McCarthy Scales Of Children Research Articles

Evaluating the association between placenta DNA methylation and cognitive functions in the offspring

The placenta plays a crucial role in protecting the fetus from environmental harm and supports the development of its brain. In fact, compromised placental function could predispose an individual to neurodevelopmental disorders. Placental epigenetic modifications, including DNA methylation, could be considered a proxy of placental function and thus plausible mediators of the association between intrauterine environmental exposures and genetics, and childhood and adult mental health. Although neurodevelopmental disorders such as autism spectrum disorder have been investigated in relation to placenta DNA methylation, no studies have addressed the association between placenta DNA methylation and child’s cognitive functions. Thus, our goal here was to investigate whether the placental DNA methylation profile measured using the Illumina EPIC array is associated with three different cognitive domains (namely verbal score, perceptive performance score, and general cognitive score) assessed by the McCarthy Scales of Children’s functions in childhood at age 4. To this end, we conducted epigenome-wide association analyses, including data from 255 mother-child pairs within the INMA project, and performed a follow-up functional analysis to help the interpretation of the findings. After multiple-testing correction, we found that methylation at 4 CpGs (cg1548200, cg02986379, cg00866476, and cg14113931) was significantly associated with the general cognitive score, and 2 distinct differentially methylated regions (DMRs) (including 27 CpGs) were significantly associated with each cognitive dimension. Interestingly, the genes annotated to these CpGs, such as DAB2, CEP76, PSMG2, or MECOM, are involved in placenta, fetal, and brain development. Moreover, functional enrichment analyses of suggestive CpGs (p < 1 × 10−4) revealed gene sets involved in placenta development, fetus formation, and brain growth. These findings suggest that placental DNA methylation could be a mechanism contributing to the alteration of important pathways in the placenta that have a consequence on the offspring’s brain development and cognitive function.

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

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

Sensitive development windows of prenatal air pollution and cognitive functioning in preschool age Mexican children.

Neurotoxicity resulting from air pollution is of increasing concern. Considering exposure timing effects on neurodevelopmental impairments may be as important as the exposure dose. We used distributed lag regression to determine the sensitive windows of prenatal exposure to fine particulate matter (PM2.5) on children's cognition in a birth cohort in Mexico. Analysis included 553 full-term (≥37 weeks gestation) children. Prenatal daily PM2.5 exposure was estimated using a validated satellite-based spatiotemporal model. McCarthy Scales of Children's Abilities (MSCA) were used to assess children's cognitive function at 4-5 years old (lower scores indicate poorer performance). To identify susceptibility windows, we used Bayesian distributed lag interaction models to examine associations between prenatal PM2.5 levels and MSCA. This allowed us to estimate vulnerable windows while testing for effect modification. After adjusting for maternal age, socioeconomic status, child age, and sex, Bayesian distributed lag interaction models showed significant associations between increased PM2.5 levels and decreased general cognitive index scores at 31-35 gestation weeks, decreased quantitative scale scores at 30-36 weeks, decreased motor scale scores at 30-36 weeks, and decreased verbal scale scores at 37-38 weeks. Estimated cumulative effects (CE) of PM2.5 across pregnancy showed significant associations with general cognitive index ( = -0.35, 95% confidence interval [CI] = -0.68, -0.01), quantitative scale ( = -0.27, 95% CI = -0.74, -0.02), motor scale ( = -0.25, 95% CI = -0.44, -0.05), and verbal scale ( = -0.2, 95% CI = -0.43, -0.02). No significant sex interactions were observed. Prenatal exposure to PM2.5, particularly late pregnancy, was inversely associated with subscales of MSCA. Using data-driven methods to identify sensitive window may provide insight into the mechanisms of neurodevelopmental impairment due to pollution.

