Ferran Ballester

Urinary concentrations of phthalates and phenols in a population of Spanish pregnant women and children

BACKGROUNDnPhthalate and phenol exposure is prevalent among the general population and of potential concern for pregnant women and children because of their suspected susceptibility to endocrine effects.nnnOBJECTIVESnTo evaluate the extent of exposure to several phthalates and phenols in a sample of Spanish pregnant women - according to their individual characteristics (age, social class, education, and body mass index) - and children who participated in the INMA - Infancia y Medio Ambiente (Environment and Childhood) project.nnnMETHODSnOne spot urine sample was taken during the third trimester of pregnancy from 120 pregnant women and from 30 4-year old children belonging to 5 Spanish birth cohorts, and analyzed for 11 phthalate metabolites and 9 phenols.nnnRESULTSnThree metabolites of di(2-ethylhexyl) phthalate, mono-2-ethyl-5-carboxypentyl phthalate, mono-2-ethyl-5-hydroxyhexyl phthalate, and mono-2-ethyl-5-oxohexyl phthalate; two metabolites of dibutyl phthalates, mono-isobutyl phthalate and mono-n-butyl phthalate; monoethyl phthalate (MEP), the main metabolite of diethyl phthalate; and two phenols, methyl paraben (M-PB) and 2,5-dichlorophenol were detected in the urine samples of all women. The highest urinary concentrations were for MEP and M-PB. Urinary concentrations of all phthalate metabolites and of 2,4-dichlorophenol, 2,5-dichlorophenol, and bisphenol A were lower in the pregnant women than in the children. Among women, a positive relationship with social class and education was shown for most of the phthalate metabolites and phenols. Almost all phthalate metabolites varied by region even after adjusting for social class and education.nnnCONCLUSIONSnPhthalate and phenol exposures are prevalent in a group of pregnant women and young children, two susceptible populations, and these exposures might be positively related to social class.

MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine

To cite this article: Bousquet J, Anto J, Auffray C, Akdis M, Cambon‐Thomsen A, Keil T, Haahtela T, Lambrecht BN, Postma DS, Sunyer J, Valenta R, Akdis CA, Annesi‐Maesano I, Arno A, Bachert C, Ballester F, Basagana X, Baumgartner U, Bindslev‐Jensen C, Brunekreef B, Carlsen KH, Chatzi L, Crameri R, Eveno E, Forastiere F, Garcia‐Aymerich J, Guerra S, Hammad H, Heinrich J, Hirsch D, Jacquemin B, Kauffmann F, Kerkhof M, Kogevinas M, Koppelman GH, Kowalski ML, Lau S, Lodrup‐Carlsen KC, Lopez‐Botet M, Lotvall J, Lupinek C, Maier D, Makela MJ, Martinez FD, Mestres J, Momas I, Nawijn MC, Neubauer A, Oddie S, Palkonen S, Pin I, Pison C, Rancé F, Reitamo S, Rial‐Sebbag E, Salapatas M, Siroux V, Smagghe D, Torrent M, Toskala E, van Cauwenberge P, van Oosterhout AJM, Varraso R, von Hertzen L, Wickman M, Wijmenga C, Worm M, Wright J, Zuberbier T. MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine. Allergy 2011; 66: 596–604.

Reproducibility and validity of a food frequency questionnaire among pregnant women in a Mediterranean area

BackgroundStudies exploring the role of diet during pregnancy are still scarce, in part due to the complexity of measuring diet and to the lack of valid instruments. The aim of this study was to examine the reproducibility and validity (against biochemical biomarkers) of a semi-quantitative food frequency questionnaire (FFQ) in pregnant women.MethodsParticipants were 740 pregnant women from a population-based birth cohort study in Valencia (INMA Study). We compared nutrient and food intakes from FFQs estimated for two periods of pregnancy (reproducibility), and compared energy-adjusted intake of several carotenoids, folate, vitamin B12, vitamin C and α-tocopherol of the FFQ in the first trimester with their concentration in blood specimens (validity).ResultsSignificant correlations for reproducibility were found for major food groups and nutrients but not for lycopene (r=0.06); the average correlation coefficients for daily intake were 0.51 for food groups and 0.61 for nutrients. For validity, statistically significant correlations were observed for vitamin C (0.18), α-carotene (0.32), β-carotene (0.22), lutein-zeaxantin (0.29) and β-cryptoxantin(0.26); non-significant correlations were observed for retinol, lycopene, α-tocopherol, vitamin B12 and folate (r≤0.12). When dietary supplement use was considered, correlations were substantially improved for folate (0.53) and to a lesser extent for vitamin B12 (0.12) and vitamin C (0.20).ConclusionThis study supports that the FFQ has a good reproducibility for nutrient and food intake, and can provide a valid estimate of several important nutrients during pregnancy.

