Suchergebnisse

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. ; This study was funded by Grants from European Union (FP7-ENV-2011 code 282957 and HEALTH.2010.2.4.5-1), Spain: Instituto de Salud Carlos III (ISCIII) (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI09/00090, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI13/02187, PI14/00891, PI14/01687, PI16/1288, and PI17/00663), Generalitat Valenciana: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat ...

Ferritin status during prenatal brain development may influence the risk of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood. We investigated the association of maternal ferritin in pregnancy and ADHD-like symptoms in offspring. A total of 1095 mother-child pairs from three birth cohorts of the INMA Project (Spain) were studied. Maternal plasma ferritin in pregnancy was measured at 11.57 weeks of gestation. Children's ADHD-like symptoms at ages 4-5 years were assessed using the ADHD Rating Scale-IV. The count model of the zero-inflated Poisson regression model showed a significant inverse association between ferritin (continuous variable) and inattention, β = -0.19 (-0.32, -0.07), for boys. Comparing ferritin level by tertiles, significant differences were observed between the first tertile ([1.98, 20.92]) and the second ([20.92, 38.79]) and third tertiles ([38.79, 216.5]) (mg/L).The number of symptoms was lower for those in the third tertile, β = -0.3 (-0.55, -0.5), and for those in the second one, β = -0.37 (-0.6, -0.14). The model stratification by sex also showed this inverse association for boys only, β = -0.21 (-0.34, -0.08). No associations were found between ferritin level and hyperactivity or total ADHD symptoms. High ferritin levels during pregnancy show a protective association with child inattentive-type ADHD symptoms. ; Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI06/0867, FIS-PI09/00090 and FIS-PI13/02187), CIBERESP, Department of Health of the Basque Government (2005111093, 2009111069 and 2013111089) and the Provincial Government of Gipuzkoa (DFG06/002 and DFG08/001). Sabadell: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; and PI081151 including support from the European Regional Development Fund (ERDF), Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. Valencia: This study was funded by grants from the European Union (FP7-ENV-2011, grant number: 282957 and HEALTH.2010.2.4.5-1); Spain (ISCIII: G03/176; FIS-ERDF: PI11/01007, PI11/02591, PI11/02038, PI12/00610, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, and PI17/00663; Miguel Servet-European Regional Development Fund CP11/00178, CP15/00025, and MSII16/00051); Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249); and the Alicia Koplowitz Foundation (2017); Instituto de Salud Carlos III through the projects "CP14/00108 and PI16/00261" (Co-funded by European Regional Development Fund "A way to make Europe"). Jordi Julvez holds the Miguel Servet-II contract (CPII19/00015) awarded by the Instituto de Salud Carlos III (co-funded by the European Social Fund "Investing in your future").

Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041), (FIS-PI13/2429, PI041436, PI042018, PI06/0867, PI07/0252, PI08/1151, PI09/02311, y FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, y MS13/00054), Generalitat de Catalunya-CIRIT 1999SGR 00241, Conselleria de Sanitat, Generalitat Valenciana, Departamento de Salud del Gobierno Vasco (2005111093 y 2009111069), Gobierno Provincial de Guipúzcoa (DFG06/004 and DFG08/001), Obra Social Cajastur, Universidad de Oviedo, European Union Commission (QLK4-1999-01422, QLK4-2002-00603 and CONTAMED FP7-ENV-212502), Consejería de Salud de la Junta de Andalucía (183/07), y Fundació Roger Torné.

Fundamentos: Los estudios publicados no son concluyentes sobre el impacto de determinadas exposiciones ocupacionales en el embarazo, evidenciando la necesidad de considerar el doble rol, profesional y familiar, de las mujeres. El objetivo del presente trabajo fue evaluar el efecto de la situación laboral y de la carga doméstica de trabajo en la duración de la gestación y en el desarrollo fetal. Métodos: Mediante modelos de regresión univariante y multivariante, se estudió la asociación entre partos pretérmino (PPT) (<37 semanas), recién nacidos con bajo peso a término (BPT) (<2500g) y pequeños para su edad gestacional (PEG) (

