Environmental Health Tracking and Biomonitoring Program
October 8, 2013 Advisory Panel Meeting Agenda
Time
Agenda Item
Presenters
Description/expected outcome
1:00
Welcome &
Introductions
Patricia
McGovern,
Chair
Panel members & audience are invited
to introduce themselves
1:05
Agenda Overview
Jean Johnson
A brief of overview of topics and
discussion items for today’s meeting
1:10
Pregnancy and
Newborns Exposure
Study: Data Analysis
Jessica Nelson
Discussion item: Jessica Nelson will
discuss preliminary analysis of the cord
blood hematocrit and mercury findings.
1:20
Discussion
1:30
A Recruitment Protocol
for Pregnant Women &
Their Newborns
Questions to the panel:
• Other ideas re why Hg levels were
higher in cord blood than in NBS?
• Has EHTB explored the role of
hematocrit sufficiently?
Dr. Ruby Nguyen,
University of
Minnesota
Principal
investigator
Discussion item: Ruby Nguyen will
review key elements of the recruitment
protocol for The Infant Development &
Environment Study (TIDES).
Question to the panel:
• How does the TIDES study protocol
help inform MDH enrollment and
biomonitoring of newborns?
1:50
Public Health Laboratory
Progress Report (metals
analysis)
Betsy Edhlund
Chemist, Public
Health Laboratory
Information item: Betsy Edhlund will
discuss the laboratory’s progress on
refinement and validation of methods
used to measure mercury in newborns.
2:05
Choice of Specimen for
Monitoring Exposure in
Newborns
Jean Johnson
Jean will review the characteristics of
dried blood spots vs. cord blood for
surveying Hg exposure in MN newborns.
2:15
Discussion
2:35
Refreshments
Decision item: Panel members are
asked to recommend the most useful
specimen for ongoing monitoring of
newborn exposure by MDH.
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2:45
Biomonitoring Summit
Report and Sustainability
Plan
Barbara Deming,
Consultant,
Management
Analysis Division
Discussion item: Barbara will briefly
report on Summit outcomes and
proposed sustainability planning.
Questions to the panel
• Which strategies for sustainability
are most likely to be successful?
• Would panel members be willing to
serve on a task force to explore
funding?
3:05
PFC3: Draft Protocol for
East Metro Follow up
Study
Jessica Nelson
Christy Rosebush
Discussion item.
Questions to the panel:
• Is the proposed sampling strategy
the best for answering our key
questions about PFC exposures in
the East Metro?
• Can panel members suggest how
best to recruit new residents in the
East Metro, who are less familiar
with, and likely less motivated by,
the topic?
3:15
Discussion
3:35
Biomonitoring Updates
• National Children’s
Study
• Riverside Study
3:40
Tracking Updates
• New portal content
• Community profiles
demo
• GovDelivery survey
• CDC projects update
Chuck Stroebel
Matthew
Montesano
Information item. Chuck and Matthew
will give a brief preview of new
community profiles. Panel members are
invited to ask questions or comment on
the updates.
3:50
Administrative Item
Pat McGovern
3:55
New Business
Panel members whose terms end on
12/31/2013 will receive forms for
renewal applications. The Secretary of
State will post Notices of Vacancy on
Nov 4. Please apply in November.
4:00
Motion to adjourn
No presentation. Panel members are
invited to ask questions and comment
on written updates.
Note to audience: The panel asks that audience members hold comments and questions on discussion
items until the end of the panel’s discussion. Meetings are recorded on audiotape.
2
Table of Contents
Section Overview: Pregnancy and Newborns Exposure Study ..................................................................... 5
Section Overview: A Recruitment Protocol for Pregnant Women and their Newborns ........................... 13
Section Overview: Public Health Laboratory Progress in Metals Analysis.................................................. 23
Section Overview: Choosing the Best Specimen for Monitoring Mercury Exposure in Newborns ........... 25
Section Overview: Biomonitoring Summit—Reflection & Next Steps for Sustainability ............................ 29
Section Overview: PFC3: Draft Protocol for East Metro PFC Biomonitoring III ......................................... 35
Section Overview: Biomonitoring Updates................................................................................................. 47
Section Overview: Tracking Updates .......................................................................................................... 51
Section Overview: Other Information......................................................................................................... 59
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Section Overview: Pregnancy and Newborns Exposure Study
The Pregnancy and Newborns Exposure Study, an EHTB collaboration with University of
Minnesota investigator Dr. Ruby Nguyen, is an add-on to The Infant Development and
Environment Study (TIDES). The MDH study compared mercury levels in paired cord blood and
newborn bloodspot (NBS) samples and measured lead and cadmium levels in cord blood.
Forty-eight paired samples of NBS and cord blood were available. Among the 16 paired
samples with detectable mercury in both NBS and cord blood, mercury levels were slightly
higher in cord blood samples: the average cord-to-NBS ratio was 1.3 + 0.4, ranging from 0.5 to
2.1. Mercury levels in the two sample types were moderately correlated, with a Spearman
correlation coefficient of 0.58 (p = 0.02). Using information reported by participants in a survey
administered to the mothers during the first trimester, mercury levels in cord blood were
associated with seafood meals per week (in women reporting 2-3 seafood meals, cord blood
had a geometric mean (GM) mercury level of 1.4 µg/L compared to 0.4 for those reporting 0
seafood meals, p <0.0001) and education.
The finding that cord blood mercury levels were 30% higher on average than NBS mercury
levels may reflect a biological difference or arise from the differing analytical methods used for
the two sample types. We will review several hypotheses for explaining the difference and ask
the panel’s advice on the questions below.
Questions to the panel:
•
•
Can the panel suggest other ideas about why mercury levels were higher in cord blood
than in NBS?
Have we adequately explored the role of hematocrit or other factors in this
relationship?
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6
Pregnancy and Newborns Exposure Study: Update and new results
Introduction and summary of past results
The Pregnancy and Newborns Exposure Study, an EHTB collaboration with University of
Minnesota investigator Dr. Ruby Nguyen, is an add-on to The Infant Development and
Environment Study (TIDES). The MDH study compared mercury levels in paired cord blood and
newborn bloodspot (NBS) samples and measured lead and cadmium levels in cord blood.
Preliminary results were presented to the Advisory Panel in June 2013 (in the Advisory Panel
book and in Supplemental Tables handed out at the meeting). Participants were highly
educated, had relatively high incomes, and were predominantly white. Mercury was detected
in 39% of NBS and 65% of cord blood samples. This difference is due to the fact that the
method detection limit (MDL) was higher for the NBS analyses than for the cord blood analyses
(0.7 µg/L for mercury in NBS v. 0.3 µg/L for cord blood). Only 1 NBS sample (2% of total
samples) was above 5.8 µg/L, the level corresponding to the U.S. EPA’s Reference Dose for
methyl mercury. In comparison, 10% of Minnesota babies tested in the Mercury in Newborns
in the Lake Superior Basin study were above 5.8 µg/L.
Forty-eight paired samples of NBS and cord blood were available. Among the 16 paired
samples with detectable mercury in both NBS and cord blood, mercury levels were slightly
higher in cord blood samples: the average cord-to-NBS ratio was 1.3 + 0.4, ranging from 0.5 to
2.1. Mercury levels in the two sample types were moderately correlated, with a Spearman
correlation coefficient of 0.58 (p = 0.02). Using information reported by participants in a survey
administered to the mothers during the first trimester, mercury levels in cord blood were
associated with seafood meals per week (in women reporting 2-3 seafood meals, cord blood
had a geometric mean (GM) mercury level of 1.4 µg/L compared to 0.4 for those reporting 0
seafood meals, p <0.0001) and education.
New results and interpretation
Difference between cord v. NBS mercury levels and hematocrit analysis
Our finding that cord blood mercury levels were 30% higher on average than NBS mercury
levels may reflect either a biological difference or be due to the differing analytical methods
used for the two sample types. The MDH Public Health Laboratory (PHL) will investigate the
latter hypothesis this fall. The issue is that the mercury in the cord blood samples is simply
extracted from the blood with a basic extraction diluent, whereas the mercury in the NBS
sample must be extracted from blood that has been dried on filter paper. This is an overnight
process that may lead to lower recovery levels compared to the cord blood analysis. Although
the recoveries of a standard reference material (SRM) for the two sample types were
comparable and acceptable, the SRM contains a relatively high mercury concentration; similar
experiments have not yet been performed on an SRM at a mercury concentration that is closer
to the concentrations found in this study.
7
A biological reason for the difference between cord and NBS mercury levels is harder to explain.
Both cord and spot blood are fetal blood, and are collected within 24-48 hours of each other.
The half-life of methyl mercury in blood is around 50 days. If the higher mercury levels in cord
blood are “true,” the mercury would have to be removed from the newborn’s circulating blood
and either excreted or sequestered in another tissue in those first days of life.
We explored whether hematocrit could be involved in the relationship between cord and NBS
mercury levels. Hematocrit is the volume percentage of red blood cells (RBCs) in blood.
Because developing babies need to maximize the amount of oxygen they receive in utero, they
have higher hematocrit than the mother and can thus take up more oxygen. Maternal
hematocrit is typically around 35%, whereas fetal hematocrit is around 55%. As methyl
mercury binds to hemoglobin, the part of the RBC that carries oxygen, this is thought to be the
main reason why mercury levels are greater in cord blood than in maternal blood (Stern and
Smith 2003). The average cord-to-maternal ratio is 1.7.
