Associations between pre- and postnatal exposure to air pollution and lung health in children and assessment of CC16 as a potential mediator.

BACKGROUND: Early life exposure to air pollution can affect lung health. Previous studies have not assessed the implications of both pre- and postnatal exposure to air pollutants on lung function at repeated ages during childhood. In addition, there is the need to identify potential mediators of such effect. OBJECTIVES: To longitudinally assess the association between pre- and postnatal air pollution exposure and lung function during childhood. We also aimed to explore the role of Club cell secretory protein (CC16) as a potential mediator in this association. METHODOLOGY: We included 487 mother-child pairs from the INMA (INfancia y Medio Ambiente) Sabadell birth cohort, recruited between 2004 and 2006. Air pollution exposure was estimated for pregnancy, pre-school age, and school-age using temporally adjusted land use regression (LUR) modelling. Lung function was measured at ages 4, 7, 9 and 11 by spirometry. At age 4, serum CC16 levels were determined in 287 children. Multivariable linear regression models and linear mixed modelling were applied, while considering potential confounders. RESULTS: Prenatal exposure to Particulate Matter (PM)10 and PMcoarse had the most consistent associations with reduced lung function in cross-sectional models. Associations with postnatal exposure were less consistent. Increasing CC16 levels at 4 years were associated with an increase in FEF25-75 (ß = 120.4 mL, 95% CI: 6.30, 234.5) from 4 to 11 years of age. No statistically significant associations were found between pre- or postnatal air pollution and CC16 at age 4. CONCLUSION: Increasing levels of air pollution exposure, particularly prenatal PM10 and PMcoarse exposure, were associated with a reduction in lung function. We were not able to confirm our hypothesis on the mediation role of CC16 in this association, however our results encourage further exploration of this possibility in future studies.

Time Trends and Sociodemographic Factors Associated With Overweight and Obesity in Children and Adolescents in Spain.

Importance: Time-trend studies of overweight and obesity in childhood by sociodemographic factors are important for prioritizing public health initiatives. However, little is known about these trends in Spain, where high levels of obesity are found and where important demographic changes have occurred during the last 2 decades. Objective: To examine how time trends in the prevalence and incidence of overweight and obesity among children and adolescents differ by age, sex, socioeconomic status, urban/rural residence, and nationality. Design, Setting, and Participants: This cohort study included 1.1 million children and adolescents (aged 2-17 years) with at least 1 measure of height and weight in Catalonia, Spain, from 2006 to 2016. Electronic health records were accessed from the Information System for Research in Primary Care. Data analysis was conducted from January to December 2018. Main Outcomes and Measures: Prevalence and incidence rates and trends of overweight/obesity and obesity (overweight/obesity defined as having of BMI z score greater than 2.0 among children aged <5 years and greater than 1.0 among children aged ≥5 years; obesity defined as having of BMI z score greater than 3.0 among children aged <5 years and greater than 2.0 among children aged ≥5 years) between 2006 and 2016 were calculated and stratified by sociodemographic characteristics (ie, age, sex, deprivation index, urban/rural residence, and nationality). Results: The study population included 1 166 609 children and adolescents (570 982 [48.9%] girls; median [interquartile range] age at entry to electronic health record system, 2.4 [0-7.7] years; 1 006 892 [86.3%] with Spanish nationality). Of 941 041 children (80.7%) who lived in urban areas, 197 427 (20.7%) lived in the most deprived areas. Overall, the prevalence of overweight/obesity and obesity decreased between 2006 and 2016 in all sex and age groups; for example, among boys and girls aged 6 to 11 years, overweight/obesity prevalence decreased from 41.9% (95% CI, 41.5%-42.2%) to 39.9% (95% CI, 39.6%-40.3%) and from 39.7% (95% CI, 39.3%-40.2%) to 37.6% (95% CI, 37.3%-38.0%), respectively. Incidence rates of overweight/obesity and obesity were highest among children aged 6 to 7 years (overweight/obesity among boys: 11.9 [95% CI, 11.8-12.0] new cases per 100 person-years; obesity among boys: 4.9 [95% CI, 4.8-4.9] new cases per 100 person-years). Prevalence and incidence rates were highest in the most deprived areas, in urban areas, and among children with North, Central, or South American nationalities. Between 2006 and 2016, prevalence increased in the most deprived areas in almost all sex and age groups. Among girls aged 6 to 11 years living in the most deprived areas, the obesity prevalence ratio increased from 1.59 (95% CI, 1.46-1.74) to 2.03 (95% CI, 1.88-2.19) compared with those living in the least deprived areas. Furthermore, during this period, prevalence increased among children with non-Spanish nationalities, especially in the African and Asian nationality groups (eg, boys aged 6-11 years with Asian nationality compared with Spanish nationality, 2006: prevalence rate, 0.78 [95% CI, 0.60-1.01]; 2016: prevalence rate, 1.27 [95% CI, 1.15-1.39]). Incidence rates decreased among younger groups (eg, ≤7 years: incidence rate ratio for January 1, 2006, to June 30, 2011, vs July 1, 2011, to December 31, 2016: 0.94; 95% CI, 0.91-0.98) but remained stable in older groups. Conclusions and Relevance: In this study, the overall prevalence and incidence rates of childhood overweight/obesity and obesity slightly decreased during the last decade. However, increased deprivation disparities in childhood obesity were found, given that the prevalence increased among children living in deprived areas and with non-Spanish nationalities.

