scores as predictors (in separate models), adjusting for confounders. Results: At baseline, children were 8.3 (SD 1.3) years (49% males). Three scales out of 18 examined had statistically significant associations. Parent‐reported adaptive skills were inversely associated with concurrent soda intake (β = −2.29 with 95% CI −4.27 to −0.31). Parent‐reported internalizing problems (higher = more problems) were related to higher change in soda intake from childhood to adolescence (β = 5.83 with 95% CI 0.98‐10.68; N = 191). Self‐reported school problems were associated with a higher change in soda intake over time (β = 9.46 with 95% CI 2.10‐16.82; N = 122). Conclusions: Parent‐ and self‐reported emotional and behavioral difficulties in childhood were associated with soda consumption and changes in soda consumption over time. [ABSTRACT FROM AUTHOR]

• We investigated the association between prenatal PM 2.5 and behavioral development. • Behavioral development was assessed in 4-6 year olds using the BASC-2. • Higher first trimester PM 2.5 was associated with reduced Adaptive Skills scores. • PM 2.5 effects were consistent across subscales, including Functional Communication. • Our results suggest that PM 2.5 impacts behavioral domains as well as cognition. Childhood exposure to air pollution has been linked with maladaptive cognitive development; however, less is known about the association between prenatal fine particulate matter (PM 2.5) exposure and childhood behavior. Our aim was to assess the association between prenatal PM 2.5 exposure and behavioral development in 4-6 year old children residing in Mexico City. We used data from 539 mother-child pairs enrolled in a prospective birth cohort in Mexico City. We estimated daily PM 2.5 exposure using a 1 km2 satellite-based exposure model and averaged over each trimester of pregnancy. We assessed childhood behavior at 4-6 years of age using the parent-completed Behavioral Assessment Scale for Children (BASC-2) composite scores and subscales. We used linear regression models to estimate change in BASC-2 T-scores with trimester specific 5-μg/m3 increases in PM 2.5. All models were mutually adjusted for PM 2.5 exposures during the other trimesters, maternal factors including age, education, socioeconomic status, depression, and IQ, child's age at study visit, and season. We additionally assessed sex-specific effects by including an interaction term between PM 2.5 and sex. Higher first trimester PM 2.5 exposure was associated with reduced Adaptive Skills scores (β: -1.45, 95% CI: -2.60, -0.30). Lower scores on the Adaptive Skills composite score and subscales indicate poorer functioning. For PM 2.5 exposure during the first trimester, decrements were consistent across adaptive subscale scores including Adaptability (β: -1.51, 95% CI: -2.72, -0.30), Social Skills (β: -1.63, 95% CI: -2.90, -0.36), and Functional Communication (β: -1.21, 95% CI: -2.21, -0.21). The association between 1st trimester PM 2.5 and depression was stronger in males than females (β for males: 1.52, 95% CI: -0.41, 3.45; β for females: -0.13, 95% CI: -1.99, 1.72; p -int: 0.07). Exposure to PM 2.5 during early pregnancy may be associated with impaired behavioral development in children, particularly for measures of adaptive skills. These results suggest that air pollution impacts behavioral domains as well as cognition, and that the timing of exposure may be critical. [ABSTRACT FROM AUTHOR]

• Lead is a neurotoxicant associated with neurodevelopmental deficits. • Prepulse inhibition (PPI) deficits are associated with neurological disorders. • We estimated the causal effect of prenatal lead exposure on PPI in children. • Our findings suggest prenatal lead exposure causes PPI deficits in children. • PPI may be an objective biomarker of neurotoxicant effects on the brain. During pregnancy, maternal lead from earlier exposures mobilizes and crosses placental barriers, placing the developing fetus at risk for lead exposure and neurodevelopmental deficits. Some neuronal circuits known to be affected in neurodevelopment disorders can be probed with simple physiological behavioral paradigms. One such neural biomarker is Pre-Pulse Inhibition (PPI), an indicator of adequate sensorimotor gating processing. In clinical studies, deficits in PPI have been associated with neurodevelopmental disorders in human subjects. To our knowledge, no studies have examined the use of PPI as a biomarker of toxicant effects on the brain in epidemiological studies. We aimed to estimate the causal effect of prenatal lead exposure, assessed by maternal cortical bone lead concentrations, on PPI in 279 children from Mexico City. in vivo maternal cortical bone lead measurements were taken at four weeks postpartum at the mid-tibia shaft using a K-Shell X-ray fluorescence instrument. PPI recording occurred in an isolated clinical setting and eye blink responses were measured using electromyography. We assessed if the conditions for causal inference held in our study and used the results of our assessment to estimate the causal effect of prenatal lead exposure on PPI using an ordinary least squares regression model, a marginal structural model, and the parametric g-formula. Results were consistent across the three modeling approaches. For the parametric g-formula, a one standard deviation (10.0 μg/g) increase in prenatal lead significantly reduced PPI by approximately 19.0 % (95 % CI: 5.4 %, 34.3 %). This decrease is similar in magnitude to clinical studies on schizophrenia, which have observed PPI impairments in patients with schizophrenia as compared to controls. Our results are consistent with findings from other studies establishing an association between lead exposure and neurodevelopmental disorders in children and suggest that PPI may be useful as an objective biomarker of toxicant effects on the brain. [ABSTRACT FROM AUTHOR]

• There are few validated tests of working memory in young children. • Tests of working memory in young children would help delineate the onset of developmental problems. • The DSAT can be administered to pre-literate children. • The DSAT is associated with age, sex and IQ. • Lead exposure is not associated with DSAT performance at 18 or 24 months. Working memory (WM) is critical for problem solving and reasoning. Beginning in infancy, children show WM capacity increasing with age but there are few validated tests of WM in very young children. Because rapid brain development may increase susceptibility to adverse impacts of prenatal neurotoxicant exposure, such as lead, tests of WM in very young children would help to delineate onset of developmental problems and windows of susceptibility. Our objective was to assess the feasibility of administering a Delayed Spatial Alternation Task (DSAT) to measure WM among 18- and 24-month old children enrolled in an ongoing longitudinal birth cohort study and compare DSAT performance with age and general cognitive development. We further explored whether prenatal lead exposure impacted DSAT performance. We assessed 457 mother-child pairs participating in the Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) Study in Mexico City. The DSAT and Bayley Scales of Infant Development (BSID-III) were administered at 18- and 24-months. Lead was measured in maternal blood collected during pregnancy (MBPb) and in a subsample of children at 24-months (CBPb). We regressed DSAT measures on MBPb and CBPb, child sex, and maternal age, education, socioeconomic status, and household smoking. We compared DSAT performance to BSID-III performance with adjusted residuals. 24-month children perform better on the DSAT than 18-month children; 24-month subjects reached a higher level on the DSAT (3.3 (0.86) vs. 2.4 (0.97), p < 0.01), and had a higher number of correct responses (20.3 vs. 17.2, p < 0.01). In all DSAT parameters, females performed better than males. Maternal education predicted better DSAT performance; household smoking predicted worse DSAT performance. A higher number of correct responses was associated with higher BSID-III Cognitive scales at 18 months (r = 0.20, p < 0.01) and 24 months (r = 0.27, p < 0.01). MBPb and CPBb did not significantly predict DSAT performance. Improved performance on the DSAT with increasing age, the positive correlation with the BSID-III cognitive and language scales and the correlation with common sociodemographic predictors of neurodevelopment demonstrate the validity of the DSAT as a test of infant development. [ABSTRACT FROM AUTHOR]

