european birth cohorts overview some lessons from data pooling
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European Birth Cohorts Overview Some lessons from data pooling. Martine Vrijheid. Background. Foetus and infant are especially vulnerable to the effects of environmental contaminants, and that these effects may manifest themselves throughout the lifetime and even over generations. - PowerPoint PPT PresentationTRANSCRIPT
European Birth CohortsEuropean Birth Cohorts
- OverviewOverview- Some lessons from data Some lessons from data poolingpooling
Martine Vrijheid
BackgroundBackground
Foetus and infant are especially vulnerable to the effects of environmental contaminants, and that these effects may manifest themselves throughout the lifetime and even over generations.
In Europe, there are many pregnancy and birth cohorts currently collecting a wealth of information on environmental exposure and child outcomes.
Pregnancy and birth cohort studies have played an important role in studying these effects.
Data are often of fragmented nature and there is relatively little coordination to structure and consolidate scattered research.
Aim
Coordination of European birth cohort research in the area of environmental exposures.
Objectives
• Inventory of birth cohort data
• Evaluate exposure, health and exposure-response data
• Attempt to combine data from various cohorts
• Make recommendations
Methods
• Inventory questionnaires to cohorts
• Working Groups – expert evaluation of cohort data
• Workshops involving all cohorts
ENRIECOENRIECO
Objectives1. Inventory of data from cohorts and registries
2. Evaluation of existing information
3. Recommendations for research action in key areas of policy concern
4. Recommendations for improved contribution of mother-child cohort research to policy at European level
5. Dissemination
AimTo develop a strategy for mother-child cohort research in Europe through the coordination of European cohorts.
Faroes
DNBC
Co.N.ER
INUENDO
Duisburg
EDEN
Generation XXI
FLEHS I
HUMIS
INMA-old
REPRO_PL
KANC
LUKAS
PCB cohortINUENDO
RHEA
Czech
Leicester MAS
NINFEA
GASPII
INUENDO
GINIplus
BAMSE
PÉLAGIE
MoBa
ABCDGeneration R
KOALAPIAMA
LISAplusALSPAC
BiB
Size of circle:
< 1,000
1-5,000
5-20,000
100,000
INMA-new
DARC
PARIS
ArcRisk-Norway
Krákow
37 birth cohorts
T1 T2 T3
Leicester I 1985Faroes 1 1986
MAS 1990ALSPAC 1991
Leicester II 1993BAMSE 1994Faroes 2 1994
Czech 1994GINIplus 1995
DNBC 1996PIAMA 1996Faroes 3 1997
INMA old 1997LISAplus 1997
DARC 1998MoBa 1999
Duisburg 2000KOALA 2000Krákow 2000
Generation R 2001PCB cohort 2001
FLEHS I 2002HUMIS 2002
INUENDO 2002LUKAS 2002
PÉLAGIE 2002ABCD 2003EDEN 2003
GASPII 2003PARIS 2003
Co.N.ER 2004Generation XXI 2004
INMA new 2004NINFEA 2005
ArcRisk-Norway 2007BiB 2007
Faroes 5 2007KANC 2007
REPRO_PL 2007RHEA 2007ELFE 2011
Cohort 18m-5yr 5-10yr 10+ yrStart Pregnancy Birth 1-6m 6-18m
www.birthcohortsenrieco.net
B: blood, CB: cord blood, U: urine, P: placenta, BM: breastmilk, S: saliva, H: hair,
ExposuresExposures
Cohort Metals Persistent Organic Pollutants and other pesticides Tobacco smoking Other chemicals
ALSPAC As, Cd, Hg, Mn, Pb, Se*, TMS
PFCs* cotinine -
ArcRisk-Norway As, Cd, Co, Hg, Mb, Mn , Pb chlordane, DDT/DDE, HCB, PCBs - planned
BAMSE - - cotinine -
Czech - - cotinine PAHs
DNBC - PFCs - -
Duisburg Cd, Hg, Pb, Se DDT/DDE, HCB*, HCH, PCBs, PCDDs, PCDFs, PFCs cotinine* BPA, phthalates
EDEN B, Cd, Mn, Hg, Pb - cotinine phthalates, phenols (incl BPA)
ELFE Al*, As*, Cd*, Hg*, Pb* BFRs*, organochlorines*, PFCs*, PCBs*, PCDDs*, PCDFs*, organophosphates*, pyrethroids*
cotinine* BPA*, phthalates*
Faroes Hg, Pb, Se BFRs*, chlordane, DDT/DDE, dieldrin/endrin, heptachlor, HCB, β-HCH, mirex, organometallic compounds, PCBs, PFCs*, toxaphene
- BPA*, phthalates*
FLEHS I Cd, Pb DDT/DDE, dioxin-like compounds, HCB, PCBs - -
Generation R - organochlorines*, organophosphates - BPA, phthalates
GINIplus - - cotinine -
HUMIS Hg*, Pb* BFRs, DDT/DDE, HCB, HCH, mirex, PCBs, PCDDs, PCDFs, PFCs, toxaphene
- phthalates
INMA old Hg, Pb*, TMS* aldrin/dieldrin/endrin, BFRs, DDT/DDE, endosulphan, lindane, methoxychlor, mirex, HCB, HCH, PCBs
cotinine phthalates, phenols (incl BPA)