Personal assessment of the external exposome during pregnancy and childhood in Europe.

The human exposome affects child development and health later in life, but its personal external levels, variability, and correlations are largely unknown. We characterized the personal external exposome of pregnant women and children in eight European cities. Panel studies included 167 pregnant women and 183 children (aged 6-11 years). A personal exposure monitoring kit composed of smartphone, accelerometer, ultraviolet (UV) dosimeter, and two air pollution monitors were used to monitor physical activity (PA), fine particulate matter (PM2.5), black carbon, traffic-related noise, UV-B radiation, and natural outdoor environments (NOE). 77% of women performed the adult recommendation of ≥150 min/week of moderate to vigorous PA (MVPA), while only 3% of children achieved the childhood recommendation of ≥60 min/day MVPA. 11% of women and 17% of children were exposed to daily PM2.5 levels higher than recommended (≥25µg/m3). Mean exposure to noise ranged from Lden 51.1 dB in Kaunas to Lden 65.2 dB in Barcelona. 4% of women and 23% of children exceeded the recommended maximum of 2 Standard-Erythemal-Dose of UV-B at least once a week. 33% of women and 43% of children never reached the minimum NOE contact recommendation of ≥30 min/week. The variations in air and noise pollution exposure were dominated by between-city variability, while most of the variation observed for NOE contact and PA was between-participants. The correlations between all personal exposures ranged from very low to low (Rho < 0.30). The levels of personal external exposures in both pregnant women and children are above the health recommendations, and there is little correlation between the different exposures. The assessment of the personal external exposome is feasible but sampling requires from one day to more than one year depending on exposure due to high variability between and within cities and participants.

Assessment of metabolic phenotypic variability in children's urine using 1H NMR spectroscopy.

The application of metabolic phenotyping in clinical and epidemiological studies is limited by a poor understanding of inter-individual, intra-individual and temporal variability in metabolic phenotypes. Using 1H NMR spectroscopy we characterised short-term variability in urinary metabolites measured from 20 children aged 8-9 years old. Daily spot morning, night-time and pooled (50:50 morning and night-time) urine samples across six days (18 samples per child) were analysed, and 44 metabolites quantified. Intraclass correlation coefficients (ICC) and mixed effect models were applied to assess the reproducibility and biological variance of metabolic phenotypes. Excellent analytical reproducibility and precision was demonstrated for the 1H NMR spectroscopic platform (median CV 7.2%). Pooled samples captured the best inter-individual variability with an ICC of 0.40 (median). Trimethylamine, N-acetyl neuraminic acid, 3-hydroxyisobutyrate, 3-hydroxybutyrate/3-aminoisobutyrate, tyrosine, valine and 3-hydroxyisovalerate exhibited the highest stability with over 50% of variance specific to the child. The pooled sample was shown to capture the most inter-individual variance in the metabolic phenotype, which is of importance for molecular epidemiology study design. A substantial proportion of the variation in the urinary metabolome of children is specific to the individual, underlining the potential of such data to inform clinical and exposome studies conducted early in life.

Transfer of perfluoroalkyl substances from mother to fetus in a Spanish birth cohort.

