Environmental Health Tracking & Biomonitoring Program
Summary: October 8, 2013 Advisory Panel Meeting
Advisory Panel: Bruce Alexander, Alan Bender, David De Groote, Jill Heins Nesvold, Pat
McGovern, Geary Olsen, Cathy Villas-Horns, Lisa Yost
MDH staff: Betsy Edhlund, Tess Gallagher, Jean Johnson, Jim Kelly, Mary Jeanne Levitt, Aggie
Leitheiser, Mary Manning, Pat McCann, Matthew Montesano, Paul Moyer, Barbara Scott
Murdock, Jessica Nelson, Christina Rosebush, Chuck Stroebel, Paul Swedenborg, Janis Taramelli
MAD consultants: Barbara Deming, Kris Van Amber
Welcome and introductions: Patricia McGovern, chair, welcomed the attendees and invited the
panel members and audience to introduce themselves.
Agenda Overview
Jean Johnson briefly reviewed the topics and discussion items. Explaining that the first half of
the meeting would focus on mercury in newborns, she asked the panel to consider the material
presented in the first three presentations and then, given the program’s limited funding, to
consider how best to move forward with future mercury projects. She asked panel members to
discuss and vote on the best blood specimen (cord blood or newborn spots).
Pregnancy and Newborn Exposure Study: Data Analysis
Jessica Nelson reported on the cord blood to newborn bloodspot (NBS) comparison project
carried out in collaboration with Dr. Ruby Nguyen, principal investigator for the University of
Minnesota’s arm of The Infant Development and Exposure Study (TIDES). The project
measured mercury in 48 paired newborn bloodspot–cord blood samples and found detectable
mercury in both cord and newborn bloodspots in 16 paired samples. Among these 16 paired
samples, mercury levels were slightly higher in cord blood: 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 using the Spearman test. Using information reported by the mothers during their
first trimester, mercury levels in cord blood were associated with seafood meals per week.
This Advisory Panel presentation explored the finding that cord blood mercury levels were 30%
higher on average than NBS mercury levels. Given that cord blood is fetal blood and that NBS
are collected within two days of birth and should be very similar, Jessica said that the
divergence required an explanation. Did it arise from the differing analytical methods used to
measure the two sample types in the laboratory, or did it reflect a biological difference?
Jessica reviewed possible reasons why laboratory methods might explain the disparity: The
laboratory must use different analytical methods for the two sample types. One method is
used to extract mercury from whole cord blood. The other must extract mercury from small
spots of blood dried on filter paper, an overnight process. This difference may lead to lower
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recoveries in bloodspots compared to cord blood. Recoveries of the standard reference
materials (SRMs) were acceptable, but the SRMs were not comparable to the low mercury
concentrations seen in this study.
She then considered the possible biological explanations for the disparity. Both specimen types
are newborn blood collected within 24-48 hours of each other. The halflife of methylmercury in
blood is ~50 days, so it’s unlikely that the mercury could decrease so quickly. Mercury levels in
cord blood and newborn spots should be very similar. So staff explored the idea of whether
hematocrit—the percent of red blood cells in a unit of blood—could be involved. The higher
mercury concentrations seen in cord blood compared to maternal blood have been attributed
to the fact that hematocrit is higher in the developing fetus than the mother, so we
hypothesized that this could be involved here as well.
Staff assessed the hematocrit in a sample of cord blood from each infant. Staff then compared
the hematocrit with mercury levels in the cord blood and bloodspots gathered from the 16
infants with detectable mercury. Hematocrit was not correlated either with cord mercury or
with the cord-NBS mercury ratio. A comparison of samples with low v. high hematocrit showed
that the correlation between cord and NBS mercury was similar when tested using Pearson
correlations on log-transformed values. (Spearman correlations were different, but Jessica said
staff decided to primarily use Pearson results because these met the statistical assumptions,
and the test has greater power.) In regression models of cord v. spot mercury, adding
hematocrit to the model did not appreciably change the estimate or the R2 value, nor was
hematocrit a significant predictor of cord mercury.
These results, Jessica said, are limited by the small sample size. We don’t know for sure
whether hematocrit may explain the higher mercury levels in cord blood because we don’t have
hematocrit measurements in spot blood and cannot make this direct comparison. Hematocrit
may explain the variability of mercury levels in cord blood v. newborn bloodspots, but this
project did not see evidence for this. More work is necessary to resolve the question.
Jessica gave a few other updates about the statistical analysis. Results using data from
questionnaires administered during the mothers’ third trimester were similar to those using
data from first trimester questionnaires: reported number of seafood meals per week was
positively associated with cord mercury. Jessica also discussed the correlation statistic used,
and said that, after more exploration, staff decided to use the Pearson test on log-transformed
values; other papers in the literature use this approach, and the test has greater power. The
overall correlation is stronger using this approach than the Spearman test (r=0.82 compared to
0.58). Because the main message from these findings is that measuring mercury in NBS may
underestimate fetal exposure (as measured by cord blood), staff decided to flip the cord-to-NBS
ratio to present the NBS-to-cord ratio instead in preparing the manuscript. The NBS-to-cord
ratio is 0.85, compared to the cord-to-NBS ratio of 1.3.
Finally, Jessica showed a slide that put these cord blood mercury results in the context of other
studies (Table 1). The slide summarized the results of 7 studies in the US and Canada, including
2
the MDH-UMN project. The MDH-UMN project’s small population primarily comprised well
educated Caucasian women, and only one child had a mercury level above the 5.8 µg/L
reference limit. Our results were similar to studies in Rhode Island and Quebec, but lower than
studies in a number of other places, including New York City and Hawaii, where much higher
percentages of participants had levels above 5.8 µg/L. Results of the other studies indicated
that higher cord blood mercury levels occurred more often among babies of women of minority
or foreign birth, including African American and China-born Asian women.
The project’s next steps include…
•
•
•
•
Submitting a manuscript to the journal, Environmental Research, as a “Report from the
Field.”
Learning more about laboratory investigation of spot v. cord differences in mercury
analyses.
Speciating a subset of the cord blood samples to identify the proportion of
methylmercury (from fish) and the proportion of inorganic mercury (from other sources,
such as metallic mercury or mercury in skin lightening creams).
Eventually, a summary of the project results will be placed on the EHTB website.
Jessica then asked panel members to consider the following questions:
•
•
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?
3
Table 1. Hg in cord blood: other studies
Population
n
MDL
% ND
GM
(µg/L)
MDH 2012
Women receiving prenatal care at a
clinic in Minneapolis
52
0.3
35%
0.6
Rhode Island
Women giving birth at a community
hospital in Pawtucket, RI
538
0.2
43%
0.5
Study
NYC 2001
Baltimore 2004-05
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)
46
280
Median
(µg/L)
0.7
95th
Max % > 5.8
%ile
(µg/L) µg/L
(µg/L)
3.5
8.3
2%
39.9
7%
32%
2.1
0.2
0.3%
83
294
0.3
Quebec
Women receiving prenatal care at a
clinic in SW Quebec
92
0.2
Brooklyn 2007-09
Women receiving prenatal care at a
clinic in Brooklyn (41% Caribbean/
West Indian, 43% African American)
78
0.2
Hawaii 2004-05
Women giving birth at hospital in
Honolulu (wide variety of ethnicities,
8% white)
188
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%
4
Discussion
The discussion was short, to provide more time for a joint discussion of all of the mercury
presentations together. Bruce Alexander asked whether laboratory staff could create a blood
spot with cord blood, and laboratory chemist Betsy Edhlund said that they could. Bruce added
that hematocrit might be a red herring, but that we need to know whether the blood spot can
characterize the mercury in the cord blood.
MDH Assistant Commissioner Aggie Leitheiser asked whether “seafood” in the survey applied
to fish in general. Jessica explained that the survey was designed before the joint project
existed and asked only one general question about seafood.1 She added that the lack of
specificity about the meaning of the term, seafood, is a limitation in the collaborative study.
During her presentation, Jessica had mentioned that delayed cord clamping during cord blood
collection might affect hematocrit. Pat McGovern asked Jessica to tell the group more about
this. Jessica explained that, until recently, the standard of care in a birth was to clamp and cut
the umbilical cord immediately after the birth. Some clinicians are now waiting longer before
clamping the cord to allow more blood to flow into the infant. Waiting even 2 minutes or more
can raise the iron level in the baby. 2
Pat McCann asked, is cord mercury actually higher than spot mercury, given the strong Pearson
correlation results? Jessica answered that the two blood measures are strongly correlated, but
that doesn’t mean they reflect the same absolute amount. These findings are preliminary, but
it looks as though the two measures are strongly correlated, and cord mercury is higher than
spot mercury (this difference is statistically significant). Pat McGovern then commented that
the key to the question is for the laboratory to test cord bloodspots.
1
Exact wording for the question was: “At how many meals [in a typical week since you became pregnant] did you
consume seafood?” Respondents answered with the number of meals per week.
2
JAMA. 2007;297(11):1241-1252 (original report). The placenta and umbilical cord can contain up to 200 ml of
blood, which contains hematopoietic stem cells as well as important reserves of iron for the infant. According to
the Journal of the American Medical Association, roughly 20-40 ml of blood can ‘pulse’ from the placenta to the
newborn during birth. Current industry benchmarks for cord blood collections are a minimum of 50 ml of blood.
Given the amount of blood likely to flow out of the placenta at the time of birth, there is typically plenty to be
stored for later use. Retrieved 12/9/13; Source: http://cordadvantage.com/delayed-clamping-cord-bloodbanking.html
5
A recruitment protocol for pregnant women and their newborns
Ruby Nguyen, collaborator and UMN principal investigator in the MDH-UMN Pregnancy and
Newborn Exposure Study, reviewed key elements of the way The Infant Development and
Environment Study (TIDES) protocol was adapted to recruiting and obtaining consent from
pregnant women in the MDH-UMN study (Note: the full TIDES Recruitment Protocol is in both
the June and October 2013 Advisory Panel books). The MDH-UMN study was an add-on to the
original Minnesota TIDES. The participants had been in TIDES since their first trimester of
pregnancy and knew the TIDES staff. Thus, when TIDES staff met with the study participants at
their third trimester clinic and TIDES visit, the women knew and trusted the staff and were
willing to learn about the new study and to sign consents for themselves and their babies.
In addition, TIDES staff already had developed good relationships with the hospital staff. TIDES
study staff prepared and delivered all of the MDH-UMN study specimen collection kits.
Delivering clinicians collected the cord blood, and hospital staff who collect newborn screening
spots collected extra spots for the study. TIDES staff also provided gift cards as compensation
to participants. New studies in other hospitals and clinics would have to develop these
relationships from the start.
Ruby identified several potential barriers to recruiting pregnant women that could affect future
studies of the distribution of mercury exposure in Minnesota’s newborns. She listed five
factors in the TIDES effort that made the MDH-UMN collaboration work well and then listed
likely hurdles that could arise in new studies.
Table 2. Important Factors in Recruitment and Consent in Studies of Pregnant Women
TIDES
Future Studies
•
Relationship with women
•
“Cold contact”
•
Relationship with clinic and hospital
•
New relationship with clinics and hospital
•
Population generally willing to participate
•
•
Access to birth records in real-time
Population of unknown willingness to
participate
•
On-going contact for notification of results
•
Multiple birth records system
•
Address at time of consent for notification
Future studies of interest to EHTB would seek more diverse populations than those in TIDES. To
find diverse populations, MDH staff would have to contact and build relationships with
hospitals and clinics in the Metro and outstate. Noting that recruiting populations that are not
predominantly highly educated Caucasians can be difficult, Ruby said that some populations of
minority and disadvantaged women might not be willing to participate. She also pointed out
that different hospitals often use different systems for birth records; having no access to realtime birth records makes it difficult for staff to prepare effectively for the cord blood collection
and also means that the record does not provide an extra check on the correct number of
samples. Moreover, because people in disadvantaged populations often change addresses, the
6
address a participant gave at the time of consent might not be valid when staff send out the
results. To ensure that the addresses are current, staff would need to keep in close contact
with the participants. Ruby suggested that MDH approach multiple clinics. In the Metro, she
recommended approaching Hennepin County Medical Center and Allina physicians who are tied
closely to UMN research programs.
Discussion
Pat McGovern asked, if a cord blood study involved several different hospitals, could the
women themselves be empowered to request the attending physicians to collect cord blood at
the birth? Ruby Nguyen replied that, in TIDES, some women who were in labor were sent to
other hospitals because the birthing rooms at the study hospital were full. In that case, she
explained, even if we sent a collection kit for the cord and newborn spots, we could not know
whether the other hospital could handle the cord blood properly. The biggest problem would
be in storing the cord blood sample at – 20oC, rather than the blood collection itself. Bruce
Alexander wondered whether women in labor might forget to bring the kit in their haste to
reach the hospital. Ruby replied that, before they go into labor, women often pack a travel bag
to bring to the hospital when labor begins. Studies could give the women a bag with the study
logo, a cord blood collection kit, and instructions for specimen collection and handling.
In the MDH-UMN study, Bruce asked, how much time elapsed between the time the blood was
collected and the time the study staff could send the results to the mothers? Ruby replied that
the study looked at babies born between June and January. The results were sent in batches
and the time interval ranged from three to nine months. Bruce said that he was concerned that
someone else might be at the address a participant had given when she entered the study. He
suggested staff should track the addresses to ensure that the participants receive the results.
Jessica Nelson said, this issue is the same for all biomonitoring results, and suggested that using
something like certified mail might add an extra layer of security.
Pat McGovern asked how much the study used social media technology to communicate with
the participants. Ruby replied that TIDES did not use much because they saw the participants
frequently, but the study did use email to let potential participants know about the meetings.
Public Health Laboratory Progress Report
Metals chemist Betsy Edhlund briefly described the MDH Public Health Laboratory’s
responsibilities and progress in developing and validating methods for measuring mercury and
other metals in newborn blood spots and in cord blood. The PHL is a Level 1 laboratory in the
federal Emergency Response Network. In this role, the PHL’s metals laboratory has been
adding more metals to its list of analysis methods and is taking part in emergency response
exercises that require the lab to analyze 500 samples in as short a time period as possible
(hours, rather than days). The laboratory also participates in proficiency tests (PTs) three times
per year. The laboratory also provides the metals analyses in both blood and urine for MDH
biomonitoring projects.
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Table 3. Current MDH PHL Metals Laboratory Responsibilities
•
•
•
Laboratory Response Network
• Blood Metals, Urine Metals, Arsenic Speciation
•
3 PTs/year
•
Emergency Response and biomonitoring
•
GLRI – 6 analyses in house (more than 20 analytes)
•
Fish are Important for Superior Health – blood metals, fatty acids
EH
EHTB
• TIDES
• National Children’s Study (Supplemental Methodological Study: Newborn
Mercury Biomarker Validation)
• Riverside bloodspots
• Future projects
Currently, the laboratory has only one instrument for analyzing metals in blood and urine, and
the instrument is used for both biomonitoring and emergency response. But the lab has
updated and validated metals methods for blood and urine for both uses and has expanded the
urine method to 16 metals. The laboratory has been awarded an Association of Public Health
Laboratories (APHL) fellowship. This person will assist with clinical testing and biomonitoring
support over the term of the fellowship. The lab may also obtain another instrument for metals
analysis. Both of these will greatly enhance the laboratory’s capacity for metals analysis.
