Birth weight and prenatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE): a meta-analysis within 12 European Birth Cohorts.

OBJECTIVES: Exposure to high concentrations of persistent organochlorines may cause fetal toxicity, but the evidence at low exposure levels is limited. Large studies with substantial exposure contrasts and appropriate exposure assessment are warranted. Within the framework of the EU (European Union) ENRIECO (ENvironmental Health RIsks in European Birth Cohorts) and EU OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life) projects, we examined the hypothesis that the combination of polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) adversely affects birth weight. METHODS: We used maternal and cord blood and breast milk samples of 7,990 women enrolled in 15 study populations from 12 European birth cohorts from 1990 through 2008. Using identical variable definitions, we performed for each cohort linear regression of birth weight on estimates of cord serum concentration of PCB-153 and p,p´-DDE adjusted for gestational age and a priori selected covariates. We obtained summary estimates by meta-analysis and performed analyses of interactions. RESULTS: The median concentration of cord serum PCB-153 was 140 ng/L (range of cohort medians 20-484 ng/L) and that of p,p´-DDE was 528 ng/L (range of cohort medians 50-1,208 ng/L). Birth weight decreased with increasing cord serum concentration of PCB-153 after adjustment for potential confounders in 12 of 15 study populations. The meta-analysis including all cohorts indicated a birth weight decline of 150 g [95% confidence interval (CI): -250, -50 g] per 1-µg/L increase in PCB-153, an exposure contrast that is close to the range of exposures across the cohorts. A 1-µg/L increase in p,p´-DDE was associated with a 7-g decrease in birth weight (95% CI: -18, 4 g). CONCLUSIONS: The findings suggest that low-level exposure to PCB (or correlated exposures) impairs fetal growth, but that exposure to p,p´-DDE does not. The study adds to mounting evidence that low-level exposure to PCBs is inversely associated with fetal growth.

Biomonitoring and biomarkers to unravel the risks from prenatal environmental exposures for later health outcomes.

An increasing number of studies have addressed the concern that environmental pollutants may contribute to the early origin of diseases. Epidemiologic studies suggest that prenatal exposure to air pollutants, several food contaminants, and chemicals present in consumer products are associated with nongenetically transmitted adverse health effects, which manifest after birth. Changes in neurobehavior, sexual development, the prevalence of asthma and allergy, and growth curves have been shown to be associated with pollutant exposure at early life stages. This review focuses on human molecular epidemiologic studies that contribute knowledge by introducing biomarker measurements to obtain a mechanistic understanding of the relation between early life exposures and health outcome. It has been hypothesized that subtle effects induced by pollutant exposure during development can lead to functional deficits and altered programming, which leads to increased disease or dysfunction risk later in life. Biomarker analysis may provide sensitive tools to trace these subtle changes and obtain mechanistic insight about the causal pathway between external exposure and health effects in human population studies. Biomarkers of exposure can be measured in mothers before conception, during pregnancy, or after birth. Different biological tissues-such as peripheral or cord blood samples, hair samples, meconium, and urine-provide specific information that reflects the actual dose during pregnancy or at birth. Biomarkers of effect may include changes in hormone concentrations, oxidative stress variables, changes in gene expression levels, and epigenetic changes.

Application of non-invasive biomarkers in a birth cohort follow-up in relation to respiratory health outcome.

Asthma-related symptoms can manifest in children during the early years, but only some of the children will develop the disease. This feasibility study showed that it is possible to apply non-invasive markers (in urine, exhaled nitric oxide (FENO) and exhaled breath condensate (EBC)) in 3-year-old children, and evaluated the biomarkers in relation to health outcomes and potential modifiers. FENO was correlated with respiratory allergy, and was borderline significantly correlated with wheezing, but not with the asthma predictive index (mAPI). EBC pH and urinary 8-oxo-deoxyguanosine were not significantly correlated with these clinical outcomes. An EBC proteolytic peptide pattern was developed, which could distinguish between mAPI-positive and -negative children. Non-invasive biomarkers may become a promising tool for investigating respiratory health in children but further research is needed.

Non-invasive biomarker sampling and analysis of the exhaled breath proteome.

Exhaled breath condensate (EBC) is a biological fluid that contains trace amounts of secreted pulmonary proteins, and is emerging as a potentially valuable and non-invasively obtained source of disease biomarkers. Proteome analysis of these samples could lead to the identification of prognostic indicators of airway diseases. The objective of this study was to develop a protocol for proteome analysis of EBC samples. In this report, an improved procedure for EBC sample preparation and concentration is presented, together with a method for comparison of the protein profiles between two groups. The presented approach enabled to study the condensed exhaled breath proteome for biomarker analysis, and revealed proteins not previously identified in an EBC proteomics approach. In a comparative pilot study, EBC protein profiles obtained from smokers and non-smokers showed distinct differences and are illustrative for its potential in clinical studies. EBC from smokers contained higher concentrations of the more abundant proteins, such as cytokeratins, compared to non-smokers, and calgranulin B was identified uniquely in EBC samples from smokers.

The allergic cascade: review of the most important molecules in the asthmatic lung.

Asthma is the most common chronic inflammatory disorder of the airways among children. It is a complex clinical disease characterized by airway obstruction, airway inflammation and airway hyperresponsiveness to a variety of stimuli. The development of allergic asthma exists of three phases, namely the induction phase, the early-phase asthmatic reaction (EAR) and the late-phase asthmatic reaction (LAR). Each phase is characterized by the production and interplay of various cell-derived mediators. In the induction phase, T helper cytokines are important in the development of asthma. Most important mediators in the EAR are preformed mediators, newly synthesized lipid mediators and cytokines that are produced by mast cells. During the LAR, inflammatory molecules are produced by various cell types, such as eosinophils, neutrophils, T cells, macrophages, dendritic cells, and structural cells. Chronical inflammation leads to structural changes of the airway architecture. In this review, the most important mediators involved in the induction phase, the early-phase and late-phase asthmatic reaction are discussed.