Search

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., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2023 Serván-Mori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Efforts to identify the predictors of maternal knowledge on Early Child Development (ECD) have proven inconclusive thus far, particularly with respect to socially deprived contexts in Low- and Middle-Income Countries (LMICs). We quantified the extent of ECD knowledge among mothers who were the primary caregivers of 0-38-month-old infants in marginalized communities in Mexico. We also explored the characteristics of the children, both individually and with regard to their households, given the influence of these factors on childhood development., Methods: We analyzed primary data obtained through a questionnaire administered to mothers who were the primary caregivers of 1045 girls and boys 0-38 months of age. The instrument was specifically designed for our study in order to explore the knowledge of participants about physical, neurological and psycho-affective development during childhood. We performed fractional regression analysis to assess the predictors of ECD knowledge., Results: The mean score of maternal ECD knowledge increased with their age and schooling as well as with their levels of cognitive ability and self-esteem. Irrespective of age at first birth, mean knowledge was relatively high for women with high school education and low for women with elementary or no formal education, a gradient with respect to age at fist birth was more marked among women with middle school education. ECD knowledge scores increased among mothers from households enjoying higher socioeconomic levels and from households with health insurance. Scores were lower for indigenous households regardless of their participation in social programs., Conclusion: Public policies on ECD should promote programs that are not only adapted to specific contexts, but also designed to improve shared child-rearing, early childhood care and as well as psycho-emotional education skills as a pathway to healthier ECD. The participation of families and communities in sensitive childhood care should form part of multisectoral programs involving education, health and wellbeing., Competing Interests: Competing interest The authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2022. The Author(s).)

Background: Variability in the FADS2 gene, which codifies the Delta-6 Desaturases and modulates the conversion of essential n-3 and n-6 fatty acids into long-chain polyunsaturated fatty acids, might modify the impact of prenatal supplementation with n-3 docosahexaenoic acid (DHA) on neurodevelopment., Objective: To assess if maternal FADS2 single nucleotide polymorphisms (SNPs) modified the effect of prenatal DHA on offspring development at 5 years., Design: We conducted a post-hoc interaction analysis of the POSGRAD randomized controlled trial (NCT00646360) of prenatal supplementation with algal-DHA where 1094 pregnant women originally randomized to 400 mg/day of preformed algal DHA or a placebo from gestation week 18-22 through delivery. In this analysis, we included offspring with information on maternal genotype and neurodevelopment at 5 years (DHA = 316; Control = 306) and used generalized linear models to assess interactions between FADS2 SNPs rs174602 or rs174575 and prenatal DHA on neurodevelopment at 5 years measured with McCarthy Scales of Children's Abilities (MSCA)., Results: Maternal and offspring characteristics were similar between groups. At baseline, mean (±standard deviation) maternal age was 26 ± 5 years and schooling was 12 ± 4 years. Forty-six percent (46%) of the children were female. Maternal minor allele frequencies were 0.37 and 0.33 for SNPs rs174602 and rs174575, respectively. There were significant variations by SNP rs174602 and intervention group (p for interactions <0.05) where children in the intervention group had higher MSCA scores on the quantitative (DHA: mean ± SEM = 22.6 ± 0.9 vs. Control = 19.1 ± 0.9, mean difference (Δ) = 3.45; p = 0.01) and memory (DHA = 27.9 ± 1.1 vs. Control = 23.7 ± 1.1, Δ = 4.26; p = 0.02) scales only among offspring of TT (minor allele homozygotes)., Conclusions: Maternal FADS2 SNP rs174602 modified the effect of prenatal DHA on cognitive development at 5 years. Variations in the genetic make-up of target populations could be an important factor to consider for prenatal DHA supplementation interventions., (Copyright © 2021. Published by Elsevier Ltd.)

Background: 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., Objectives: 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., Methods: 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 km 2 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/m 3 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., Results: 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 1 st 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)., Conclusions: 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., (Copyright © 2020. Published by Elsevier B.V.)

