Physical activity and body mass related to catch-up lung function growth in childhood: a population-based accelerated cohort study.

OBJECTIVE: The existence of catch-up lung function growth and its predictors is uncertain. We aimed to identify lung function trajectories and their predictors in a population-based birth cohort. METHODS: We applied group-based trajectory modelling to z-scores of forced expiratory volume in 1 second (zFEV1) and z-scores of forced vital capacity (zFVC) from 1151 children assessed at around 4, 7, 9, 10, 11, 14 and 18 years. Multinomial logistic regression models were used to test whether potential prenatal and postnatal predictors were associated with lung function trajectories. RESULTS: We identified four lung function trajectories: a low (19% and 19% of the sample for zFEV1 and zFVC, respectively), normal (62% and 63%), and high trajectory (16% and 13%) running in parallel, and a catch-up trajectory (2% and 5%) with catch-up occurring between 4 and 10 years. Fewer child allergic diseases and higher body mass index z-score (zBMI) at 4 years were associated with the high and normal compared with the low trajectories, both for zFEV1 and zFVC. Increased children's physical activity during early childhood and higher zBMI at 4 years were associated with the catch-up compared with the low zFEV1 trajectory (relative risk ratios: 1.59 per physical activity category (1.03-2.46) and 1.47 per zBMI (0.97-2.23), respectively). No predictors were identified for zFVC catch-up growth. CONCLUSION: We found three parallel-running and one catch-up zFEV1 and zFVC trajectories, and identified physical activity and body mass at 4 years as predictors of zFEV1 but not zFVC catch-up growth.

Hair cortisol determinants in 11-year-old children: Environmental, social and individual factors.

INTRODUCTION: Children's exposure to chronic stress is associated with several health problems. Measuring hair cortisol concentration is particularly useful for studying chronic stress but much is unknown about hair cortisol determinants in children and adolescents, and previous research has often not considered the simultaneous exposure of multiple variables. This research is focused on investigating the relationship between environmental, social and individual factors with hair cortisol concentration in children. METHODS: The data used in this study are from the INMA prospective epidemiological cohort study. The assessment of chronic stress was made on the basis of hair samples taken at the age of 11 years in the INMA-Gipuzkoa cohort (n = 346). A metamodel summarizing the hypothesized relationships among environmental, social and individual factors and hair cortisol concentration was constructed based on previous literature. Structural Equation Modelling was performed to examine the relationships among the variables. RESULTS: In the general model higher behavioural problems were associated with higher cortisol levels and an inverse relationship between environmental noise and cortisol levels was observed, explaining 5 % of the variance in HCC. Once stratified by sex these associations were only hold in boys, while no significant effect of any of the study variables was related with cortisol levels in girls. Importantly, maternal stress was positively related to behavioural difficulties in children. Finally, higher traffic-related air pollution and lower exposure to neighborhood greenness were related to higher environmental noise. DISCUSSION: This study highlights that simultaneous exposure to different environmental, social and individual characteristics may determine the concentration of hair cortisol. More research is needed and future studies should include this complex view to better understanding of hair cortisol determinants in children.

Children who sleep more may have longer telomeres: evidence from a longitudinal population study in Spain.

BACKGROUND: Inadequate sleep duration has been suggested as a chronic stressor associated with changes in telomere length (TL). This study aimed to explore the association between sleep duration and TL using the INMA birth cohort study data. METHODS: A total of 1014 children were included in this study (cross-sectional: 686; longitudinal: 872). Sleep duration (h/day) was reported by caregivers at 4 years and classified into tertiles (7-10 h/day; >10-11 h/day; >11-14 h/day). Leucocyte TL at 4 and 7-9 years were measured using quantitative PCR methods. Multiple robust linear regression models, through log-level regression models, were used to report the % of difference among tertiles of sleep duration. RESULTS: In comparison to children who slept between >10 and 11 h/day, those in the highest category (more than 11 h/day) had 8.5% (95% CI: 3.56-13.6) longer telomeres at 4 years. Longitudinal analysis showed no significant association between sleep duration at 4 years and TL at 7-9 years. CONCLUSION: Children who slept more hours per day had longer TL at 4 years independently of a wide range of confounder factors. Environmental conditions, such as sleep duration, might have a major impact on TL during the first years of life. IMPACT: Telomere length was longer in children with longer sleep duration (>11 h/day) independently of a wide range of confounder factors at age 4 and remained consistent by sex. Sleep routines are encouraged to promote positive child development, like the number of hours of sleep duration. Considering the complex biology of telomere length, future studies still need to elucidate which biological pathways might explain the association between sleep duration and telomere length.