Background: There is increasing interest in the potential effects of polybrominated diphenyl ethers (PBDEs) on children's neuropsychological development, but only a few small studies have evaluated such effects. Objectives: Our goal was to examine the association between PBDE concentrations in colostrum and infant neuropsychological development and to assess the influence of other persistent organic pollutants (POPs) on such association. Methods: We measured concentrations of PBDEs and other POPs in colostrum samples of 290 women recruited in a Spanish birth cohort. We tested children for mental and psychomotor development with the Bayley Scales of Infant Development at 12–18 months of age. We analyzed the sum of the seven most common PBDE congeners (BDEs 47, 99, 100, 153, 154, 183, 209) and each congener separately. Results: Increasing Σ7PBDEs concentrations showed an association of borderline statistical significance with decreasing mental development scores (β per log ng/g lipid = –2.25; 95% CI: –4.75, 0.26). BDE-209, the congener present in highest concentrations, appeared to be the main congener responsible for this association (β = –2.40, 95% CI: –4.79, –0.01). There was little evidence for an association with psychomotor development. After adjustment for other POPs, the BDE-209 association with mental development score became slightly weaker (β = –2.10, 95% CI: –4.66, 0.46). Conclusions: Our findings suggest an association between increasing PBDE concentrations in colostrum and a worse infant mental development, particularly for BDE-209, but require confirmation in larger studies. The association, if causal, may be due to unmeasured BDE-209 metabolites, including OH-PBDEs (hydroxylated PBDEs), which are more toxic, more stable, and more likely to cross the placenta and to easily reach the brain than BDE-209. ; This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-PI06/0867, and FIS-PS09/00090), Spanish Ministry of Health (FIS-PI041436 and FIS- PI081151), Generalitat de Catalunya-CIRIT (1999SGR 00241), Department of Health of the Basque Government (2005111093 and 2009111069), the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), and Fundación Roger Torné

BACKGROUND: Mitochondria are sensitive to environmental toxicants due to their lack of repair capacity. Changes in mitochondrial DNA (mtDNA) content may represent a biologically relevant intermediate outcome in mechanisms linking air pollution and fetal growth restriction. OBJECTIVE: We investigated whether placental mtDNA content is a possible mediator of the association between prenatal nitrogen dioxide (NO2) exposure and birth weight. METHODS: We used data from two independent European cohorts: INMA (n = 376; Spain) and ENVIRONAGE (n = 550; Belgium). Relative placental mtDNA content was determined as the ratio of two mitochondrial genes (MT-ND1 and MTF3212/R3319) to two control genes (RPLP0 and ACTB). Effect estimates for individual cohorts and the pooled data set were calculated using multiple linear regression and mixed models. We also performed a mediation analysis. RESULTS: Pooled estimates indicated that a 10-μg/m3 increment in average NO2 exposure during pregnancy was associated with a 4.9% decrease in placental mtDNA content (95% CI: -9.3, -0.3%) and a 48-g decrease (95% CI: -87, -9 g) in birth weight. However, the association with birth weight was significant for INMA (-66 g; 95% CI: -111, -23 g) but not for ENVIRONAGE (-20 g; 95% CI: -101, 62 g). Placental mtDNA content was associated with significantly higher mean birth weight (pooled analysis, interquartile range increase: 140 g; 95% CI: 43, 237 g). Mediation analysis estimates, which were derived for the INMA cohort only, suggested that 10% (95% CI: 6.6, 13.0 g) of the association between prenatal NO2 and birth weight was mediated by changes in placental mtDNA content. CONCLUSION: Our results suggest that mtDNA content can be one of the potential mediators of the association between prenatal air pollution exposure and birth weight. ; The research leading to these results was funded by the Spanish Ministry of Health (FIS-PI11/00610, FIS-PI041436, FIS-PI081151, FIS-PI042018, and FIS-PI09/02311), the European Union (EU) (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), the Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, CP11/00178, FIS-PI06/0867, and FIS-PS09/00090), the Conselleria de Sanitat Generalitat Valenciana, the Generalitat de Catalunya-CIRIT (1999SGR 00241), the Obre Social Cajastur, the Universidad de Oviedo, the Department of Health of the Basque Government (2005111093 and 2009111069), and the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001). The ENVIRONAGE cohort is supported by the EU Program "Ideas" (ERC-2012- StG 310898) and by the Flemish Fund for Scientific Research (FWO 1516112N and G073315N).