Background: We evaluated: (1) associations of prenatal manganese (Mn) levels with child neurodevelopment at 4-6 years; (2) effect modification by maternal anemia and iron deficiency; and (3) sex-specific effects., Methods: We measured blood Mn, hemoglobin, and serum ferritin in mothers at the second trimester, third trimester, and at birth, and in cord blood from a prospective birth cohort in Mexico City (n = 571). McCarthy Scales of Children's Abilities were measured at 4-6 years. Using linear regression, we estimated associations between prenatal Mn and neurodevelopment, examined anemia and iron deficiency as effect modifiers, and analyzed associations by child sex., Results: No direct associations were observed between Mn, anemia, or iron deficiency and McCarthy Scales. Second trimester iron deficiency and third trimester anemia modified the effect of Mn on child neurodevelopment. For instance, second trimester Mn was positively associated child memory scores in mother's with normal ferritin (1.85 (0.02, 3.45)), but negatively associated in mother's with low ferritin (-2.41 (-5.28, 0.47), interaction P value = 0.01), a pattern observed across scales. No effect modification at birth or in cord blood was observed., Conclusions: Anemia/iron deficiency during pregnancy may modify Mn impacts on child neurodevelopment, particularly in boys.

Background: 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., Purpose: 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., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier B.V.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Child neurodevelopment has been positively linked to maternal intake of polyunsaturated fatty acids (PUFAs) during pregnancy; however, it is unknown if that relationship persists among populations exposed to environmental neurotoxicants., Objective: The aim of this work was to assess whether maternal dietary intake of PUFAs during pregnancy is positively associated with child neurodevelopment, whose mothers were environmentally exposed to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT)., Methods: A prospective cohort study with 276 mother-child pairs was performed in Mexico. Neurodevelopment was assessed by Bayley Scales II from children age 1 to 30 months. Dietary PUFAs intake was estimated by Food Frequency Questionnaire at 1st and 3rd trimester of pregnancy. DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene, the main metabolite of DDT) maternal serum levels were determined by electron capture gas chromatography. Longitudinal multivariate linear mixed-effects analysis, which combines mental (MDI) and motor (PDI) Bayley scales in a single model, were performed., Results: Our results show that in a sample environmentally exposed to DDT, maternal ingestion of DPA during the first trimester of pregnancy was positively associated with MDI (β = 0.10, 95% CI 0.02, 0.18) in children from 1 to 30 months. Likewise, our results suggest that dietary ALA may be also related to MDI., Conclusion: DPA may benefit neurodevelopment even in populations exposed to DDT. Our results strengthen the importance of PUFAs intake during the prenatal period.

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.

Adequate nutrition is important for neurodevelopment. Although nutrients are ingested in combination, the impact of specific nutrients within the context of a nutrient mixture has not been studied with respect to health, such as neurodevelopment. Therefore, we examined the impact of prenatal and childhood nutrient mixtures on neurodevelopmental outcomes. Participants included mother⁻child pairs in the Programming Research in Obesity, Growth, Environment, and Social Stress (PROGRESS) prospective birth cohort in Mexico City. We assessed prenatal and child micro- and macronutrient profiles among 65 and 329 children, respectively, via food frequency questionnaires. Neurodevelopmental outcomes of 4⁻6-year-old children were measured using the McCarthy Scales of Children's Abilities (MSCA). We conducted weighted quantile sum (WQS) regression analyses to calculate indices reflecting "good" and "poor" prenatal and childhood nutrition. After adjusting for maternal education, socioeconomic status, the Home Observation for Measurement of the Environment (HOME) score, and total caloric intake, the good prenatal and childhood nutrition indices predicted more favorable neurodevelopment, while both poor nutrition indices predicted poorer neurodevelopment. These associations were stronger in prenatal than childhood models. Monounsaturated fats predicted various neurodevelopmental abilities relatively strongly in both models. Prenatal and childhood consumption of combinations of beneficial nutrients may contribute to more favorable neurodevelopment., Competing Interests: The authors declare no conflicts of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; and in the decision to publish the results.

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.