Prenatal folate and vitamin B12 status have been linked to child neuropsychological development, but less is known about maternal genetic influences on this association. We conducted an exploratory longitudinal study of 181 mother–child pairs to assess whether maternal MTHFR 677C>T genotype modifies the association between maternal plasma folate and vitamin B12 in the first trimester of pregnancy and child neuropsychological development. Maternal plasma folate and vitamin B12 were determined by radioimmunoassay, and MTHFR 677C>T genotypes by PCR. We evaluated child neuropsychological development at 1, 3, 6, 12, 18, 24, and 30 month old using the Bayley Scales of Infant Development II. We analyzed the data using mixed-effects multivariate linear regression. The MTHFR 677C>T genotype distribution among the mothers was 18.2% CC, 49.8% CT, and 32.0% TT. The Mental Development Index (MDI) was inversely associated with maternal plasma folate among offspring of MTHFR 677CC mothers (β = -2.18 per twofold increase, 95% CI -4.07; -0.30, corrected P value = 0.02); no significant associations were observed among children born to women of other genotypes. The Motor Development Index (PDI) was not significantly associated with maternal plasma folate in any maternal MTHFR 677C>T genotype group, nor were MDI or PDI significantly associated with maternal plasma vitamin B12 in any maternal MTHFR 677C>T genotype group. This study suggests that maternal MTHFR 677CC genotype interacts with first-trimester plasma folate to influence offspring mental development. [ABSTRACT FROM AUTHOR]

Background: Humans are exposed to mixtures of chemicals across their lifetimes, a concept sometimes called the "exposome." Mixtures likely have temporal "critical windows" of susceptibility like single agents and measuring them repeatedly might help to define such windows. Common approaches to evaluate the effects of chemical mixtures have focused on their effects at a single time point. Our goal is to expand upon these previous techniques and examine the time-varying critical windows for metal mixtures on subsequent neurobehavior in children.Methods: We propose two methods, joint weighted quantile sum regression (JWQS) and meta-weighted quantile sum regression (MWQS), to estimate the effects of chemical mixtures measured across multiple time points, while providing data on their critical windows of exposure. We compare the performance of both methods using simulations. We also applied both techniques to assess second and third trimester metal mixture effects in predicting performance in the Rapid Visual Processing (RVP) task from the Cambridge Neuropsychological Test Automated Battery (CANTAB) assessed at 6-9 years in children who are part of the PROGRESS (Programming Research in Obesity, GRowth, Environment and Social Stressors) longitudinal cohort study. The metals, arsenic, cadmium (Cd), cesium, chromium, lead (Pb) and antimony (Sb) were selected based on their toxicological profile.Results: In simulations, JWQS and MWQS had over 80% accuracy in classifying exposures as either strongly or weakly contributing to an association. In real data, both JWQS and MWQS consistently found that Pb and Cd exposure jointly predicted longer latency in the RVP and that second trimester exposure better predicted the results than the third trimester. Additionally, both JWQS and MWQS highlighted the strong association Cd and Sb had with lower accuracy in the RVP and that third trimester exposure was a better predictor than second trimester exposure.Conclusions: Our results indicate that metal mixtures effects vary across time, have distinct critical windows and that both JWQS and MWQS can determine longitudinal mixture effects including the cumulative contribution of each exposure and critical windows of effect. [ABSTRACT FROM AUTHOR]

• Caregiver-infant interactions were assessed with a standardized observational task. • Quality of caregiving interactions is associated with expressive language in infants. • Stimulation and growth-fostering behaviors may be important areas to target. Early caregiving is one of the strongest influences on children's development, and among the most significant modifiable environmental factor. The aim of this study was to explore the association between quality of caregiver-infant interactions and neurodevelopment of infants living in banana-growing communities in rural Costa Rica characterized as having environmental toxic exposures. Home visits were conducted with 94 caregiver-infant dyads from the Infants' Environmental Health Study (ISA), living within Matina county, Limón province. One-year infant neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development®, Third Edition (Bayley-III). Quality of caregiver-infant interaction was assessed with a standardized observational task: Nursing Child Assessment Satellite Training Teaching scale (NCATS) at around two years of age. Multiple regression analyses examined associations between components of caregiver-infant interactions and neurodevelopmental outcomes, adjusting for mancozeb and manganese exposure and other potential confounders. Compared to NCATS normative data for U.S. Hispanic mothers, 35% of the sample had overall caregiving interaction scores ≤10th percentile cut-off, indicating less than optimal interactions. Higher quality of caregiver-infant interaction was associated with higher expressive communication ability in infants [ß = 0.03 (95% CI: 0.01, 0.06)], controlling for pesticide exposure and confounders. Aspects of caregiving such as stimulation and growth-fostering of infants were most strongly associated with language outcomes. Results suggest an association between positive caregiving on language development for infants living in a rural agricultural area in Costa Rica, and highlight aspects of caregiving that could be targeted to improve resilience of these children who live in vulnerable conditions. [ABSTRACT FROM AUTHOR]

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 (β = -0.02, 95% CI: 0.03, -0.01, p = 0.004), waist circumference (β = -0.12 cm, 95% CI: 0.22, -0.03, p = 0.01), sum of skinfolds (β = -0.29 mm, 95% CI: 0.50, -0.08, p = 0.007) and body fat percentage (β = -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. [ABSTRACT FROM AUTHOR]

• In children, Prepulse inhibition (PPI) deficits are associated with neurodevelopmental disorders. • We used a data-driven prediction model to identify six important predictors of PPI. • We found that typical predictors of neurodevelopmental disorders also predict PPI. • Our findings underscore the potential utility of PPI as a biological marker of neurodevelopmental disorders. Prepulse inhibition (PPI) is a sensorimotor gating mechanism that reduces interfering influences to the neural processing of incoming stimuli, and is associated with several neurodevelopmental disorders. To date, research on PPI and neurodevelopmental disorders has primarily been in cross-sectional, clinical settings. In this prospective, epidemiologic study, we used a data-driven prediction model to identify socio-demographic predictors of PPI in children and adolescents from Mexico City to inform future etiologic studies evaluating PPI. We conducted variable selection and validation using a modified version of the multiple imputation random lasso (MIRL) variable selection algorithm. MIRL identified six predictors of PPI at a stimulus onset asynchrony of 120 ms or 240 ms. Of those six predictors, maternal education, birthweight, and total breastfeeding months were highlighted as previously unstudied variables associated with enhanced PPI. Our findings highlight the potential value of PPI as an adjunct screening tool for identifying children at risk for neurodevelopmental disorders and underscore the relevance for validation research on this topic. [ABSTRACT FROM AUTHOR]

