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.

Prenatal exposure to multiple persistent organic pollutants in association with adiposity markers and blood pressure in preadolescents.

BACKGROUND: Several studies have reported that prenatal exposure to some persistent organic pollutants (POPs) is associated with higher adiposity in childhood. Few studies have assessed whether this finding persists into adolescence, and few have considered exposure to POPs as a mixture. This study aims to assess the association between prenatal exposure to multiple POPs and adiposity markers and blood pressure in preadolescents. METHODS: This study included 1667 mother-child pairs enrolled in the PELAGIE (France) and the INMA (Spain) mother-child cohorts. Three polychlorobiphenyls (PCB 138, 153 and 180, treated as a sum of PCBs) and three organochlorine pesticides (p,p'-Dichlorodiphenyldichloroethylene [p,p'-DDE], ß-hexachlorocyclohexane [ß-HCH], and hexachlorobenzene [HCB]) were assessed in maternal or cord serum. Body mass index z-score (zBMI), abdominal obesity (waist-to-height ratio > 0.5), percentage of fat mass, and blood pressure (mmHg) were measured at around 12 years of age. Single-exposure associations were studied using linear or logistic regressions, and the POP mixture effect was evaluated using quantile G-computation (qgComp) and Bayesian Kernel Machine Regression (BKMR). All models were adjusted for potential confounders and performed for boys and girls together and separately. RESULTS: Prenatal exposure to the POP mixture was associated with higher zBMI (beta [95 % CI] of the qgComp = 0.15 [0.07; 0.24]) and percentage of fat mass (0.83 [0.31; 1.35]), with no evidence of sex-specific association. These mixture effects were also statistically significant using BKMR. These associations were driven mainly by exposure to HCB and, to a lesser extent, to ß-HCH. In addition, the single-exposure models showed an association between ß-HCH and p,p'-DDE and higher systolic blood pressure, especially in girls (p,p'-DDE for girls = 1.00 [0.15; 1.86]). No significant associations were found for PCBs. CONCLUSION: This study suggests that prenatal exposure to POPs, particularly organochlorine pesticides, remains associated with unfavorable cardiometabolic health up to the age of 12.

Early-childhood BMI trajectories in relation to preclinical cardiovascular measurements in adolescence.

Cardiovascular diseases are the leading causes of morbidity and mortality. Overweight, obesity, and accelerated growth during early childhood have been associated with adverse cardiovascular outcomes in later life. Few studies have assessed whether trajectories of accelerated growth in early childhood are associated with preclinical cardiovascular measurements. We aimed to evaluate the associations between childhood body mass index (BMI) growth trajectories and measures of macro- and microvascular function in early adolescence. Measurements of macrovascular function (systolic and diastolic blood pressure (SBP and DBP), pulse wave velocity (PWV), and microvascular function (central retinal arteriolar/veinular equivalent) were assessed at 11 years old in a Spanish birth cohort study (n = 489). BMI trajectories from birth to 9 years were identified using latent class growth analysis. Multiple linear regression assessed the associations between the BMI trajectories and macro- and microvascular function. Compared to children with average birth size and slower BMI gain (reference), children with a lower birth size and accelerated BMI gain had increased SBP [ß = 6.57; (95% CI 4.00, 9.15)], DBP [ß = 3.65; (95% CI 1.45, 5.86)], and PWV [ß = 0.14; (95% CI 0.01, 0.27)]. Children with higher birth size and accelerated BMI gain had increased SBP [ß = 4.75; (95% CI 1.79, 7.71) compared to the reference. No significant associations between BMI trajectories and the microvascular measurements were observed. In conclusion, we found that childhood BMI trajectories characterized by accelerated growth are associated with preclinical macrovascular measurements in young adolescents.

Risk of child poverty and social exclusion in two Spanish regions: social and family determinants / Riesgo de pobreza infantil y exclusión social en dos regiones españolas: determinantes sociales y familiares

Objective: Describe the risk of poverty and social exclusion in children aged 8-11 years from Gipuzkoa and Valencia (Spain), through AROPE (At Risk of Poverty or Social Exclusion) indicators, and evaluate their associated factors in the INMA Project (Childhood and Environment). Method: Families in Gipuzkoa and Valencia (394 and 382, respectively) completed a questionnaire in 2015-2016. Low work intensity (LWI), at risk of poverty (RP) and material deprivation (MD) were estimated. AROPE consisted in meeting any of the previous sub-indicators. Socio-demographic, family and parental characteristics were considered. Frequencies, Venn's diagrams, and chi-square and Fisher tests were used in bivariate analysis and logistic regression in multivariate analysis. Results: For LWI, RP, MD and AROPE, prevalence of 2.5%, 5.6%, 2.3% and 7.2% were obtained in Gipuzkoa, and 8.1%, 31.5%, 7.8% and 34.7% in Valencia, respectively. In the multivariate analysis, the AROPE was associated in both areas with maternal social class and non-nuclear families. In Gipuzkoa, it was also related to maternal education. In Valencia, other factors were the mother's foreign origin, and paternal education and smoking. Conclusion: There is higher AROPE prevalence in Valencia. Social class and family type were shared factors, but a differential pattern is observed in other social determinants. It is essential to implement social policies to reduce this axis of inequalities in health, especially in childhood. (AU)

Objetivo: Describir el riesgo de pobreza y exclusión social en niños/as de 8-11 años de Gipuzkoa y Valencia (España), mediante los indicadores AROPE (At Risk Of Poverty or Social Exclusion), y evaluar sus factores asociados en el Proyecto INMA (Infancia y Medio Ambiente). Método: Familias de Gipuzkoa y Valencia (394 y 382, respectivamente) completaron un cuestionario en 2015-2016. Se estimaron la baja intensidad de trabajo (BIT), el riesgo de pobreza (RP) y la privación material (PM). AROPE consistió en cumplir cualquiera de estos subindicadores. Se consideraron características sociodemográficas, familiares y parentales. Se usaron diagramas de Venn, los test de Ji-cuadrado y Fisher en los análisis bivariados, y regresión logística en los análisis multivariados. Resultados: Se obtuvieron prevalencias para BIT, RP, PM y AROPE del 2,5%, 5,6%, 2,3% y 7,2% en Gipuzkoa, y del 8,1%, 31,5%, 7,8% y 34,7% en Valencia, respectivamente. En el análisis multivariado, el AROPE se asoció en ambas áreas con la clase social materna y la familia no nuclear. En Gipuzkoa, también se relacionó con la educación materna. En Valencia, otros factores fueron el origen extranjero materno y la educación y el tabaquismo paternos. Conclusión: Hay un AROPE más alto en Valencia. La clase social y el tipo de familia fueron factores compartidos, pero se observa un patrón diferencial en otros determinantes sociales. Es esencial implementar políticas sociales para reducir este eje de desigualdad en salud, especialmente en la infancia. (AU)

Risk of child poverty and social exclusion in two Spanish regions: social and family determinants.

OBJECTIVE: Describe the risk of poverty and social exclusion in children aged 8-11 years from Gipuzkoa and Valencia (Spain), through AROPE (At Risk Of Poverty or Social Exclusion) indicators, and evaluate their associated factors in the INMA Project (Childhood and Environment). METHOD: Families in Gipuzkoa and Valencia (394 and 382, respectively) completed a questionnaire in 2015-2016. Low work intensity (LWI), at risk of poverty (RP) and material deprivation (MD) were estimated. AROPE consisted in meeting any of the previous sub-indicators. Socio-demographic, family and parental characteristics were considered. Frequencies, Venn's diagrams, and chi-square and Fisher tests were used in bivariate analysis and logistic regression in multivariate analysis. RESULTS: For LWI, RP, MD and AROPE, prevalence of 2.5%, 5.6%, 2.3% and 7.2% were obtained in Gipuzkoa, and 8.1%, 31.5%, 7.8% and 34.7% in Valencia, respectively. In the multivariate analysis, the AROPE was associated in both areas with maternal social class and non-nuclear families. In Gipuzkoa, it was also related to maternal education. In Valencia, other factors were the mother's foreign origin, and paternal education and smoking. CONCLUSION: There is higher AROPE prevalence in Valencia. Social class and family type were shared factors, but a differential pattern is observed in other social determinants. It is essential to implement social policies to reduce this axis of inequalities in health, especially in childhood.

Integrating Clinical and Epidemiologic Data on Allergic Diseases Across Birth Cohorts: A Harmonization Study in the Mechanisms of the Development of Allergy Project.

The numbers of international collaborations among birth cohort studies designed to better understand asthma and allergies have increased in the last several years. However, differences in definitions and methods preclude direct pooling of original data on individual participants. As part of the Mechanisms of the Development of Allergy (MeDALL) Project, we harmonized data from 14 birth cohort studies (each with 3-20 follow-up periods) carried out in 9 European countries during 1990-1998 or 2003-2009. The harmonization process followed 6 steps: 1) organization of the harmonization panel; 2) identification of variables relevant to MeDALL objectives (candidate variables); 3) proposal of a definition for each candidate variable (reference definition); 4) assessment of the compatibility of each cohort variable with its reference definition (inferential equivalence) and classification of this inferential equivalence as complete, partial, or impossible; 5) convocation of a workshop to agree on the reference definitions and classifications of inferential equivalence; and 6) preparation and delivery of data through a knowledge management portal. We agreed on 137 reference definitions. The inferential equivalence of 3,551 cohort variables to their corresponding reference definitions was classified as complete, partial, and impossible for 70%, 15%, and 15% of the variables, respectively. A harmonized database was delivered to MeDALL investigators. In asthma and allergy birth cohorts, the harmonization of data for pooled analyses is feasible, and high inferential comparability may be achieved. The MeDALL harmonization approach can be used in other collaborative projects.

Urban upbringing and childhood respiratory and allergic conditions: A multi-country holistic study.

OBJECTIVE: We integratively assessed the effect of different indoor and outdoor environmental exposures early in life on respiratory and allergic health conditions among children from (sub-) urban areas. METHODS: This study included children participating in four ongoing European birth cohorts located in three different geographical regions: INMA (Spain), LISAplus (Germany), GINIplus (Germany) and BAMSE (Sweden). Wheezing, bronchitis, asthma and allergic rhinitis throughout childhood were assessed using parental-completed questionnaires. We designed "environmental scores" corresponding to different indoor, green- and grey-related exposures (main analysis, a-priori-approach). Cohort-specific associations between these environmental scores and the respiratory health outcomes were assessed using random-effects meta-analyses. In addition, a factor analysis was performed based on the same exposure information used to develop the environmental scores (confirmatory analysis, data-driven-approach). RESULTS: A higher early exposure to the indoor environmental score increased the risk for wheezing and bronchitis within the first year of life (combined adjusted odds ratio: 1.20 [95% confidence interval: 1.13-1.27] and 1.28 [1.18-1.39], respectively). In contrast, there was an inverse association with allergic rhinitis between 6 and 8 years (0.85 [0.79-0.92]). There were no statistically significant associations for the outdoor related environmental scores in relation to any of the health outcomes tested. The factor analysis conducted confirmed these trends. CONCLUSION: Although a higher exposure to indoor related exposure through occupants was associated with an increased risk for wheezing and bronchitis within the 1st year, it might serve as a preventive mechanism against later childhood allergic respiratory outcomes in urbanized environments through enhanced shared contact with microbial agents.