This study was funded by Grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), and from Spain: Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-FEDER 03/1615,04/1509, 04/1112, 04/1931, PI041436, FIS-PI042018, 05/1079, 05/1052, 06/1213, FIS-PI06/0867, 07/0314, 081151, 09/02647, 09/02311, 09/00090, 11/0178, 11/02591, 11/02038, 13/1944, 13/2032, 13/02429, 13/02187, 14/0891, 14/1687, CP14/00108, CP16/00261 and Miguel Servet-FEDER MS15/0025, MS13/00054, CP0610034, MS14/00108), CIBERESP (Ref. AA08_012), the Conselleria de Sanitat de la Generalitat Valenciana, Generalitat de Catalunya (CIRIT 1999SGR 00241), Fundació La Marató de TV3 (090430), Obra Social Cajastur/Fundación Liberbank, Universidad de Oviedo, Department of Health of the Basque Government (2005111093, 2009111069, 2013111089 and 2015111065), and the Provincial Government of Gipuzkoa (DFG06/002, DFG08/001 and DFG15/221). Annual agreements with the city council of the study area in Gipuzkoa (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya.

BACKGROUND: Exposure to perfluoroalkyl substances (PFASs) may increase risk for metabolic diseases; however, epidemiologic evidence is lacking at the present time. Pregnancy is a period of enhanced tissue plasticity for the fetus and the mother and may be a critical window of PFAS exposure susceptibility. OBJECTIVE: We evaluated the associations between PFAS exposures and metabolic outcomes in pregnant women. METHODS: We analyzed 1,240 pregnant women from the Spanish INMA [Environment and Childhood Project (INfancia y Medio Ambiente)] birth cohort study (recruitment period: 2003-2008) with measured first pregnancy trimester plasma concentrations of four PFASs (in nanograms/milliliter). We used logistic regression models to estimate associations of PFASs (log10-transformed and categorized into quartiles) with impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM), and we used linear regression models to estimate associations with first-trimester serum levels of triglycerides, total cholesterol, and C-reactive protein (CRP). RESULTS: Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were positively associated with IGT (137 cases) [OR per log10-unit increase=1.99 (95% CI: 1.06, 3.78) and OR=1.65 ( 95% CI: 0.99, 2.76), respectively]. PFOS and PFHxS associations with GDM (53 cases) were in a similar direction, but less precise. PFOS and perfluorononanoate (PFNA) were negatively associated with triglyceride levels [percent median change per log10-unit increase=-5.86% (95% CI: -9.91%, -1.63%) and percent median change per log10-unit increase=-4.75% (95% CI: -8.16%, -0.61%, respectively], whereas perfluorooctanoate (PFOA) was positively associated with total cholesterol [percent median change per log10-unit increase=1.26% (95% CI: 0.01%, 2.54%)]. PFASs were not associated with CRP in the subset of the population with available data (n=640). CONCLUSIONS: Although further confirmation is required, the findings from this study suggest that PFAS exposures during pregnancy may influence lipid metabolism and glucose tolerance and thus may impact the health of the mother and her child. https://doi.org/10.1289/EHP1062. ; This study was funded in part by grants from the European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), the Instituto de Salud Carlos III, the Spanish Ministry of Health (Red INMA G03/176; CB06/02/0041; FIS-PI12/01890, FIS-PI041436, FIS- PI081151, FIS-PI06/0867, FIS-PS09/00090; FIS-FEDER: 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, 11/02038, 13/1944, 13/2032, 14/00891, and 14/01687; Miguel Servet-FEDER CP11/0178, MS13/00054, and CPII16/00051; and PFIS-FI14/00099), Generalitat Valenciana (FISABIO: UGP 15-230, UGP-15-244, and UGP-15-249), the Department of Health of the Basque Government (2005111093 and 2009111069), the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), the Generalitat de Catalunya-CIRIT (1999SGR 00241), and the National Institutes of Health/National Institute of Environmental Health Sciences (grant number ES021477). This study has been reviewed and approved by the accredited committees of the following institutions: The Municipal Institute of Sanitary Assistance of Barcelona, La Fe University Hospital of Valencia, and The Donostia Hospital.