In our study, hematocrit was measured in cord blood. In the 16 participants with mercury
detected in cord and NBS, hematocrit was not correlated with either cord mercury (Spearman
r= -0.13, p=0.4) or with the cord-NBS ratio (Spearman r= -0.12, p=0.4). Cord mercury levels
were slightly higher in samples with hematocrit above the median (median hematocrit = 47.5)
compared to those below the median, but the difference was not statistically significant. The
cord-NBS ratio was also slightly closer to 1 in the group above the median (1.27 compared to
1.41). Cord and NBS samples were similarly correlated in the two hematocrit groups using
Pearson correlations, but results for Spearman correlations were different (Table 1). In
regression models looking at cord v. NBS mercury levels, adjusting for hematocrit did not
substantially alter the R2 value, and hematocrit was not a significant predictor in these models.
For all of these analyses, the sample size is small, making the results difficult to interpret.
For hematocrit to explain the higher mercury levels we saw in cord v. spot blood, hematocrit
would have to be higher in cord blood. Our study did not include measurements of hematocrit
in spot blood, so we cannot directly assess this question. Hematocrit does start to fall after
birth, but it’s not clear if this happens quickly enough to account for the difference we
observed. A paper that aggregated data on hematocrit from over 40,000 newborns to establish
reference ranges found a linear decrease in hematocrit during the first 28 days after birth
(Jopling et al. 2009). From day 0 to day 2 of life, hematocrit appears to have decreased from 54
to 50. Another study found that blood methyl mercury declines in infants between birth and 13
weeks, though this decrease was not evident at 4 days (Bjornberg et al. 2005). The authors
attributed the decrease at 13 weeks to increased body weight and decreased hematocrit.
Hematocrit may be involved in the variability in the cord-NBS ratio we observed, though the
results from our analysis described above do not provide clear evidence for this. Our results
are limited by the small sample size.
More research needs to be done to better understand these questions and other factors that
may be involved. These could include how quickly the cord was clamped, which affects blood
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flow to the infant right after birth and is known to be associated with the infant’s iron status;
the mechanisms by which mercury is transported across the placenta; and whether serum
albumin in the different sample types could have a role.
3rd trimester questionnaire data
We re-analyzed certain survey responses using data collected during participants’ third
trimester, a time point much closer to birth, when biological samples were collected, than the
first trimester survey data analyzed previously. We found similar results to those using first
trimester responses: cord blood mercury levels were positively associated with reported
seafood meals per week. Women reporting 2 meals per week had a GM mercury level of 1.1
µg/L compared to 0.3 µg/L for those reporting 0 meals (p <0.0001). (In third trimester data, no
participants reported eating 3 meals per week. Levels in the 2 meals per week group were
quite similar to the one meal per week group.) Once again, smoking rates were very low in third
trimester responses; only one woman reported smoking in the last week and one reported
being near someone else who smoked.
Correlation statistic
Following the method used by other papers in the literature, we looked at the correlation
between cord and NBS mercury levels again using the Pearson test on log-transformed data.
Results were somewhat different from those using the Spearman test, and indicated a stronger
correlation between the two measures. The Pearson correlation coefficient using logtransformed values was 0.82 (p = 0.0001), compared to the Spearman correlation coefficient of
0.58 (p = 0.02).
Comparison to other studies
Table 2 compares our cord blood results to similar studies in other North American populations.
Mean mercury levels in our study were similar to those in babies born in Rhode Island and
southwestern Quebec and were lower than those found in other locations including New York
City, Hawaii, Brooklyn, and Baltimore. These latter studies included substantial proportions of
babies born to non-white mothers and found that certain racial/ethnic groups, such as African
Americans and some Asian populations, had higher exposure levels than white participants.
The study in Rhode Island found that babies born to African American mothers had GM
mercury levels of 2.1 µg/L, compared to 0.5 µg/L for the population as a whole. In the New
York City study, the highest mercury levels were seen in babies born to China-born Asian
women; the GM level was 12.6 µg/L, compared to 4.4 µg/L in the New York City population as a
whole and 0.6 µg/L in our Minnesota study population. Our study was largely white and did not
include mothers from the racial/ethnic groups that appear to be at increased risk for mercury
exposure, most likely due to higher consumption of mercury-containing fish. Most other
studies included information on the percent of participants with cord mercury greater than
5.8 µg/L. Our result of 2% (n=1) was lower than all others except Baltimore. The New York City
population was the highest, at 32%.
9
Next steps
We have completed a draft manuscript presenting results of the NBS-cord blood comparison,
which we will submit this fall. Also this fall, the PHL will speciate mercury in the cord blood
samples and further investigate differences in the NBS v. cord blood method. Once these are
complete, we will summarize and post results from the project on the EHTB web site.
10
Table 1. Cord-NBS Correlation by Median Hematocrit (n=16)
< hematocrit median (n=8)
Spearman r
0.29
p-value
0.49
Pearson (log-transformed values) r
0.77
p-value
0.03
>= hematocrit median (n=8)
0.90
0.002
0.84
0.009
Table 2. Studies of Mercury in Cord Blood
Study
MDH 2012
Rhode Island (King et al. 2013)
NYC 2001 (Lederman et al.
2008)
Baltimore 2004-05 (Wells et
al. 2011)
Quebec (Takser et al. 2005)
Brooklyn 2007-09 (Geer et al.
2012)
Hawaii 2004-05 (Sato et al.
2006)
Population
Women receiving prenatal care at
a clinic in Minneapolis
Women giving birth at a
community hospital in Pawtucket,
RI
African American participants
Women giving birth at 3 hospitals
within 2 miles of the WTC site
China-born Asian participants
Births at Johns Hopkins Hospital
(70% African American)
Women receiving prenatal care at
a clinic in SW Quebec
Women receiving prenatal care at
a clinic in Brooklyn (41%
Caribbean/West Indian, 43%
African American)
Women giving birth at hospital in
Honolulu (wide variety of
ethnicities, 8% white)
GM
(µg/L)
Median
(µg/L)
95th
%ile
(µg/L)
0.7
3.5
n
MDL
%
ND
52
0.3
35%
0.6
538
0.2
43%
0.5
46
280
8.3
2%
39.9
7%
32%
2.1
0.2
0.3%
83
294
0.3
92
0.2
78
0.2
188
Max
%>
(µg/L) 5.8µg/L
2.4%
4.4
4.3
63
12.6
15.8
63
1.4
1.4
3.0
(90th)
0.6
1.6
2.1
4.8
(mean)
16.5
9.2
2%
16%
20
28%
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References
Bjornberg KA, Vahter M, Berglund B, Niklasson B, Blennow M, Sandborgh-Englund G.
2005. Transport of methylmercury and inorganic mercury to the fetus and breast-fed
infant. Environmental Health Perspectives 113:1381-1385.
Geer LA, Persad MD, Palmer CD, Steuerwald AJ, Dalloul M, Abulafia O, et al. 2012.
Assessment of prenatal mercury exposure in a predominately caribbean immigrant
community in brooklyn, NY. Journal of Environmental Monitoring : JEM 14:1035-1043.
Jopling J, Henry E, Wiedmeier SE, Christensen RD. 2009. Reference ranges for
hematocrit and blood hemoglobin concentration during the neonatal period: Data from
a multihospital health care system. Pediatrics 123:e333-337.
King E, Shih G, Ratnapradipa D, Quilliam DN, Morton J, Magee SR. 2013. Mercury, lead,
and cadmium in umbilical cord blood. Journal of Environmental Health 75:38-43.
Lederman SA, Jones RL, Caldwell KL, Rauh V, Sheets SE, Tang D, et al. 2008. Relation
between cord blood mercury levels and early child development in a world trade center
cohort. Environmental Health Perspectives 116:1085-1091.
Sato RL, Li GG, Shaha S. 2006. Antepartum seafood consumption and mercury levels in
newborn cord blood. American Journal of Obstetrics and Gynecology 194:1683-1688.
Stern AH, Smith AE. 2003. An assessment of the cord blood:Maternal blood
methylmercury ratio: Implications for risk assessment. Environmental Health
Perspectives 111:1465-1470.
Takser L, Mergler D, Baldwin M, de Grosbois S, Smargiassi A, Lafond J. 2005. Thyroid
hormones in pregnancy in relation to environmental exposure to organochlorine
compounds and mercury. Environmental Health Perspectives 113:1039-1045.
Wells EM, Jarrett JM, Lin YH, Caldwell KL, Hibbeln JR, Apelberg BJ, et al. 2011. Body
burdens of mercury, lead, selenium and copper among Baltimore newborns.
Environmental Research 111:411-417.
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Section Overview: A Recruitment Protocol for Pregnant Women
and their Newborns
MDH staff are planning and preparing for ongoing newborn biomonitoring for mercury
and other contaminants to meet these public health goals:
To measure the extent to which newborns in different parts of the state are exposed to
potentially harmful levels of mercury during prenatal development,
To determine whether some groups are more exposed than others, and
To identify what sources, in addition to fish consumption, contribute to the exposure.