Association between telomere length and neuropsychological function at 4–5 years in children from the INMA project: a cross-sectional study

Shortened telomere length (TL) has been associated with lower cognitive performance, different neurological diseases in adults, and certain neurodevelopmental disorders in children. However, the evidence about the association between TL and neuropsychological developmental outcomes in children from the general population is scarce. Therefore, this study aimed to explore the association between TL and neuropsychological function in children 4–5 years of age. We included 686 children from the INMA Project, a population-based birth cohort in Spain. Leucocyte TL was determined by quantitative PCR method, and neuropsychological outcomes were measured using the McCarthy Scales of Children’s Abilities (MCSA). Multiple linear regression models were used to estimate associations adjusted for potential confounding variables. Main findings showed that a longer TL was associated with a higher mean working memory score (β = 4.55; 95% CI = 0.39, 8.71). In addition, longer TL was associated with a higher mean global quantitative score (β = 3.85; 95% CI = −0.19, 7.89), although the association was marginally significant. To our knowledge, this is the first study that shows a positive association between TL and better neuropsychological outcomes in children. Although further research is required to confirm these results, this study supports the hypothesis that TL is essential in protecting and maintaining a child’s health, including cognitive functions such as working memory.

Relation of prenatal and postnatal PM2.5 exposure with cognitive and motor function among preschool-aged children

The literature informing susceptible periods of exposure on children's neurodevelopment is limited. We evaluated the impacts of pre- and postnatal fine particulate matter (PM2.5) exposure on children's cognitive and motor function among 1303 mother-child pairs in the Spanish INMA (Environment and Childhood) Study. Random forest models with temporal back extrapolation were used to estimate daily residential PM2.5 exposures that we averaged across 1-week lags during the prenatal period and 4-week lags during the postnatal period. The McCarthy Scales of Children's Abilities (MSCA) were administered around 5 years to assess general cognitive index (GCI) and several subscales (verbal, perceptual-performance, memory, fine motor, gross motor). We applied distributed lag nonlinear models within the Bayesian hierarchical framework to explore periods of susceptibility to PM2.5 on each MSCA outcome. Effect estimates were calculated per 5 μg/m3 increase in PM2.5 and aggregated across adjacent statistically significant lags using cumulative β (βcum) and 95% Credible Intervals (95%CrI). We evaluated interactions between PM2.5 with fetal growth and child sex. We did not observe associations of PM2.5 exposure with lower GCI scores. We found a period of susceptibility to PM2.5 on fine motor scores in gestational weeks 1–9 (βcum = −2.55, 95%CrI = −3.53,-1.56) and on gross motor scores in weeks 7–17 (βcum = −2.27,95%CrI = −3.43,-1.11) though the individual lags for the latter were only borderline statistically significant. Exposure in gestational week 17 was weakly associated with verbal scores (βcum = −0.17, 95%CrI = −0.26,-0.09). In the postnatal period (from age 0.5–1.2 years), we observed a window of susceptibility to PM2.5 on lower perceptual-performance (β = −2.42, 95%CrI = −3.37,-1.46). Unexpected protective associations were observed for several outcomes with exposures in the later postnatal period. We observed no evidence of differences in susceptible periods by fetal growth or child sex. Preschool-aged children's motor function may be particularly susceptible to PM2.5 exposures experienced in utero whereas the first year of life was identified as a period of susceptibility to PM2.5 for children's perceptual-performance.

Latent Childhood Exposure to Mixtures of Metals and Neurodevelopmental Outcomes in 4–5-Year-Old Children Living in Spain