Background: Disinfection by-products (DBPs) constitute a complex mixture of prevalent chemicals in drinking water and there is evidence of neurotoxicity for some of them. Objectives: We evaluated the association between estimates of DBP exposure during pregnancy and child neuropsychological outcomes at 1 and 4–5 years of age. Methods: We conducted a population-based mother-child cohort study in Spain with recruitment at first trimester of gestation (INMA Project, 2003–2008). Neuropsychological development was measured at 1 year of age using the Bayley Scales of Infant Development and at 4–5 years with the McCarthy Scales of Children's Abilities. Modeled tap water concentrations of trihalomethanes (THM) were combined with personal ingestion, showering and bathing habits to estimate exposure as ingestion uptake, all route (showering, bathing, ingestion) uptake (μg/day) and crude levels (μg/l) in the residence. Chloroform, brominated THMs (bromodichloromethane, dibromochloromethane, bromoform) and total THMs (chloroform and brominated THMs) were analysed separately. Nine haloacetic acids levels were available in one of the areas. Linear regression was used to estimate associations in 1855 subjects adjusting for covariables. Results: The median concentration of total THMs, chloroform, brominated THMs, total haloacetic acids, dichloroacetic acid, and trichloroacetic acid were, respectively 30.3 μg/L, 9.4 μg/L, 11.6 μg/L, 10.5 μg/L, 2.7 μg/L, and 3.1 μg/L. The associations between THM exposure and neuropsychological outcomes were null, except for total and brominated THM uptake though all routes and the general cognitive score at 4–5 years, with a decrease in − 0.54 points (95%CI − 1.03, − 0.05) and − 0.64 (95%CI − 1.16, − 0.12), respectively, for doubling total and brominated THM uptake. A positive association found between dichloroacetic acid and the mental score at 1 year did not persist at 4–5 years. Conclusions: Minor associations observed between DBP exposure during gestation and child neuropsychological development at 1 year disappeared at 4–5 years. Although a suggestive association is identified for exposure to brominated THMs and the cognitive score at 4–5 years, chance cannot be ruled out. ; This study was funded by Grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), and from Spain: Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, PI041436, FIS-PI042018, 05/1079, 05/1052, 06/1213, FIS-PI06/0867, 07/0314, 081151, 09/02647, 09/02311, 09/00090, 11/0178, 11/02591, 11/02038, 13/1944, 13/2032, 13/02429, 13/02187, 14/0891, 14/1687, CP14/00108, CP16/00261 and Miguel Servet-FEDER MS15/0025, MS13/00054, CP0610034, MS14/00108), CIBERESP (Ref. AA08_012), the Conselleria de Sanitat de la Generalitat Valenciana, Generalitat de Catalunya (CIRIT 1999SGR 00241), Fundació La Marató de TV3 (090430), Obra Social Cajastur/Fundación Liberbank, Universidad de Oviedo, Department of Health of the Basque Government (2005111093, 2009111069, 2013111089 and 2015111065), and the Provincial Government of Gipuzkoa (DFG06/002, DFG08/001 and DFG15/221). Annual agreements with the city council of the study area in Gipuzkoa (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya.

Objectives: We examined the use of low (<400 μg/day, including no use) and high folic acid supplement (FAS) dosages (≥1000 μg/day) among pregnant women in Spain, and explored factors associated with the use of these non-recommended dosages. Design: Population-based cohort study. Setting Spain. Participants We analysed data from 2332 pregnant women of the INMA study, a prospective mother-child cohort study in Spain. Main outcome measures We assessed usual dietary folate and the use of FAS from preconception to the 3rd month (first period) and from the 4th to the 7th month (second period), using a validated food frequency questionnaire. We used multinomial logistic regression to estimate relative risk ratios (RRRs). Results Over a half of the women used low dosages of FAS in the first and second period while 29% and 17% took high dosages of FAS, respectively. In the first period, tobacco smoking (RRR=1.63), alcohol intake (RRR=1.40), multiparous (RRR=1.44), unplanned pregnancy (RRR=4.20) and previous spontaneous abortion (RRR=0.58, lower use of high FAS dosages among those with previous abortions) were significantly associated with low FAS dosages. Alcohol consumption (RRR=1.42), unplanned pregnancy (RRR=2.66) and previous spontaneous abortion (RRR=0.68) were associated with high dosage use. In the second period, only tobacco smoking was significantly associated with high FAS dosage use (RRR=0.67). Conclusions A high proportion of pregnant women did not reach the recommended dosages of FAS in periconception and a considerable proportion also used FAS dosages ≥1000 μg/day. Action should be planned by the Health Care System and health professionals to improve the appropriate periconceptional use of FAS, taking into consideration the associated factors. ; This study was funded by grants from Instituto de Salud Carlos III and Spanish Ministry of Health (Red INMA G03/176; CB06/02/0041; FIS 97/0588; 00/0021–2, PI061756; PS0901958; FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314; 09/02647; FIS-PI041436, FIS-PI081151, FIS-PI06/0867; FIS-PS09/00090, FIS-PI042018, FIS-PI09 02311, FIS PI11/01007, FISPI13/02429) Universidad de Oviedo, Conselleria de Sanitat Generalitat Valenciana, Generalitat de Catalunya-CIRIT 1999SGR 00241, Department of Health of the Basque Government (2005111093 and 2009111069) and the Provincial Government of Guipuzcoa (DFG06/004 and DFG08/001).