At our last Advisory Panel meeting, we reviewed recruitment procedures, challenges
and successes from the EHTB pilot projects as well as the protocols that were evaluated
by the National Children’s Study (NCS). The NCS studies found that a Provider-Based
Recruitment Strategy, working with prenatal care providers and clinics, was the most
efficient for identifying pregnant women in a study community, and enrolled a high
percentage of the women (75%). This approach was also successful in achieving racial
and ethnic diversity of participants (35% non-white, 14% Hispanic).
At this meeting, we will continue this discussion of recruitment protocols and strategies.
Dr. Ruby Nguyen will review the methods used for clinic-based recruitment and consent
in the TIDES project, both in Minneapolis and in sister TIDES studies elsewhere in the US
(see background in this section.) Dr. Nguyen will also describe the modifications to this
protocol that were made for adding cord blood and blood spot collection for the MDH
Pregnancy and Newborns Exposure Study. Panel members are asked to discuss lessons
learned and recommendations from this project for ongoing biomonitoring.
Questions for the panel:
•
•
How can the TIDES study protocols and recent experience with the Pregnancy
and Newborns Exposure Study help inform future MDH recruitment and
enrollment of newborns ?
Can the Panel recommend ways to improve on these methods?
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14
Protocol for Pregnancy Cohorts: The Infant Development & Environment
Study (TIDES)
Ruby Nguyen, PhD
Introduction
The protocol outlined here reflects that of an NIH-funded pregnancy cohort that
recruited women during 2010–2012, with infants born as recently as January 2013. The
aim of “The Infant Development and Environment Study” (TIDES) was to determine the
association of an environmental toxicant during pregnancy with the urinary-genital–
reproductive anatomy of neonates, and to provide normative data on these anatomic
measures. The NIH-funded study represents four geographically diverse centers, one of
which was from the University of Minnesota. Women were enrolled in the first
trimester of pregnancy and contacted each trimester for data collection. A survey and a
biospecimen were provided in each trimester. Biospecimen collection was timed to
match with women’s general obstetric visits. The study also required consent to
examine the neonate before hospital discharge to measure anatomy and to abstract
medical charts for characteristics of the labor, delivery, and neonate.
Approximately 200 pregnant women consented and completed the study in Minnesota.
Minnesota participants tended to be more homogeneous; therefore, when appropriate,
this document will describe methods that other sites used to incorporate a greater
distribution of racial and socio-demographic characteristics.
Description of the clinic
The University of Minnesota site recruited pregnant women from their first
trimester of pregnancy and followed them through the discharge of the mother and
child from the hospital after delivery. Pregnant women were recruited in one obstetrics
clinic affiliated with the University. The study excluded women who planned to deliver
their infant at hospitals that were not affiliated with the University, although women
who unexpectedly delivered elsewhere and whose hospital allowed a clinical exam at
birth were asked if they would like to continue in the study. The obstetrics clinic is in
Minneapolis, on the University of Minnesota-Fairview campus. The clinic originally was
staffed exclusively by University clinicians, but about one year into the study, the clinic
merged with providers from the Fairview system. Most clinicians at the Fairview clinic
were already affiliated with the University of Minnesota, often as clinical preceptors,
medical students, or adjunct faculty members. After the merger, the sampling
population comprised all patients seen in the combined clinic.
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Developing clinical collaboration
Identification of an appropriate clinic for sampling and collaboration
The TIDES study aimed to determine the effect of a ubiquitous exposure and to
provide normative data on neonate anatomy from mothers and neonates across the
country. Therefore no particular population of pregnant women was targeted in
Minnesota. The study investigators identified appropriate obstetrics clinics with the
following parameters in mind:
1) A clinical protocol that involved a clinic visit for a woman in her first trimester of
pregnancy;
2) A sufficient number of women who were seen in the first trimester of pregnancy;
3) A sufficient number of women who continued care until the third trimester of
pregnancy;
4) A sufficient number of women who delivered at the affiliated hospital;
5) An established history of collaboration with researchers.
Establishing collaboration with the clinic and hospital administration
After identifying a potential clinic for collaboration, the investigators approached the
clinic’s medical director. For the Minnesota study, the medical director was a faculty
member of the University of Minnesota medical school who was familiar with the study
investigators. Discussions with the medical director included:
1) The aims and public health importance of the study;
2) The nature of the involvement of the participants;
3) The preliminary nature of the involvement of the study staff; and the impact of
this study on the field and potentially on the individual patients themselves.
In these discussions, we emphasized that we considered the medical director and her
staff as collaborators and that both parties would design their involvement together.
After the medical director had considered our request and taken it to her
administration, we considered her to be a full collaborator and named her as an
investigator on the study.
Establishing collaboration with the clinic staff
Once the medical director and other administrative staff had agreed to
participate, we established the details for the study, from identification of potential
participants, to pre-clinic visit and visit recruitment, and data collection during defined
clinic visits.
We sought collaboration through multiple face-to-face meetings with all levels of the
clinic staff. Study investigators met with the physicians and nurse midwives at their
monthly providers’ meeting to describe the study and answer questions ranging from
16
the scientific rationale and significance of the project, to the required activities of the
providers. As our study involved no appreciable effort from the physicians and nurse
midwives, we sought to involve the certified nursing assistants with recruitment (see
below). The provider meetings offered important insights into the clinic visits and the
procedures for labor and delivery, which were needed for the neonate assessment.
Finally, the clinicians were able to inform the study epidemiologist about the
demographics of the clinic population, including characteristics of women who might
not seek a first trimester clinic visit (and would therefore be ineligible for our study, lest
they create potential bias).
In collaborative meetings with the nursing staff, the study coordinator and other study
staff met with the nursing supervisor and certified nursing assistants (CNAs) who
roomed the patients (see below). Through these in-person meetings, the study and
clinic staff developed a flow of work that would minimize the unpaid effort from the
CNAs, yet provide sufficient support for study recruitment. In addition, these meetings
helped to develop an overall protocol that would minimize intrusion of the study on the
operational needs of the clinic staff (e.g. space, number of people in the clinic).
Establishing collaboration with the laboratory staff
The study coordinator and investigators consulted with the clinic and laboratory
staff multiple times to establish procedures to acquire blood from the study
participants. The obstetrics clinic sends patients to Fairview’s outpatient laboratory for
blood collection. Therefore, study staff needed to provide a laboratory request sheet
for each woman. The one-time blood sample was collected as a part of each woman’s
routine blood draw, with an excess amount provided to the study. With the laboratory
request sheet and multiple consultations with the study staff, the outpatient laboratory
was able to collect the whole blood and store it at an appropriate temperature for the
short term. Study staff knew when a woman was expected to provide her blood sample
and could thereby schedule a pick-up of samples from the laboratory within a few days.
Our study also collected maternal urine in each trimester. Urine collection,
unlike blood collection, is performed in the obstetrics clinic. Study staff were able to
anticipate when a woman would next come for a clinic visit in which she would provide
a routine urine sample. After the clinic staff tested the urine for routine medical
parameters (e.g. glucose and protein), the remaining sample was available for the study.
Study staff then aliquoted the urine into study-specific containers, placed into a study
identified box, and temporarily froze samples in the clinic laboratory’s freezer.
Recruiting pregnant women
Identification of potentially eligible women using scheduling calendars
Our collaborating clinic used an electronic scheduling system. When women
scheduled their first obstetrics appointment, the scheduler entered the visit as an
“OB1,” a first obstetric visit. Using this term, our study staff worked with clinic staff to
identify lists of women coming to the clinic each week who were denoted as OB1. At
17
the beginning of the study, our study coordinator was given access to the schedule, but
we learned that it was just as efficient for clinic staff to provide lists of women coming
for their OB1. Using the latter approach minimized the study staff’s need to access clinic
records. Originally, we had proposed that the study staff identify these women to
reduce the often unpaid effort of the clinic staff, but in the end, the request was
minimal, so the clinic staff provided the names and home addresses for potentially
eligible women.
Pre-clinic visit notification about the study to potentially eligible women
Once a woman was identified as a potential participant, she was sent a letter
signed by the medical director of the clinic and the principal investigator of the study.
The letter told the woman that she had been identified as someone who potentially fit
the criteria of a study in which the obstetrics clinic was collaborating. The letter gave
the study coordinator’s name and contact information, and told the recipient that a
study team member/recruiter would likely be at her first clinic visit to discuss any
questions that she might have, and to consent and enroll her into the study. The letter
also included a flyer about the study that featured the study logo. Note: A detailed
human subjects protocol is used for contacting potential participants using medical lists,
such as scheduling, because these lists contain medical information (in this case, that
the woman is pregnant).
A fluid recruitment protocol
Study staff worked with the clinic to develop a fluid recruitment protocol that
allowed contact with the potential participant at each stage of her initial clinic visit.
Study staff were present in the clinic waiting room at times when the clinic expected a
high attendance of OB1 patients, or when a patient had expressed interest in speaking
with the study staff. Staff generally had a small sign with the study’s logo (?) that
signified their role as study staff. When possible, study staff were also given a small
space behind the clinic receptionists to converse privately with potential participants.
Printed material in the exam room
Study staff developed a flyer that was placed in each of the clinic exam rooms.