INMA new Hg, Pb, TMS* BFRs, DDT/DDE, HCB, HCH, PCBs cotinine phthalates, phenols (incl BPA)
INUENDO Cd*, Hg*, Pb* BFRs*, DDT/DDE, HCB*, PCBs, PFCs* - BPA*, phthalates*
Krákow Cd, Hg, Pb - cotinine Phthalates, PAHs, benzo[a]pyrene-adducts
LISA - - cotinine -
LUKAS As, Cd, Hg, Pb, Se BFRs, DDT/DDE, organometallic compounds, PCBs, PCDDs, PCDFs, polychlorinated naphthalene
- phthalates*
MAS - - cotinine -
MoBa planned BFRs*, DDT/DDE*, PCBs*, organophosphates - BPA, phthalates
NINFEA - - - -
PCB cohort Hg, Pb DDT/DDE, HCB, HCH, PCBs, PFCs* - phthalates*
PÉLAGIE Hg aldrin, BFRs, DDT/DDE, dieldrin/endrin, heptachlor, HCB, PCBs, acetolachlore, alachlore, metolachlore, organophosphorous, propoxur, triazines
- phthalates
REPRO_PL Cd, Hg, Pb, Se, Zn, Cu PCBs, PCDDs, PCDFS cotinine PAHs (1-hydroxypyrene)
RHEA As, Cd, Hg, Mn, Pb DDT/DDE*, HCB*, PCBs*, PCDDs*, PFCs* NNAL, cotinine phthalates*
Exposure BiomarkersExposure Biomarkers
0 5 10 15 20 25 30 35 40
SEXUAL MATURATION
METABOLIC SYNDROME
GROWTH & OBESITY
CANCER
Food allergies
Respiratory infections
Eczema
Allergic rhinitis
Allergies
Asthma
ALLERGIES & ASTHMA
Personality
Mental health
School achievements/performance
Hyperactivity disorders
Autism symptoms
Behaviour
Cognitive function
NEURODEVELOPMENT
Ultrasound measurement
Mode of delivery
Birth weight
Gestational age
Spontaneous abortion/stillbirths/terminations
Congenital anomalies
Time to pregnancy
BIRTH OUTCOMES
Number of cohorts
doneongoingplanned
www.birthcohorts.net
Combining data – ongoing:Combining data – ongoing:
POPs & birth outcomes
Smoking, SHS & asthma and allergies
Alcohol consumption & birth outcomes
Socioeconomic inequalities & birth outcomes
Maternal occupation & birth outcomes
Fish consumption & birth outcomes
Maternal complications & asthma and allergies
Obesity – BMI as predictor of body fat
Other EU projects: air pollution, water DBPs, biological agents, etc.
Govarts et al. 2011. EHP. In Press. Prenatal exposure to polychlorinated biphenyls (PCB) and dichlorodiphenyldichloroethylene (DDE) and fetal growth: a meta-analysis within 12 European birth cohorts.
Association of cord serum concentrations of PCB 153 (ng/L) with birth weight (grams
Case studies to evaluate combined data analyses…
…using the original raw data from European birth cohorts on allergy / asthma
to examine associations between:
indoor environmental exposures (a. dampness/mould; b. second hand tobacco smoke)
allergies
(asthma, allergic rhinitis, eczema)Courtesy: Thomas Keil
Step 1: Willingness to participate
Step 2: Assess eligibility of cohorts
Step 3: Collect individual participant data
Step 4: Harmonise data
Step 5: Perform analyses (indiv. cohorts and meta-a.)
Courtesy: Thomas Keil
Step 1: Willingness to participate
Trust building
- Personal contact, if possible
- Transparency throughout (propose analysis strategy,
discuss analysis plan, agree!, abstracts, publications)
- Regular information on progress
Courtesy: Thomas Keil
Cohorts in WG 1 (dampness/mould)
1. ALSPAC2. BAMSE3. CO.N.ER4. DARC5. GINI6. KOALA7. Leicester8. LISA9. MAS10. NINFEA11. PIAMA-NHS
Cohorts in WG 2 (smoke+asthma 4-6y)
1. ALSPAC2. AMICS3. BAMSE4. DARC5. GINI6. PIAMA-NHS7. KOALA8. Leicester9. LISA10. MAS
Cohorts in WG 3(smoke+wheeze 0-2y)
1. ALSPAC2. AMICS3. BAMSE4. CO.N.ER5. DARC6. Generation R7. GINI8.-11. INMA A, G, S, V 12. KOALA13. Leicester14. LISA15. MAS16. NINFEA17. PIAMA-NHS18. EDEN19. RHEA
Step 2: Eligibility of Cohorts
Courtesy: Thomas Keil
Step 3: Delays in data collection process because of
• Variables not send in correct order• Labels did not often include the whole translated
questions• Half of the variables were wrongly or not
translated at all• Plausibility checks showed categories were
sometimes wrong (eg non-smokers with 10 cig/day)
Courtesy: Thomas Keil
Step 4: Data Harmonization
Homogeneous data only for some outcome variables (ISAAC questions were often modified)
Very heterogeneous data for:- Main exposures (mould/dampness, smoking)- Potential confounders (breast feeding, smoking, educational level etc)
- Variation in time points of exposure and follow-up assessment
Courtesy: Thomas Keil
Adjusted for sex, parental asthma, parental education, birth weight and older siblings.