Environmental health knowledge of healthcare professionals: Instrument development and validation using the Rasch model.

INTRODUCTION: environmental risk factors constitute a major public health issue, calling for preventive actions and interventions at multiple levels. An important step in this direction is increasing the environmental health (EH) knowledge of the healthcare professionals. In this context, tools designed to measure such knowledge are of imperative importance. The aim of the present study was to develop an EH knowledge tool for healthcare professionals. METHODS: a group of experts defined the knowledge areas of the EH tool and their corresponding items. An online pilot and a validation study were performed. Internal consistency reliability was measured with the Kuder-Richardson 20 (KR-20) estimate, the construct validity and uni-dimensionality of the tool were assessed with the Rasch model. Known-groups validity was analysed with the two-sample t-test. RESULTS: a total of n = 151 and n = 444 healthcare professionals and end-year medical and nursing students, participated in the pilot and the validation study, respectively. The resulting 33-item EH knowledge questionnaire for healthcare professionals (EHKQ-HP) obtained a KR-20 = 0.82. The scale is uni-dimensional. Its construct validity was verified, and its items cover a wide range of difficulties. Separation statistics were adequate and known-groups behaved as hypothesized. CONCLUSIONS: the EHKQ-HP is a valuable resource for measuring the EH knowledge of the healthcare professionals. As such it will be useful in detecting EH knowledge gaps, and helping public health agents in making informed decisions when developing interventions for increasing this very knowledge. This would consequently help in improving the health of the general population.

Association of maternal prenatal urinary fluoride levels with ADHD symptoms in childhood.

BACKGROUND: Health concerns about the potential impact of exposure to fluoride via drinking water (DW) on neuropsychological development include behavioral outcomes such as ADHD. OBJECTIVE: We aimed to examine the association between prenatal maternal urinary fluoride and symptoms associated with attention-deficit/hyperactivity disorder (ADHD) at the age of 8 and 11 years. METHOD: Data from 255 to 236 mother-child pairs from the "Infancia y Medio Ambiente" (INMA) birth cohort (Gipuzkoa; Spain) with maternal urinary F adjusted for creatinine (MUFcr) during pregnancy (first and third trimester) and child assessments of ADHD-like symptoms reported by Conners' Rating Scales-Revised at age of 8 and 11 years was available. Clinical approach was also used: cut off criteria (T > 66). Multiple linear regression models were fitted when outcomes were analyzed as continuous, and logistic regression models when the outcomes were analyzed with a categorical clinical approach. Covariates related to maternal characteristics, birth outcomes, childhood, quality of family context and biomarkers of neuro-toxicants were used. RESULTS: No association was found between MUFcr levels during pregnancy and cognitive problems-inattention, hyperactivity or ADHD index score of symptoms at 8 or 11 years. When results were analyzed from the perspective of a clinical approach, at the age of 11 years, there were significant inverse association between MUFcr and being categorized as a cognitive problems-inattention case. ORs were also indicative of a lower risk, although not significant, for ADHD index at age 11. Sensitivity analyses, taking into consideration quality of family context or the levels of other toxicants during pregnancy showed similar results. CONCLUSIONS: Higher levels of MUFcr in pregnant women were associated with a lower risk of cognitive problems-inattention at 11 years. These findings are inconsistent with those from previous studies and indicate the need for other population-based studies to confirm or overturn these results.