Through conversations with the clinic staff, we learned that women/potential
participants spent some time in their exam room alone, and that seeing and reading
printed material about the study would assist recruiting.
Clinic staff to notify the women about the study
Through discussions with the clinic staff, we learned that the CNAs who did the
patient “rooming” were the people who spent the most time with the patients/potential
participants, aside from the physicians and nurse midwives, who were too busy to
discuss research opportunities. Therefore, the study staff contacted the nursing
supervisor to request that the CNAs introduce the study to the potential participant.
Their message was something to the effect of: “The clinic is involved in a study that you
may be interested in. A person from that study is here today. Let me know if you are
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interested in speaking with her at the end of your visit. She can tell you more about the
study and how to get involved.”
Study personnel to answer questions after the clinic exam
If a woman expressed interest in the study, a study team member was available
to meet with her after her clinic visit. The study staff worked with the clinic
administration to find an appropriate space to speak with the woman in private or semiprivate. The space available to our staff was a small room directly behind the clinic’s
reception desk. Because it had no door, we could not achieve complete privacy, but the
nature of the conversation did not warrant complete privacy. During this conversation,
the study staff described the study, its requirements and compensation, and then
discussed the consent. If the woman agreed to participate, she provided written
consent at that time with the study staff as witness.
Consenting pregnant women
Women were consented for the study in person at the same clinic visit in which
they were recruited. At the Minnesota site, only English speakers were eligible to
participate. At other geographic sites, written consent forms were also available in
Spanish. Women could provide consent to each aspect of the study, for herself and for
her neonate’s involvement. A separate consent, if given, allowed future use of stored
biospecimens for purposes unrelated to the primary aim of this study. The human
subjects committee for this study was a joint entity between the University of
Minnesota and the Fairview Health System. All consents for the main study were listed
on one form with the ability to indicate (check) “yes” for consent.
Consent for involvement during pregnancy and medical chart abstraction
Women provided written consent for the collection of survey information and
biospecimens in each trimester of the pregnancy. In addition, women provided consent
for study staff to review their medical charts for specific items related to labor and
delivery for the pregnancy.
Consent for involvement of the neonate
Women provided written consent for the physical examination of the neonate
and medical record abstraction on defined variables related to the neonate at delivery
(such as gestation age, birth weight, length, defects).
Consent for storing biospecimens for future research
Women provided written consent to allow stored biospecimens to be used for
purposes aside from the main aim of the study (e.g., aside from determination of the
primary environmental toxicant).
19
Follow-up data collection from pregnant women
Communication throughout the study
Almost all of the women in our study preferred e-mail for study-related
communication. Communication e-mails occurred before the clinic visits in which we
hoped to meet the woman to collect a biospecimen (such as urine during each
trimester), or an e-mail to alert (or remind her) that a trimester-specific survey was
available online for her. E-mail also allowed the study staff to provide other reminders
to the participants, such as notifying the labor and delivery staff of their participation as
the women’s due date approached.
Dropping participants from the study
Our study maintained a strong collaboration with the obstetrics clinic. Although
the following two items may not be obviously related to the aims of recruiting and
retention for a future study, we argue that having these policies in place at the
beginning of a study assists in maintaining a strong relationship with the clinic, its
administration, staff, and patients. The greater the satisfaction of the clinical partners,
the more successful the study may be with recruitment and retention of participants.
Women who actively wish to stop participating
In keeping with our human subjects approval, women were able to discontinue
participation at any time during the study. Once a woman notified the study staff that
she no longer wanted to participate, we provided a thank you and best wishes letter.
We also noted any reason for her discontinuation in our records.
Women who passively stop participating
Throughout the pregnancy component of the study, women were approached
for survey and biospecimen data. If multiple attempts to contact a woman to complete
a trimester-specific survey or to meet her at a trimester-specific clinic visit to collect a
biospecimen were unsuccessful, we considered this behavior as her passive way to
indicate that she no longer wanted to participate. In that situation, the woman would
receive a letter notifying her that she had not provided enough data to remain in the
study, and that we thanked her for her participation.
Women who experience an event that does not allow them to continue participation
In the event that a woman experienced an event that would not allow her to
participate, the study developed a protocol to acknowledge the event and thank her for
her participation to that point. An example might be a pregnancy loss, either
spontaneous or induced. This protocol was presented and approved by the human
subjects committee. If staff contacted a participant for a study-related visit or
completion of a survey, and the woman notified the study coordinator that she had
experienced a loss, the study coordinator would send the woman a letter endorsed by
the study staff offering our condolences, wishing her well through her difficult time, and
thanking her for her participation. The study coordinator then recorded it in our logs as
20
a censored event due to pregnancy loss. Other events that would lead to this type of
letter include moving out of the area or knowing that a woman would not deliver at the
affiliated hospital.
Summary
In summary, this document outlines the procedures that our successful
pregnancy cohort employed to recruit and retain 200 women throughout pregnancy to
investigate an environmental exposure’s effect on fetal development. Some of our
procedures may be relevant only to academic-medical partnerships, however, as many
of the procedural steps are not, nor could be, adapted to meet the needs of a pregnancy
cohort developed in a community setting.
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Section Overview: Public Health Laboratory Progress in Metals
Analysis
PHL chemist Betsy Edhlund will describe the MDH Public Health Laboratory’s progress in
developing and validating methods for measuring mercury and other metals in newborn
blood spots and in cord blood. She will also describe some of the challenges that
laboratory staff face in refining and validating these methods.
Discussion Item
Panel members are invited to comment on these methods and challenges during the discussion
of the choice of specimen for monitoring exposure in newborns.
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Section Overview: Choosing the Best Specimen for Monitoring
Mercury Exposure in Newborns
Panel members will be asked to consider the advantages and disadvantages of two
different specimen types for monitoring newborn exposure to mercury: newborn
bloodspots and umbilical cord blood. Staff seek the panel’s recommendation for the
specimen type that best meets the criteria in Minnesota Statute for a biospecimen “that
most accurately represents body [prenatal or newborn] concentration of the chemical
of interest.”
Panel members are asked to consider the specimen availability, ease and cost of
collection, interpretability of the results with other studies and reference groups,
capacity to conduct additional analyses with the same specimen, laboratory quality
assurance and validity issues.
Decision Item
After discussion of the mercury studies, laboratory analyses, and questions presented
this afternoon, panel members are asked to recommend which specimen should be
collected for biomonitoring in newborns. This recommendation will be directed to the
Commissioner of Health and to EHTB staff. The EHTB goal is to collect specimens in
representative samples of Minnesota populations in order to identify groups whose
pregnant women and newborns are being exposed to mercury at levels of concern.
Question to the panel:
Which specimen type should MDH collect for ongoing biomonitoring of mercury in
newborns to meet our stated public health goals (below)?
•
•
•
To measure the extent to which newborns in different parts of the state are
exposed to potentially harmful levels of mercury during prenatal development,
To determine whether some groups are more exposed than others, and
To identify what sources, in addition to fish consumption, contribute to the
exposure
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Table 1. Comparison of Newborn Specimens for Ongoing Mercury Biomonitoring
NBS (Newborn Screening Bloodspots)
Umbilical Cord Blood
Advantage: Readily available specimen on a
statewide population at no additional cost to
MDH for specimen collection.
Bloodspots are stored in the MDH lab for 71
days for all babies whose mothers consent to
newborn screening. With additional informed
consent from the mothers, the spots may be
stored for up to 18 years and used for
research purposes under current law.
Disadvantage: Cord blood specimens for
biomonitoring must be collected in hospitals
and birthing centers with informed consent in
advance, and are transported to the MDH
laboratory after collection.
Collection procedures require establishing
contracts with hospitals, training staff,
providing collection kits, and establishing
collection and transport protocols.
Disadvantage: Specimen volume is limited
with routinely collected newborn screening
blood spots. This allows only a total mercury
analysis. Only residual blood is available
following the screening procedures, so
multiple analyses of chemicals on the same
specimen are generally not possible. Quality
control procedures are limited.
Advantage: large volume of whole blood
specimen for additional analyses.
Cord blood collection provides a larger blood
volume for analysis (from 4 to 40 ml depending
on the method) for banking and additional
analytical work with consent. A metals suite
(Pb, Hg, Cd) can be analyzed currently, with
potential for adding more analytes in the
future.
Disadvantage: Detection limits for mercury in
NBS have been close to the population
median concentration and exceed the
median in some cases. Thus, only the highest
exposures (e.g., 75th or 95th percentile) can be
reported. In the Riverside population, 61% of
spots tested were non-detects. In Lake
Superior study, 48% were non-detect and
many are “qualified,” meaning that levels fall
below the laboratory report level.
Advantage: lower detection limit for mercury
A lower detection limit allows for the full range
of exposures to be described (e.g., percentiles,
means, medians) for the general population.
Results are not as likely to be limited only to
those in the upper percentiles.
Disadvantage: Methods for NBS speciation
are not currently available and are limited by
small blood volume. Only total mercury
concentrations are available. Thus, lab
methods cannot distinguish methyl mercury
(from fish consumption) versus mercury from
inorganic sources (e.g. skin-lightening creams)
Advantage: mercury speciation can
identify the methyl mercury/inorganic
components.