INTRODUCTION: Prenatal exposure to perfluoroalkyl substances (PFAS) might affect child health; thus estimating PFAS fetal burden is relevant. PFAS fetal burden is best estimated in cord samples; previous studies have used either maternal plasma or serum during pregnancy as proxy, but their validity is not clear. We aimed to evaluate PFAS transfer between mother and fetus and determine its predictors in a Spanish birth cohort. METHODS: We measured perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA) in maternal blood and cord serum from 66 mother-child pairs. We used Spearman's rank coefficients to correlate PFAS concentrations in first trimester maternal plasma and serum, with cord serum samples. We assessed PFAS placental transfer by calculating maternal to cord ratios and examined their association with maternal socio-demographic characteristics and child sex using linear regression models. RESULTS: Median concentrations of PFAS (ng/mL) of PFHxS, PFOS, PFOA, and PFNA in maternal plasma (0.79, 6.18, 2.85 and 0.84, respectively) and serum (0.84, 6.99, 2.97 and 0.85) were higher than in cord serum (0.40, 1.86, 1.90 and 0.32). PFBS was not detected. Positive Spearman's correlations (p-values<0.001) were found between maternal plasma and serum (⍴≥0.80), maternal plasma and cord (⍴≥0.66), and maternal serum and cord samples (⍴≥0.67). Maternal plasma to cord ratios were above 1 (PFHxS: 2.35 [95%CI: 2.05, 2.70], PFOS: 3.33 [3.05, 3.62], PFOA: 1.37 [1.27, 1.48], PFNA: 2.39 [2.18, 2.63]); maternal serum to cord ratios were similar. Maternal to cord ratios decreased with maternal age, but not with other socio-demographic factors. CONCLUSIONS: Our results suggest that PFAS fetal body burden can be assessed using as proxy maternal plasma or serum collected early in pregnancy. Maternal age might influence PFAS placental transfer.

Assessment of exposure to trace metals in a cohort of pregnant women from an urban center by urine analysis in the first and third trimesters of pregnancy.

Prenatal exposure to trace metals, whether they are essential, non-essential, or toxic, must be assessed for their potential health effects in the offspring. Herein is reported an approach to this end which involved collection of urine samples during the first and third trimesters of pregnancy from 489 mothers from Sabadell (Catalonia, Spain), a highly industrialized town. These samples were analyzed for cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), selenium (Se), arsenic (As), molybdenum (Mo), cadmium (Cd), antimonium (Sb), cesium (Cs), thallium (Tl), and lead (Pb). An acid digestion method was developed and validated for inductively coupled plasma quadruple mass spectrometry (Q-ICP-MS) analysis of these 12 metals. The median concentrations of metals ranged from 0.13 to 290 µg/g creatinine, the highest levels were found for Zn and the lowest for Th. The mean concentrations of most metals except As, Ni, Th, and Pb showed statistically significant differences between both trimesters. The concentrations of Mo, Se, Cd, Cs, and Sb were higher in the first than in the third trimester, whereas the opposite was found for Co, Cu, and Zn. The concentrations of all metals in both sampling periods showed statistically significant correlations (p<0.01 for Mo and Cu, p<0.001 for the others). The significant correlations of metal urine concentrations in the first and third trimesters of pregnancy suggest that the observed differences between both periods are related to physiological changes. Accordingly, the measured urine concentrations during either the first or third trimesters can be used as estimates of exposure during pregnancy and can serve as markers for prenatal intake of these metals in the studied cohort.

Dietary and sociodemographic determinants of bisphenol A urine concentrations in pregnant women and children.

Bisphenol A (BPA) exposure during early life may have endocrine-disrupting effects, but the dietary and sociodemographic predictors of BPA exposure during pregnancy and childhood remain unclear. Our aim was to evaluate the correlations between, and sociodemographic and dietary predictors of, serial urinary BPA concentrations measured during pregnancy and childhood in a Spanish birth cohort study. BPA was measured in two spot urine samples collected from 479 women during the first and third trimester of pregnancy and in one urine sample from their 4-year old children (n=130). Average dietary intakes were reported in food frequency questionnaires during the first and third pregnancy trimester and at age 4years. Multivariate mixed models and linear regression models were used to estimate associations between sociodemographic and dietary factors and BPA concentrations. A small, but statistically significant correlation was found between serial maternal BPA concentrations measured during pregnancy (r=0.17). Pregnant women who were younger, less-educated, smoked, and who were exposed to second-hand tobacco smoke (SHS) had higher BPA concentrations than others. BPA concentrations were also higher in children exposed to SHS. High consumption of canned fish during pregnancy was associated with 21% [GM ratio=1.21; 95%CI 1.02, 1.44] and 25% [GM ratio=1.25; 95%CI 1.05, 1.49] higher urinary BPA concentrations in the first and third pregnancy trimester, respectively, compared to the lowest consumption group. This study suggests that canned fish may be a major source of BPA during pregnancy in Spain, a country of high canned fish consumption. Further evaluation of specific BPA exposure sources in the sociodemographic group of younger women who smoke, are exposed to SHS, and have a low educational level is needed. Studies identifying sources of exposure would benefit from repeat BPA measurements and questionnaires specifically focused on dietary and packaging sources.

Environmental exposure assessment in European birth cohorts: results from the ENRIECO project.