Characterization of PCDD/F and dl-PCB levels in air in Gipuzkoa (Basque Country, Spain).

This research examines the levels and trends of pollutants, specifically 17 congeners of PCDD/Fs and 12 dl-PCBs, in the air measured in the province of Gipuzkoa (Basque Country, Spain). The study used PCDD/Fs, dl-PCB, and the sum of dioxin-like compounds as separate response variables. A total of 113 air samples were collected and analyzed using the method described in the European Standard (EN-1948:2006) from two industrial areas. The results were analyzed using non-parametric test to assess the variability of these pollutants based on different factors (year, season and day of the week) and General Linear Models to assess the weight of each factor. The study found that the toxic equivalents (TEQs) for PCDD/Fs were 12.29 fg TEQm-3 and for dl-PCBs were 1.63 fg TEQm-3, which were in a similar range or lower than those observed in other national and international studies in industrial areas. The results showed temporal variations, with higher levels of PCDD/Fs in autumn-winter than in spring-summer and higher levels of PCDD/Fs and dl-PCBs during weekdays than on weekends. The industrial area where the energy recovery plant (ERP) will be located had higher levels of air pollutants due to the presence of two PCDD/Fs emitting industries nearby, as indicated by the Spanish Registry of Polluting Emission Sources. Both industrial areas showed similar profiles of PCDD/Fs and dl-PCBs, with the PCDD/F profiles dominated by OCDD, 1,2,3,4,6,7,8-HpCDD, and 1,2,3,4,6,7,8-HpCDF in terms of concentrations and 1,2,3,7,8-PeCDD, 2,3,4,7,8-PeCDF, and 2,3,7,8-TCDD in terms of TEQs. The dl-PCB profiles were dominated by PCB 118, PCB 105, and PCB 77 in terms of concentrations and PCB 126 in terms of TEQs. The findings of this study can serve as an indicator of the potential impact of ERP on the health of the resident population and the environment.

Serum levels of PCDDs, PCDFs and dl-PCBs in general population residing far and near from an urban waste treatment plant under construction in Gipuzkoa, Basque Country (Spain).

This research focused on investigating the basal serum concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) in the general population residing in two urban-industrial zones near and far from an energy recovery plant under construction in Gipuzkoa, Basque Country (Spain). The study used a cross-sectional design and included 227 participants who were randomly selected from municipal censuses in both areas. The participants were stratified based on age (ranging from 18 to 70 years) and sex. Serum samples were collected from the participants and analysed following the established protocol to measure the concentrations of PCDD/Fs and dl-PCBs. The study used multiple linear regression models to assess the impact of various sociodemographic variables, lifestyle factors, reproductive history, and diet on the variability of the measured compounds in the participants' serum. The median total toxicity equivalent (TEQ) in serum, was 10.58 pg WHO-TEQ2005 g-1 lipid. Serum PCDD levels were lower in the population residing in the "far" zone than the "near" zone. Age was positively associated with both PCDD/F and dl-PCB levels, indicating that older participants had higher concentrations of these compounds in their serum. This finding might be attributed to cumulative exposure over time. In terms of sex differences, women exhibited lower levels of dl-PCBs compared to men. Among lifestyle factors, smokers showed lower levels of dl-PCBs compared to non-smokers. Furthermore, daily alcohol consumption was significantly associated with higher serum levels of these compounds, with daily drinkers showing higher levels than non-drinkers. Consumption of local poultry was associated with significantly higher serum levels and oil consumption with low levels of PCDD/Fs.

Susceptible windows of exposure to fine particulate matter and fetal growth trajectories in the Spanish INMA (INfancia y Medio Ambiente) birth cohort.