The larger volume and lower detection limit
mean that speciation of whole blood samples
can be performed for concentrations that
exceed the detection levels. Identifying the
methyl vs. inorganic components of mercury
help to identify the source of the exposure and
target appropriate interventions.
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Neutral: Difficult to achieve a populationbased sample. Although spots are collected
for nearly all births and potentially offer a
statewide population-based sampling frame,
participation rates in MN for women
contacted by mail to give consent for
additional spot testing have been low, less
than 50%. In addition, 25% of NBS spots were
judged insufficient for analysis in the pilot
study. Hospital or clinic based consent
procedures may improve participation rates.
Neutral: Difficult to achieve a populationbased sample. Participation rates for consent
obtained prenatally in hospitals and clinics
vary. National Children’s Study analysis
obtained nearly an 80% participation rate using
hospital/clinic based sampling. Some cord
blood specimens may be missed due to
complications during delivery that prevent
hospital staff from completing the collection
procedures (unplanned delivery at another
hospital, for example).
Disadvantage: NBS analysis method at MDH
is currently not a published method and has
not been externally validated with other labs.
Thus, it is considered a research method only,
and cannot be used for diagnostic purposes.
Advantage: Published and externally
validated methods. Whole blood analytical
methods for mercury are published and
validation is standard across laboratories. MDH
laboratory participates in proficiency programs
with CDC and other labs for quality assurance.
In some labs, the method can be used for
clinical diagnostic purposes with CLIA
certification (although not currently at MDH).
Disadvantage: No reference level for total
mercury exposure in newborn bloodspots has
been established. No published data
establishing a reference level for mercury
exposure in newborn bloodspots currently
exists, although a statewide study underway
in Utah may provide a population-based
reference in the future. NBS have been
suggested as a screening tool. But NBS
methods appear to underestimate individual
level exposures in paired comparison to cord
blood for reasons that are not yet understood.
Advantage: Exposure measured with cord
blood specimens can be directly compared to
published reference levels. EPA reference
dose, used to establish a safe level of methyl
mercury in blood, is based on studies using
cord blood for methyl mercury exposure
assessment. Published studies of cord blood
mercury levels in US newborns are found in the
literature.
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Section Overview: Biomonitoring Summit—Reflection & Next Steps
for Sustainability
In June, MDH partnered with Wilder Research to sponsor a State Biomonitoring Summit,
held at the Dakota Lodge in St. Paul. Nearly 100 participants attended, representing
state and local government agencies, academic institutions, private and non-profit
businesses, health laboratories, advocacy groups and the Minnesota Legislature, along
with leaders from state biomonitoring programs in California, Minnesota, Washington,
and Wisconsin. The Summit provided a platform for sharing our accomplishments since
Minnesota’s program began in 2007, learning from other states’ experiences and
envisioning the future.
During the sessions, participants considered questions about the sustainability of
Minnesota’s Biomonitoring Program. Barbara Deming, a consultant from Minnesota
Management and Budget’s Management Analysis Division, will briefly report on the
outcomes of the Summit and on EHTB’s proposed sustainability planning.
Questions to the Panel:
Panel members are invited to discuss and comment on the Summit Report and
recommended strategies, and consider these questions:
•
•
Which strategies are likely to be most successful for sustaining a state
biomonitoring program?
Would you be willing to serve on a task force to provide additional guidance to
staff as we explore potential new funding sources?
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The Biomonitoring Summit—Reflection & Next Steps for Sustainability
Background
On June 27, 2013, MDH partnered with Wilder Research to sponsor a State
Biomonitoring Summit, held at the Dakota Lodge in St. Paul. Nearly 100 participants
from a variety of disciplines attended representing state and local government agencies,
academic institutions, private and non-profit businesses, health laboratories, advocacy
groups and the Minnesota Legislature, along with leaders from state biomonitoring
programs in California, Minnesota, Washington and Wisconsin. The Summit provided a
platform for sharing our accomplishments since Minnesota’s program began in 2007,
learning from other states’ experiences and envisioning the future.
Please review the Biomonitoring Summit Report at
http://www.health.state.mn.us/divs/hpcd/tracking/biomonitoring/summit.html
In the afternoon sessions, participants were asked to consider questions about the
sustainability of Minnesota’s Biomonitoring Program, and they responded with a wide
range of suggestions. To follow up, staff met with management consultant and
facilitator, Barbara Deming, to discuss the implications of the June 2013 Biomonitoring
Summit for the program’s ongoing work. Although many recommendations from the
roundtable discussions were already underway or planned, and reflected participants’
agreement with the direction of the program, some new recommendations deserve
further reflection.
The Issue: Minnesota’s Sustainability
In the 2011 MN Legislature, funding for state biomonitoring was changed from an
ongoing appropriation established in the 2007 Legislation to a one-time appropriation
that directed MDH to complete work on PFCs and mercury. For FY 2014-15, funding has
been provided to MDH for two specific biomonitoring projects over the next two years:
one direct legislative appropriation for continued PFC monitoring in the East Metro, and
one received through the MDH/MPCA’s Environmental Health Risks Initiative. Yet
ongoing state funding for implementation of the 2007 law and Minnesota’s
Environmental Health Tracking and Biomonitoring program was not restored, and there
is no assurance of continued state support beyond 2015.
The 2013 Environmental Health Tracking and Biomonitoring Legislative Report included
the program’s long-range vision, purposes, and strategies for implementation of an
ongoing biomonitoring program:*
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The Vision
• Minnesotans will lead healthier lives and live in safer environments.
The Purposes
• Biomonitoring will identify differences in the levels of chemicals in people
among Minnesota’s diverse populations, which may differ by income,
ethnicity, culture, or geographic location.
•
Biomonitoring will assess the need for public health policy and action.
•
Biomonitoring will track changes over time to find out whether actions taken
to reduce chemical exposures in Minnesota communities have been effective.
Strategy: Protect Future Generations
• A targeted approach will focus resources on monitoring populations in our
state that are most vulnerable to chemical exposure, including pregnant
women, newborns, children, and disadvantaged communities.
Strategy: Choose Chemicals Wisely So People Can Take Action
• Chemical selection will ensure that results of biomonitoring can be used to
inform decisions and actions at all levels (state, community, individual) for
protecting health and addressing disparities.
Strategy: Use a Smart, Cost-Effective Tracking Approach
• Study designs will allow for ongoing surveillance (repeated measures),
participant follow-up and banking of specimens with informed consent for
tracking trends over time, assessing the efficacy of interventions, source and
outcome investigation, and responding to emerging concerns.
These elements, along with the program’s enabling legislation and lessons learned from
the pilot program, make up the framework of a long-term biomonitoring program. What
is needed is a sustainability plan to bring that program into reality.
*These statements of vision, purpose and strategies are the result of strategic planning
activities with advisory panel and program stakeholders since the inception of the
program in 2007, and comprise our recommendations for an ongoing program,
consistent with Minnesota’s original legislation.
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Sustainability Planning Proposal
We propose to develop and initiate a new three-part plan for addressing sustainability.
1. Funding strategy: In accordance with the “duties of the advisory panel” as
described in the Minnesota’s legislation, form a task force to explore potential
funding for an ongoing biomonitoring program, including federal, state,
foundation, and business sources.
2. Evaluation strategy: Evaluate and describe the impact of biomonitoring as a tool
for health improvement in Minnesota.
3. Communication (marketing/PR) strategy: Develop multiple approaches to raising
the visibility and promoting understanding of the public health value of a state
biomonitoring program.
Questions to the Panel
Panel members are invited to discuss and comment on the Summit Report and the
strategies we recommend, and to consider these questions:
•
•
Which strategies for a sustainable state biomonitoring program are likely to be
most successful?
Would you be willing to serve on a task force to provide additional guidance to
staff as we explore potential new funding sources?
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Section Overview: PFC3: Draft Protocol for East Metro PFC
Biomonitoring III
After the 2004 discovery of contamination of East Metro drinking water supplies with
PFCs, In September 2012, the EHTB Advisory Panel recommended that MDH continue
biomonitoring for PFCs in the East Metro. Their recommendation involved two parts:
1. Collect a third blood sample from participants in the original cohort to ensure
that levels are continuing to decline in this population, and
2. Expand the sample in the East Metro so that more people, including new
residents, are represented. Measuring PFC levels in new residents will help
answer the question of whether people who moved to the community after the
public health intervention are being exposed to elevated levels of PFCs.
Questions to the panel:
•
•
Is the proposed sampling strategy the best for answering our key questions
about PFC exposures in the East Metro?
Can panel members suggest how best to recruit new residents in the East Metro,
who are less familiar with, and likely less motivated by the topic.
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PFC3: Draft Protocol for East Metro PFC Biomonitoring III
Purpose
The PFC3 project has three primary purposes:
1. To measure the change over time in blood levels of perfluorochemicals (PFCs),
including PFOA, PFOS and PFHxS, in a population of long-time Washington
County, MN residents who had past exposure to PFCs in drinking water. MDH
measured blood levels in 2008 and 2010 in this population; this study will add a
third time point in 2014.
2. To measure exposure levels in new East Metro residents (people who entered
the community after public health interventions drastically reduced PFC levels in
drinking water) and
3. To compare these results with US general population levels.
PFC3 will evaluate the effectiveness of public health intervention in reducing the body
burden of PFCs in long-term residents and assess whether new residents have blood
levels comparable to the general population. In addition, it will further demonstrate the
value of biomonitoring to public health practice.
Background
After the 2004 discovery of contamination of East Metro drinking water supplies with
PFCs, investigation by the Minnesota Pollution Control Agency (MPCA) and the
Minnesota Department of Health (MDH) revealed widespread contamination of
groundwater that supplied drinking water to the City of Oakdale and surrounding
communities. Between 2005 and 2007, public health interventions to reduce residents’
PFC exposures from drinking water included installing a granular activated carbon (GAC)
system on the Oakdale Municipal Water System, providing whole-house GAC systems
for some private well owners, and extending the Lake Elmo public water system to other
private well owners. These interventions have reduced drinking water exposure to PFCs
to below health-based limits.
In 2007, the Minnesota Legislature passed a law that created the Environmental Public
Health Tracking and Biomonitoring (EHTB) program at MDH and directed MDH to
conduct four biomonitoring pilot projects. The 2008 East Metro PFC Biomonitoring Pilot
Project investigated the range and distribution of PFCs in a sample of 196 residents of
two communities likely to be exposed. Eligible participants included:
1. Adults living in Lake Elmo and Cottage Grove whose private wells had PFOA
and/or PFOS contamination above trace levels (>.1 ppb) and
2. Adults living in households served by the Oakdale Municipal Water Supply.
37
Participants were people who had lived in their current home prior to January 1, 2005,
before public health interventions began. The methods for sample selection,
recruitment, specimen collection, analysis and results can be found at
http://www.health.state.mn.us/divs/hpcd/tracking/biomonitoring/projects/pfcfinalrpt2009.pdf
Staff found measurable levels of PFOA, PFOS, and PFHxS in all 196 participants. These
values were elevated compared to levels in the US general population measured in the
National Health and Nutrition Examination Survey (NHANES).
PFC
Geometric mean
PFOA
15.4 ng/mL
PFOS
35.9 ng/mL
PFHxS
8.4 ng/mL
On recommendations from the EHTB Advisory Panel, MDH conducted the East Metro
PFC Biomonitoring Follow-up Project in 2010-2011. This project aimed to measure the
two-year change in serum PFCs in Pilot Project participants to assess whether exposure
reduction efforts were effective. Blood levels of PFOS, PFOA, and PFHxS declined
substantially from 2008 to 2010 among most of the 164 project participants. On
average, individual PFOS levels went down by 26%, PFOA by 21%, and PFHxS by 13%.
The results show that efforts to reduce drinking water exposure to PFCs in the East
Metro had been successful. Still, the 2010 levels in this population were elevated
compared to the most recent PFC levels seen in the U.S. general population.
Results from a questionnaire sent to Follow-up Project participants indicated that
people who had consumed unfiltered water for more years had higher PFC levels than
people who had consumed unfiltered water for less time. Except for a possible link
between recent carpet treatment and PFCs, possible sources of exposure other than
unfiltered water consumption were not associated with higher PFC levels in this
community.
In September 2012, the EHTB Advisory Panel recommended that MDH continue
biomonitoring for PFCs in the East Metro. Their recommendation involved two parts:
3. Collect a third blood sample from participants in the original cohort to ensure
that levels are continuing to decline in this population, and
4. Expand the sample in the East Metro so that more people, including new
residents, are represented.
Measuring PFC levels in new residents will help answer the question of whether people
who moved to the community after the public health intervention are being exposed to
elevated levels of PFCs.
38
Hypothesis
This study will test two hypotheses:
1. That blood levels for PFOS, PFOA, and PFHXS have declined among the Follow-up
Project participants in the four years between blood collection in 2010/11 and
PFC3 blood collection in 2014.
2. That blood levels of PFOS, PFOA, and PFHXS in Oakdale municipal water
consumers who moved to the East Metro after exposure reduction will not be
significantly different from the most recent US general population levels.
Study Design
Study Population: This study will comprise two distinct populations:
1) East Metro PFC Biomonitoring Pilot/Follow-up Project participants (“original
cohort”).
2) Oakdale municipal water consumers who are new residents to the East Metro
(“new resident population”).
The original cohort includes residents of two communities originally identified for the
2008 East Metro PFC Biomonitoring Pilot Project. These participants were selected
through a randomized sampling strategy to represent Oakdale municipal water
consumers and Lake Elmo/Cottage Grove residents with contaminated private wells.
The new resident population includes residents of Oakdale living in homes served by the
Oakdale Municipal Water System and who first lived in Oakdale on or after November 1,
2006. The Oakdale Municipal Water System GAC system was installed in October 2006.
Choosing November 1, 2006 as a cut-off date ensures that participants were not
exposed to Oakdale municipal drinking water with PFCs above health-based limits.
Eligibility: A total of 183 individuals are eligible from the original cohort. All individuals
who took part in the Follow-up Project and consented to be contacted for future
research studies are eligible (n=162). Pilot Project participants who had consented to be
contacted for future research studies but did not participate in the Follow-up Project are
also eligible (n=21).
New resident participants must be adults (≥ 20 years of age) living in the city of Oakdale
and served by the Oakdale Municipal Water System. These residents are eligible if they
first lived in Oakdale no earlier than November 1, 2006.
Study Methods
For the original cohort, all eligible adults will be contacted for PFC3.
For the new resident population, a complete list, including name and address, of all City
of Oakdale residents served by the Oakdale Municipal Water System will be obtained
from city water customer billing records. The list will be restricted to customers who
39
started service no earlier than November 1, 2006. About 500 households will be
randomly selected from this list, and each will be sent a letter containing a household
survey form. The letter will explain the study and affirm that participation is voluntary.
The survey will ask for the names and ages of current adult household members, the
year each household member began living in the current residence, gender of the
household members, and a contact number for each household member. The survey
will ask whether each individual lived in any household in Oakdale prior to November 1,
2006. Data from returned surveys will be entered into a secure database from which
200 eligible adults from 200 different households will be randomly selected.
Participant Recruitment and Informed Consent: Each eligible participant will be mailed a
letter explaining the purpose of PFC3 and inviting them to participate. The letter will
include the study consent forms. The consent will detail what will be expected of
participants and will review the risks and benefits of the study. The study consent form
will include a section detailing the storage of the participant’s biological specimen for
future non-genetic research. Storage of samples for future research will be optional.
The letter will also include the study questionnaire. Participants will be asked to
complete the questionnaire after consenting and return all documents in the postagepaid envelope.
People who do not return the consent materials within two weeks will receive a followup phone call by a trained interviewer to again invite their participation. People who
refuse to participate will be asked to describe the reasons for their refusal.
Once consent materials and the questionnaire have been returned by the participant,
he/she will receive a phone call from the interviewer. Questionnaires will be checked
for accuracy and completeness; if information is missing, the interviewer will ask for it.
The interviewer will thank the participant for their participation, ask if they have any
questions, and let them know they will be sent directions for making their clinic
appointment shortly.
Participants will then be sent a second letter detailing how and where to make their
blood draw appointments. They will be asked to contact the clinic for appointment
times, and will receive a map and directions. They will be provided with the labels to be
applied to their sample, which they will be asked to bring to their appointment. A
reminder postcard will be included with the letter so the participant can note the date
and time of their appointment.
Population Characteristics and Exposure Questionnaire: Participants will fill out the
study questionnaire and send it back with the consent materials. The original cohort and
new resident population will receive separate questionnaires. Table 1 describes the
factors to be measured in the new resident population. The original cohort will receive a
shorter version focusing on current water consumption and emerging or time-varying
exposures of interest.
40
Blood Sample Collection, Storage and Transport: A health clinic under contract with
MDH (Health East Oakdale Clinic) and located near the study communities will collect
blood samples by venipuncture from study participants. The lab will have the names of
participants to ensure that only these individuals are included in the data collection. The
study ID number will not be attached to this list, thereby limiting any health information
that would be available to the clinic. Only the study coordinator will have the key for
identification of an individual from a study ID number. The study participants will be
provided with the labels to be applied to their blood sample, and will bring them to the
blood draw appointment. After the blood clots, clinic lab staff will spin the blood
samples and extract a serum sample. Serum samples will be frozen and stored at the
clinic and transported by MDH staff to the MDH Public Health Laboratory (PHL), where
they will be stored at -70°C until analysis. Samples designated for storage for future
research will be kept at the MDH PHL; all other samples will be destroyed after analysis.
The study protocol and accompanying materials will be submitted to the MDH and
Health East IRBs for approval.
Laboratory Analysis Methods
Samples will be analyzed using a method that the MDH PHL developed in 2008 adapted
from the CDC reference method for determining PFCs in serum. Samples will be
analyzed for the same seven PFCs measured in 2008 and 2010: PFBA, PFPeA, PFHxA,
PFOA, PFBS, PFHxS and PFOS. The PHL will also measure perfluorononanoic acid (PFNA),
a chemical of interest because NHANES data show that serum levels of PFNA have
increased in the US general population since 1999/2000. The sample preparation uses
solid-phase extraction; analysis is performed on a high performance liquid
chromatography–tandem mass spectrometry (LC-MS/MS) system. The report level for
this method is 0.1 ng/mL.