Background: Maternal 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) serum levels during pregnancy have been negatively linked to child neurodevelopment in contrast to intake of omega-3 and -6 (ω-3 and ω-6) fatty acids., Objectives: To assess whether maternal dietary intake of ω-3 and ω-6 during pregnancy modifies the association between exposure to DDE and child neurodevelopment from age 42-60 months., Methods: Prospective cohort study with 142 mother-child pairs performed in Mexico. DDE serum levels were determined by electron capture gas chromatography. Dietary ω-3 and ω-6 intake was estimated by questionnaire. Child neurodevelopment was assessed by McCarthy Scales., Results: Docosahexaenoic (DHA) fatty acid intake significantly modified the association between DDE and motor component: increased maternal DDE was associated with lower motor development in children whose mothers had lower DHA intake (β log2DDE  = -1.25; 95% CI: -2.62, 0.12), in contrast to the non-significant increase among children whose mothers had higher DHA intake (β log2DDE-motor  = 0.50; 95% CI: 0.55, 1.56). Likewise, arachidonic fatty acid (ARA) intake modified the association between DDE and memory component: increased maternal DDE was associated with a significantly larger reduction in the memory component in children whose mothers had lower ARA intake (β log2DDE  = -1.31; 95% CI: -2.29, -0.32) than children whose mothers had higher ARA intake (β log2DDE-memory  = 0.17; 95% CI: -0.78, 1.11)., Conclusions: Dietary intake of DHA and ARA during pregnancy may protect against child neurodevelopment damage associated with prenatal maternal DDE levels., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: The purpose of the study was to examine whether access to an at-scale, group-based parenting education program ("Educación Inicial") had differential effects on parenting behaviors and child cognitive development according to mother's age at the birth of her first child, with a focus on adolescent mothers in rural Mexico., Methods: This was a secondary analysis of a cluster-randomized controlled trial (n = 728 households, n = 106 communities). We conducted intent-to-treat analyses and examined the interaction between treatment group and mother's age at first birth. The primary outcomes were parenting behaviors (Family Care Indicators) and children's cognitive development (McCarthy Scales of Children's Abilities) at ages 3-5 years., Results: We found that children of mothers who began childbearing in adulthood (20-30 years) scored higher on tests of cognitive development when randomized to weekly parenting support than their counterparts in the comparison group. Whereas, the children of mothers who began childbearing in adolescence (≤16 years) did not have higher scores associated with the parenting program (difference in magnitude of associations: Verbal = -8.19; 95% CI = -15.50 to -.88; p = .03; Memory = -7.22; 95% CI = -14.31 to -.14; p = .05). The higher scores among the children of mothers who began childbearing in adulthood were only significant when Educación Inical was supported by Prospera, the conditional cash transfer program., Conclusions: Our study results suggest that the Educación Inicial parenting intervention did not adequately address the needs of women who began childbearing in adolescence. One reason may be that adolescent mothers are more socially marginalized and less able to benefit from parenting programs., (Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

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.

We examined effects on child development of a group-based parenting support program ( Educación Inicial - EI) when combined with Mexico's conditional cash transfer (CCT) program ( Prospera , originally Oportunidades and Progresa ). 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 EI in the community; or (T2) T1 plus promotion of the EI 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 EI received support and promotion from the CCT program (T₂ vs. T₀: General Cognitive Index, β = 3.90; 95% CI [0.51, 7.30], Verbal Score, β = 4.28; 95% CI [0.51, 8.05], and Memory Score, β = 4.14; 95% CI [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, EI 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. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Background: Docosahexanoic acid (DHA) is an important constituent of the brain. Evidence from well-designed intervention trials of the long-term benefits of increasing DHA intake during pregnancy has been sparse., Objective: We evaluated global cognition, behavior, and attention at age 5 y in the offspring of Mexican women who participated in a randomized controlled trial of prenatal DHA supplementation., Design: A total of 1094 women were randomly assigned to receive 400 mg of either DHA or placebo/d from 18 to 22 wk of pregnancy until delivery. We assessed cognitive development and behavioral and executive functioning, including attention, in 797 offspring at age 5 y (82% of 973 live births) with the use of the McCarthy Scales of Children's Abilities (MSCA), the parental scale of the Behavioral Assessment System for Children, Second Edition (BASC-2), and the Conners' Kiddie Continuous Performance Test (K-CPT). We compared the groups on raw scores, T-scores, and standardized scores, as appropriate. We examined heterogeneity by the quality of the home environment, maternal intelligence, and socioeconomic status., Results: There were no group differences for MSCA scores (P > 0.05), but the positive effect of the home environment at 12 mo on general cognitive abilities was attenuated in the DHA group compared with in the placebo group (P-interaction < 0.05). There were no differences between groups on the BASC-2. On the K-CPT, offspring in the DHA group showed improved mean ± SD T-scores compared with those of the placebo group for omissions (DHA: 47.6 ± 10.3; placebo: 49.6 ± 11.2; P < 0.01) with no differences (P > 0.05) for the other K-CPT scores or of the proportion who were clinically at risk of attention deficit hyperactivity disorders after Bonferroni correction for multiple comparisons., Conclusion: Prenatal exposure to DHA may contribute to improved sustained attention in preschool children. This trial was registered at clinicaltrials.gov as NCT00646360., (© 2016 American Society for Nutrition.)