While prior studies report associations between fine particulate matter (PM2.5) exposure and fetal growth, few have explored temporally refined susceptible windows of exposure. We included 2328 women from the Spanish INMA Project from 2003 to 2008. Longitudinal growth curves were constructed for each fetus using ultrasounds from 12, 20, and 34 gestational weeks. Z-scores representing growth trajectories of biparietal diameter, femur length, abdominal circumference (AC), and estimated fetal weight (EFW) during early (0-12 weeks), mid- (12-20 weeks), and late (20-34 weeks) pregnancy were calculated. A spatio-temporal random forest model with back-extrapolation provided weekly PM2.5 exposure estimates for each woman during her pregnancy. Distributed lag non-linear models were implemented within the Bayesian hierarchical framework to identify susceptible windows of exposure for each outcome and cumulative effects [ßcum, 95% credible interval (CrI)] were aggregated across adjacent weeks. For comparison, general linear models evaluated associations between PM2.5 averaged across multi-week periods (i.e., weeks 1-11, 12-19, and 20-33) and fetal growth, mutually adjusted for exposure during each period. Results are presented as %change in z-scores per 5 µg/m3 in PM2.5, adjusted for covariates. Weeks 1-6 [ßcum = -0.77%, 95%CrI (-1.07%, -0.47%)] were identified as a susceptible window of exposure for reduced late pregnancy EFW while weeks 29-33 were positively associated with this outcome [ßcum = 0.42%, 95%CrI (0.20%, 0.64%)]. A similar pattern was observed for AC in late pregnancy. In linear regression models, PM2.5 exposure averaged across weeks 1-11 was associated with reduced late pregnancy EFW and AC; but, positive associations between PM2.5 and EFW or AC trajectories in late pregnancy were not observed. PM2.5 exposures during specific weeks may affect fetal growth differentially across pregnancy and such associations may be missed by averaging exposure across multi-week periods, highlighting the importance of temporally refined exposure estimates when studying the associations of air pollution with fetal growth.

Associations of early-life pet ownership with asthma and allergic sensitization: A meta-analysis of more than 77,000 children from the EU Child Cohort Network.

BACKGROUND: Studies examining associations of early-life cat and dog ownership with childhood asthma have reported inconsistent results. Several factors could explain these inconsistencies, including type of pet, timing, and degree of exposure. OBJECTIVE: Our aim was to study associations of early-life cat and dog ownership with asthma in school-aged children, including the role of type (cat vs dog), timing (never, prenatal, or early childhood), and degree of ownership (number of pets owned), and the role of allergic sensitization. METHODS: We used harmonized data from 77,434 mother-child dyads from 9 birth cohorts in the European Union Child Cohort Network when the child was 5 to 11 years old. Associations were examined through the DataSHIELD platform by using adjusted logistic regression models, which were fitted separately for each cohort and combined by using random effects meta-analysis. RESULTS: The prevalence of early-life cat and dog ownership ranged from 12% to 45% and 7% to 47%, respectively, and the prevalence of asthma ranged from 2% to 20%. There was no overall association between either cat or dog ownership and asthma (odds ratio [OR] = 0.97 [95% CI = 0.87-1.09] and 0.92 [95% CI = 0.85-1.01], respectively). Timing and degree of ownership did not strongly influence associations. Cat and dog ownership were also not associated with cat- and dog-specific allergic sensitization (OR = 0.92 [95% CI = 0.75-1.13] and 0.93 [95% CI = 0.57-1.54], respectively). However, cat- and dog-specific allergic sensitization was strongly associated with school-age asthma (OR = 6.69 [95% CI = 4.91-9.10] and 5.98 [95% CI = 3.14-11.36], respectively). There was also some indication of an interaction between ownership and sensitization, suggesting that ownership may exacerbate the risks associated with pet-specific sensitization but offer some protection against asthma in the absence of sensitization. CONCLUSION: Our findings do not support early-life cat and dog ownership in themselves increasing the risk of school-age asthma, but they do suggest that ownership may potentially exacerbate the risks associated with cat- and dog-specific allergic sensitization.