Data Management and Analysis
Individual analytical results identified only by the unique study ID will be sent by the
MDH PHL to biomonitoring staff for entry into a secure database. The database will be
housed on a secure server on a secure floor of the MDH building. All physical copies of
study data will be filed and kept by the study coordinator in a locked file cabinet on a
secure floor.
For the original cohort, a descriptive analysis will include the percent detection, mean,
median, and distribution of the eight PFCs, and findings will be compared to the most
recent published results from NHANES for the US population. Data analysis will also
compare the distribution of 2014 blood levels for PFOA, PFOS, and PFHxS with levels
found in 2010 and 2008 and calculate the overall percent decline in PFC blood levels
over four (2010-2014) and six (2008-2014) year periods for this population. Paired ttests on the log-transformed data will be used to determine whether statistically
significant changes in exposure have occurred. For PFBA and PFBS, the percent
detection in the population will be determined and compared to previous detection
percentages using chi-square tests.
41
Percent detection, mean, median, and distribution of the eight PFCs will be determined
for the new resident population, and findings will be compared to the most recent
published NHANES results. Differences in serum PFC levels by demographic
characteristics and questionnaire responses (e.g. occupational history, diet, product use)
will be examined. Final models will control for possible confounding or modifying
factors. ANOVA and linear regression models will be used to examine the association
between length of residence in Oakdale since November 1, 2006 and PFC blood levels.
Although PFC levels in Oakdale city water are below health-based limits, low levels of
PFCs are still present in some water samples. This study will seek to determine whether
this low-level exposure results in elevated PFC blood levels. If this is happening, it is
expected to be the case in people who have lived in Oakdale for 3-5 or more years due
to the long half-lives of PFCs.
Communication of Biomonitoring Results to Participants
Biomonitoring results for each individual participant will be provided to all participants
who elect to receive them, along with a letter explaining the comparison of their results
to other participants in the study and to national studies. For the original cohort, results
will include comparisons of 2014 PFC blood levels to their Pilot Project and Follow-up
Project blood levels and to the most recent data from the US general population.
Results of the new resident group’s 2014 PFC blood levels will be compared to the most
recent data from the US general population. General information about drinking water
quality, health risks, actions to prevent exposure to PFCs, and additional resources will
be provided. Participants will also be offered private individual counseling regarding
their results by telephone with an MDH Medical Consultant.
Staff will provide a written report to PFC3 participants, city officials, and legislators that
summarizes the aggregate study results and their implications for the community.
Data Privacy
All information about individual participants collected by MDH in this study will be
private and will be protected in accordance with the Minnesota Government Data
Practices Act and federal laws. No individuals will be identified in reports or
publications. Only summary information that does not identify individuals will be public.
Limitations
It will not be possible to compare PFC levels in the full new resident population directly
to those in the original cohort because the two groups have very different age
distributions. The original cohort is older (mean age in 2014 will be 60 years), whereas
newer residents to Oakdale will tend to be younger. Age is highly correlated with PFC
blood levels in the original cohort, largely because age is related to years of residence in
the community. It may be possible to make this comparison in an age-comparable
42
subset of the two populations (i.e., younger people from the original cohort and older
people from the new resident population), but the sample size will be limited.
Comparison of PFC blood levels in the new resident population to the general
population will also have limitations. PFC3 blood samples will be collected in 2014;
NHANES data will likely be available for 2011-2012, but this is still a 2-year time lag.
Because levels of many PFCs are declining in the general population, this time lag could
make interpretation difficult, particularly because any differences in PFC levels between
the new resident population and NHANES are expected to be small. In addition,
differences in population characteristics between the NHANES and PFC3 samples that
are not well quantified (e.g., socioeconomic status) could contribute to findings of
elevated PFC blood levels in the East Metro. Finally, NHANES does not measure PFBA, an
analyte of concern in the East Metro.
Additional limitations
• PFC3 will not measure PFC levels in private well users or in Cottage Grove
residents because of sample size constraints, although both groups were
included in the original cohort.
• PFC3 will not recruit additional long-term residents of these communities; if
MDH were to continue longitudinal PFC biomonitoring in the future, the group of
long-term residents exposed to contaminated drinking water would only
continue to get smaller due to attrition by death, moving from the area, or lack
of interest in additional PFC biomonitoring.
• This study will not measure health outcomes related to PFC exposure, nor will it
be able to assess all possible sources of PFC exposure.
Risks and Benefits
The risks to the participant include possible bruising, bleeding, discomfort, and pain
from the blood draw. Risk is greater for individuals with bleeding disorders, such as
aplastic anemia, and for persons on blood thinning medications (Coumadin), and other
therapies. Staff will recommend that all participants consult with their health care
provider if they have any of these conditions before visiting the clinic.
Participants who elect to receive their individual biomonitoring results will receive
analytical results of the measured concentrations of PFCs in their blood and a
comparison to national reference values. The tests will be done at no expense to the
participant. Some participants may feel anxious about chemicals detected in the body
when little is known about health effects from these chemicals, particularly for those
whose results may exceed the national reference range values. Participants will be able
to talk about their results with an MDH medical consultant if they so choose.
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Alternative Sampling Frames
The sampling frame presented in this draft protocol for the new resident population was
determined to best answer our research question about PFC exposure levels in new East
Metro residents, given the set sample size (n=200). What follows is a brief description of
two alternative sampling frames that we considered in the planning process.
•
Stratified random sample by length of residence. In this sampling strategy, we
would recruit 100 short-term and 100 long-term Oakdale residents, matching
these groups on age. This would ensure that we had enough short-term
residents and enable comparisons between these groups (which would be
problematic without the age match due to the different age distributions). We
chose not to pursue this strategy because recruiting new long-term residents is
not a priority; we have already answered the question about whether they have
higher exposures than short-term residents.
•
Random sample of short-term Oakdale residents (n=100) and those from a
reference East Metro community (n=100). In this sampling strategy, we would
recruit a reference community without a history of PFC drinking water
contamination. This would allow us to compare new Oakdale residents to a
similar MN reference population sampled at the same time. If elevated
exposures are occurring in Oakdale, we would need a minimum residency
requirement for the short-term Oakdale residents to ensure that enough time
had passed for PFCs to accumulate in participants’ blood. From a biological
perspective, this minimum time would ideally be at least one half-life, meaning
our eligible population would include people who moved to Oakdale after
11/1/06 (when the interventions were in place) but before ~2010, a very narrow
window. If we chose not to use a minimum residency requirement, a sample
size of 100 would not allow the necessary in-depth analysis of this population,
which might be a regression model to determine whether short-term residents
who lived in Oakdale longer than 3-5 years had higher levels than those who
lived there for a shorter period.
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Table 1. PFC3 New Resident Questionnaire
Demographic factors
Residential and Water Consumption
Histories
Dietary History
Age
Previous residences in the East Metro
Gender
Daily water consumption habits
(cups/day)
Frequency of consumption for
certain foods suspected to
contain PFCs
Education
Income
Use of water treatment device or
alternate water source for all drinking
(never/sometimes/usually/always)
Foods may include:
•
•
•
•
•
•
•
•
•
home-grown fruits and
vegetables
fast food
microwave popcorn
pre-packaged snacks
take-out beverages
dairy products
potatoes
red meat
local fish and game
Consumer Product
Exposure
Occupational History
Health History
Use of stain-resistant
carpet or fabric treatments
Presence of new carpeting
or upholstered furniture
Use of non-stick cookware,
waterproofing sprays
Current employment
Blood donations, frequency
Pregnancies
Parity
Breast feeding
Current/past employment with 3M
Current/past employment in specific
occupations with potential PFC
exposure
Employment in recently built or
renovated office environment
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Section Overview: Biomonitoring Updates
These updates are for information only. Panel members are invited to comment and
ask questions about these projects.
Updates:
• NCS Newborn Mercury Biomarker Validation Supplemental Methodological
Study
• Riverside Newborn Mercury Project
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Biomonitoring Updates
NCS Newborn Mercury Biomarker Validation Supplemental Methodological Study
Our application to the National Children’s Study (NCS) Supplemental Methodological
Study team was approved. This project will obtain matched cord blood, newborn
bloodspot, and maternal blood samples from participants enrolled by South Dakota
State University’s Original Vanguard Center serving Brookings SD, and Yellow Medicine,
Pipestone, and Lincoln Counties, MN. All samples (83 pairs of matched newborn
bloodspot and cord blood samples, with maternal blood samples at birth from 49 of
these mothers) have been received by the MDH Public Health Laboratory. Lab analysis
will begin this fall; all samples will be analyzed for total mercury and cord blood will also
be analyzed for speciated mercury, lead, and cadmium. Staff are currently finalizing
Data Use Agreements with the NCS.
Riverside Newborn Mercury Project
The status of this project has not changed since the June 2013 Advisory Panel meeting.
The MDH Public Health Laboratory has received 160 newborn bloodspot samples
collected from participants in the Riverside Birth Study. Lab analysis for total mercury
will begin this fall.
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Section Overview: Tracking Updates
With the exception of the Community Profiles demonstration, the following updates are
for information only. Panel members are invited to comment and ask questions about
these reports.