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

Objective: We evaluated the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring development at 18 months of age., Design: Randomized placebo double-blind controlled trial., Settings: Cuernavaca, Mexico., Participants and Methods: We followed up offspring (n = 730; 75% of the birth cohort) of women in Mexico who participated in a trial of DHA supplementation during the latter half of pregnancy. We assessed the effect of the intervention on child development and the potential modifying effects of gravidity, gender, SES, and quality of the home environment., Interventions or Main Exposures: 400 mg/day of algal DHA., Outcome Measures: Child development at 18 months of age measured using the Spanish version of the Bayley Scales of Infant Development-II. We calculated standardized psychomotor and mental development indices, and behavior rating scale scores., Results: Intent-to-treat differences (DHA-control) were: Psychomotor Developmental Index -0.90 (95% CI: -2.35, 0.56), Mental Developmental Index -0.26 (95% CI: -1.63, 1.10) and Behavior Rating Scale -0.01 (95% CI: -0.95, 0.94). Prenatal DHA intake attenuated the positive association between home environment and psychomotor development index observed in the control group (p for interaction = 0.03) suggesting potential benefits for children living in home environments characterized by reduced caregiver interactions and opportunities for early childhood stimulation., Conclusions: Prenatal DHA supplementation in a population with low intakes of DHA had no effects on offspring development at 18 months of age although there may be some benefit for infants from poor quality home environments., Trial Registration: Clinicaltrials.gov NCT00646360.

