Nitrogen dioxide exposure, attentional function, and working memory in children from 4 to 8 years: Periods of susceptibility from pregnancy to childhood.

BACKGROUND: Air pollution exposure during pregnancy and childhood has been linked to executive function impairment in children, however, very few studies have assessed these two exposure periods jointly to identify susceptible periods of exposure. We sought to identify potential periods of susceptibility of nitrogen dioxide (NO2) exposure from conception to childhood on attentional function and working memory in school-aged children. METHODS: Within the Spanish INMA Project, we estimated residential daily NO2 exposures during pregnancy and up to 6 years of childhood using land use regression models (n = 1,703). We assessed attentional function at 4-6 years and 6-8 years, using the Conners Kiddie Continuous Performance Test and the Attention Network Test, respectively, and working memory at 6-8 years, using the N-back task. We used distributed lag non-linear models to assess the periods of susceptibility of each outcome, adjusting for potential confounders and correcting for multiple testing. We also stratified all models by sex. RESULTS: Higher exposure to NO2 between 1.3 and 1.6 years of age was associated with higher hit reaction time standard error (HRT-SE) (0.14 ms (95 % CI 0.05; 0.22) per 10 µg/m3 increase in NO2) and between 1.5 and 2.2 years of age with more omission errors (1.02 (95 % CI 1.01; 1.03) of the attentional function test at 4-6 years. Higher exposure to NO2 between 0.3 and 2.2 years was associated with higher HRT-SE (10.61 ms (95 % CI 3.46; 17.75) at 6-8 years only in boys. We found no associations between exposure to NO2 and working memory at 6-8 years. CONCLUSION: Our findings suggest that NO2 exposure during the first two years of life is associated with poorer attentional function in children from 4 to 8 years of age, especially in boys. These findings highlight the importance of exploring long-term effects of traffic-related air pollution exposure in older age groups.

Ambient air temperature exposure and foetal size and growth in three European birth cohorts.

INTRODUCTION: Ambient air temperature may affect birth outcomes adversely, but little is known about their impact on foetal growth throughout pregnancy. We evaluated the association between temperature exposure during pregnancy and foetal size and growth in three European birth cohorts. METHODS: We studied 23,408 pregnant women from the English Born in Bradford cohort, Dutch Generation R Study, and Spanish INMA Project. Using the UrbClimTM model, weekly ambient air temperature exposure at 100x100m resolution at the mothers' residences during pregnancy was calculated. Estimated foetal weight, head circumference, and femur length at mid and late pregnancy and weight, head circumference, and length at birth were converted into standard deviation scores (SDS). Foetal growth from mid to late pregnancy was calculated (grams or centimetres/week). Cohort/region-specific distributed lag non-linear models were combined using a random-effects meta-analysis and results presented in reference to the median percentile of temperature (14 °C). RESULTS: Weekly temperatures ranged from -5.6 (Bradford) to 30.3 °C (INMA-Sabadell). Cold and heat exposure during weeks 1-28 were associated with a smaller and larger head circumference in late pregnancy, respectively (e.g., for 9.5 °C: -1.6 SDS [95 %CI -2.0; -0.4] and for 20.0 °C: 1.8 SDS [0.7; 2.9]). A susceptibility period from weeks 1-7 was identified for cold exposure and a smaller head circumference at late pregnancy. Cold exposure was associated with a slower head circumference growth from mid to late pregnancy (for 5.5 °C: -0.1 cm/week [-0.2; -0.04]), with a susceptibility period from weeks 4-12. No associations that survived multiple testing correction were found for other foetal or any birth outcomes. CONCLUSIONS: Cumulative exposure to cold and heat during pregnancy was associated with changes in foetal head circumference throughout gestation, with susceptibility periods for cold during the first pregnancy trimester. No associations were found at birth, suggesting potential recovery. Future research should replicate this study across different climatic regions including varying temperature profiles.

Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project) - study protocol.