Maternal occupational exposure to chemicals and child cognitive function.

BACKGROUND: Limited data exist regarding child neurodevelopment in relation to maternal occupational exposure to endocrine-disrupting chemicals (EDCs). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. IMPACT: 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.

Association of prenatal phthalate exposure with pubertal development in Spanish boys and girls.

BACKGROUND: Phthalates are widespread, anti-androgenic chemicals known to alter early development, with possible impact on puberty timing. AIM: To investigate the association of prenatal phthalate exposure with pubertal development in boys and girls. METHODS: Urinary metabolites of six different phthalate diesters (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP) and non-phthalate plasticizer DINCH® were quantified in two urine samples collected during pregnancy from mothers participating in the INMA Spanish cohort study. Pubertal assessment of their children at age 7-10 years (409 boys, 379 girls) was conducted using the parent-reported Pubertal Development Scale. Modified Poisson and Weighted Quantile Sum (WQS) regression was employed to examine associations between prenatal phthalates and risk of puberty onset, adrenarche, and gonadarche. Effect modification by child weight status was explored by stratified analysis. RESULTS: Prenatal exposure to DEHP was associated with higher risk of puberty onset (relative risk [RR] = 1.32, 95% CI = 1.09-1.59 per each log-unit increase in concentrations) and gonadarche (RR = 1.23, 95% CI = 1.00-1.50) in boys and higher risk of adrenarche (RR = 1.25, 95% CI = 1.03-1.51) in girls at age 7-10 years. In boys, prenatal exposure to DEP, DnBP, and DEHP was also associated with higher risk of adrenarche or gonadarche (RRs = 1.49-1.80) in those with normal weight, and BBzP and DINCH® exposure with lower risk of adrenarche (RR = 0.49, 95% CI = 0.27-0.89 and RR = 0.47, 95% CI = 0.24-0.90, respectively) in those with overweight/obesity. In girls, DiBP, DnBP, and DINCH® were associated with slightly higher risk of gonadarche (RRs = 1.14-1.19) in those with overweight/obesity. In the WQS model, the phthalate mixture was not associated with puberty in boys or girls. CONCLUSION: Prenatal exposure to certain phthalates was associated with pubertal development at age 7-10 years, especially earlier puberty in boys with normal weight and girls with overweight/obesity. However, there was no evidence of effect of the phthalate mixture on advancing or delaying puberty in boys or girls.

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

BACKGROUND: Prenatal arsenic (As) exposure could negatively affect child neuropsychological development, but the current evidence is inconclusive. OBJECTIVES: To 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 METHODS: Study 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). RESULTS: The 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. ß [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. DISCUSSION: An 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.

Prenatal exposure to fluoride and neuropsychological development in early childhood: 1-to 4 years old children.

BACKGROUND: Cross-sectional and prospective studies have provided evidence of the neurotoxic effect of early exposure to fluoride (F) in pregnancy. It has been negatively associated with cognitive development during childhood, with most research conducted in areas with high F levels in community drinking water (CDW). METHOD: Data from 316 to 248 mother-child pairs from the Infancia y Medio Ambiente (Childhood and Environment, INMA) birth cohort project with maternal urinary F level adjusted for creatinine (MUFcr) measurements in the first and third trimesters of pregnancy. Children's cognitive domains and intelligence indexes were evaluated using the Bayley Scales (age of 1) and the McCarthy Scales (age of 4). Multiple linear regression analyses were carried out adjusting for a wide range of covariates related to the child, mother, family context and other potential neurotoxicants. RESULTS: No association was found between MUFcr levels and Bayley Mental Development Index score. Nevertheless, regarding the McCarthy scales, it was found that per unit (mg/g) of MUFcr across the whole pregnancy, scores in boys were greater for the verbal, performance, numeric and memory domains (ß = 13.86, CI 95%: 3.91, 23.82), (ß = 5.86, CI 95%: 0.32, 11.39), (ß = 6.22, CI 95%: 0.65, 11.79) and (ß = 11.63, CI 95%: 2.62, 20.63) respectively and for General Cognitive Index (ß = 15.4, CI 95%: 6.32, 24.48). For girls there was not any cognitive score significantly associated with MUFcr, being the sex-F interactions significant (P interaction <0.05). Including other toxicants levels, quality of family context or deprivation index did not substantially change the results. CONCLUSIONS: In boys, positive associations were observed between MUFcr and scores in cognitive domains at the age of 4. These findings are inconsistent with those from some previous studies and indicate the need for other population-based studies to confirm or overturn these results at low levels of F in CDW.