Attention Deficit Hyperactivity Disorder (ADHD) is the most commonly diagnosed and studied cognitive and behavioral disorder in school-age children. The etiology of ADHD and ADHD-related behavior is unclear, but genetic and environmental factors, such as pesticides, have been hypothesized. The objective of this study was to investigate the relationship between in utero exposure to chlorpyrifos, chlorpyrifos-methyl, and/or 3,5,6-trichloro-2-pyridinol (TCPY) and ADHD in school-age Mexican children using TCPY as a biomarker of exposure. The temporal reliability of repeated maternal urinary TCPY concentrations across trimesters was also explored (N=21). To explore associations with ADHD-related outcomes in children, third trimester urinary TCPY concentrations in were measured in 187 mother-child pairs from a prospective birth cohort. Child neurodevelopment in children 6-11 years of age was assessed using Conners' Parental Rating Scales-Revised (CRS-R), Conners' Continuous Performance Test (CPT), and Behavior Assessment System for Children-2 (BASC-2). Multivariable linear regression models were used to test relationships for all children combined and also stratified by sex. Intraclass correlation coefficients (ICC) calculations were based on a random effects model. The ICC was 0.41 for uncorrected TCPY, and ranged from 0.29 to 0.32 for specific gravity-corrected TCPY. We did not observe any statistically significant associations between tertiles of maternal TCPY concentrations and ADHD-related outcomes in children. However, compared to the lowest tertile we found suggestive evidence for increased ADHD index in the highest TCPY tertile in boys (β=5.55 points; 95% CI (-0.19, 11.3); p=0.06) and increased attention problems for the middle tertile in girls (β=5.81 points; 95% CI (-0.75, 12.4); p=0.08). Considering the continued widespread agricultural and possible residential use of chlorpyrifos and chlorpyrifos-methyl in Mexico and the educational implications of cognitive and behavior deficits, these relationships deserve further study., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Objective: To evaluate the association between prenatal exposure to molybdenum (Mo) and infant neurodevelopment during the first 30 months of life., Methods: We selected a random sample of 147 children who participated in a prospective cohort study in four municipalities in the State of Morelos, Mexico. The children were the products of uncomplicated pregnancies with no perinatal asphyxia, with a weight of ≥2 kg at birth, and whose mothers had no history of chronic illnesses. These women were monitored before, during, and after the pregnancy. For each of these children a maternal urine sample was available for at least one trimester of pregnancy, and urine Mo levels were determined by electrothermal atomic absorption spectrometry. Neurodevelopment was evaluated using the psychomotor (PDI) and mental development indices (MDI) of the Bayley scale. Association between prenatal exposure to Mo and infant neurodevelopment was estimated using generalized mixed effect models., Results: The average urinary concentrations of Mo adjusted for creatinine varied between 45.6 and 54.0 µg/g of creatinine at first and third trimester, respectively. For each doubling increase of Mo (μg/g creatinine) during the third trimester of pregnancy, we observed a significant reduction on PDI (β = -0.57 points; P = 0.03), and no effect on MDI (β = 0.07 points; P = 0.66)., Discussion: As this is the first study that suggests a potential negative association between prenatal Mo exposure and infant neurodevelopment, these results require further confirmation.

Background: Previous studies suggest that prenatal phthalate exposure affects neurodevelopment and behavior during the first years of life., Objectives: To evaluate the effect of maternal urinary concentrations of phthalate metabolites during pregnancy on mental and psychomotor development in children 24-36 months of age., Methods: This analysis was conducted on the first three years of life among a subsample of 136 mother-child pairs from the ELEMENT cohort studies conducted in Mexico City. Maternal urine samples collected during the third trimester of pregnancy were analyzed for 9 phthalate metabolites: Mono-ethyl phthalate (MEP), Mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), Mono-3-carboxypropyl phthalate (MCPP), and four di-2-ethylhexyl phthalate (DEHP) metabolites [mono-2-ethylhexyl-phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)]. Among the 136 children, 135 (99.3%) completed the study period. Child neurodevelopment was assessed using mental and psychomotor development indexes (MDI and PDI) from a Bayley (BSID II) test at 24, 30, and 36 months of age. The effect of prenatal phthalate exposure on neurodevelopment was estimated using linear regression models for longitudinal data clustered at the individual level., Results: No significant associations were observed among all children combined, but differential effects by gender were found. Among girls, there was a negative association between MDI and DEHP metabolites MEHP (β=-2.11 [95% CI: -3.73, -0.49]), MEHHP (β=-1.89 [95% CI: -3.64, -0.15]), MEOHP (β=-1.80 [95% CI: -3.58, -0.03]) MECPP (β=-2.52 [95% CI: -4.44, -0.61]), and ΣDEHP (β=-3.41 [95% CI: -5.26, -1.55]); there was no significant effect among boys. Male PDI was positively related to MBzP (β=1.79 [95% CI: 0.14, 3.45]) and MCPP (β=1.64 [95% CI: 0.15, 3.12]); there was no significant effect on PDI among girls., Conclusion: This study demonstrates that sex plays a role of an effect modifier in the association between prenatal phthalate exposure and neurodevelopment., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To examine longitudinal associations of prenatal, infancy, and early childhood lead exposure during sensitive periods with height and body mass index (BMI)., Study Design: A total of 773 participants were recruited between 1994 and 2005 in Mexico City. Lead exposure history categories were constructed for the prenatal period (maternal patellar lead concentration) and for infancy and childhood (mean child blood lead concentration at birth to 24 months and 30-48 months, respectively). Linear regression models were used to study lead exposure history with height and BMI at 48 months., Results: Mean height at age 48 months was significantly lower in children with a blood lead level exceeding the median during infancy (-0.84 cm; 95% CI, -1.42 to -0.25) than in children with a level below the median. Prenatal lead exposure was not associated with height at 48 months. Results for attained BMI generally trended in the same direction as for height., Conclusion: Our findings suggest an effect of lead exposure early in life on height attainment at 48 months, with the exposure window of greatest sensitivity in infancy., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: 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 × continuous lead; mental development score, β = -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.

