European mother-child cohort studies

Transcription

1 European mother-child cohort studies Lisbeth E. Knudsen & Marie Pedersen University of Copenhagen, Institute of Public Health European Conference on Human Biomonitoring contribution of research Paris November the 5 th 2008 Outline Critical windows of exposures and vulnerability Pros and cons of using mother-child cohorts for biomonitoring Collaboration on existing and new cohorts NewGeneris an example of a research collaboration using mother-child cohorts Perspectives

2 Critical windows of exposures and vulnerability The unborn and newborn child is of increased susceptible to adverse exposures due to rapid development and growth, immature metabolism, immune system, neurological and reproductive system, etc. Induction of DNA damage early in life may increase the risk of development of chronically diseases such as cancer later in life There are gaps in our understanding of the potential links between maternal exposures, in uterus exposures and adverse health effects Critical periods in human development (Needham L. et al., 2008)

3 Public concerns a lack of internal exposure data 42 maternal blood samples and 27 umbilical cord blood samples March families from 12 EU countries Oct 2005 incl. Belgium, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Latvia, Luxembourg, Poland and Sweden PFOS

4 !"#$#% & '(') (Monroy et al.2008)

5 Pros of using mother-child cohorts for biomonitoring Provide essential data for perinatal epidemiological studies including studies on environment - life style - gene interactions Potentials for follow-up & nested case-control studies Evidence for future prevention of adverse environmental exposure early in life and optimizations of health recommendations? Cons of using mother-child cohorts for biomonitoring Large sample sizes are required for the case-control (e.i., most cost-efficient way to utilize biological samples from cohort studies) Data and samples are not always available for biomonitoring or processed in the optimized way Ethical issues of future use may not be foreseen at time of informed consent "

6 ~ participants in different European birth cohorts aims to facilitate collaborations The idea behind is to encourage collaborative studies focusing on a specific genotoxic exposure or on a specific outcome suspected to arise from gene-environment interactions Advantages of this approach would be feasibility and low costs A prerequisite for this strategy is that the cohorts are well documented and that information about design and data on the existing cohorts is collected in a comparable form and easily accessible #

7 provides information on cohorts - such as which biological samples are within the cohorts *

8 Collaboration on existing and new cohorts is needed To increase statistical power to evaluate new hypotheses, sufficient know-how, and a wide spectrum of exposures, diseases, and genetic backgrounds To allow for selective sampling for outcomes, exposures and genetic traits using cohort or nested case-control designs could be done so as to maximize efficiency To replicate results Differences in contextual and environmental factors between populations are obvious and prominent, and these differences are valuable when biological pathways are to be distinguished from social pathways (Kogevinas et al., 2004) Collaboration may be an alternative to large new cohorts The existing birth cohorts are heterogeneous in design and focus, but for specific purposes data from multiple cohorts could be successfully pooled together The number of existing and planned mother-child cohorts is increasing In principle, any group of children followed over time or with a possibility to be followed up, and for whom any kind of information on their mother was collected, could create a mother-child cohort. Also, intervention studies carried out during pregnancy are potential mother-child cohorts

9 NewGeneris - Newborns and Genotoxic exposure risks Development and application of biomarkers of dietary exposure to genotoxic and immunotoxic chemicals, and of biomarkers of early effects, using mother-child birth cohorts and biobanks Existing mother-child cohorts in Norway (MoBa), Denmark (DNBC), Spain (IMNA), United Kingdom (UK women & BiB) and new mother-child cohorts in Greece (RHEA) and Denmark (DKB) ~1000 mother-child pairs will donate samples for measurements of biomarkers related to the FFQs etc. and early biological effects such as heterocyclic amines, nitroamines, vitamins, dioxin and dioxin-like activity, hemoglobin adducts, gene expression profiles, proteomics, DNA damage & repair, DNA adducts, micronuclei and genotypes of selected SNPs Collection of maternal and fetal blood at the time of birth - logistics and preliminary results Lisbeth E. Knudsen*, Tina Mose, Marie Frederiksen, Marie Pedersen and Franco D. Merlo Institute of Public Health, University of Copenhagen, Denmark and National Institute for Cancer research, Genova, Italy * Correspondences: L.Knudsen@pubhealth.ku.dk This poster presents our experiences on collection and processing of blood samplings from pregnant women and placenta (Figure 1). In extension of the ongoing ex vivo human placenta perfusion studies in Copenhagen the collection of pairs of maternal peripheral blood and umbilical cord blood samples a long with an extensive maternal questionnaire was launched by the end of 2006 for pilot studies within NewGeneris (Newborns & Genotoxic exposure risks), an integrated project 6th FP (FOOD-CT ) (Figure 2). Figure 2. The geno- and immuno-toxic exposures of interest; (e.g., polycyclic aromatic hydrocarbons (BaP), heterocyclic amines (IQ & PhIP), acrylamides (monoacrylamide),nitrosamines (NDMA), myco-toxins (AFB1 & DON), nonylphenol (NP), organochlorins (TCDD & PCB 153), DNA reactive aldehydes (4-HNE & MDA), and alcohol). The general aim of this Danish mother-child biobank is to provide biological samples from healthy pregnant women adequately processed and stored, that will enable measurements of a range of existing and new biomarkers. No follow-up of study participants is included. Blood samples are collected and processed for the measurements of exposures and early effects related to environmental exposures through maternal nutrition during pregnancy (Figure 3). Figure 1. A schematic overview of the common protocol on the processing of maternal blood and umbilical cord blood. Recommendations Figure 3. An overview of the biomarkers included in NewGeneris The Danish biobank has been developed related to ongoing projects with placental perfusion studies and two PhD programs including environmental monitoring of exposures to air pollution. Invitation of participants Agreements on blood samplings and collection of samples sets demands on logistics as well as the processing, storage and distribution of samples Development of novel biomarkers Acknowledgements European Conference on Human Biomonitoring contribution of research Paris November the 5 th 2008 The following financial contributions are acknowledged: NewGeneris (Contract no. FOOD-CT ), The Danish Research Council of Health and Disease (Contract no ) and the Faculty of Health, University of Copenhagen (PhD stipendium for Marie Pedersen). +

10 Perspectives Background exposure levels Age differences Gene-environment-life style interactions Harmonized/comparable protocols for data collections - Informed consent - Questionnaires - Sample collections - Analyses - Data reporting - Disseminations Data sharing (I4C) Acknowledgements ChildrenGenoNetwork (QLK4-CT ) NewGeneris (FOOD-CT ) ESBIO (SSPE )