Shared DNA methylation signatures in childhood allergy: The MeDALL study.

BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema. OBJECTIVE: We sought to identify DNA methylation profiles associated with childhood allergy. METHODS: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discovery study included 219 case patients and 417 controls at age 4 years and 228 case patients and 593 controls at age 8 years from 3 birth cohorts, with replication analyses in 325 case patients and 1111 controls. We performed additional analyses on 21 replicated sites in 785 case patients and 2124 controls by allergic symptoms only from 8 cohorts, 3 of which were not previously included in analyses. RESULTS: We identified 80 differentially methylated CpG sites that showed a 1% to 3% methylation difference in the discovery phase, of which 21 (including 5 novel CpG sites) passed genome-wide significance after meta-analysis. All 21 CpG sites were also significantly differentially methylated with allergic symptoms and shared between asthma, rhinitis, and eczema. The 21 CpG sites mapped to relevant genes, including ACOT7, LMAN3, and CLDN23. All 21 CpG sties were differently methylated in asthma in isolated eosinophils, and 10 were replicated in respiratory epithelium. CONCLUSION: Reduced whole blood DNA methylation at 21 CpG sites was significantly associated with childhood allergy. The findings provide novel insights into the shared molecular mechanisms underlying asthma, rhinitis, and eczema.

Prenatal manganese serum levels and neurodevelopment at 4 years of age.

BACKGROUND: The excess of manganese (Mn) causes severe deleterious effects in the central nervous system, and the developing brain is especially sensitive to Mn overload. However, results of prospective studies regarding Mn neurodevelopmental effects remain inconclusive. The present study aims at studying the association of prenatal Mn exposure and neurodevelopment at 4-5 years of age. METHODS: Mn serum concentration was measured in 1465 pregnant women from the INMA (INfancia y MedioAmbiente, Environment and Childhood) Project. Neurodevelopment was assessed using a standardized version of the McCarthy Scales of Children's Abilities (MSCA). Multivariate regression models were used for data analysis. RESULTS: No association was found between Mn levels in serum and any of the McCarthy scales. However, the stratification by sex showed a positive and beneficial association of prenatal Mn levels and the verbal, quantitative and general-cognitive scales in girls (ß (95%CI): 4 (0.03, 7.96), 4.5 (0.43, 8.57) and 4.32 (0.6, 8.05), respectively). CONCLUSIONS: A beneficial association was found for the first time between prenatal Mn levels measured in serum and neurodevelopment of female offspring at 4 years of age, which could have implications on public health policies, specifically on the establishment of policies promoting prenatal health related to dietary deficits of micronutrients such as Mn.

Urinary arsenic species and methylation efficiency during pregnancy: Concentrations and associated factors in Spanish pregnant women.