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 (β(1T) = -0.02) and mental (β(2T) = -0.03 and β(3T) = -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.

Objective: To investigate the effects of prenatal and postnatal lead exposure and polymorphisms in dopamine metabolism genes on neurocognitive development of Mexican children at 24 months (n = 220) and 48 months (n = 186) of age., Study Design: We genotyped the dopamine transporter gene (DAT1; SLC6A3) variable nucleotide tandem repeat and the dopamine receptor D2 (DRD2) Taq1A single nucleotide polymorphism. Children were assessed at 24 months with Bayley Scales of Infant Development (Mental Development Index and Psychomotor Development Index) and at 48 months with McCarthy Scales of Children's Abilities., Results: Blood lead concentration (BLL) in umbilical cord was 6.6 ± 3.3 μg/dL (measured in 1995-96), 8.1 ± 4.4 μg/dL at 24 months, and 8.1 ± 3.6 μg/dL at 48 months. Cord BLL was negatively associated with Mental Development Index (P < .01) and Psychomotor Development Index (P < .1), but not McCarthy scores. The 48-month BLL, but not the 24-month BLL, was negatively associated with children's scores. Children with DRD2 TT genotype (variant) scored higher than children with CC genotype (wild type) on the Mental Development Index and McCarthy memory scale. Neither polymorphism modified the relationship between BLL (either prenatal or postnatal) and neurocognitive development., Conclusion: Lead exposure was adversely associated with neurocognitive measures, whereas the DRD2 Taq1A TT variant was positively associated with neurocognitive measures. We found no evidence of gene-environment interactions on developmental outcomes in early childhood., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Recent evidence suggests that low-level environmental exposure to manganese adversely affects child growth and neurodevelopment. Previous studies have addressed the effects of prenatal exposure, but little is known about developmental effects of early postnatal exposure., Methods: We studied 448 children born in Mexico City from 1997 through 2000, using a longitudinal study to investigate neurotoxic effects of early-life manganese exposure. Archived blood samples, collected from children at 12 and 24 months of age, were analyzed for manganese levels using inductively coupled plasma mass spectrometry. Mental and psychomotor development were scored using Bayley Scales of Infant Development at 6-month intervals between 12 and 36 months of age., Results: At 12 months of age, the mean (SD) blood manganese level was 24.3 (4.5)microg/L and the median was 23.7 microg/L; at 24 months, these values were 21.1 (6.2) microg/L and 20.3 microg/L, respectively. Twelve- and 24-month manganese concentrations were correlated (Spearman correlation = 0.55) and levels declined over time ([beta] = -5.7 [95% CI = -6.2 to -5.1]). We observed an inverted U-shaped association between 12-month blood manganese and concurrent mental development scores (compared with the middle 3 manganese quintiles, for the lowest manganese quintile, [beta] = -3.3 [-6.0 to -0.7] and for the highest manganese quintile, [beta] = -2.8 [-5.5 to -0.2]). This 12-month manganese effect was apparent but diminished with mental development scores at later ages. The 24-month manganese levels were not associated with neurodevelopment., Conclusions: These results suggest a possible biphasic dose-response relationship between early-life manganese exposure at lower exposure levels and infant neurodevelopment. The data are consistent with manganese as both an essential nutrient and a toxicant.

Objective: To identify the relationship between stimulation at home and motor development among 36 month-old children., Materials and Methods: The development of gross and fine motor skills of 169 infants (50.9% boys and 49.1% girls) was assessed at the age of 36 months with the Peabody Developmental Motor Scale. The quality of home stimulation was determined during a prior evaluation (at 30 months) by means of the HOME Scale., Results: Total stimulation at home was significantly associated with better performance in the gross and fine motor areas. Particular aspects of this home stimulation were related to better gross and fine motor functions., Conclusion: Static balance and locomotion (gross motor skills) and grasping and visual-motor integration (fine motor skills) are associated with particular aspects of home stimulation, such as parent-child interaction, verbal reinforcement of the child's positive actions and providing the child with clear boundaries.