INTRODUCTION: The European Environment Agency estimates that 75% of the European population lives in cities. Despite the many advantages of city life, the risks and challenges to health arising from urbanisation need to be addressed in order to tackle the growing burden of disease and health inequalities in cities. This study, Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project), aims to investigate the complex association between the urban environmental exposures (UrbEEs) and health. METHODS AND ANALYSIS: DAS-EP is a Spanish multiregional cross-sectional project that combines population health surveys (PHS) and geographical information systems (GIS) allowing to collect rich individual-level data from 17 000 adult citizens participating in the PHS conducted in the autonomous regions of the Basque Country, Andalusia, and the Valencian Community, and the city of Barcelona in the years 2021-2023. This study focuses on the population living in cities or metropolitan areas with more than 100 000 inhabitants. UrbEEs are described by objective estimates at participants' home addresses by GIS, and subjective indicators present in PHS. The health outcomes included in the PHS and selected for this study are self-perceived health (general and mental), prevalence of chronic mental disorders, health-related quality of life, consumption of medication for common mental disorders and sleep quality. We aim to further understand the direct and indirect effects between UrbEEs and health, as well as to estimate the impact at the population level, taking respondents' sociodemographic and socioeconomic characteristics, and lifestyle into consideration. ETHICS AND DISSEMINATION: The study was approved by the regional Research Ethics Committee of the Basque Country (Ethics Committee for Research Involving Medicinal Products in the Basque Country; PI2022138), Andalusia (Biomedical Research Ethics Committee of the Province of Granada; 2078-N-22), Barcelona (CEIC-PSMar; 2022/10667) and the Valencian Community (Ethics Committee for Clinical Research of the Directorate General of Public Health and Center for Advanced Research in Public Health; 20221125/04). The results will be communicated to the general population, health professionals, and institutions through conferences, reports and scientific articles.

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.

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 ß (ßcum) 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 (ßcum = -2.55, 95%CrI = -3.53,-1.56) and on gross motor scores in weeks 7-17 (ßcum = -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 (ßcum = -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 (ß = -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.

Susceptible windows of prenatal and postnatal fine particulate matter exposures and attention-deficit hyperactivity disorder symptoms in early childhood.

Few prior studies have explored windows of susceptibility to fine particulate matter (PM2.5) in both the prenatal and postnatal periods and children's attention-deficit/hyperactivity disorder (ADHD) symptoms. We analyzed data from 1416 mother-child pairs from the Spanish INMA (INfancia y Medio Ambiente) Study (2003-2008). Around 5 years of age, teachers reported the number of ADHD symptoms (i.e., inattention, hyperactivity/impulsivity) using the ADHD Diagnostic and Statistical Manual of Mental Disorders. Around 7 years of age, parents completed the Conners' Parent Rating Scales, from which we evaluated the ADHD index, cognitive problems/inattention, hyperactivity, and oppositional subscales, reported as age- and sex-standardized T-scores. Daily residential PM2.5 exposures were estimated using a two-stage random forest model with temporal back-extrapolation and averaged over 1-week periods in the prenatal period and 4-week periods in the postnatal period. We applied distributed lag non-linear models within the Bayesian hierarchical model framework to identify susceptible windows of prenatal or postnatal exposure to PM2.5 (per 5-µg/m3) for ADHD symptoms. Models were adjusted for relevant covariates, and cumulative effects were reported by aggregating risk ratios (RRcum) or effect estimates (ßcum) across adjacent susceptible windows. A similar susceptible period of exposure to PM2.5 (1.2-2.9 and 0.9-2.7 years of age, respectively) was identified for hyperactivity/impulsivity symptoms assessed ~5 years (RRcum = 2.72, 95% credible interval [CrI] = 1.98, 3.74) and increased hyperactivity subscale ~7 years (ßcum = 3.70, 95% CrI = 2.36, 5.03). We observed a susceptibility period to PM2.5 on risk of hyperactivity/impulsivity symptoms ~5 years in gestational weeks 16-22 (RRcum = 1.36, 95% CrI = 1.22, 1.52). No associations between PM2.5 exposure and other ADHD symptoms were observed. We report consistent evidence of toddlerhood as a susceptible window of PM2.5 exposure for hyperactivity in young children. Although mid-pregnancy was identified as a susceptible period of exposure on hyperactivity symptoms in preschool-aged children, this association was not observed at the time children were school-aged.

Association of Gestational Free and Total Triiodothyronine With Gestational Hypertension, Preeclampsia, Preterm Birth, and Birth Weight: An Individual Participant Data Meta-analysis.

CONTEXT: Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes. OBJECTIVE: To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes. METHODS: We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders. RESULTS: The final study population comprised 33 118 mother-child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA. CONCLUSION: This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.

Sociodemographic, lifestyle, and environmental determinants of vitamin D levels in pregnant women in Spain.