Abstract Introduction Manganese (Mn) is an essential nutrient but also a toxicant at high exposures, when it can induce oxidative stress (OS). Mn uptake is inversely correlated with iron status, therefore anemic individuals may be more susceptible to Mn overload induced-OS, which can manifest as changes in mitochondrial DNA copy number (mtDNA CN). Our objectives were to: 1) determine stage-specific associations of prenatal Mn exposure with cord blood MtDNA CN; and 2) investigate effect modification by maternal anemia, ferritin, and mean corpuscular volume (MCV). Materials and methods We measured whole blood Mn, hemoglobin, serum ferritin, and MCV in the 2nd and 3rd trimester, in maternal blood at birth, and in cord blood from a prospective birth cohort in Mexico City, Mexico (n = 485). We then extracted DNA from cord blood leukocytes to determine mtDNA CN. We used robust regression to measure associations between Mn and mtDNA CN at each trimester and at birth. Anemia (hemoglobin ≤11 g/dL), iron deficiency (ferritin ≤15 ng/mL) and MCV (stratified at median), were examined as effect modifiers. Results Mn levels increased throughout pregnancy, and Mn was inversely correlated with ferritin. We observed a positive association between Mn in the 3rd trimester and Mn in cord blood and mtDNA CN (β = 0.04–0.05; 95% CI = 0.01, 0.08). Anemia significantly modified the association between mtDNA CN and Mn in the 2nd trimester. We found a positive association between 2nd trimester Mn and mtDNA CN in mothers with normal hemoglobin, and a negative association in those with low hemoglobin. (β high = 0.06; 95% CI = 0.01, 0.11; p = 0.01 and β low = −0.06; 95% CI = 0.03, −0.13; p = 0.06). No associations were detected between anemia, iron deficiency and MCV and mtDNA CN. Conclusions Maternal blood Mn in the 3rd trimester and in cord blood was positively associated with mtDNA CN, suggesting that higher late pregnancy prenatal Mn exposures can impact newborn mitochondria by promoting OS. Furthermore, 2nd trimester Mn was positively associated with mtDNA in non-anemic mother-child pairs but inversely associated in anemic individuals, indicating potential interactions between Mn and chronic anemia. Highlights • Mn in 3rd trimester blood and in cord blood was positively associated with mtDNA CN. • The relationship between 2nd trimester Mn and mtDNA CN was modified by anemia. • Mn in maternal blood at birth was not associated with cord blood mtDNA content. • Maternal anemia, serum ferritin, and MCV were not associated with mtDNA CN. [ABSTRACT FROM AUTHOR]

Abstract Introduction Lead (Pb) crosses the placenta and can cause oxidative stress, reduced fetal growth and neurological problems. The principal source of oxidative stress in human cells is mitochondria. Therefore, disruption of normal mitochondrial function during pregnancy may represent a primary mechanism behind the adverse effects of lead. We sought to assess the association of Pb exposure during pregnancy with mitochondrial DNA (mtDNA) content, a sensitive marker of mitochondrial function, in cord blood. Materials and methods This study comprised mother-infant pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a prospective birth-cohort that enrolled 1050 pregnant women from Mexico City who were receiving prenatal care between December 2007 and July 2011. Quantitative PCR was used to calculate relative MtDNA content (mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA)) in cord blood. Lead concentrations in both maternal blood (2nd and 3rd trimester and at delivery day) and in cord blood were measured by ICP-MS. Multivariable regression models adjusting for multiple confounders were fitted with 410 mother-infant pairs for whom complete data for mtDNA content, lead levels, and covariates were available. Results Maternal blood Pb measured in the second (mean 3.79 μg/dL, SD 2.63; β = 0.059, 95% CI 0.008, 0.111) and third trimester (mean 3.90 μg/dL; SD 2.84; β = 0.054, 95% CI 0.002, 0.107) during pregnancy and PB in cord blood (mean 3.50 μg/dL, SD 2.59; β = 0.050, 95% CI 0.004; 0.096) were associated with increased cord blood mtDNA content (mean 1.46, SD 0.44). In two-way interaction analyses, cord blood Pb marginally interacted with gestational age leading to an increase in mtDNA content for pre-term births (Benjamini-Hochberg False Discovery Rate correction; BH-FDR = 0.08). Conclusion This study shows that lead exposure in pregnancy alters mtDNA content in cord blood; therefore, alteration of mtDNA content might be a mechanism underlying the toxicity of lead. Highlights • Third trimester maternal blood Pb is associated with greater mtDNA content. • Preterm birth, C-section and premature rupture of membranes altered mtDNA content. • Gestational age marginally influences Pb effects on mtDNA content. [ABSTRACT FROM AUTHOR]

Background: The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a computerized tool used to measure cognitive function in diverse populations and is sensitive for assessing developmental changes in children. Although CANTAB has been used in several countries, its applicability in a Mexican child population is unknown. This study examined developmental trends on CANTAB in a large sample of urban Mexico City youth and tested the hypothesis that their performance would be similar to a large US normative sample. Method: As part of a birth cohort, Early Life Exposures in Mexico to Environmental Toxicants, 826 children, ages 5-15 years, completed CANTAB. Subtests measured planning (Stockings of Cambridge; SOC), short-term memory (Delayed Matching to Sample; DMS), sustained attention (Rapid Visual Information Processing; RVP), ability to match visual stimuli (Match to Sample Visual Search; MTS), flexibility (Intra-extra Dimensional Set Shift; IED), and response inhibition (Stop Signal Task; SST). Determinants of performance on the CANTAB, including age, maternal/child IQ, and sex, were analyzed using Spearman correlation and Welch t tests. Equivalence testing compared performance with existing norms. Results: Performance improved with age on all measures. Child IQ was mildly associated with measures of memory and attention but not executive functioning, consistent with US norms. Maternal IQ was not associated with any outcomes, and males performed better on IED. Mexican norms were comparable to US norms on almost all outcomes, with the exception of a short-term visual recognition memory task (DMS). Conclusions: This study provides the largest normative data for CANTAB performance in a community sample of Mexican youth. Findings demonstrate the expected maturational effects of executive function, specifically in cognitive shifting and inhibition. Levels of executive function performance demonstrated by a Mexican sample were consistent with normative values reported in US youth. These findings, as well as expected associations with child IQ, indicate high applicability of CANTAB for Mexican youth in neurobehavioral studies. [ABSTRACT FROM AUTHOR]