Neurodevelopmental disorders are increasing globally, and metal exposure may play a significant role as an environmental factor. This cross-sectional study aimed to identify metal mixture patterns and assess their impact on children’s neurodevelopment. Data from 962 children (aged 4–5 years) participating in the Spanish INMA cohort study were analysed. Urinary metal concentrations (cobalt (Co), copper (Cu), molybdenum (Mo), selenium (Se), lead (Pb), zinc (Zn), and arsenic speciation) were used as exposure biomarkers. Principal component analysis (PCA) revealed four latent exposure variables representing uncorrelated metal mixture patterns. Linear regression analyses examined the associations between these variables and children’s neuropsychological functions assessed through the McCarthy Scales of Children’s Abilities. The first latent exposure variable (Cu, Se, Pb, Zn) and the second (inorganic arsenic, monomethylarsonic acid) showed negative associations with verbal executive function (ß = − 1.88, 95% confidence interval (CI) = − 3.17 to − 0.59) and gross motor function (ß = − 1.41, 95% CI = − 2.36 to − 0.46), respectively. Conversely, the third variable (Mo, Co) and the fourth (arsenobetaine) exhibited positive associations with visual and verbal span functions (ß = 1.14, 95% CI = 0.16 to 2.12) and fine motor function (ß = 1.01, 95% CI = 0.11 to 1.92), respectively. This study suggests that even relatively low levels of metal latent exposures, notably inorganic arsenic and a mixture of metals including Pb, adversely affect children’s neuropsychological development function scores, while exposure to arsenobetaine and a mixture of Co and Mo has a positive impact.

Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children.

We explored the influence of child and maternal single nucleotide polymorphisms (SNPs) in genes related to neurological function and arsenic metabolism (i.e., ABCA1, ABCB1, PON1, CYP3A, BDNF, GSTP1, MT2A, and APOE as well as AS3MT) on the association between prenatal arsenic (As) exposure and methylation efficiency and neuropsychological development in 4-5-year-old children. Participants were 549 mother-child pairs from the INMA (Environment and Childhood) Spanish Project. We measured inorganic arsenic (iAs) and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in urine samples collected during pregnancy. Neuropsychological development was assessed at the age of 4-5 years using the McCarthy Scales of Children's Abilities (MSCA). Several SNPs were determined in maternal and child DNA; AS3MT and APOE haplotypes were inferred. The median ∑As (sum of iAs, DMA, and MMA) was 7.08 μg/g creatinine. Statistically significant interactions for children's APOE haplotype were observed. Specifically, ε4-carrier children had consistently lower MSCA scores in several scales with increasing ∑As and MMA concentrations. These results provide evidence regarding the neurotoxic effects of early life exposure to As, observing that the APOE ε4 allele could make children more vulnerable to this exposure.

Sleep duration in preschool age and later behavioral and cognitive outcomes: an individual participant data meta-analysis in five European cohorts

Short sleep duration has been linked to adverse behavioral and cognitive outcomes in schoolchildren, but few studies examined this relation in preschoolers. We aimed to investigate the association between parent-reported sleep duration at 3.5 years and behavioral and cognitive outcomes at 5 years in European children. We used harmonized data from five cohorts of the European Union Child Cohort Network: ALSPAC, SWS (UK); EDEN, ELFE (France); INMA (Spain). Associations were estimated through DataSHIELD using adjusted generalized linear regression models fitted separately for each cohort and pooled with random-effects meta-analysis. Behavior was measured with the Strengths and Difficulties Questionnaire. Language and non-verbal intelligence were assessed by the Wechsler Preschool and Primary Scale of Intelligence or the McCarthy Scales of Children’s Abilities. Behavioral and cognitive analyses included 11,920 and 2981 children, respectively (34.0%/13.4% of the original sample). In meta-analysis, longer mean sleep duration per day at 3.5 years was associated with lower mean internalizing and externalizing behavior percentile scores at 5 years (adjusted mean difference: − 1.27, 95% CI [− 2.22, − 0.32] / − 2.39, 95% CI [− 3.04, − 1.75]). Sleep duration and language or non-verbal intelligence showed trends of inverse associations, however, with imprecise estimates (adjusted mean difference: − 0.28, 95% CI [− 0.83, 0.27] / − 0.42, 95% CI [− 0.99, 0.15]). This individual participant data meta-analysis suggests that longer sleep duration in preschool age may be important for children’s later behavior and highlight the need for larger samples for robust analyses of cognitive outcomes. Findings could be influenced by confounding or reverse causality and require replication.