This section contains status reports on the following projects:
•
New Portal Content
o Biomonitoring (arsenic, cotinine)
o Health Insurance
o How-to Guide (videos)
•
•
•
Community Profiles (demonstration)
GovDelivery Survey
CDC National Tracking Network Projects
o
o
o
o
Community EH Profiles
Health Impact Assessment Toolkit
Mapping of Risk Areas for Private Well Contamination
Economic Burden of Environmentally-related Disease in Children
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Tracking Updates
New Portal Content
Biomonitoring (arsenic, cotinine)
In September we added new biomonitoring data for cotinine and arsenic to the portal.
These national data, derived from NHANES, provide reference ranges for levels of these
chemicals in the US population as a whole. These exposure data complement several
other existing health outcome, exposure, and hazard data on the portal, and provide
context for interpreting the results of state and local biomonitoring projects. But no
data are available to estimate population-level trends for Minnesotans.
The NHANES data show that, overall in the US, the percentage of non-smokers who are
exposed to environmental tobacco smoke declined significantly from 53% to 40%
between 1999 and 2008. Age and racial disparities were also observed and tracked.
See new charts and messaging at:
Cotinine: https://apps.health.state.mn.us/mndata/biomonitoring_cotinine
Arsenic: https://apps.health.state.mn.us/mndata/biomonitoring_arsenic
Health Insurance
In August we added new state and county-level data for health insurance coverage to
the portal. These data provide an important baseline to evaluate implementation of the
Affordable Care Act, and they reveal disparities in health insurance coverage by
race/ethnicity, age, gender, and geography. Among our findings, we noted that the
percentage of Minnesotans without health insurance has risen significantly over the last
decade. About 10 percent of Minnesotans under age 65 were uninsured in 2011. See
more here:
Insurance Facts and Figures (state-level):
https://apps.health.state.mn.us/mndata/insurance_basic
Population Characteristics (county-level):
https://apps.health.state.mn.us/mndata/population_query
How-to Guide (videos)
This summer, we published a new how-to guide about how to use the portal, including
short videos with screen shots to demonstrate features (browsing topics, custom
queries, maps).
View the guide and videos at: How-to Guide:
https://apps.health.state.mn.us/mndata/howto
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Community Profiles (demonstration)
In the late Fall, we will add new functionality to the portal that will enable users to
select a county of interest and generate a report of all available tracking indicators. The
reports may be downloaded in several file formats (pdf, csv, xls, doc) for use in reports,
presentations, and meetings. This is an enhancement over the current functions, which
require portal users to visit topic by topic.
Phase one of this project is focused on generating reports that provide tracking network
data by county. If resources are available, we will continue this project to incorporate
additional data and geographies of interest. See related CDC project on Community
Environmental Health Profiles below. Questions? Contact: Matthew Montesano at
[email protected].
GovDelivery Survey
This summer, we surveyed subscribers to our program’s two GovDelivery email lists,
which have over 2,300 subscribers. From this survey, we learned key lessons about our
subscribers: how they use the portal, what they prefer, and how they respond to our
email bulletins. This will help inform our work as we continue on a process of iterative
design, enhancing the Data Portal and our outreach to identify, engage, and serve data
users.
Survey results identified, for example, that 43% of respondents work for state, local, or
regional government; 20% of respondents work for hospitals, clinics, or other medical
facilities; and 12% work for a nonprofit or community-based organization. This
information highlights the importance of outreach to some new audiences, such as
health care organizations, who may use tracking data to prepare community health
assessments now required under the Affordable Care Act. Results also identified top
topics of interest on the portal, which include health insurance, poverty and income,
and cancer.
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Question:
What topics are you most interested in on the Data Access Portal? (Select all that apply.)
Not sure/Don't know
Birth Defects
Environmental Tobacco Smoke
Childhood Lead Poisoning
Reproductive and Birth Outcomes
Air Quality
Childhood Immunizations
Cancer
Health Insurance
Poverty and Income
0
20
40
60
80
100
120
The survey also showed that respondents use the portal data to prepare grants, support
research projects, and conduct local health assessments, among other activities.
Question: Have you used information in the Data Access Portal?
Other, Please Specify
To prepare a grant
To support a research project
To support a community action
Have not used information
To support a local health assessment
To get health information for me or…
I browse the portal out of curiosity
To perform work duties
0
20
40
60
80
100
120
Questions? Contact: Matthew Montesano at [email protected].
CDC National Tracking Network Projects
MN Environmental Public Health Tracking is participating in 4 of 8 national CDC project
teams to increase Network visibility and promote use of tracking data. These projects
will be completed by Spring 2014 with specific products for use by states, CDC and
others. Descriptions of the project follow.
Community EH profiles
This CDC project team has been exploring options for Community Environmental Health
Profiles that can offer users an overview of environmental health issues in their
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community (i.e., viewing data by location for multiple indicators on the
state/grantee/national portals).
The team has considered many different approaches and formats for what could
constitute a Community Environmental Health Profile, and has dedicated significant
time to cooperatively engaging key users and stakeholders so that each grantee on the
project team better understands what product might be the most useful for the discrete
needs of constituents.
Working with this project team, we have discussed our plan for implementing
Community Profiles on Minnesota’s data portal, MN Public Health Data Access. We also
have provided input from local health department data users and others in MN to
understand how they would like to use the tool, and to inform the design and
development of profiles. Questions? Contact: Matthew Montesano at
[email protected].
Health impact assessment toolkit
This team is developing a toolkit to promote the use of tracking data to inform health
impact assessments (HIAs). HIAs are a means of assessing the health impacts of policies,
plans, and projects in diverse economic sectors using quantitative, qualitative, and
participatory techniques (WHO). HIAs complement existing environmental review
processes by evaluating community-level data and concerns relevant to health,
demographics, land use, and other factors.
This new CDC team has prepared a list of indicators to identify tracking data available
for HIAs by sector (transportation, land use, climate change). The team is now
developing a web page for the CDC National Tracking Network, with links to
resources/data, case studies, and a users’ guide that showcases how tracking data may
be used to inform HIAs.
In Minnesota, the Tracking Program and Health Impact Assessment Program are
collaborating to use tracking data in HIAs. The Tracking Program has the expertise and
data to prepare custom maps at fine spatial scales, where possible (e.g., zip code,
census tract). Tracking also can provide cross-disciplinary expertise in GIS,
communication, and epidemiology to develop maps, charts, and messaging
(interpretation). Finally, the Tracking Program is participating in a new HIA Coalition to
provide support and coordination among local government, non-profit organizations,
and others to promote use of HIAs in Minnesota.
Questions? Contact: Chuck Stroebel, MN Environmental Public Health Tracking
Program, [email protected].
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Mapping of risk areas for private well contamination
The goals of this project team are
1) To create and display the private well data metrics developed and piloted by the
CDC Private Well Task Force (PWTF);
2) To use these metrics as well as similar metrics associated with USGS modeling
efforts to create vulnerability maps which identify sub-county areas likely to be
at risk from high levels of contaminants in private well water;
3) To assist public health practitioners at the state and local level to use these maps
for public health actions in affected communities; and
4) To provide guidance for states with limited private well data on how best to use
those data.
The PWTF has identified two contaminants of concern: arsenic and nitrate. Most of the
participating states have completed or made substantial progress on mapping of arsenic
and/or nitrate data using guidance for the display of private well data developed by the
PWTF. Current efforts are focused on identifying potential users of the data and
targeting messaging to identified user groups.
Minnesota is currently assembling “Arsenic in Private Wells” materials for display at
MDH’s data portal, Minnesota Public Health Data Access. Much of the mapping has
been completed; messaging is under development and will incorporate the project
team’s recommendations.
Questions? Contact: Ed Schneider, MDH Environmental Health Division,
[email protected] or Chuck Stroebel, MN Environmental Public Health Tracking
Program, [email protected].
Economic burden of environmentally-related disease in children
A team of 5 Tracking states (CA, MN, NH, UT, OR) and CDC is working to develop a statelevel method for reporting the environmental attributable fraction (EAF) and economic
burden of children’s diseases that are related to environmental causes. “Environment”
is defined broadly to include contaminants in air, water, foods, products, and homes,
but excludes causes related to behaviors (e.g., tobacco, alcohol, medicines). Specific
diseases for the project will include asthma, two childhood cancers (leukemia and
brain), and blood lead poisoning. CA is also including neurological conditions (autism,
ADHD). Each state will produce a state report that policymakers can use to help
determine the impact of environmental actions/policies on disease prevention and cost
savings. This fall, Minnesota Tracking staff will be working with partners in the Asthma
program, the state cancer registry, and blood lead surveillance to gather the data and
complete this report, expected next spring.
Questions? Contact: Jean Johnson, MN Environmental Public Health Tracking Program,
[email protected].
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Section Overview: Other Information
This section includes documents that may be of interest to panel members.
•
•
•
•
•
•
2014 Advisory Panel Meeting dates
June 2013 Advisory Panel Meeting Summary
Advisory Panel Roster
Biographical Sketches of Advisory Panel Members
Biographical Sketches of Staff
Environmental Health Tracking and Biomonitoring Legislation
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2014 Advisory Panel Meetings
Tuesday, February 11
1-4 PM
Tuesday, June 10
1-4 PM
Tuesday, October 7
All meetings for 2014 will take place at
The American Lung Association
490 Concordia Avenue
St. Paul, Minnesota
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