Abstract Background The programming of sleep architecture begins in pregnancy and depends upon optimal in utero formation and maturation of the neural connectivity of the brain. Particulate air pollution exposure can disrupt fetal brain development but associations between fine particulate matter (PM 2.5) exposure during pregnancy and child sleep outcomes have not been previously explored. Methods Analyses included 397 mother-child pairs enrolled in a pregnancy cohort in Mexico City. Daily ambient prenatal PM 2.5 exposure was estimated using a validated satellite-based spatio-temporally resolved prediction model. Child sleep periods were estimated objectively using wrist-worn, continuous actigraphy over a 1-week period at age 4–5 years. Data-driven advanced statistical methods (distributed lag models (DLMs)) were employed to identify sensitive windows whereby PM 2.5 exposure during gestation was significantly associated with changes in sleep duration or efficiency. Models were adjusted for maternal education, season, child's age, sex, and BMI z-score. Results Mother's average age was 27.7 years, with 59% having at least a high school education. Children slept an average of 7.7 h at night, with mean 80.1% efficiency. The adjusted DLM identified windows of PM 2.5 exposure between 31 and 35 weeks gestation that were significantly associated with decreased sleep duration in children. In addition, increased PM 2.5 during weeks 1–8 was associated with decreased sleep efficiency. In other exposure windows (weeks 39–40), PM 2.5 was associated with increased sleep duration. Conclusion Prenatal PM 2.5 exposure is associated with altered sleep in preschool-aged children in Mexico City. Pollutant exposure during sensitive windows of pregnancy may have critical influence upon sleep programming. Highlights • Prenatal PM 2.5 exposure was associated with sleep disruption in preschoolers. • Higher PM 2.5 was linked to decreased sleep efficiency and altered sleep duration. • Significant associations were identified during sensitive windows of gestation. [ABSTRACT FROM AUTHOR]

Abstract Background Phthalates are known endocrine disruptors and peroxisome proliferator-activated receptor (PPAR) activators, potentially capable of promoting an obesogenic effect. Pregnant women are especially vulnerable to phthalate exposure due to physiological and metabolic changes during pregnancy, including those related to the metabolism of xenobiotics. Phthalate exposure during pregnancy has been associated with early gestational weight gain, however, its effect on long-term weight gain remains unclear. The aim of the present study was to evaluate the association between phthalate exposure during pregnancy and long-term changes in weight among women. Methods Urinary phthalate concentrations, socioeconomic, anthropometry and information on diet and socioeconomic status were collected during pregnancy from 178 women from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort. Maternal body weight and diet information was also collected up to 5 times in the first year postpartum and twice during follow-up visits 5.2–10.7 years later. A path analysis was performed to assess associations between urinary phthalate metabolite levels during pregnancy and change in weight (kg) per year after delivery, including age, education, living with/without partner, parity, daily energy intake and breastfeeding duration. Results The mean age at pregnancy was 27.3 ± 5.9 years and mean body mass index during the first postpartum year was 27.07 ± 4.22 kg/m2. On average, women gained 3.48 kg (0.52 ± 0.84 kg/year). A unit increase in log-transformed mono-3-carboxypropyl phthalate (MCPP) was associated with 0.33 kg (95% CI: 0.09, 0.56) higher weight gain per year, and mono-benzyl phthalate (MBzP) with 0.21 kg (95% CI: −0.38, −0.03) lower weight gain per year. Conclusion Exposure to certain phthalates during pregnancy may be associated with long-term weight change in women. More studies on the effects of phthalate exposure during pregnancy on women's long-term health are required. Highlights • Metabolism and lifestyle changes promote postpartum weight retention in women. • Prenatal MCPP exposure is associated with higher long-term weight gain in women. • Prenatal MBzP exposure is associated with lower long-term weight gain in women. [ABSTRACT FROM AUTHOR]

Background: A child's adaptive ability is important for personal career and social development. Maternal self-esteem may help shape a child's behavior. This study aims to investigate whether maternal self-esteem measured when their children were toddlers predicts their children's adaptive skills at school age, and whether prenatal lead exposure modifies such a relationship.Methods: We assessed prenatal lead exposure using cord blood lead and maternal bone lead around delivery (tibia and patella lead measured in vivo by K-x-ray-fluorescence) among 192 mother-child pairs investigated in Mexico from 1994 to 2011. Maternal self-esteem was measured using the Coopersmith-Self-esteem-Inventory when children were 2 years old. When children were 7-to-15 years old, we measured children's blood lead levels and administered the 2nd edition of Behavior-Assessment-System-for-Children (BASC-2) parent-rating-scales (PRS) and Self-Reports of Personality (SRP) to evaluate children's adaptive skills.Results: Median (P25, P75) values for maternal patella and tibia lead, cord blood lead and children's current blood lead levels were 12.6 (3.2, 21.7) μg/g, 10.2 (4.1, 16.0) μg/g, 5.5 (3.5, 8.1) μg/dL and 2.7 (2.0, 4.0) μg/dL, respectively. In adjusted models, increased maternal self-esteem was associated with increased adaptive T-scores on the BASC-2 PRS and SRP scales. This relationship was weaker in high prenatal lead-exposure groups (high cord blood lead or patella lead groups, P25P100) compared with low prenatal lead-exposure (low cord blood lead or patella lead groups, P1P25) groups (P-interaction values < 0.10). No significant interactions between maternal tibia lead and self-esteem on children's adaptive T-scores were observed (P-interaction values > 0.10).Conclusions: Toddlers of mothers with high (vs. low) self-esteem have better adaptive abilities when they are of school-age. Prenatal lead exposure may attenuate or eliminate this positive association. [ABSTRACT FROM AUTHOR]

Exposure to environmental mixtures can exert wide-ranging effects on child neurodevelopment. However, there is a lack of statistical methods that can accommodate the complex exposure-response relationship between mixtures and neurodevelopment while simultaneously estimating neurodevelopmental trajectories. We introduce Bayesian varying coefficient kernel machine regression (BVCKMR), a hierarchical model that estimates how mixture exposures at a given time point are associated with health outcome trajectories. The BVCKMR flexibly captures the exposure-response relationship, incorporates prior knowledge, and accounts for potentially nonlinear and nonadditive effects of individual exposures. This model assesses the directionality and relative importance of a mixture component on health outcome trajectories and predicts health effects for unobserved exposure profiles. Using contour plots and cross-sectional plots, BVCKMR also provides information about interactions between complex mixture components. The BVCKMR is applied to a subset of data from PROGRESS, a prospective birth cohort study in Mexico city on exposure to metal mixtures and temporal changes in neurodevelopment. The mixture include metals such as manganese, arsenic, cobalt, chromium, cesium, copper, lead, cadmium, and antimony. Results from a subset of Programming Research in Obesity, Growth, Environment and Social Stressors data provide evidence of significant positive associations between second trimester exposure to copper and Bayley Scales of Infant and Toddler Development cognition score at 24 months, and cognitive trajectories across 6-24 months. We also detect an interaction effect between second trimester copper and lead exposures for cognition at 24 months. In summary, BVCKMR provides a framework for estimating neurodevelopmental trajectories associated with exposure to complex mixtures. [ABSTRACT FROM AUTHOR]