The association between maternal ultra-processed food consumption during pregnancy and child neuropsychological development: A population-based birth cohort study

Maternal ultra-processed food (UPF) consumption during pregnancy may adversely affect child development. Pregnancy sugar-sweetened beverage consumption (as a part of UPF) has been associated with child cognitive dysfunction in the general population, but the role of total UPF consumption during pregnancy in later child neuropsychological development has not been studied. We aimed to analyse the association between maternal pregnancy UPF consumption and child neurodevelopment. This study involved 2377 pairs of pregnant women and their offspring from a Spanish birth cohort (recruitment period: 2004-2008, INMA project). Dietary intake was estimated using a 101-item food frequency questionnaire in the third trimester of pregnancy. The NOVA classification was used to identify UPFs, and their consumption was calculated as the daily percentage of total food consumption and categorized into tertiles. Child neuropsychological development was assessed with the Bayley Scales of Infant and Toddler Development (1-year-old, n=1929) and the McCarthy Scales of Children's Abilities (4-5 years-old, n=1679). Potential associations were analysed using multivariate linear regression models adjusted for a range of family and child characteristics. UPF consumption among pregnant women represented an average of 17% of the total diet, with sugar-sweetened beverages being the most commonly consumed type of UPF (40%). Children born to mothers in the highest tertile of UPF consumption (28.9% or more of the total diet) vs the lowest tertile (7.2% or less), showed a lower score (B=-2.29 [95% Confidence Interval (CI),-4.13;-0.46]) in the Verbal Scale of the McCarthy Scales (p-for-trend=0.02). No associations were observed with the McCarthy Scales assessing other cognitive domains or with the Bayley Scales. Of the seven cognitive domains studied, we observed an adverse association between maternal consumption of UPF during pregnancy and verbal functioning in early childhood, which is an important cognitive domain of neurodevelopment.

Maternal sleep disturbances during late pregnancy and child neuropsychological and behavioral development in early childhood.

The present study aims to explore the association of maternal sleep disturbances during late pregnancy on child neuropsychological and behavioral development in preschool years. The study included 638 mother-child pairs from the prospective Rhea mother-child cohort in Crete, Greece. Information on antenatal sleep disturbances was collected through a computer-assisted interview. Children's neuropsychological and behavioral development was assessed using the McCarthy Scales of Children's Abilities (MSCA), the Attention-Deficit Hyperactivity Disorder Test (ADHDT), and the Strengths and Difficulties Questionnaire (SDQ). Multivariate analysis showed that maternal sleep duration less than 8h was associated with reduced scores in the general cognitive scale (β = -2.28, 95% CI -4.54, -0.02, R2 = 0.417) and memory span (β = -3.24, 95% CI -5.72, -0.77, R2 = 0.304), while mild-severe daytime sleepiness was associated with reduced scores in the memory scale (β = -5.42, 95% CI -10.47, -0.37, R2 = 0.304), memory span (β = -5.44, 95% CI -10.68, -0.21, R2 = 0.304), nd functions of posterior cortex (β = -5.55, 95% CI -10.40, -0.70, R2 = 0.393) of MSCA. Snoring in late pregnancy was related to higher child hyperactivity scores in SDQ (β = 1.05, 95% CI 0.16, 1.95, R2 = 0.160). An interaction between child sex and maternal sleep duration in response to ADHD symptoms was also found (p for interaction < 0.05). Stratified analysis revealed increased hyperactivity, inattention, and ADHD total scores for girls of mothers with sleep duration less than 8h. Maternal sleep disturbances during pregnancy may be associated with impaired child neuropsychological and behavioral development during the preschool years. Early detection and intervention is necessary to reduce sleep disturbances habits in pregnancy and improve child neurodevelopment.