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 > or =2 kg, 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&#95;II; Bayley, 1993) 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.

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.

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.

Background: The impact of prenatal lead exposure on neurodevelopment remains unclear in terms of consistency, the trimester of greatest vulnerability, and the best method for estimating fetal lead exposure., Objective: We studied prenatal lead exposure's impact on neurodevelopment using repeated measures of fetal dose as reflected by maternal whole blood and plasma lead levels., Methods: We measured lead in maternal plasma and whole blood during each trimester in 146 pregnant women in Mexico City. We then measured umbilical cord blood lead at delivery and, when offspring were 12 and 24 months of age, measured blood lead and administered the Bayley Scales of Infant Development. We used multivariate regression, adjusting for covariates and 24-month blood lead, to compare the impacts of our pregnancy measures of fetal lead dose., Results: Maternal lead levels were moderately high with a first-trimester blood lead mean (+/- SD) value of 7.1 +/- 5.1 microg/dL and 14% of values >or=10 microg/dL. Both maternal plasma and whole blood lead during the first trimester (but not in the second or third trimester) were significant predictors (p < 0.05) of poorer Mental Development Index (MDI) scores. In models combining all three trimester measures and using standardized coefficients, the effect of first-trimester maternal plasma lead was somewhat greater than the effect of first-trimester maternal whole blood lead and substantially greater than the effects of second- or third-trimester plasma lead, and values averaged over all three trimesters. A 1-SD change in first-trimester plasma lead was associated with a reduction in MDI score of 3.5 points. Postnatal blood lead levels in the offspring were less strongly correlated with MDI scores., Conclusions: Fetal lead exposure has an adverse effect on neurodevelopment, with an effect that may be most pronounced during the first trimester and best captured by measuring lead in either maternal plasma or whole blood.

Prenatal folate and vitamin B[subscript 12] 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 B[subscript 12] in the first trimester of pregnancy and child neuropsychological development. Maternal plasma folate and vitamin B[subscript 12] 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 ([Beta] = -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 B[subscript 12] 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.

We examined effects on child development of a group-based parenting support program ("Educación Inicial" - EI) when combined with Mexico's conditional cash transfer (CCT) program ("Prospera," originally 'Oportunidades" and "Progresa"). This cluster-randomized trial included 204 communities (n = 1,113 children in final sample), stratified by community indigenous status, and assigned to receive either: (T[subscript 0]) CCT only; (T[subscript 1]) CCT plus availability of EI in the community; or (T[subscript 2]) [subscript 1] plus promotion of the EI 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 EI received support and promotion from the CCT program (T[subscript 2] vs. T[subscript 0]: General Cognitive Index, ß = 3.90; 95% CI [0.51, 7.30], Verbal Score, ß = 4.28; 95% CI [0.51, 8.05], and Memory Score, ß = 4.14; 95% CI [0.62, 7.66]), effects equivalent to 0.26-0.29 SD. There were no significant benefits when the programs operated independently (T[subscript 1] vs. T[subscript 0]). In stratified analyses, EI 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.

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: (T[subscript 0]) Comparison group (CCT benefits only); (T[subscript 1]) CCT benefits plus availability of "EI" in the community; or (T[subscript 2]) CCT benefits plus promotion and encouragement by the CCT program to participate in "EI." Findings were that participation in the T[subscript 2] 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 T[subscript 2] 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.