Abstract Background Epidemiologic and animal-based studies have raised concern over the potential impact of fluoride exposure on neurobehavioral development as manifested by lower IQ and deficits in attention. To date, no prospective epidemiologic studies have examined the effects of prenatal fluoride exposure on behavioral outcomes using fluoride biomarkers and sensitive measures of attention. Objective We aimed to examine the association between prenatal fluoride exposure and symptoms associated with attention-deficit/hyperactivity disorder (ADHD). Method 213 Mexican mother-children pairs of the Early Life Exposures to Environmental Toxicants (ELEMENT) birth cohort study had available maternal urinary samples during pregnancy and child assessments of ADHD-like behaviors at age 6–12. We measured urinary fluoride levels adjusted for creatinine (MUF cr) in spot urine samples collected during pregnancy. The Conners' Rating Scales-Revised (CRS-R) was completed by mothers, and the Conners' Continuous Performance Test (CPT-II) was administered to the children. Results Mean MUF cr was 0.85 mg/L (SD = 0.33) and the Interquartile Range (IQR) was 0.46 mg/L. In multivariable adjusted models using gamma regression, a 0.5 mg/L higher MUF cr (approximately one IQR higher) corresponded with significantly higher scores on the CRS-R for DSM-IV Inattention (2.84 points, 95% CI: 0.84, 4.84) and DSM-IV ADHD Total Index (2.38 points, 95% CI: 0.42, 4.34), as well as the following symptom scales: Cognitive Problems and Inattention (2.54 points, 95% CI: 0.44, 4.63) and ADHD Index (2.47 points; 95% CI: 0.43, 4.50). The shape of the associations suggested a possible celling effect of the exposure. No significant associations were found with outcomes on the CPT-II or on symptom scales assessing hyperactivity. Conclusion Higher levels of fluoride exposure during pregnancy were associated with global measures of ADHD and more symptoms of inattention as measured by the CRS-R in the offspring. Highlights • We measured urinary fluoride in 213 pregnant women living in Mexico City who were part of the ELEMENT pregnancy cohort study. • Higher concentration of maternal urinary fluoride was associated with more ADHD-like symptoms in school-age children. • Prenatal exposure to fluoride was most strongly associated with behavioral ratings of inattention, but not hyperactivity and impulse control. • Findings are consistent with the growing body of evidence suggesting neurotoxicity of early-life exposure to fluoride. [ABSTRACT FROM AUTHOR]

Abstract Background Metal exposure alters neurodevelopmental outcomes; little is known about critical windows of susceptibility when exposure exerts the strongest effect. Objective To examine associations between dentine biomarkers of manganese (Mn), zinc (Zn) and lead (Pb) and later childhood behaviors. Methods Subjects enrolled in a longitudinal birth cohort study in Mexico City provided naturally shed deciduous teeth. We estimated weekly prenatal and postnatal dentine Mn, Zn and Pb concentrations in teeth using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and measured behavior at ages 8–11 years of age using the Behavior Assessment System for Children, 2nd edition (BASC-2). We used distributed lag models and lagged weighted quantile sum regression to identify the role of individual and combined dentine biomarkers of Mn, Zn and Pb on behavioral outcomes controlling for maternal education and gestational age. Results Among the 133 subjects included in this study, prenatal and early postnatal dentine Mn appeared protective against childhood behavioral problems, specifically hyperactivity and attention. Postnatal dentine Mn was associated with increased reporting of internalizing problems, specifically anxiety. At 6 months, a 1-unit increase (unit = 1 SD of log concentration) in Mn was associated with a 0.18-unit (unit = 1 SD of BASC-2 score) increase in internalizing symptoms score and a 0.25-unit increase in anxiety. Postnatal Pb was associated with increasing anxiety symptoms; at 12 months, a 1-unit increase in Pb was associated with a 0.4 unit increase in anxiety symptoms. When examined as a metal mixture, we observed two potential windows of susceptibility to increased anxiety symptoms: the first window (0–8 months) appeared driven by Mn, the second window (8–12 months) was driven by the metal mixture and dominated by Pb. A 1-unit increase in the mixture index was associated with a 0.7-unit increase in SD of anxiety symptoms. Conclusions Childhood behaviors may demonstrate postnatal windows of susceptibility to individual and mixed metal concentrations measured in deciduous teeth. Prenatal dentine Mn may be protective, while excessive early postnatal Mn may increase risk for adverse behaviors. In combination, higher concentrations of Mn, Zn and Pb may have an adverse impact on behavior. Highlights • Tooth-matrix biomarkers were used to identify windows of susceptibility to Mn, Zn, and Pb. • Prenatal and early postnatal Mn appears protective against externalizing behavior. • Postnatal Mn is associated with higher internalizing behaviors, especially anxiety. • Co-exposure to Mn, Zn and Pb at 12 months is associated with anxiety. [ABSTRACT FROM AUTHOR]

