Urban environment during early-life and blood pressure in young children

Background: The urban environment is characterised by many exposures that may influence hypertension development from early life onwards, but there is no systematic evaluation of their impact on child blood pressure (BP). Methods: Systolic and diastolic blood pressure were measured in 4,279 children aged 4-5 years from a multi-centre European cohort (France, Greece, Spain, and UK). Urban environment exposures were estimated during pregnancy and childhood, including air pollution, built environment, natural spaces, traffic, noise, meteorology, and socioeconomic deprivation index. Single- and multiple-exposure linear regression models and a cluster analysis were carried out. Results: In multi…

Association of Gestational Weight Gain With Adverse Maternal and Infant Outcomes

Importance: Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. Objectives: To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. Design, setting, and participants: Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated…

Mechanisms of the Development of Allergy (MeDALL) : Introducing novel concepts in allergy phenotypes

Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non–IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Q…

WITHDRAWN: Scaling up strategies of the Chronic Respiratory Disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3 – Area 5)

Does early onset asthma increase childhood obesity risk? A pooled analysis of 16 European cohorts

The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3-4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3-4 years of age.Children with ph…

Variations in the prevalence of childhood asthma and wheeze in MeDALL cohorts in Europe.

While there is evidence for variations in prevalence rates of childhood wheeze and asthma between countries, longitudinal, individual-level data are needed to understand these differences. The aim of this study was to examine variations in prevalence rates of childhood asthma, wheeze and wheeze with asthma in Europe. We analysed datasets from 10 MeDALL (Mechanisms of the Development of ALLergy) cohorts in eight countries, representing 26 663 children, to calculate prevalence rates of wheeze and asthma by child age and wheeze with asthma at age 4 years. Harmonised variables included outcomes parent-reported wheeze and parent-reported doctor-diagnosed asthma, and covariates maternal education…

Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

AbstractBirth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an individual’s own genotype on BW and subsequent disease risk from indirect effects of their mother’s correlated genoty…

Prenatal exposure to phenols and lung function, wheeze, and asthma in school-age children from 8 European birth cohorts

Prenatal exposure to phenolic compounds, widely used in many consumer products, can alter lung development and increase the risk of respiratory disorders in the offspring. However, evidence is scarce and mostly focused on bisphenol-A (BPA), although there are other substitutes that could also interfere with the developing respiratory system. We aim to estimate the association between exposure to 5 phenols during pregnancy (BPA, BPAF, BPB, BPF, and BPS) and lung function, wheeze, and asthma in school-age children. We included 2685 mother-child pairs from 8 European birth cohorts. Phenols concentrations were determined in urinary maternal samples collected during pregnancy (1999-2010). Betwee…

Urban environment and cognitive and motor function in children from four European birth cohorts

[EN]Background: The urban environment may influence neurodevelopment from conception onwards, but there is no evaluation of the impact of multiple groups of exposures simultaneously. We investigated the association between early-life urban environment and cognitive and motor function in children. Methods: We used data from 5403 mother-child pairs from four population-based birth-cohorts (UK, France, Spain, and Greece). We estimated thirteen urban home exposures during pregnancy and childhood, including: built environment, natural spaces, and air pollution. Verbal, non-verbal, gross motor, and fine motor functions were assessed using validated tests at five years old. We ran adjusted multi-e…

Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth A Systematic Review and Meta-analysis

Preterm birth complicates 5% to 15% of births worldwide, and although it is the most important direct cause of morbidity and mortality in children younger than 5 years, no known risk factors can be identified in the majority of cases. However, overt hypothyroidism and hyperthyroidism during pregnancy are well-known risk factors for preterm birth, and as such, the purpose of this study was to assess whether thyroid function test abnormalities and thyroid peroxidase (TPO) antibody positivity were associated with preterm birth. The study conducted a systematic review on the association of thyroid function or autoimmunity with preterm birth published from database inception to March 18, 2018, w…