Environmental exposures during pregnancy and early life may have adverse health effects. Single birth cohort studies often lack statistical power to tease out such effects reliably. To improve the use of existing data and to facilitate collaboration among these studies, an inventory of the environmental exposure and health data in these studies was made as part of the ENRIECO (Environmental Health Risks in European Birth Cohorts) project. The focus with regard to exposure was on outdoor air pollution, water contamination, allergens and biological organisms, metals, pesticides, smoking and second hand tobacco smoke (SHS), persistent organic pollutants (POPs), noise, radiation, and occupational exposures. The review lists methods and data on environmental exposures in 37 European birth cohort studies. Most data is currently available for smoking and SHS (N=37 cohorts), occupational exposures (N=33), outdoor air pollution, and allergens and microbial agents (N=27). Exposure modeling is increasingly used for long-term air pollution exposure assessment; biomonitoring is used for assessment of exposure to metals, POPs and other chemicals; and environmental monitoring for house dust mite exposure assessment. Collaborative analyses with data from several birth cohorts have already been performed successfully for outdoor air pollution, water contamination, allergens, biological contaminants, molds, POPs and SHS. Key success factors for collaborative analyses are common definitions of main exposure and health variables. Our review emphasizes that such common definitions need ideally be arrived at in the study design phase. However, careful comparison of methods used in existing studies also offers excellent opportunities for collaborative analyses. Investigators can use this review to evaluate the potential for future collaborative analyses with respect to data availability and methods used in the different cohorts and to identify potential partners for a specific research question.

Socio-economic inequalities in health, habits and self-care during pregnancy in Spain.

Socioeconomic disadvantage can be harmful for mother's health and can influence child's health long term. The aim of this study is to analyse social inequalities between pregnant women from four INMA (INfancia y Medio Ambiente) cohorts. The analysis included 2,607 pregnant women recruited between 2004 and 2008 from four INMA cohorts. Data on maternal characteristics were collected through two questionnaires completed in the first and third trimester of pregnancy. The relationship between socioeconomic status (SES) and maternal health, dietary intake, lifestyle habits and self-care related variables was modelled using logistic regression analysis. 33.5 % of women had a university level of education and 47 % had high occupational class. Women with higher SES reported healthier habits, fewer complications during pregnancy, better weight gain control and attended more prenatal appointments than women with lower SES. The risk of sedentary behaviour and passive smoking was higher among women with a lower level of education (OR = 1.7, 95 % CI 1.3-2.2 and OR = 1.6, 95 % CI 1.2-2.3, respectively) and with less skilled occupations (OR = 1.7, 95 % CI 1.4-2.0 and OR = 1.2, 95 % CI 1.0-1.5, respectively). Although both SES indicators-occupation and education-act as social determinants of diet, occupation was a more powerful determinant than education. For other lifestyle and self-caring variables, education was a more powerful predictor than occupation. Social inequalities were observed in health, habits and self-care during pregnancy. Proper care during pregnancy requires the control of common clinical variables and the knowledge of socioeconomic conditions of the pregnant women.

Prenatal exposure to lead in Spain: cord blood levels and associated factors.

INTRODUCTION AND OBJECTIVE: Lead is a known neurotoxic. Fetuses and infants are very vulnerable to lead exposure, since their blood-brain barrier is not completely formed. Hence, there is an importance for monitoring of blood lead levels prenatally and during early infancy. The aim of this study is to evaluate the prenatal exposure to lead and its association with maternal factors in four population based mother-child cohorts in Spain. The present research was carried out within the framework of the INMA project INfancia y Medio Ambiente (Environment and Childhood). METHODS: A total of 1462 pregnant women were recruited between 2004 and 2008. Lead was analyzed in a sample of cord blood by thermal decomposition, amalgation, and Atomic Absorption Spectrometry. Maternal sociodemographic, lifestyle and dietary factors were obtained by questionnaires during pregnancy. A multivariate logistic regression model was constructed. The dependent variable was a dichotomous lead level variable (detected vs no detected, i.e. ≥ vs < 2µg/dL). RESULTS: A low percentage of cord blood samples with lead levels ≥ 2µg/dL were found (5.9%). Geometric mean and maximum were 1.06µg/dL and 19µg/dL, respectively. Smoking at the beginning of pregnancy, age, social class, weight gain during pregnancy, gravidity, and place of residence were the maternal factors associated with detectable cord blood lead levels. Mother's diet does not appear to be a determining factor of lead exposure. Nevertheless, daily intake of iron and zinc may act as a protective factor against having cord blood lead levels ≥ 2µg/dL. CONCLUSION: In the different regions of Spain taking part in this study, lead levels to which newborns are exposed are low. Mobilization of lead from bones may be the main contributor to the cord blood levels.