Abstract Background High blood pressure (BP) in childhood is frequently renal in origin and a risk factor for adult hypertension and cardiovascular disease. Shorter gestations are a known risk factor for increased BP in adults and children, due in part to a nephron deficit in children born preterm. As nephrogenesis is incomplete until 36 weeks gestation, prenatal lead exposure occurring during a susceptible period of renal development may contribute to programming for later life renal disease. The relationship between shorter gestation and children's BP has not yet been explored to identify i) critical windows using nonlinear piecewise models or ii) combined with other early life risk factors such as prenatal lead exposure. Objectives (1) To evaluate the nonlinear relationship between lower gestational age and childhood BP measured at 4–6 years of age, and (2) to investigate modification by prenatal lead exposure. Methods In a prospective longitudinal birth cohort, we assessed 565 children between 4 and 6 years of age (mean: 4.8 years) in the PROGRESS cohort in Mexico City, Mexico. Gestational age at delivery was calculated using maternal report of last menstrual period (LMP) and confirmed with Capurro physical examination at birth. We measured pregnant women's blood lead levels (BLLs) in the second trimester via inductively coupled plasma-mass spectrometry and children's BP using an automated device. We performed both linear and nonlinear piecewise regression analyses to examine associations of gestational age with children's BP adjusting for children's age, sex, height, prenatal exposure to smoke, and maternal socioeconomic status. We stratified to assess modification by prenatal lead exposure, and used a data-adaptive approach to identify a lead cutpoint. Results Maternal second trimester BLLs ranged from 0.7 to 17.8 μg/dL with 112 (20%) women above the CDC guideline level of 5 μg/dL. In adjusted linear regression models, a one week reduction in gestational age was associated with a 0.5 mm Hg (95%CI: 0.2, 0.8) increase in SBP and a 0.4 mm Hg (95%CI 0.1, 0.6) increase in DBP. Our nonlinear models suggested evidence for different magnitude estimates on either side of an estimated join-point at 35.9 weeks' gestation, but did not reach statistical significance. However, when stratified by prenatal lead exposure, we identified a cutpoint lead level of concern of 2.5 μg/dL that suggested an interaction between gestational age and blood lead. Specifically, for BLLs ≥ 2.5 μg/dL, SBP was 1.6 (95%CI: 0.3, 2.9) mm Hg higher per each week reduction in gestational age among children born before 37.0 weeks; and among children born after 37.0 weeks, this relationship was attenuated yet remained significant [β: 0.9, 95%CI (0.2, 1.6)]. At BLLs below 2.5 μg/dL, there was no appreciable association between lower gestational age and SBP. Conclusions Our findings suggest that shorter gestation combined with higher prenatal lead exposure contributes to a higher risk of increased SBP at 4–6 years of age, particularly among infants born <37 weeks gestation. Our results underscore the importance of preventing prenatal lead exposure - even levels as low as 2.5 μg/dL - especially among pregnant women at risk for preterm birth. Given that high BP in childhood is a risk factor for adult hypertension and cardiovascular disease later in life, these results may have implications that extend across the life span. Highlights • Shorter gestations combined with higher prenatal lead exposure contribute to higher 4-yr blood pressure. • Associations are particularly notable among infants born <37 weeks' gestation. • We identify a blood lead level of 2.5 μg/dL that may have implications for renal health. • We utilize nonlinear modeling to identify critical windows of susceptibility. [ABSTRACT FROM AUTHOR]

Psychomotricity plays a very important role in children’s development, especially for learning involving reading-writing and mathematical calculations. Evaluate motor development in children 3 years old and its relationship with their cognitive abilities at the age of 5 years. Based on a cohort study, we analyzed the information about motor performance evaluated at 3 years old by Peabody Motor Scale and cognitive abilities at 5 years old. The association was estimated using linear regression models adjusted by mother’s intelligence quotient, sex, Bayley mental development index at 18 months, and quality of the environment at home (HOME scale). 148 children whose motor performance was determined at age 3 and was evaluated later at age 5 to determine their cognitive abilities. Cognitive abilities (verbal, quantitative, and memory) measured by McCarthy Scales. Significant positive associations were observed between stationary balance at age 3 with verbal abilities (β = 0.67, p = .04) and memory (β = 0.81, p = .02) at 5 years. Grasping and visual-motor integration were significant and positively associated with quantitative abilities (β = 0.74, p = .005; β = 0.61, p = .01) and memory (β = 2.11, p = .001; β = 1.74, p = .004). The results suggest that early motor performance contributes to the establishment of cognitive abilities at 5 years. Evaluation and early motor stimulation before the child is faced with formal learning likely helps to create neuronal networks that facilitate the acquisition of academic knowledge. [ABSTRACT FROM AUTHOR]

Background: Postpartum depression is an important cause of morbidity in mothers and children. The Edinburgh Postpartum Depression Scale (EPDS), the most widely used self-reported measure of postpartum depression, was conceived as a one-dimensional measure. However, evidence that depressive symptoms may be experienced differentially across cultural and racial groups highlights the need to examine structural equivalence using factor analysis across populations. Variation in factor structure for the EPDS remains understudied in middle/low income countries.Methods: We examined the factor structure of the EPDS assessed 6 months postpartum in 628 Mexican women in a longitudinal Mexico City birth cohort. We performed exploratory factor analysis (EFA) to determine the optimal fit in our sample and confirmatory factor analysis (CFA) to examine the fit of two- and three-factor models previously reported in Hispanic populations.Results: The majority of participants had no more than high school education (77%), maternal age was 28 ± 5.4 years and the mean total EPDS score was 6.72 ± 5.8. Using EFA, we identified that the three-factor model provided the optimal fit, with subscales for depression, anxiety, and anhedonia. CFA confirmed that the three-factor model provided the best fit.Limitations: The study population was lower SES, potentially limiting generalizability. The single administration of the EPDS measure in the postpartum period limited our ability to assess stability over time.Conclusions: Better delineation of the multi-factorial structure of the EPDS will allow a more comprehensive understanding of psychological functioning in postpartum women and better inform diagnosis, management and policy. [ABSTRACT FROM AUTHOR]

The impact of neurotoxic chemical mixtures on children's health is a critical public health concern. It is well known that during early life, toxic exposures may impact cognitive function during critical time intervals of increased vulnerability, known as windows of susceptibility. Knowledge on time windows of susceptibility can help inform treatment and prevention strategies, as chemical mixtures may affect a developmental process that is operating at a specific life phase. There are several statistical challenges in estimating the health effects of time-varying exposures to multi-pollutant mixtures, such as: multi-collinearity among the exposures both within time points and across time points, and complex exposure-response relationships. To address these concerns, we develop a flexible statistical method, called lagged kernel machine regression (LKMR). LKMR identifies critical exposure windows of chemical mixtures, and accounts for complex non-linear and non-additive effects of the mixture at any given exposure window. Specifically, LKMR estimates how the effects of a mixture of exposures change with the exposure time window using a Bayesian formulation of a grouped, fused lasso penalty within a kernel machine regression (KMR) framework. A simulation study demonstrates the performance of LKMR under realistic exposure-response scenarios, and demonstrates large gains over approaches that consider each time window separately, particularly when serial correlation among the time-varying exposures is high. Furthermore, LKMR demonstrates gains over another approach that inputs all time-specific chemical concentrations together into a single KMR. We apply LKMR to estimate associations between neurodevelopment and metal mixtures in Early Life Exposures in Mexico and Neurotoxicology, a prospective cohort study of child health in Mexico City. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although growing evidence suggests that early-life excess manganese (Mn) impairs neurodevelopment, data on the neurodevelopmental effects of mancozeb, a fungicide containing Mn, and its main metabolite ethylenethiourea (ETU) are limited. OBJECTIVE: We examined whether prenatal mancozeb exposure and excess Mn were associated with neurodevelopment in 355 1-y-old infants living near banana plantations with frequent aerial mancozeb spraying in Costa Rica. METHODS: We measured urinary ETU, hair Mn, and blood Mn concentrations in samples collected 1-3 times during pregnancy from mothers enrolled in the Infants' Environmental Health (ISA) study. We then assessed neurodevelopment in their 1-y-old infants using the Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III). We estimated exposure-outcome associations using linear regression models adjusted for maternal education, parity, gestational age at birth, child age, Home Observation for Measurement of the Environment score, and location of neurodevelopmental assessment. RESULTS: Median (P25-P75) urinary ETU, hair Mn, and blood Mn measured during pregnancy were 3:3 lg=L (2.4-4.9; specific gravity-corrected), 1:7 lg=g (0.9-4.1), and 24:0 lg=L (20.3-28.0), respectively. Among girls, higher ETU was associated with lower social-emotional scores [b per 10-fold increase= -7:4 points (95% CI: -15:2, 0.4)], whereas higher hair Mn was associated with lower cognitive scores [-3:0 (-6:1, 0.1)]. Among boys, higher hair Mn was associated with lower social-emotional scores [-4:6 (-8:5, -0:8)]. We observed null associations for blood Mn, language, and motor outcomes. CONCLUSIONS: Our findings indicate that maternal exposure to mancozeb and excess Mn during pregnancy may have adverse and sex-specific effects on infant neurodevelopment. [ABSTRACT FROM AUTHOR]

Background Normal prenatal neurodevelopment follows stages that are potentially influenced by both chemical and psychosocial environments. Exposure to elevated manganese during this critically vulnerable period has been found to be neurotoxic. Independently, maternal prenatal depression has been associated with subsequent neurodevelopmental decrements in children. The association between child neurodevelopment and prenatal co-exposure to manganese and maternal depression has not been sufficiently studied. Methods During pregnancy and at birth, we measured maternal blood and cord blood manganese levels respectively. Maternal depression was assessed in the 3rd trimester of pregnancy using the Edinburgh Depression Scale. Neurodevelopment was evaluated at 24 months of age with the Bayley Scales of Infant Development. A multivariate multiple regression model was used to analyze cognitive, language and motor scores simultaneously for 473 children from the PROGRESS birth cohort in Mexico City. Results Over 25% of our study participants reported having depressive symptoms. 3rd trimester blood manganese as well as depressive symptoms were independently negatively associated with all neurodevelopment scores in adjusted models. In stratified analyses, the negative association between manganese (maternal as well as cord blood) and 24-month language scores was stronger among women with depressive symptoms. Receptive language was mostly affected. Inverted U-shaped curves were seen for the association between with cord blood manganese and neurodevelopment scores. Conclusions Our findings are in line with previous studies of manganese and depression neurotoxicity. The prenatal period may be particularly sensitive to manganese and depression co-exposures and should be of interest for public health interventions to promote healthy emotional and nutritional pregnancies. [ABSTRACT FROM AUTHOR]

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 ð0:35Þ mg=L and 0:82 ð0:38Þ mg=L, respectively. In multivariate models we found that an increase in maternal urine fluoride of 0:5 mg=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. [ABSTRACT FROM AUTHOR]

Background: Neurodevelopment is a complex process involving both genetic and environmental factors. Prenatal exposure to lead (Pb) has been associated with lower performance on neurodevelopmental tests. Adverse neurodevelopmental outcomes are more frequent and/or more severe when toxic exposures interact with genetic susceptibility.Methods: To explore possible loci associated with increased susceptibility to prenatal Pb exposure, we performed a genome-wide gene-environment interaction study (GWIS) in young children from Mexico (n = 390) and Bangladesh (n = 497). Prenatal Pb exposure was estimated by cord blood Pb concentration. Neurodevelopment was assessed using the Bayley Scales of Infant Development.Results: We identified a locus on chromosome 8, containing UNC5D, and demonstrated evidence of its genome-wide significance with mental composite scores (rs9642758, p meta = 4.35 × 10-6). Within this locus, the joint effects of two independent single nucleotide polymorphisms (SNPs, rs9642758 and rs10503970) had a p-value of 4.38 × 10-9 for mental composite scores. Correlating GWIS results with in vitro transcriptomic profiles identified one common gene, SLC1A5, which is involved in synaptic function, neuronal development, and excitotoxicity. Further analysis revealed interconnected interactions that formed a large network of 52 genes enriched with oxidative stress genes and neurodevelopmental genes.Conclusions: Our findings suggest that certain genetic polymorphisms within/near genes relevant to neurodevelopment might modify the toxic effects of Pb exposure via oxidative stress. [ABSTRACT FROM AUTHOR]

Background As population lead levels decrease, the toxic effects of lead may be distributed to more sensitive populations, such as infants with poor fetal growth. Objectives To determine the association of prenatal lead exposure and fetal growth; and to evaluate whether infants with poor fetal growth are more susceptible to lead toxicity than those with normal fetal growth. Methods We examined the association of second trimester maternal blood lead levels (BLL) with birthweight-for-gestational age (BWGA) z-score in 944 mother-infant participants of the PROGRESS cohort. We determined the association between maternal BLL and BWGA z-score by using both linear and quantile regression. We estimated odds ratios for small-for-gestational age (SGA) infants between maternal BLL quartiles using logistic regression. Maternal age, body mass index, socioeconomic status, parity, household smoking exposure, hemoglobin levels, and infant sex were included as confounders. Results While linear regression showed a negative association between maternal BLL and BWGA z-score ( β = − 0.06 z-score units per log 2 BLL increase; 95% CI: − 0.13, 0.003; P = 0.06), quantile regression revealed larger magnitudes of this association in the < 30th percentiles of BWGA z-score ( β range [− 0.08, − 0.13] z-score units per log 2 BLL increase; all P values < 0.05). Mothers in the highest BLL quartile had an odds ratio of 1.62 (95% CI: 0.99–2.65) for having a SGA infant compared to the lowest BLL quartile. Conclusions While both linear and quantile regression showed a negative association between prenatal lead exposure and birthweight, quantile regression revealed that smaller infants may represent a more susceptible subpopulation. [ABSTRACT FROM AUTHOR]

We examined effects on child development of a group-based parenting support program (Education Initial - El) when combined with Mexico's conditional cash transfer (CCT) program (Prospera, originally Oportunidades and Progreso). This cluster-randomized trial included 204 communities (n = 1,113 children in final sample), stratified by community indigenous status, and assigned to receive either: (T0) CCT only; (T1) CCT plus availability of El in the community; or (T2) T1 plus promotion of the El program by the CCT program. Interviews were conducted with the mother or primary caregiver of each child at baseline (2008, children 0-18 months old), and at follow-up (2012, children 3-5 years old); the intervention began after baseline and continued for all eligible households. Cognitive development was assessed with the Extended Ages and Stages Questionnaire (baseline) and the McCarthy Scales of Children's Development (follow-up); assessors were blinded to treatment. All analyses were intention to treat. There were significant effects on child development when El received support and promotion from the CCT program (T2 vs. T0: General Cognitive Index, β = 3.90; 95% Cl [0.51, 7.30], Verbal Score, β = 4.28; 95% Cl [0.51, 8.05], and Memory Score, β = 4.14; 95% Cl [0.62, 7.66]), effects equivalent to 0.26-0.29 SD. There were no significant benefits when the programs operated independently (T1 vs. T0). In stratified analyses, El showed significant effects in indigenous communities only. We found consistent results in regressions controlling for covariates, with some reductions in magnitude of differences. Our findings suggest that group-based, parenting support programs can improve child outcomes within the context of a CCT, but only when the 2 programs are integrated and mutually supportive. [ABSTRACT FROM AUTHOR]