BACKGROUND: Prenatal perfluorooctanoate (PFOA) exposure has been associated with reduced birth weight but maternal glomerular filtration rate (GFR) may attenuate this association. Further, this association remains unclear for other perfluoroalkyl substances (PFAS), such as perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA). We estimated associations between prenatal PFAS exposure and birth outcomes, and the influence of GFR, in a Spanish birth cohort. METHODS: We measured PFHxS, PFOS, PFOA, and PFNA in 1st-trimester maternal plasma (years: 2003-2008) in 1202 mother-child pairs. Continuous birth outcomes included standardized weight, length, head circumference, and gestational age. Binary outcomes included low birth weight (LBW), small-for-gestational-age, and preterm birth. We calculated maternal GFR from plasma-creatinine measurements in the 1st-trimester of pregnancy (n=765) using the Cockcroft-Gault formula. We used mixed-effects linear and logistic models with region of residence as random effect and adjustment for maternal age, parity, pre-pregnancy BMI, and fish intake during pregnancy. RESULTS: Newborns in this study weighted on average 3263g and had a median gestational age of 39.8weeks. The most abundant PFAS were PFOS and PFOA (median: 6.05 and 2.35ng/mL, respectively). Overall, PFAS concentrations were not significantly associated to birth outcomes. PFOA, PFHxS, and PFNA showed weak, non-statistically significant associations with reduced birth weights ranging from 8.6g to 10.3g per doubling of exposure. Higher PFOS exposure was associated with an OR of 1.90 (95% CI: 0.98, 3.68) for LBW (similar in births-at-term) in boys. Maternal GFR did not confound the associations. CONCLUSIONS: In this study, PFAS showed little association with birth outcomes. Higher PFHxS, PFOA, and PFNA concentrations were non-significantly associated with reduced birth weight. The association between PFOS and LBW seemed to be sex-specific. Finally, maternal GFR measured early during pregnancy had little influence on the estimated associations. ; This study was funded by grants from the European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), and from Spain: Instituto de Salud Carlos III, Ministry of Health CIBERESP, the Conselleria de Sanitat, Generalitat Valenciana, (Red INMA G03/176; CB06/02/0041; PI041436, PI081151, PI06/0867, PS09/00090, PI13/02187; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/ 02038, PI12/01890, PI13/1944, PI13/2032, PI14/00891, and PI14/1687; pre-doctoral grant PFIS - FI14/00099 and; Miguel Servet-FEDER: CP11/0178 and CPII16/00051), Department of Health of the Basque Government (2005111093 and 2009111069); the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001); and the Generalitat de Catalunya-CIRIT (1999SGR 00241)

This research was funded by grants from Spanish Institute of Health Carlos III-Ministry of Economy and Competitiveness (INMA Network G03/176, CB06/02/0041, and FIS-FEDER: PI03/1615, PI04/1436, PI08/1151,PI04/2018, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI06/0867, PI07/0314, PI09/02647, PS09/00090, PI09/02311, MS11/0178, PI13/1944, PI13/2032, PI14/00891, PI16/1288, and PI17/00663, and Miguel Servet-FEDER: MSII16/00051), Generalitat de Catalunya-CIRIT 1999SGR 00241, JCI-2011–09771–MICINN,Generalitat Valenciana (Conselleria de Sanitat-048/2010 and 060/2010 and FISABIO-UGP 15-230, 15-244, and 15-249), Alicia Koplowitz Foundation (2017), Universidad de Oviedo, Fundación Cajastur-Liberbank, Department of Health of the Basque Government (2005111093 and 2009111069), the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), and the Fundación Roger Torné. This study has been funded by Instituto de Salud Carlos III through the projects "CP14/00108 & PI16/00261" (Co-funded by European Regional Development Fund "A way to make Europe"), Fundació Maratò TV3 (201622 10). Maria-Jose Lopez-Espinosa hold a Miguel Servet contract (MS14/00108, MS13/00054 and MSII16/00051, respectively) awarded by the Spanish Institute of Health Carlos III (Ministry of Economy and Competitiveness).

Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p < 0.05) associated with exposure to particulate matter < 2.5 µm in diameter (PM2.5) at birth, one of them mapping to the MIR1296 gene. Further, by integrating gene expression with DNA methylation using Functional Epigenetic Modules algorithms, we identified 9 and 6 modules in relation to PM2.5 exposure at birth and at current address, respectively (including NR1I2, MAPK6, TAF8 and SCARA3). In conclusion, PM2.5 exposure at birth was linked to differential gene expression in children and adolescents. Importantly, we identified several significant interactome hotspots of gene modules of relevance for complex diseases in relation to PM2.5 exposure. ; European Community's 75 Seventh Framework Program under grant agreement numbers: 211250 (ESCAPE), and 76 261357 (MeDALL) ; European Research Council (grant agreement number 757919, TRIBAL) ; Swedish Research Council ; The Swedish Heart-Lung Foundation, Region Stockholm ; Strategic Research Programme (SFO) in Epidemiology, Karolinska Institutet ; Formas ; Swedish Environment Protection Agency ; Swedish Asthma and Allergy Research Foundation ; Cancer and Allergy Foundation ; Swedish Research Council for Health, Working life and Welfare (FORTE 2017-01146) ; Federal Ministry for Education, Science, Research and Technology ; Helmholtz Zentrum Munich ; Research Institute at Marien-Hospital Wesel, LMU Munich, TU Munich ; Leibniz Research-Institute for Environmental Medicine at the University of Düsseldorf ; Federal Ministry for Environment (IUF Düsseldorf, FKZ 20462296) ; Mead Johnson ; Nestlé ; Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI04/1436; PI06/0867; PI08/1151; and PI18/01142 ; Generalitat de Catalunya-CIRIT 1999SGR 00241 ; Department of Health of the Basque Government (2005111093) ; Provincial Government of Gipuzkoa (DFG06/002) ; Municipalities of the study area (Zumarraga, Urretxu , Legazpi, 101 Azkoitia y Azpeitia y Beasain) ; Accepted

BACKGROUND: Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks. OBJECTIVES: In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation. METHODS: The biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retroviruses (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated.RESULTS: A significant sex interaction was observed for AluYb8 (p-value for interaction <0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p-value<0.001), while no significant effects were found in girls (p-value=0.134). CONCLUSIONS: Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development. ; This work was supported by grants from the Spanish Ministry of Health (FIS-PI042018; FIS-PI060867; FIS-PI081151; FIS-PI09/02311; FIS-PI09/02647; FIS-PI11/00610); Instituto de Salud Carlos III [Red INMA G03/176 and CB06/02/0041]; the EU Commission (QLK4-1999-01422, QLK4-2002-00603 and CONTAMED FP7-ENV-212502), the Generalitat de Catalunya—CIRIT [1999SGR 00241]; the Consejería de Salud de la Junta de Andalucía (183/07 and 0675/10), the Diputación Foral de Gipuzkoa (DFG06/004), the Department of Health of the Basque Government (2005111093), and by the University of Oviedo, Obra Social Cajastur, the Fundación Roger Torné and La Fundació La Marató de TV3. NV was supported by an FPI Grant from the Spanish Ministry of Health (BES-2009-023933) and a Formación de Personal Investigador Grant for Short Research Stays in Foreign Institutions (BES-2009-023933). AA Baccarelli receives support from the Harvard School of Public Health and National Institute of Environmental Health Sciences Center for Environmental Health (R01 ES021357).The HUSC BioBank, integrated in the Andalusia Public Health System (SSPA) and the National Biobank Network, is financed by the Institute of Health Carlos III, (RD09/0076/00148) and the Regional Government of Andalucia