BACKGROUND: Arsenic (As) is considered to be toxic for humans, the main routes of exposure being through drinking water and the diet. Once ingested, inorganic arsenic can be methylated sequentially to monomethyl and dimethyl arsenicals. Several factors can affect both As exposure and methylation efficiency. OBJECTIVES: To describe the urinary concentrations of the different As species and evaluate the methylation efficiency during pregnancy, as well as their associated factors in a birth cohort of pregnant Spanish women. METHODS: Participants in this cross-sectional study were 1017 pregnant women from two areas of Spain who had taken part in the INMA (Environment and Childhood) project (2003-2008). Total As (organic and inorganic compounds) and its main metabolites (monomethylarsonic acid, [MMA], dimethylarsinic acid, [DMA], inorganic As [iAs]) and arsenobetaine [AB]) were measured in urine samples collected during the first trimester. Sociodemographic and dietary information was collected through questionnaires. Multivariate linear regression models were used to explore the association between As species concentrations and covariates. Arsenic methylation efficiency was determined through the percentages of the metabolites and using As methylation phenotypes, obtained from principal component analysis. RESULTS: Median urine concentrations were 33.0, 21.6, 6.5, 0.35 and 0.33 µg/g creatinine for total As, AB, DMA, MMA and iAs, respectively. Daily consumption of rice and seafood during the first trimester of pregnancy were positively associated with the concentration of As species (i.e., ß [CI95%] = 0.36 [0.09, 0.64] for rice and iAs, and 1.06 [0.68, 1.44] for seafood and AB). TAs, AB and iAs concentrations, and DMA and MMA concentrations were associated with legume and vegetable consumption, respectively. The medians of the percentage of As metabolites were 89.7 for %DMA, 5.1 for %MMA and 4.7 for %iAs. Non-smoker women and those with higher body mass index presented a higher methylation efficiency (denoted by a higher %DMA and lower %MMA). DISCUSSION: Certain dietary, lifestyle, and environmental factors were observed to have an influence on both As species concentrations and methylation efficiency in our population. Further birth cohort studies in low exposure areas are necessary to improve knowledge about arsenic exposure, especially to inorganic forms, and its potential health impact during childhood.

Association between prenatal exposure to air pollutants and newborn thyroxine (T4) levels.

BACKGROUND: Thyroid hormones play a key role in fetal and child development. Recent studies have linked prenatal exposure to atmospheric contaminants with changes in thyroid hormone levels in newborns, but the data from the few studies that have explored this issue are inconclusive. The present study aims to assess the association of total thyroxine (TT4) levels in newborns with weekly prenatal exposure to PM2.5 and NO2 and to identify sensitivity windows to exposure to air pollution in different developmental stages. METHODS: This prospective cohort study included mother-child pairs from the INMA-Gipuzkoa project. Specifically, 463 mother-child pairs with data on PM2.5 and NO2 exposure during pregnancy and TT4 levels at birth were included. PM2.5 and NO2 levels were measured by high-volume aerosol samplers and passive samplers respectively during the women's pregnancies. TT4 levels were measured in heel-prick blood samples from infants. Data on maternal and infant covariates were gathered through questionnaires administered in the first and third trimesters of pregnancy and review of clinical records. Potential associations of PM2.5 and NO2 with TT4 levels over the entire pregnancy was assessed by linear regression models and DLMs were used to identify susceptibility windows. RESULTS: The exposure of pregnant women to PM2.5 during pregnancy was positively associated with infant TT4 level at birth (ß [95% CI] = 0.198 [0.091, 0.305]. DLMs identified three different sensitivity windows, one in the periconceptional period with a negative association between PM2.5 exposure and TT4 levels at birth, and a second (weeks 12-17) and a third one (weeks 31-37) with a positive association. In addition, the later the exposure, the stronger the association. In contrast, no association was observed between NO2 exposure and TT4 levels. CONCLUSIONS: The results indicate that prenatal exposure to PM2.5 could lead to a thyroid function impairment in newborns.

Prenatal Se concentrations and anthropometry at birth in the INMA study (Spain).