Prenatal second hand smoke exposure and asthma age 4-6 years
NOTE: Weights are from random effects analysis
Overall (I-squared = 0.0%, p = 0.444)
LISA
PIAMA
MAS
DARC
BAMSE
AMICS-M
cohort
1.47 (1.22, 1.78)
1.67 (0.90, 3.10)
1.10 (0.73, 1.66)
2.83 (1.29, 6.19)
1.55 (0.56, 4.29)
1.50 (1.16, 1.94)
1.48 (0.71, 3.08)
ES (95% CI)
100.00
9.32
20.83
5.82
%
3.44
53.93
6.65
Weight
1.47 (1.22, 1.78)
1.67 (0.90, 3.10)
1.10 (0.73, 1.66)
2.83 (1.29, 6.19)
1.55 (0.56, 4.29)
1.50 (1.16, 1.94)
1.48 (0.71, 3.08)
ES (95% CI)
100.00
9.32
20.83
5.82
%
3.44
53.93
6.65
Weight
1.162 1 6.19
Step 5: Data Analyses
Courtesy: Thomas Keil
What went well?• Kick-Off Meeting successful to establish personal contacts
and interest in case studies.
• Key responsibility for coordination and communication
concentrated in one institution; with a single data
collection and harmonization process.
• Complex data questions solved by telephone contacts with
most cohorts in a fast and uncomplicated way.
Courtesy: Thomas Keil
What were the challenges?
- Time and effort for data management were
underestimated
- Heterogeneity of outcome data
- Heterogeneity of exposure data
- Frequent meetings and personal contacts essential
Compromises for outcome and exposure variables result in loss of information in harmonized datasets.
Courtesy: Thomas Keil
LessonsLessons More than 35 birth cohorts in Europe, studying more than 350 000 mother-child pairs
Data and methods are fragmented
Combining information is possible and scientifically beneficial
Combining data from existing cohorts requires careful consideration of the aims, protocols, data, ethical issues, analyses and management
it is time and labour intensive.
Future??Future??
Flexible and long-term platform/network/infrastructure for combined studies for exchange of methods/expertise
Flexible to inclusion of new cohorts
Expansion to countries outside Europe
This will only be possible with continued support for coordination.
CollaboratorsCollaboratorsProject PI: Mark Nieuwenhuijsen (CREAL)Postdoc: Maribel Casas (CREAL)WP leaders: Martine Vrijheid, Ulrike Gehring, Remy Slama, Joachim
Heinreich, Thomas Keil, Manolis Kogevinas
Cohort representatives: Anna Bergström, Amanda Carmichael, Sylvaine Cordier, Merete Eggesbø, Esben Eller, Maria P Fantini, Marieta F Fernández, Ana Fernández-Somoano, Regina Grazuleviciene, Cynthia Hohmann, Anne M Karvonen, Gudrun Koppen, Ursula Krämer, Claudia E Kuehni, Per Magnus, Renata Majewska, Anne Marie Nybo Andersen, Evridiki Patelarou, Maria Skaalum Petersen, Frank H Pierik, Kinga Polanska, Daniela Porta, Lorenzo Richiardi, Ana Cristina Santos, Radim J Sram, Carel Thijs, Christina Tischer, Gunnar Toft, Tomáš Trnovec, Stephanie Vandentorren, Tanja GM Vrijkotte, Michael Wilhelm, John Wright
The full evaluation reports are publically available through the ENRIECO website: www.enrieco.orgInventory: www.birthcohortsenrieco.net
www.chicosproject.eu
Project PI: - Martine VrijheidPartners: • ALSPAC cohort (Bristol, UK) - Debbie Lawlor, Particia Lucas
• Danish National Birth Cohort - Anne-Marie Nybo Andersen
• Generation R cohort (Netherlands) - Vincent Jaddoe, Hein Raat, Johan de Jongste, Liesbeth Duijts
• INMA cohort (Spain) - Jordi Sunyer, Mark Nieuwenhuijsen
• MoBa cohort (Norway) - Camilla Stoltenberg, Per Magnus
• NINFEA cohort (Turin) - Franco Merletti, Lorenz Richiardi
• RHEA cohort (Crete) - Manolis Kogevinas, Leda Chatzi