Background Lead and psychosocial stress disrupt similar but not completely overlapping mechanisms. Exposure during the prenatal period to each of these insults singularly has been found to alter normal neurodevelopment; however, longitudinal associations with stress modifying the effect of lead have not been sufficiently analyzed in epidemiologic studies. Objective To evaluate prenatal stress as an effect modifier of gestational lead neurotoxicity. Methods We used a structural equations modeling approach with a trivariate response to evaluate cognitive, language and motor scores of the Bayley Scales of Infant Development-III in 24 month-old children ( n = 360). Maternal blood lead levels were measured at the 2nd and 3rd trimester and psychosocial stress during pregnancy was assessed using a negative life events (NLE) scale derived from the CRYSIS questionnaire. Results 3rd trimester lead (mean 3.9 ± 3.0 SD μg/dL) and stress (median = 3 NLE) were negatively associated with Bayley III scores. Using the model's results we generated profiles for 0, 2, 4 and 6 NLE across lead levels (up to 10 μg/dL) and observed a dose–response for the developmental scores when lead levels were below 2 μg/dL. Each NLE curve had a different shape across increasing lead levels. Higher stress (NLE = 6) resulted in lower cognitive scores for both sexes, in lower language scores in girls but not boys. In the absence of stress we saw a negative association with lead for all scores, however for language and motor scores, higher stress seemed to mask this association. Conclusions Our work examined and confirmed prenatal stress exposure as a modifier of the well-known neurotoxic effects of prenatal lead. It adds to the existing evidence pointing at the importance of studying the co-exposure of chemical and non-chemical exposures, specifically of considering the emotional environment of children at early developmental stages of life. [ABSTRACT FROM AUTHOR]

Lead exposure during pregnancy remains a public health problem with potential lifelong impacts on children's growth and development. Mexico is unique in that stunting and obesity are both major public health concerns in children. This situation might be exacerbated by lead exposure which remains more common in Mexico than in the United States due in part to the use of lead glazed pottery in food preparation and storage. Our objective is to determine how lead exposure during pregnancy is associated with children's growth parameters, including height, weight, body mass index and percentage body fat measured between ages 4–6 years old in a Mexico City pregnancy cohort. Blood lead was collected in the 2nd and 3rd trimester of pregnancy as well as at delivery. Bone lead was assessed in mothers as a long term exposure biomarker. We performed multivariable linear regression analyses to assess the association between each of these lead exposure biomarkers and child anthropometry. We found a significant negative association between maternal 3rd trimester blood lead concentration and offspring height for age (β−0.10; 95% CI −0.19, −0.01), and a negative association between maternal 3rd trimester blood lead concentration and weight for age (β−0.11; 95% CI −0.22,−0.003). Our results in this Mexican population add to previous findings of an association of lead and decreased stature and weight in early childhood. Ongoing follow-up and longitudinal analyses may help elucidate how this impacts growth trajectory and other children's health outcomes. [ABSTRACT FROM AUTHOR]

Conditional cash transfer programs (CCTs) have shown mixed effects on child development outcomes in the context of poverty. Direct parenting support integrated with CCTs may improve the effectiveness of CCTs for children’s development, and benefits could occur via improvements in parenting practices or the home environment. Here, we use data from a randomized effectiveness trial to examine the pathways connecting parenting support and child development. The parenting program (EI: Educación Inicial) was implemented at scale among beneficiaries of Prospera (a CCT, previously Oportunidades and Progresa). Participants included children between the ages of 3 and 5 years old (n = 1,362) from 91 rural communities in three Mexican states. Communities were stratified by indigenous classification and randomized to one of three arms: (T0) Comparison group (CCT benefits only); (T1) CCT benefits plus availability of EI in the community; or (T2) CCT benefits plus promotion and encouragement by the CCT program to participate in EI. Findings were that participation in the T2 arm of the study was associated with a 13% increase in the number of play activities that parents engaged in with their children, particularly shared storybook reading and singing. Parents in T2 showed nearly two times greater odds of reading daily to their children. In mediation analyses, the amount of play activities and shared book reading explained up to 32% of the effects of the EI parenting program on child development outcomes. In this study, collaboration and integration of two social programs was critical for program impact, which occurred through pathways relating to parental engagement in reading and play. [ABSTRACT FROM AUTHOR]

Background: Temperament is a psychological construct that reflects both personality and an infant's reaction to social stimuli. It can be assessed early in life and is stable over time Temperament predicts many later life behaviors and illnesses, including impulsivity, emotional regulation and obesity. Early life exposure to neurotoxicants often results in developmental deficits in attention, social function, and IQ, but environmental predictors of infant temperament are largely unknown. We propose that prenatal exposure to both chemical and non-chemical environmental toxicants impacts the development of temperament, which can itself be used as a marker of risk for maladaptive neurobehavior in later life. In this study, we assessed associations among prenatal and early life exposure to lead, mercury, poverty, maternal depression and toddler temperament.Methods: A prospective cohort of women living in the Mexico City area were followed longitudinally beginning in the second trimester of pregnancy. Prenatal exposure to lead (blood, bone), mercury, and maternal depression were assessed repeatedly and the Toddler Temperament Scale (TTS) was completed when the child was 24 months old. The association between each measure of prenatal exposure and performance on individual TTS subscales was evaluated by multivariable linear regression. Latent profile analysis was used to classify subjects by TTS performance. Multinomial regression models were used to estimate the prospective association between prenatal exposures and TTS performance.Results: 500 mother-child pairs completed the TTS and had complete data on exposures and covariates. Three latent profiles were identified and categorized as predominantly difficult, intermediate, or easy temperament. Prenatal exposure to maternal depression predicted increasing probability of difficult toddler temperament. Maternal bone lead, a marker of cumulative exposure, also predicted difficult temperament. Prenatal lead exposure modified this association, suggesting that joint exposure in pregnancy to both was most toxic.Conclusions: Maternal depression predicts difficult temperament and concurrent prenatal exposure to maternal depression and lead predicts a more difficult temperament phenotype in 2 year olds. The role of temperament as an intermediate variable in the path from prenatal exposures to neurobehavioral deficits and other health effects deserves further study. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]