A COMPARATIVE STUDY OF CHILDREN’S COGNITIVE ABILITY IN MALAYSIAN PUBLIC AND PRIVATE PRE-SCHOOLS

Background and Purpose: A child’s cognitive, physical, and socioeconomic development must be stimulated as early as possible to ensure it is on the right path. However, only a few studies have been conducted to investigate the difference in cognitive abilities between public and private pre-schoolers in Malaysia.&#x0D; &#x0D; Methodology: A total of 121 students aged five to six were selected from public and private pre-schools in Kuala Lumpur using a purposive sampling method. The children's general cognitive abilities were assessed using the McCarthy Scales of Children’s Abilities (MSCA).&#x0D; &#x0D; Findings: The findings showed that the general cognitive abilities of public and private pre-school children are at a moderate level. The results also indicated no statistically significant effect of the type of pre-school, parents’ level of education, and parents’ income level on children’s cognitive ability.&#x0D; &#x0D; Contributions: This research provides insights into the children’s cognitive ability in some selected public and private preschools in Malaysia. The outcome is essential in determining the general cognitive abilities of the children. Possible future works are suggested to explore the topic from different perspectives in order to improve children’s cognitive ability.&#x0D; &#x0D; Keywords: Cognitive abilities, pre-school children, type of pre-school, parents’ education, parents’ income.&#x0D; &#x0D; Cite as: Hutagalung, F. D., Chew, F. P., Adams, D., &amp; Fitriana, N. (2022). A comparative study of children’s cognitive ability in Malaysian public and private pre-schools. Journal of Nusantara Studies, 7(2), 377-398. http://dx.doi.org/10.24200/jonus.vol7iss2pp377-398

0490 Longitudinal associations between sleep and behavior and cognition in preschoolers from five European birth-cohorts

Abstract Introduction There has been little focus on sleep and its relation to behavior and cognition in preschool-aged children. We aimed to investigate the association between sleep duration in early preschoolers (» 3.5 years of age) and later behavioral and cognitive outcomes (» 5 years of age) in European children. Methods We used harmonized data from five cohorts from the EU Child Cohort Network, established by the LifeCycle Project (n=16.444 children): ALSPAC and SWS from UK, EDEN and ELFE from France and INMA from Spain. Within all cohorts, total sleep duration per day and behavioral and cognitive information were reported by parents. Internalizing and externalizing behaviors were measured with the Strengths and Difficulties Questionnaire and treated as percentile scores. Verbal and non-verbal intelligence were assessed by the Wechsler Preschool and Primary Scale of Intelligence or with the McCarthy Scales of Children’s Abilities depending on the cohort and treated as standardized scores. All scores were cohort specific. Associations between sleep duration during early preschool age and later behavior and/or cognition were estimated using linear regression and pooled with two-stage individual participant data meta-analysis adjusted for child, maternal and household information. Analyses were done in DataSHIELD. Results Global mean sleep duration was 11h54 ± 1h00 per day at mean age 3.5 years but differed by country, with children from France showing longer sleep duration than children from the UK or Spain. In multivariate meta-analysis, 1 hour of additional sleep duration per day at mean age 3.5 years was associated with reduced internalizing and externalizing behavior percentile scores at mean age 5.1 years (internalizing behavior: badjusted= -1.05, 95%-CI [-1.93, -0.18], I2: 30.3%; externalizing behavior: badjusted= -2.12, 95%-CI [-2.78, -1.47], I2: 0.0%). No association was observed between sleep duration and subsequent verbal or non-verbal intelligence Conclusion Longer sleep duration in early preschool age (» 3.5 years of age) was associated with subsequent lower internalizing and externalizing behavior scores (» 5 years of age), but not with verbal or non-verbal intelligence. Adequate sleep duration at an early age is important for children’s later mental health. Support (If Any) KG was granted a LifeCycle fellowship.

Maternal occupational exposure to chemicals and child cognitive function.