DNA methylation in childhood asthma

Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4–5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially m…

Influence of fetal glutathione S-transferase copy number variants on adverse reproductive outcomes

A nested case-control association study was designed to investigate the influence of maternal and fetal copy number variants (CNVs) on reproductive outcomes. Genotypes of ten CNVs encompassing GST and CYP genes were assessed. Significant associations were only found for child CNV genotypes. In particular, the child GSTM1 insertion allele was associated with prematurity protection (odds ratio, 95% CI: 0.67, 0.51-0.89; P < 0.01), whereas the child GSTT2B insertion allele was associated with an increased risk of being small for gestational age (odds ratio, 95% CI: 1.33, 1.07-1.67; P = 0.01). The study highlights the role of the fetal genome in prenatal development and also the need to analyse …

Air Pollution During Pregnancy and Childhood Cognitive and Psychomotor Development: Six European Birth Cohorts

Background: Accumulating evidence from laboratory animal and human studies suggests that air pollution exposure during pregnancy affects cognitive and psychomotor development in childhood. Methods: We analyzed data from 6 European population-based birth cohorts-GENERATI ON R (The Netherlands), DUISBURG (Germany), EDEN (France), GASPII (Italy), RHEA (Greece), and INMA (Spain)-that recruited mother-infant pairs from 1997 to 2008. Air pollution levels-nitrogen oxides (NO2, NOx) in all regions and particulate matter (PM) with diameters of <2.5, <10, and 2.5-10 mu m (PM2.5, PM10, and PMcoarse, respectively) and PM2.5 absorbance in a subgroup-at birth addresses were estimated by land-use regressi…

Associations between air pollution and pediatric eczema, rhinoconjunctivitis and asthma: A meta-analysis of European birth cohorts

Background: Uncertainly continues to exist regarding the role of air pollution on pediatric asthma and allergic conditions, especially as air pollution levels have started to decrease in recent decades. Objective: We examined associations of long-term air pollution levels at the home address with pediatric eczema, rhinoconjunctivitis and asthma prevalences in five birth cohorts (BIB, EDEN, GASPII, RHEA and INMA) from seven areas in five European countries. Methods: Current eczema, rhinoconjunctivitis and asthma were assessed in children aged four (N = 6527) and eight years (N = 2489). A multi-morbidity outcome (≥2 conditions versus none) was also defined. Individual outdoor levels of nitrog…

Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts

ObjectiveTo assess the separate and combined associations of maternal pre‐pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact.DesignIndividual participant data meta‐analysis of 39 cohorts.SettingEurope, North America, and Oceania.Population265 270 births.MethodsInformation on maternal pre‐pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used.Main outcome measuresGestational hypertension, pre‐eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth.ResultsHigher maternal pre‐pregnancy BMI and gesta…

Fish and seafood consumption during pregnancy and the risk of asthma and allergic rhinitis in childhood

Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis. Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence was collected using validated questionnaires. The time periods of interest were: infancy (0-2 ye…

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 a…

Prenatal exposure to PCB-153, p,p'-DDE and birth outcomes in 9000 mother-child pairs: exposure-response relationship and effect modifiers.

Low-level exposure to polychlorinated biphenyl-153 (PCB-153) and dichlorodiphenyldichloroethylene (p-p′-DDE) can impair fetal growth; however, the exposure–response relationship and effect modifiers of such association are not well established. This study is an extension of an earlier European meta-analysis. Our aim was to explore exposure–response relationship between PCB-153 and p-p′-DDE and birth outcomes; to evaluate whether any no exposure–effect level and susceptible subgroups exist; and to assess the role of maternal gestational weight gain (GWG). We used a pooled dataset of 9377 mother–child pairs enrolled in 14 study populations from 11 European birth cohorts. General additive mode…

Changes in parental smoking during pregnancy and risks of adverse birth outcomes and childhood overweight in Europe and North America

Background Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. Methods and findings We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/bir…

Association of Exposure to Ambient Air Pollution With Thyroid Function During Pregnancy

Key Points Question Is exposure to ambient air pollution in the first trimester associated with thyroid function throughout pregnancy? Findings Among 9931 pregnant women in 4 European cohorts and 1 US cohort, an increase of 5 μg/m3 in exposure to particulate matter with an aerodynamic diameter of 2.5 μm or less was associated with 20% higher odds of hypothyroxinemia. Meaning The findings of this study raise the possibility that exposure to particulate matter might disrupt thyroid function in pregnant women.

Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: An individual participant data meta-analysis

Background Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. Methods and findings We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, No…

Paving the way of systems biology and precision medicine in allergic diseases: the Me DALL success story

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sen…

Influence of the Urban Exposome on Birth Weight

Background: The exposome is defined as the totality of environmental exposures from conception onwards. It calls for providing a holistic view of environmental exposures and their effects on human health by evaluating multiple environmental exposures simultaneously during critical periods of life. Objective: We evaluated the association of the urban exposome with birth weight. Methods: We estimated exposure to the urban exposome, including the built environment, air pollution, road traffic noise, meteorology, natural space, and road traffic (corresponding to 24 environmental indicators and 60 exposures) for nearly 32,000 pregnant women from six European birth cohorts. To evaluate associatio…

Fish Intake in Pregnancy and Child Growth: A Pooled Analysis of 15 European and US Birth Cohorts

Importance Maternal fish intake in pregnancy has been shown to influence fetal growth. The extent to which fish intake affects childhood growth and obesity remains unclear. Objective To examine whether fish intake in pregnancy is associated with offspring growth and the risk of childhood overweight and obesity. Design, Setting, and Participants Multicenter, population-based birth cohort study of singleton deliveries from 1996 to 2011 in Belgium, France, Greece, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, Spain, and Massachusetts. A total of 26 184 pregnant women and their children were followed up at 2-year intervals until the age of 6 years. Exposures Consumption of fish dur…

Maternal and fetal genetic contribution to gestational weight gain

Background: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. Participants and methods: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspri…

The Urban Exposome during Pregnancy and Its Socioeconomic Determinants

Background: The urban exposome is the set of environmental factors that are experienced in the outdoor urban environment and that may influence child development. Objective: The authors’ goal was to describe the urban exposome among European pregnant women and understand its socioeconomic determinants. Methods: Using geographic information systems, remote sensing and spatio-temporal modeling we estimated exposure during pregnancy to 28 environmental indicators in almost 30,000 women from six population-based birth cohorts, in nine urban areas from across Europe. Exposures included meteorological factors, air pollutants, traffic noise, traffic indicators, natural space, the built environment…

Environmental Risk Score of subclinical Psychopathology risk in children

Current knowledge on environmental causation for psychiatric disorders suggests a complex picture with a multitude of social, physical and chemical exposures occurring at different stages of life. ...

Shared DNA methylation signatures in childhood allergy: The MeDALL study

Contains fulltext : 232514.pdf (Publisher’s version ) (Open Access) BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema. OBJECTIVE: We sought to identify DNA methylation profiles associated with childhood allergy. METHODS: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discove…

Postnatal weight growth and trihalomethane exposure during pregnancy.

Abstract Background Impaired postnatal growth after chloroform exposure in utero has been observed in rodents without an effect on birth weight. We aimed to study the relationship between exposure to trihalomethanes (THMs) during pregnancy and postnatal weight growth during infancy. Methods We analysed 2216 mother–child pairs recruited in Gipuzkoa, Sabadell, Valencia (Spain, INMA Project, enrolment: 2003–2008) and Crete (Greece, RHEA Study, enrolment: 2007–2008). Drinking water habits and water-related activities ascertained through personal interviews were combined with THM measurements in drinking water to estimate THM exposure through different exposure routes during pregnancy. Weight me…

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother–child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03–1.20) compared with unexposed children. Risk of wheeze was further …