We assessed whether prenatal selenium (Se) exposure is associated with anthropometry at birth, placental weight and gestational age. Study subjects were 1249 mother-child pairs from the Valencia and Gipuzkoa cohorts of the Spanish Childhood and Environment Project (INMA, 2003-2008). Se was determined in serum samples taken at the first trimester of pregnancy. Socio-demographic and dietary characteristics were also collected by questionnaires. Mean (SD) serum Se concentration was 79.57 (9.64) µg/L. Se showed weak associations with both head circumference and gestational age. The association between serum Se concentration and birth weight and length was negative, and direct for placental weight and probability of preterm birth, although the coefficients did not reach statistical significance. Individuals with total mercury (THg) levels >15 µg/L reversed the serum Se concentration effect on head circumference. Significant interactions were found between sex and both gestational age and prematurity. Spontaneous birth gestational ages were estimated to be lower for males and their probability of prematurity was higher. In conclusion, prenatal Se exposure may be associated with lower head circumference and lower gestational ages at spontaneous birth. Interactions with THg exposure and gender should be considered when assessing these relationships.

Associations of Maternal Cell-Phone Use During Pregnancy With Pregnancy Duration and Fetal Growth in 4 Birth Cohorts.

Results from studies evaluating potential effects of prenatal exposure to radio-frequency electromagnetic fields from cell phones on birth outcomes have been inconsistent. Using data on 55,507 pregnant women and their children from Denmark (1996-2002), the Netherlands (2003-2004), Spain (2003-2008), and South Korea (2006-2011), we explored whether maternal cell-phone use was associated with pregnancy duration and fetal growth. On the basis of self-reported number of cell-phone calls per day, exposure was grouped as none, low (referent), intermediate, or high. We examined pregnancy duration (gestational age at birth, preterm/postterm birth), fetal growth (birth weight ratio, small/large size for gestational age), and birth weight variables (birth weight, low/high birth weight) and meta-analyzed cohort-specific estimates. The intermediate exposure group had a higher risk of giving birth at a lower gestational age (hazard ratio = 1.04, 95% confidence interval: 1.01, 1.07), and exposure-response relationships were found for shorter pregnancy duration (P < 0.001) and preterm birth (P = 0.003). We observed no association with fetal growth or birth weight. Maternal cell-phone use during pregnancy may be associated with shorter pregnancy duration and increased risk of preterm birth, but these results should be interpreted with caution, since they may reflect stress during pregnancy or other residual confounding rather than a direct effect of cell-phone exposure.

Prenatal Omega-6:Omega-3 Ratio and Attention Deficit and Hyperactivity Disorder Symptoms.

OBJECTIVE: To evaluate whether higher omega-6:omega-3 (n-6:n-3) long-chain polyunsaturated fatty acid ratio in cord plasma is associated with more symptoms of attention deficit and hyperactivity disorder (ADHD) at 4 and 7 years of age. STUDY DESIGN: This study was based on a population-based birth cohort in Spain. N-6 arachidonic acid and n-3 eicosapentaenoic and docosahexaenoic acid concentrations were measured in cord plasma. At 4 years old, ADHD symptoms were reported by teachers through the ADHD Diagnostic and Statistical Manual of Mental Disorders, 4th ed checklist (n = 580). At 7 years old, ADHD symptoms were reported by parents through the Conners' Rating Scale-Revised (short form; n = 642). The ADHD variable was treated as continuous (score) and as dichotomous (symptom diagnostic criteria). Child and family general characteristics were prospectively collected through questionnaires. We applied pooled zero-inflated negative binomial and logistic regressions adjusted for covariates. RESULTS: A higher omega-6:omega-3 long-chain polyunsaturated fatty acid ratio in cord plasma was associated with a higher ADHD index (incidence rate ratio, 1.13; 95% CI, 1.03, 1.23) at 7 years old. The association was not observed at 4 years old (incidence rate ratio, 1.04; 95% CI, 0.92-1.18). No associations were found using ADHD symptom diagnostic criteria. CONCLUSIONS: High prenatal omega-6:omega-3 long-chain polyunsaturated fatty acid ratio preceded the appearance of subclinical ADHD symptoms during mid-childhood. Our findings suggest that maternal diet during pregnancy may modulate the risk to develop long-term ADHD symptoms in the offspring.