Limited data exist regarding child neurodevelopment in relation to maternal occupational exposure to endocrine-disrupting chemicals (EDCs). We included 1058 mother-child pairs from the INfancia y Medio Ambiente (INMA) project (2003-2008). Using a job-exposure matrix, exposure probability scores for ten EDC groups were assigned to each mother based on her longest held job during pregnancy. At the child's 5-year visit, the McCarthy Scales of Children's Abilities was administered, yielding the general cognitive index and scales for specific cognitive domains. We analyzed region-specific associations between EDC exposures and each outcome separately using adjusted linear regression and combined region-specific effect estimates using random-effects meta-analyses. Approximately 24% of women were exposed to at least one EDC group, but exposure to most individual EDC groups was low (<5%). Maternal organic solvent exposure was associated with lower quantitative scores among children (-5.8 points, 95% confidence interval: -11.0, -0.5). Though statistically non-significant, exposures to polycyclic aromatic hydrocarbons, phthalates, alkylphenolic compounds, and miscellaneous chemicals were associated with poorer offspring performance for most or all cognitive domains. This study found limited evidence for a role of maternal occupational EDC exposures on child cognition. Further research is needed to better characterize exposures among pregnant workers. Using data from a prospective birth cohort, we help fill an important research gap regarding the potential consequences of work-related exposure to endocrine-disrupting chemicals (EDCs) among pregnant women on child neurodevelopment. We expand on existing literature-largely limited to pesticide and organic solvent exposures-by using a job-exposure matrix to estimate exposure to several EDC groups. We found limited evidence of an association between maternal occupational EDC exposure and children's overall cognition. We did observe specific associations between exposure to organic solvents and lower quantitative reasoning scores.

Improving motor skills in early education: using smartphones on the Brazilian – Bolivian border

ABSTRACT Background: Smartphones are a resource noticeably inserted into people’s daily lives, but they are not nearly as present within the various educational systems around the world. The improper use of smartphones can certainly carry some risks, such as a sedentary lifestyle or even addiction. For the aforementioned reasons, promoting literacy by using smartphones responsibly from an early age can be a promising element in early childhood education. In fact, there are some previous experiences where mobile technology alongside adequate teaching planning has led to students obtaining positive outcomes, especially within the areas of vulnerability and strong linguistic, cultural, economic, and social differences. Purpose: This research aims to analyse the impact of the educational use of mobile phones on motor development in a diverse context of early childhood education. Method: To achieve this goal, an educational programme was implemented with students in the second year of preschool (aged 4–5 years) and the first year of primary education (aged 5–6 years) at a Brazilian public school located on the border with Bolivia. This included a series of activities using smartphones, linked to complementary activities of a more traditional nature. The study consisted of a quasi-experimental design with a control (n = 28) and experimental group (n = 68). Measurements included the McCarthy Scales of Children’s Abilities, assessed qualitatively and administered as a pre-test and post-test. Results: The results showed how the group of students that participated in the educational programme improved their motor skills (24.544; p < .001) much more than the control group (6.593; p < .001) with a large effect size (.813). The analysis of variance showed significant differences between the experimental group and the control group in the pre-test and post-test for all the dependent variables that fulfilled the assumptions. To explain further, the variable called arms (throwing and catching) accounted for almost 30% of the variance due to the didactic-technological intervention (F = 38.006; p < .001; ηp 2 = .292), and was over 50% for the variable called draw-a-child (F = 93.188; p < .001; ηp 2 = .503) and 60% for the variable called general index (F = 138.599; p < .001; ηp 2 = .601). Conclusions: The main results of the study showed how the smartphone is a social tool, but it can also be a useful ally in the teaching-learning process in early childhood education. Planned mobile literacy can lead to improved motor skills, and it is a break from the stereotype of a sedentary lifestyle linked to smartphones, with especial reference to younger students in contexts of socio-cultural diversity.

Prenatal arsenic exposure, arsenic methylation efficiency, and neuropsychological development among preschool children in a Spanish birth cohort

BackgroundPrenatal arsenic (As) exposure could negatively affect child neuropsychological development, but the current evidence is inconclusive. ObjectivesTo explore the relationship between prenatal urinary total As (TAs) concentrations, the As species and the methylation efficiency, and child neuropsychological development in a Spanish birth cohort. We also studied the effect modification produced by sex and several nutrients and elements. Materials and methodsStudy subjects were 807 mother–child pairs participating in the INMA (Childhood and Environment) Project. Urinary TAs and its metabolites, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), inorganic As (iAs) and arsenobetaine were measured in the first trimester of pregnancy. Methylation efficiency was determined through the percentages of the metabolites and using principal component analysis. Children's neuropsychological development was assessed at the age of 4–5 years using the McCarthy Scales of Children's Abilities (MSCA). Multivariable linear regression models were built to assess the association between TAs, the As species and the maternal methylation efficiency, and the neuropsychological scores. We explored effect modification by sex, iron status, maternal nutrients status (serum manganese and selenium, and urinary zinc), and maternal vitamins intake (folate, and vitamins B12 and B6). ResultsThe geometric mean (95%CI) of ∑As (sum of DMA, MMA and iAs) was 7.78 (7.41, 8.17) μg/g creatinine. MMA concentrations were inversely associated with the scores for the general, verbal, quantitative, memory, executive function and working memory scales (i.e. β [CI95%] = −1.37 [-2.33, −0.41] for the general scale). An inverse association between %MMA and the memory scores was found. Children whose mothers had lower manganese, zinc and ferritin concentrations obtained lower scores on several MSCA scales with decreasing As methylation efficiency. DiscussionAn inverse association was observed between MMA concentrations and children's neuropsychological development. Maternal levels of manganese, zinc and ferritin affected the association between As methylation efficiency and MSCA scores.

Maternal FADS2 single nucleotide polymorphism modified the impact of prenatal docosahexaenoic acid (DHA) supplementation on child neurodevelopment at 5 years: Follow-up of a randomized clinical trial

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. To assess if maternal FADS2 single nucleotide polymorphisms (SNPs) modified the effect of prenatal DHA on offspring development at 5 years. 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 400mg/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). 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). 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.

Maternal occupational exposure to chemicals and neurocognitive development at 4-5 years of age

BACKGROUND AND AIM: Despite evidence that suggests fetal brain development is particularly sensitive to endocrine disrupting chemicals (EDCs), limited data exist regarding childhood neurodevelopment in relation to maternal exposure to EDCs at levels relevant to occupational settings. This study’s objective was to examine the association between maternal occupational EDC exposures and childhood neurocognitive function at 4-5 years of age. METHODS: This analysis included 1,058 mother-child pairs in the {INfancia y Medio Ambiente} (INMA) project (2003-2008). Likelihood of exposure to several EDC groups was estimated using a job-exposure matrix and assigned to each mother based on her self-reported longest held job during her index pregnancy. At her child’s 4-5-year follow-up visit, the McCarthy Scales of Children’s Abilities was administered by a trained psychologist, yielding a general cognitive index and sub-scales of verbal, perceptive-performance and quantitative reasoning. We imputed missing covariate data and analyzed associations separately for each cohort using linear regression, weighting for inverse probability of attrition and adjusting for covariates informed by a directed acyclic graph: maternal age, education, country of birth, parity, gestational weight gain, pre-pregnancy body mass index, smoking and alcohol use during pregnancy, verbal intelligence, child sex and age at assessment, and the psychologist who administered the assessment. Finally, we combined cohort-specific effect estimates using random-effects meta-analysis. RESULTS:We observed an association between maternal occupational exposure to organic solvents and decreased quantitative reasoning scores at age 4-5 (-5.8, 95% confidence interval: -11.0, -0.5). Associations of similar magnitude and direction were observed for the same domain in relation to exposure to alkylphenolic compounds, phthalates and miscellaneous chemicals (i.e., benzophenones, parabens and siloxanes), though these were not statistically significant. CONCLUSIONS:This study found limited evidence for a role of maternal occupational EDC exposures on childhood cognitive function. Further research should consider the combined impact of multiple workplace exposures. KEYWORDS: neurodevelopmental outcomes, chemical exposures, occupational exposures, endocrine disrupting chemicals, solvents, occupational epidemiology

Maternal mild thyroid dysfunction and offspring cognitive and motor development from infancy to childhood: the Rhea mother–child cohort study in Crete, Greece

BackgroundMaternal thyroid hormones’ supply is crucial for fetal neurodevelopment; however, the role of maternal mild thyroid dysfunction is not clear. We aimed to assess the association of maternal mild thyroid...