Objective: To explore anthropometric indicators and mental development in very-low-income children in the second year of life. Design: Cross-sectional survey. Setting: Low-income areas (income < 20th percentile) in semi-urban Mexico (defined as towns or cities with 2500-50 000 inhabitants). Subjects: Eight hundred and ninety-six children aged 12.5-23.5 months surveyed from September to December 2001. Methods: Questionnaire survey and anthropometric survey of households. Multivariate regression models evaluated differences across age in anthropometry (height-for-age Z-score (HAZ) and weight-for-height Z-score) and cognitive function (Mental Development Index (MDI) of the Bayley Scales of Infant Development) while controlling for socio-economic and parental characteristics. Results: There was a significant decline in HAZ and in age-adjusted MDI score across the second year of life. Although the children showed MDI scores close to the mean, normed US values at 13-14 months, the scores were significantly lower than expected in older children (P < 0.0001), even after controlling for socio-economic status and parental characteristics. At 13-14 months, only 3% of children received scores below 70 (less than minus two standard deviations), whereas by 19-20 months, almost 17% of children were performing below this level. No socio-economic or parental characteristics were significant predictors of HAZ or MDI. Conclusions: Parallel deficits are evident in both height-for-age and cognitive functioning during the second year of life in low-income Mexican infants. The consistency of these growth and development findings further stresses the need for targeted interventions to reduce the vulnerability of low-income Mexican children very early in life.

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]

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 and Objective: Omega-3 polyunsaturated fatty acids are important for brain development and cognition. Maternal supplementation during pregnancy has shown mixed impacts on child cognitive performance. This study assessed whether offspring FADS genotype modified the impact of prenatal DHA supplementation on cognitive scores at age 5 years. Methods: POSGRAD (Prenatal Omega-3 Supplementation and Child Growth And Development) was a double-blind randomized controlled trial conducted in Mexico, in which 1094 women were randomly assigned at 18-22 weeks gestation to receive 400 mg/day algal docosahexaenoic acid (DHA) or placebo through delivery. We included children born to mothers enrolled in the original trial who had genetic data and cognitive outcomes at age 5 years assessed using the McCarthy Scales of Child Abilities (MSCA) which includes subscales for verbal, perceptual, quantitative, memory, and motor abilities. Generalized linear models were used to assess interactions between FADS1 and FADS2 SNPs (rs175446, rs174602, rs1535, rs174448, rs174583) and DHA supplementation on child cognitive outcomes at age 5 years. Results: 502 children (DHA= 254, placebo = 248) were included. Mean (SD) composite MSCA scores (sum of verbal, perceptual, quantitative) at age 5 years were 121.5 (22.5), and 121.0 (23.5) for the DHA and placebo groups, respectively. There were no significant differences by offspring FADs genotype (overall) on cognitive scores (all p > .05), neither was there evidence of effect modification of prenatal DHA supplementation (all p-interaction >.05). Conclusions: Variations in offspring FADS genotype appear not to influence child cognition at age 5 years and not to modify the impact of DHA on cognition. [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]

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: 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]

Background: Cumulative prenatal lead exposure, as measured by maternal bone lead burden, has been associated with smaller weight of offspring at birth and 1 month of age, but no study has examined whether this effect persists into early childhood. Objective: We investigated the association of perinatal maternal bone lead, a biomarker of cumulative prenatal lead exposure, with children's attained weight over time from birth to 5 years of age. Methods: Children were weighed at birth and at several intervals up until 60 months. Maternal tibia and patella lead were measured at 1 month postpartum using in vivo K-shell X-ray fluorescence. We used varying coefficient models with random effects to assess the association of maternal bone lead with weight trajectories of 522 boys and 477 girls born between 1994 and 2005 in Mexico City. Results: After controlling for breast-feeding duration, maternal anthropometry, and socio- demographic characteristics, a 1-SD increase in maternal patella lead (micrograms per gram) was associated with a 130.9--g decrease in weight [95% confidence interval (CI), -227.4 to -34.4 g] among females and a 13.0--g nonsignificant increase in weight among males (95% CI, -73.7 to 99.9 g) at 5 years of age. These associations were similar after controlling for concurrent blood lead levels between birth and 5 years. Conclusions: Maternal bone lead was associated with lower weight over time among female but not male children up to 5 years of age. Given that the association was evident for patellar but not tibial lead levels, and was limited to females, results need to be confirmed in other studies. [ABSTRACT FROM AUTHOR]

Copyright of Salud Pública de México is the property of Instituto Nacional de Salud Publica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)