Reducing ambient levels of fine particulates could substantially improve health: a mortality impact assessment for 26 European cities

Recently new European policies on ambient air quality—namely, the adoption of new standards for fine particulate matter (PM2.5), have generated a broad debate about choosing the air quality standards that can best protect public health. The Apheis network estimated the number of potential premature deaths from all causes that could be prevented by reducing PM2.5 annual levels to 25 μg/m3, 20 μg/m3, 15 μg/m3 and 10 μg/m3 in 26 European cities. The various PM2.5 concentrations were chosen as different reductions based on the limit values proposed by the new European Directive, the European Parliament, the US Environmental Protection Agency and the World Health Organization, respectively. The Apheis network provided the health and exposure data used in this study. The concentration-response function (CRF) was derived from the paper by Pope et al (2002). If no direct PM2.5 measurements were available, then the PM10 measurements were converted to PM2.5 using a local or an assumed European conversion factor. We performed a sensitivity analysis using assumptions for two key factors—namely, CRF and the conversion factor for PM2.5. Specifically, using the “at least” approach, in the 26 Apheis cities with more than 40 million inhabitants, reducing annual mean levels of PM2.5 to 15 μg/m3 could lead to a reduction in the total burden of mortality among people aged 30 years and over that would be four times greater than the reduction in mortality that could be achieved by reducing PM2.5 levels to 25 μg/m3 (1.6% vs 0.4% reduction) and two times greater than a reduction to 20 μg/m3. The percentage reduction could grow by more than seven times if PM2.5 levels were reduced to 10 μg/m3 (3.0% vs 0.4%). This study shows that more stringent standards need to be adopted in Europe to protect public health, as proposed by the scientific community and the World Health Organization.

Prenatal exposure to residential air pollution and infant mental development: modulation by antioxidants and detoxification factors.

Background: Air pollution effects on children’s neurodevelopment have recently been suggested to occur most likely through the oxidative stress pathway. Objective: We aimed to assess whether prenatal exposure to residential air pollution is associated with impaired infant mental development, and whether antioxidant/detoxification factors modulate this association. Methods: In the Spanish INfancia y Medio Ambiente (INMA; Environment and Childhood) Project, 2,644 pregnant women were recruited during their first trimester. Nitrogen dioxide (NO2) and benzene were measured with passive samplers covering the study areas. Land use regression models were developed for each pollutant to predict average outdoor air pollution levels for the entire pregnancy at each residential address. Maternal diet was obtained at first trimester through a validated food frequency questionnaire. Around 14 months, infant mental development was assessed using Bayley Scales of Infant Development. Results: Among the 1,889 children included in the analysis, mean exposure during pregnancy was 29.0 μg/m3 for NO2 and 1.5 μg/m3 for benzene. Exposure to NO2 and benzene showed an inverse association with mental development, although not statistically significant, after adjusting for potential confounders [β (95% confidence interval) = –0.95 (–3.90, 1.89) and –1.57 (–3.69, 0.56), respectively, for a doubling of each compound]. Stronger inverse associations were estimated for both pollutants among infants whose mothers reported low intakes of fruits/vegetables during pregnancy [–4.13 (–7.06, –1.21) and –4.37 (–6.89, –1.86) for NO2 and benzene, respectively], with little evidence of associations in the high-intake group (interaction p-values of 0.073 and 0.047). Inverse associations were also stronger in non-breast-fed infants and infants with low maternal vitamin D, but effect estimates and interactions were not significant. Conclusions: Our findings suggest that prenatal exposure to residential air pollutants may adversely affect infant mental development, but potential effects may be limited to infants whose mothers report low antioxidant intakes.

Preterm birth and exposure to air pollutants during pregnancy

BACKGROUNDnResearch has shown that prenatal exposure to air pollutants may have a detrimental effect on fetal development, with the strength of the relationship depending on the effect being studied. The evidence to date, however, is insufficient to establish a direct causal link between such exposure and preterm delivery. This study evaluates the specific effect of prenatal exposure to NO(2) and benzene on preterm births.nnnMETHODSnThe population under study comprised 785 pregnant women who formed part of the INMA cohort in Valencia, Spain (2003-2005). Multiple regression models were used for mapping outdoor nitrogen dioxide (NO(2)) and benzene levels throughout the area. Individual exposure was assigned as the estimated outdoor levels at each womans home measured during each trimester as well as throughout the entire pregnancy. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated in order to assess the association between preterm birth and exposure to NO(2) and benzene. The shape of the exposure-response curve between air pollution and the risk of preterm birth was analyzed with a flexible approach, introducing a natural cubic spline for air pollution levels into the model.nnnRESULTSnPregnant women exposed to NO(2) and benzene have an increased risk of preterm birth. This risk was shown to be significant when women were exposed to NO(2) levels >46.2 μg/m(3) during the second and third trimesters as well as throughout the entire pregnancy and to benzene levels >2.7 μg/m(3) throughout the entire pregnancy.nnnCONCLUSIONnThese results suggest that maternal exposure to traffic-related air pollution is associated with preterm birth.

Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity

The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P < 1.67 × 10(-8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.

Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: a Mechanisms of the Development of Allergy (MeDALL) seminar.

Mechanisms of the Development of Allergy (MeDALL), a Seventh Framework Program European Union project, aims to generate novel knowledge on the mechanisms of initiation of allergy. Precise phenotypes of IgE-mediated allergic diseases will be defined in MeDALL. As part of MeDALL, a scientific seminar was held on January 24, 2011, to review current knowledge on the IgE-related phenotypes and to explore how a multidisciplinary effort could result in a new integrative translational approach. This article provides a summary of the meeting. It develops challenges in IgE-related phenotypes and new clinical and epidemiologic approaches to the investigation of allergic phenotypes, including cluster analysis, scale-free models, candidate biomarkers, and IgE microarrays; the particular case of severe asthma was reviewed. Then novel approaches to the IgE-associated phenotypes are reviewed from the individual mechanisms to the systems, including epigenetics, human inxa0vitro immunology, systems biology, and animal models. The last chapter deals with the understanding of the population-based IgE-associated phenotypes in children and adolescents, including age effect in terms of maturation, observed effects of early-life exposures and shift of focus from early life to pregnancy, gene-environment interactions, cohort effects, and time trends in patients with allergic diseases. This review helps to define phenotypes of allergic diseases in MeDALL.

Sociodemographic, reproductive and dietary predictors of organochlorine compounds levels in pregnant women in Spain.

Organochlorine pesticides and polychlorinated biphenyls (PCBs) are consistently found in human tissues. Serum levels of organochlorine compounds (OC) in pregnant women in particular have raised concern about possible harm to humans in the early phases of physical and behavioural development. The objective of the present study was to evaluate the association between concentration of OCs in serum of two cohorts of pregnant women from Gipuzkoa and Sabadell in Spain and socioeconomic, reproductive and dietary variables. Concentration of polychlorinated biphenyls (PCBs: 28, 52, 101, 118, 138, 153 and 180), hexachlorobenzene (HCB), beta and gamma-hexachlorocyclohexane (β-HCH and γ-HCH), heptachlor epoxide, dichlorodiphenyl dichloroethylene (p,p-DDE) and dichlorodiphenyl trichloroethane (p,p-DDT) were measured in the serum of 1259 pregnant women. Associations between OCs and potential predictor variables were assessed using linear regression models adjusted for potential confounders. The compounds most commonly found in the serum were p,p-DDE (99% of the samples) and PCB-153 (95% of the samples). Geometric means of serum concentrations (ng g⁻¹ lipid) of organochlorine pesticides were 110.0, 19.1, and 33.5 for p,p-DDE, β-HCH, and HCB respectively, while the geometric means of PCBs were 21.8, 38.9 and 26.9 for PCB 138, 153, and 180 respectively. The levels of all OCs increased with age. BMI was positively associated with the concentration of organochlorine pesticides but inversely related to PCB concentrations. The serum levels of OCs fell only after a cumulative period of breastfeeding of over a year. Levels of PCBs were related to fish intake, but in general dietary factors did not improve the explained variability of the concentrations of OCs. Overall, the levels of OCs found in the study are at the lower end of the range reported in Spain and other countries.

Concentrations and determinants of organochlorine levels among pregnant women in Eastern Spain

Persistent organic pollutants (POPs) comprise a large variety of toxic substances with ample distribution. While exposure to these toxins occurs mainly through diet, maternal POP levels may be influenced by certain sociodemographic, environmental, or lifestyle factors. This is important given that these substances may have adverse effects on fetal development. The aim of this study is to examine the sociodemographic, environmental, lifestyle, and dietary determinants of the levels of hexachlorobenzene (HCB), b-hexachlorocyclohexane (b-HCH), 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (4,4-DDT), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (4,4-DDE), and polychlorinated biphenyls (PCB congeners 118, 138, 153, 180) measured in the blood of pregnant women participating in a mother-child cohort study conducted in Valencia (Spain). The study population consisted of 541 pregnant women who formed part of the INMA (Childhood and the Environment) cohort (2004-2006). POP levels were determined in blood taken during the 12th week of pregnancy with the aid of gas chromatography with electron capture detection. Sociodemographic, environmental, and dietary information was obtained from a questionnaire. Multivariate Tobit regression models were constructed in order to assess the association between POP levels and selected covariates. The results showed that all the women had detectable levels of at least one of these compounds while in 43% of the subjects, all eight compounds were detected. The compounds found in the greatest number of women were 4,4-DDE (100%) and PCBs 153 and 180 (95%). The most important determinants of high POP levels were the mothers age, country of origin, increased body mass index, and number of weeks of breastfeeding after previous pregnancies. With regard to diet, 4,4-DDT and 4,4-DDE levels increased with the intake of meat, fruit, and cereal. PCB 153 levels increased with the intake of seafood. The levels of HCB, b-HCH, 4,4-DDT, and 4,4-DDE observed in this study were slightly higher than in other studies, whereas the PCB levels were similar.