Early Gestational Exposure to High-Molecular-Weight Phthalates and Its Association with 48-Month-Old Children’s Motor and Cognitive Scores

In utero phthalate exposure has been associated with neurodevelopmental disorders, nevertheless, trimester-specific susceptibility remains understudied. Our aim was to identify susceptible windows to the effects of gestational High-Molecular-Weight Phthalates (HMWP) exposure on 48 months’ neurodevelopment. We measured six HMWP metabolites (MEHP, MEHHP, MEOHP, MECPP, MBzP and MCPP) in urine samples collected during each trimester from women in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort (n = 218). We assessed children’s motor (MS), cognitive (GCI) and memory (MeS) abilities using McCarthy Scales of Children’s Abilities (MSCA). We used linear regression models to examine associations between trimester-specific phthalate metabolites and MSCA scores, adjusted for sex, gestational age, breastfeeding, and maternal IQ. Although phthalate concentrations were similar across trimesters, first and second trimester phthalates were inversely associated with MS and GCI, with first trimester associations with MS being the strongest and statistically significant. Stronger associations were seen with MS and GCI among boys compared to girls, however interaction terms were not statistically significant. Our results suggest that early gestation is a sensitive window of exposure to HMWP for neurodevelopment, particularly in boys. Regulations on phthalate content in food as well as pregnancy consumption guidelines are necessary to protect future generations.

Association of placental concentrations of phenolic endocrine disrupting chemicals with cognitive functioning in preschool children from the Environment and Childhood (INMA) Project

Aim: To examine the association of placental concentrations of several phenolic endocrine disrupting chemicals (EDCs), including bisphenol A (BPA), parabens (PBs), and benzophenones (BzPs), with cognitive development in preschool children from the Environment and Childhood (INMA) Project in Spain. Methods: Concentrations of BPA, four PBs (methylparaben [MePB], ethylparaben [EtPB], propylparaben [PrPB], and butylparaben [BuPB]), and six BzPs (BzP-1, BzP-2, BzP-3, BzP-6, BzP-8, and 4-hydroxybenzophenone [4-OH-BzP]) were measured in placenta samples randomly selected from five INMA cohorts collected between 2000 and 2008. Neuropsychological assessment of cognitive and motor function was performed with the McCarthy Scales of Children’s Abilities (MSCA) at the age of 4-5 years. Associations were assessed in a sub-sample of 191 mother-child pairs using linear and logistic regression models adjusted for confounding factors. Results: PB compounds were detected in &gt;71% of placentas, BPA in 62%, 4-OH-BzP in 50%, and the remaining BzPs in &lt;9%. After adjustment for confounders, BPA was associated with greater odds of scoring lower (&lt;20th percentile) in the verbal area (odds ratio [OR]= 2.78, 95% confidence interval [CI]=1.00; 5.81 for upper vs. first tertile, p-trend=0.05), whereas PrPB was inversely associated with scores in memory (β=-4.96, 95%CI=-9.54; -0.31 for detected vs. undetected), span memory (OR=2.50, 95%CI=0.95; 6.92 and 2.71, 95%CI=0.97; 6.64, respectively for middle and upper tertiles, p-trend=0.03), and motor function (β=-5.15, 95%CI=-9.26; -0.01 for upper vs. first tertile, p-trend=0.04). EtPB and total PB concentrations (∑PBs) in the middle tertile were also inversely associated with visual function of posterior cortex and quantitative scores, respectively, but linear trends were not statistically significant. Conclusions: These associations of BPA and PrPB with poorer verbal, memory, and motor skills are novel observations that warrant further attention. Larger prospective studies are required to confirm whether prenatal exposure to BPA and other phenols is associated with impaired cognitive development.