INTRODUCTION: Vitamin D deficiency (<20 ng/mL circulating levels) is a worldwide public health concern and pregnant women are especially vulnerable, affecting the health of the mother and the fetus. This study aims to evaluate the sociodemographic, lifestyle, and environmental determinants associated with circulating vitamin D levels in Spanish pregnant women. METHODS: We used data from the Spanish INMA ("Infancia y Medio Ambiente") prospective birth cohort study from the regions of Gipuzkoa, Sabadell, and Valencia. 25-hydroxyvitamin D3 (25(OH)D3) was measured in plasma collected in the first trimester of pregnancy. Information on 108 determinants was gathered: 13 sociodemographic, 48 lifestyle including diet, smoking and physical activity, and 47 environmental variables, representing the urban and the chemical exposome. Association of the determinants with maternal 25(OH)D3 levels was estimated in single- and multiple-exposure models. Machine learning techniques were used to predict 25(OH)D3 levels below sufficiency (30 ng/mL). RESULTS: The prevalence of < 30 ng/mL 25(OH)D3 levels was 51 %. In the single-exposure analysis, older age, higher socioeconomic status, taking vitamin D, B12 and other sup*plementation, and higher humidity, atmospheric pressure and UV rays were associated with higher levels of 25(OH)D3 (IQR increase of age: 1.2 [95 % CI: 0.6, 1.8] ng/mL 25(OH)D3). In the multiple-exposures model, most of these associations remained and others were revealed. Higher body mass index, PM2.5 and high deprivation area were associated with lower 25(OH)D3 levels (i.e., Quartile 4 of PM2.5 vs Q1: -3.6 [95 % CI: -5.6, -1.5] ng/mL of 25(OH)D3). History of allergy and asthma, being multiparous, intake of vegetable fat, vitamin B6, alcohol consumption and molybdenum were associated with higher levels. The machine learning classification model confirmed some of these associations. CONCLUSIONS: This comprehensive study shows that younger age, higher body mass index, higher deprived areas, higher air pollution and lower UV rays and humidity are associated with lower 25(OH)D3 levels.

Prenatal Exposure to Multiple Endocrine-Disrupting Chemicals and Childhood BMI Trajectories in the INMA Cohort Study.

BACKGROUND: Prenatal exposure to endocrine-disrupting chemicals (EDCs) may disrupt normal fetal and postnatal growth. Studies have mainly focused on individual aspects of growth at specific time points using single chemical exposure models. However, humans are exposed to multiple EDCs simultaneously, and growth is a dynamic process. OBJECTIVE: The objective of this study was to evaluate the associations between prenatal exposure to EDCs and children's body mass index (BMI) growth trajectories using single exposure and mixture modeling approaches. METHODS: Using data from the INfancia y Medio Ambiente (INMA) Spanish birth cohort (n=1,911), prenatal exposure to persistent chemicals [hexachlorobenzene (HCB), 4-4'-dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCB-138, -150, and -180), 4 perfluoroalkyl substances (PFAS)] and nonpersistent chemicals (8 phthalate metabolites, 7 phenols) was assessed using blood and spot urine concentrations. BMI growth trajectories were calculated from birth to 9 years of age using latent class growth analysis. Multinomial regression was used to assess associations for single exposures, and Bayesian weighted quantile sum (BWQS) regression was used to evaluate the EDC mixture's association with child growth trajectories. RESULTS: In single exposure models exposure to HCB, DDE, PCBs, and perfluorononanoic acid (PFNA) were associated with increased risk of belonging to a trajectory of lower birth size followed by accelerated BMI gain by 19%-32%, compared with a trajectory of average birth size and subsequent slower BMI gain [e.g., relative risk ratio (RRR) per doubling in DDE concentration=1.19 (95% CI: 1.05, 1.35); RRR for PFNA=1.32 (95% CI: 1.05, 1.66)]. HCB and DDE exposure were also associated with higher probability of belonging to a trajectory of higher birth size and accelerated BMI gain. Results from the BWQS regression showed the mixture was positively associated with increased odds of belonging to a BMI trajectory of lower birth size and accelerated BMI gain (odds ratio per 1-quantile increase of the mixture=1.70; credible interval: 1.03, 2.61), with HCB, DDE, and PCBs contributing the most. DISCUSSION: This study provides evidence that prenatal EDC exposure, particularly persistent EDCs, may lead to BMI trajectories in childhood characterized by accelerated BMI gain. Given that accelerated growth is linked to a higher disease risk in later life, continued research is important. https://doi.org/10.1289/EHP11103.

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.

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.

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.

Nutritional Modulation of Associations between Prenatal Exposure to Persistent Organic Pollutants and Childhood Obesity: A Prospective Cohort Study.

BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs) may contribute to the development of childhood obesity and metabolic disorders. However, little is known about whether the maternal nutritional status during pregnancy can modulate these associations. OBJECTIVES: The main objective was to characterize the joint associations and interactions between prenatal levels of POPs and nutrients on childhood obesity. METHODS: We used data from to the Spanish INfancia y Medio Ambiente-Environment and Childhood (INMA) birth cohort, on POPs and nutritional biomarkers measured in maternal blood collected at the first trimester of pregnancy and child anthropometric measurements at 7 years of age. Six organochlorine compounds (OCs) [dichlorodiphenyldichloroethylene, hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH) and polychlorinated biphenyls 138, 153, 180] and four per- and polyfluoroalkyl substances (PFAS) were measured. Nutrients included vitamins (D, B12, and folate), polyunsaturated fatty acids (PUFAs), and dietary carotenoids. Two POPs-nutrients mixtures data sets were established: a) OCs, PFAS, vitamins, and carotenoids (n=660), and b) OCs, PUFAs, and vitamins (n=558). Joint associations of mixtures on obesity were characterized using Bayesian kernel machine regression (BKMR). Relative importance of biomarkers and two-way interactions were identified using gradient boosting machine, hierarchical group lasso regularization, and BKMR. Interactions were further characterized using multivariate regression models in the multiplicative and additive scale. RESULTS: Forty percent of children had overweight or obesity. We observed a positive overall joint association of both POPs-nutrients mixtures on overweight/obesity risk, with HCB and vitamin B12 the biomarkers contributing the most. Recurrent interactions were found between HCB and vitamin B12 across screening models. Relative risk for a natural log increase of HCB was 1.31 (95% CI: 1.11, 1.54, pInteraction=0.02) in the tertile 2 of vitamin B12 and in the additive scale a relative excess risk due to interaction of 0.11 (95% CI: 0.02, 0.20) was found. Interaction between perfluorooctane sulfonate and ß-cryptoxanthin suggested a protective effect of the antioxidant on overweight/obesity risk. CONCLUSION: These results support that maternal nutritional status may modulate the effect of prenatal exposure to POPs on childhood overweight/obesity. These findings may help to develop a biological hypothesis for future toxicological studies and to better interpret inconsistent findings in epidemiological studies. https://doi.org/10.1289/EHP11258.

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.

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.

Childhood exposure to non-persistent pesticides and pubertal development in Spanish girls and boys: Evidence from the INMA (Environment and Childhood) cohort.

This study assessed cross-sectional associations between urinary metabolites of non-persistent pesticides and pubertal development in boys and girls from urban and rural areas in Spain and examined effect modification by body mass index (BMI). Four metabolites of insecticides (TCPy, metabolite of chlorpyrifos; IMPy, metabolite of diazinon; DETP, non-specific metabolite of organophosphates; 3-PBA, metabolite of pyrethroids) and the metabolite of ethylene-bis-dithiocarbamate fungicides (ETU) were quantified in urine collected in 2010-2016 from 7 to 11-year-old children (606 girls, 933 boys) participating in the INMA Project. Pubertal development was ascertained by Tanner stages and/or parent-reported Pubertal Development Scale (PDS). Associations between pesticide metabolites and odds of being in stage 2+ for breast development (girls), genital development (boys), pubic hair growth (girls and boys), and/or overall puberty onset, gonadarche, and adrenarche (PDS for girls and boys) were examined by mixed-effect logistic regression. Effect modification by BMI was explored by interaction terms and stratified analysis. In girls, DETP and ETU concentrations>75th percentile (P75) were associated with higher odds of overall puberty development (OR [95%CI] = 1.86 [1.07-3.24] and 1.71 [1.03-2.83], respectively, for > P75 vs. undetected concentrations), while ETU > P75 was also associated with higher odds of breast development (OR [95%CI] = 5.55 [2.83-12.91]), particularly in girls with underweight/normal weight (OR [95%CI] = 10.08 [2.62-38.76]). In boys, detection of TCPy (40%) and 3-PBA (34%) was associated with higher odds of genital development (OR [95%CI] = 1.97 [1.08-3.57] and 2.08 [1.15-3.81], respectively), and the association with 3-PBA was observed in boys with overweight/obesity alone. In addition, ETU > P75 was associated with higher odds of genital development in boys with underweight/normal weight (OR [95%CI] = 2.89 [1.08-7.74]) but higher DETP with lower odds of puberty in boys with overweight/obesity (OR [95%CI] = 0.94 [0.89-0.99] per log-unit increase in concentration). Results suggest an association of childhood exposure to ETU and certain insecticides with earlier puberty in girls and boys that may be modified by child BMI.

Environmental Noise Exposure and Sleep Habits among Children in a Cohort from Northern Spain.

Environmental noise is considered the second most serious environmental risk factor in Europe. However, little evidence exists regarding its impact on health and sleep in children, and the results are inconclusive. In this study, we aim to analyse the effect of environmental noise exposure on 11-year-old children's sleep habits. Data were collected from 377 participants in the INMA-Gipuzkoa (INfancia y Medio Ambiente) cohort project using both parent-reported and actigraphic sleep measures. The results revealed that 60% of children have a day-evening-night environmental noise exposure (Lden) of above 55 dB, which is defined as a "high noise level". No differences in noise exposure were observed between different socioeconomic groups. However, no effect of environmental noise was found on sleep variables. The paper highlights the importance of studying how environmental noise may affect children's sleep.

Exposure to natural environments during pregnancy and birth outcomes in 11 European birth cohorts.

Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas.