Grantee Research Project Results
2005 Progress Report: Children's Vulnerability to Environmental Immunotoxicant Exposure
EPA Grant Number: R830758Title: Children's Vulnerability to Environmental Immunotoxicant Exposure
Investigators: Grandjean, Philippe , Weihe, Pal
Institution: Harvard University
EPA Project Officer: Aja, Hayley
Project Period: May 5, 2003 through May 4, 2006 (Extended to May 4, 2007)
Project Period Covered by this Report: May 5, 2005 through May 4, 2006
Project Amount: $750,000
RFA: Children's Vulnerability to Toxic Substances in the Environment (2002) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
The objective of this research project is to determine the immunotoxic risk in children exposed prenatally and postnatally to polychlorinated biphenyls (PCBs). Experimental animal studies with Aroclor 1254, used by the U.S. Environmental Protection Agency (EPA) for calculating a reference dose (RfD) for PCBs, suggest that immunotoxicity may be critical, but current exposures, especially those from breast-feeding, greatly exceed the RfD.
Progress Summary:
The research project was started as planned, and the approved protocol has been followed without any necessary changes. Thus, the procedures of contacting subjects, informed consent, blood sampling, and clinical examination have not deviated in any way from the approved grant proposal. To date, the birth cohort followup for age 5 is complete and has achieved the following accomplishments:
The total cohort was comprised of 656 Faroese children (including seven sets of twins), 547 of which were funded by EPA as the main cohort, who had a nitric oxide synthase examination at 2 weeks of age, and also had data on mercury and persistent organic pollutant (POP) exposure at birth. (Additional funds for the other children were provided by the Arctic Environment Program and the Danish Environmental Protection Agency.)
At age 5 years, 505 of the main cohort children participated in the follow-up examinations (92%). We obtained a blood sample (before vaccination) from 485 of these cohort members (88%). We subsequently obtained a blood sample approximately 4 weeks after vaccinations from 398 of these children (82%).
In total, we were able to draw blood from 557 of 594 participating children. These results are quite satisfactory. Some of the children and their parents decided in advance not to take the blood test, but this was after they underwent the examination. Others decided not to take the blood test at the time of the examination; we tried but did not succeed to draw blood after first and sometimes repetitive tries, despite the best efforts of the technician.
The reasons for not participating in the followup (for the total of 42 nonparticipants of the main cohort) are:
- Moved to Denmark (18).
- Moved to Iceland (1) and Spain (1) .
- Retracted from the study, no reason revealed (13).
- Did not want to participate in the 5-year examination, though perhaps later on (8).
- Fear of needles (1).
At the second follow-up examination, blood tests were done at about 4-6 weeks subsequent to the scheduled 5-year vaccinations. In this case, we succeeded to get blood samples from 458 cohort members.
In connection with the first blood test, we aimed at securing 30 mL of blood from the children:
- 5 mL of blood was for mercury analysis.
- 5 mL of whole blood was for hematological examination.
- 2 mL serum was for POP analysis.
- 1 mL serum was for vaccination antibody response.
- 1 mL serum was for IgE.
- 2 x 2 mL was for C-reactive protein, IgA–M, albumin, bilirubin, tryglycerides, and cholesterol.
We also obtained a hair sample for mercury analysis.
With the second blood test, we took only 5 mL of blood in a single vial, which, after centrifugation, revealed the 2 mL of serum needed for antibody concentration measurement.
Samples of blood and hair were transferred to the Department of Environmental Medicine at the University of Southern Denmark (SDU), and the results have been reported (Table 1).
Table 1. Hair and Blood Mercury Levels
| 60 months | N |
Minimum |
Maximum |
Mean |
Std. Deviation |
Blood mercury |
554 |
00 |
36.5 |
4.02 |
4.17 |
Hair mercury |
580 |
89 |
9.48 |
2.10 |
1.24 |
These results are in accordance with expectation.
The PCB analyses at SDU have not yet been completed but are expected in August 2006.
Vials from the first examination have been transferred to the analytical laboratory at Statens Serum Institut, which will conduct the antibody measurements. These assessments have been delayed because of the lack of capacity at the immunology laboratory, but results should be completed in August 2006.
Stored maternal pregnancy serum for AhR activation assays has been transferred to the laboratory at Boston University, and the analyses have been initiated. Samples storage is otherwise maintained in the Faroes.
Although no results can be reported at this stage, the project is moving forward as anticipated in accordance with the time schedule. The participation rates are considered highly satisfactory.
The 7-year examination of Cohort 3 children for this project has been initiated (with support from the National Institute of Environmental Health Sciences). Although no project results can be reported at this stage, the project is moving forward as anticipated and in accordance with the time schedule for the clinical examinations, although delays have occurred, however, in the laboratory schedules. The participation rates are considered highly satisfactory.
There have been no publications to date in regard to this grant because data collection still is ongoing; however, the findings of the pilot study that were first outlined as preliminary data in the original application have been finalized for publication and will appear in PLoS Medicine in August 2006.
Future Activities:
The analyses of the serum samples for PCBs and for antibody concentrations will be completed. Data analysis will include careful evaluation of potential confounders (which are not expected to be of major importance) as outlined in the grant proposal, with bivariate associations, multiple regression analyses, and structural equation models. Letters have been sent to all members of the cohort, with information about the clinical results of the examinations at age 5 years and about the next stage of the project (7-year examinations). As a result, many children already are consented for the next stage of the project (supported by NIEHS).
Journal Articles on this Report : 1 Displayed | Download in RIS Format
| Other project views: | All 16 publications | 14 publications in selected types | All 13 journal articles |
|---|
| Type | Citation | ||
|---|---|---|---|
|
|
Heilmann C, Grandjean P, Weihe P, Nielsen F, Budtz-Jorgensen E. Reduced antibody responses to vaccinations in children exposed to polychlorinated biphenyls. PLoS Medicine 2006;3(8):e311. |
R830758 (2005) R830758 (Final) |
Exit Exit |
Supplemental Keywords:
cumulative effects, dioxin, dose-response, epidemiology, human health, hypersusceptibility, infants, marine food contamination, methylmercury, mixed exposure, prenatal exposure delayed response, risk assessment, sensitive populations,, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, INTERNATIONAL COOPERATION, ENVIRONMENTAL MANAGEMENT, HUMAN HEALTH, Health Risk Assessment, Physical Processes, Risk Assessments, Environmental Policy, Exposure, Children's Health, Biochemistry, Risk Assessment, dietary exposure, health effects, Human Health Risk Assessment, post-natal exposure, exposure model, pesticides, developmental toxicity, pesticide exposure, prenatal exposure, polychlorinated biphenyl, animal model, immunotoxicology, PCB, pregnant women, developmental effects, children's vulnerablity, children's environmental health, exposure assessmentRelevant Websites:
http://www.chef-project.dk/ Exit
http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030311 Exit
Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.