In comparing the advantages and disadvantages of analyzing mercury—and possibly other
metals—in cord blood versus newborn blood spots, Betsy reviewed the following factors:
Table 4. Advantages and Disadvantages of Cord Blood and Newborn Blood Spots
Whole blood
•
•
•
•
•
•
Gives sufficient amount to measure Hg, Cd, Pb
Standard reference materials (SRMs) are
available
Standard network-wide method
Regular PTs
Simpler method
Homogeneous sample
•
Requires more storage space
Blood spots
•
•
•
•
•
In MN, lab now can do Hg only, but Utah also
does Cd & Pb
Chemists must assume the amount &
homogeneity in the very small blood sample
Less efficient sample throughput
More complicated extraction process
Easier to store (require little storage space)
The bottom line, Betsy said, is that blood spots take more preparation and data analysis time.
8
Discussion
Pat McGovern asked Betsy to list the metals that the lab can measure. They are:
Table 5. Current PHL Metals Suite
1.
2.
3.
4.
5.
6.
7.
8.
Antimony
Arsenic
Barium
Beryllium
Cadmium
Cesium
Cobalt
Lead
9. Manganese
10. Mercury
11. Molybdenum
12. Strontium
13. Thallium
14. Tin
15. Tungsten
16. Uranium
Currently, staff are halfway through the methods validation of all these metals and expect to
finish all of them in the next few weeks.
9
Table 6. Comparison of Newborn Specimens for Ongoing Mercury Biomonitoring
NBS (Newborn Screening Bloodspots)
Umbilical Cord Blood
Advantage: Specimens from a statewide MN
population. Low cost. Bloodspots stored for 71
days, but with informed consent, may be
stored & used for research for up to 18 years.
Disadvantage: Cord blood is collected in
hospitals/birthing centers with advance
informed consent. Higher cost: contracts with
hospitals, staff training, collection kits,
collection & transport protocols.
Disadvantage: Spot blood volume is limited.
Lab analysis can determine total mercury only.
Quality control is limited.
Advantage: Large volume of whole blood
allows more analyses; e.g., a metals suite (Pb,
Hg, Cd).
Disadvantage: NBS have a small blood
Advantage: A more sensitive detection limit
volume. Detection limits for mercury are less
for mercury allows staff to describe a wider
sensitive than those for cord blood. Only the
range of exposures, from low to high.
th
th
highest exposures (e.g., 75 or 95 percentile)
can be reported.
Disadvantage: Spots have a small blood
volume, so staff cannot distinguish
methylmercury (from fish) from inorganic
sources of mercury (e.g., skin-lightening
creams)
Neutral: Difficult to achieve a representative
sample from the population. Spots are
collected for nearly all births, so MDH could
contact mothers by mail to ask consent for
testing, but participation is low. Hospital/clinic
consent may improve participation.
Advantage: Greater blood volume & lower
detection limit allow staff to analyze methyl- &
inorganic mercury to identify exposure
sources. MDH can work to prevent exposure.
Neutral: Difficult to achieve a populationbased sample. Participation rates for consent
obtained prenatally in hospitals/clinics vary;
the National Children’s Study Alternative
Recruitment Study obtained nearly 80%
participation through hospitals/clinics.
Problems during delivery may prevent hospital
staff from collecting cord blood.
Disadvantage: NBS analysis method at MDH is Advantage: Published and externally validated
not yet a published method.
methods.
Disadvantage: No reference level for total
mercury exposure in newborn bloodspots has
been established to date.
Advantage: Exposure measured with cord
blood specimens can be compared to
published reference levels.
10
Choice of Mercury Specimens: Bloodspots v. Cord Blood
Jean Johnson reviewed the advantages and disadvantages of both newborn bloodspots (NBS)
and cord blood for measuring mercury and other metals in newborn blood (Table 6). A more
detailed table is in the Advisory Panel background book for the October 8, 2013 meeting.
She asked for the panel’s recommendation for the specimen type that best meets the criteria in
Minnesota Statutes3 for a biospecimen “that most accurately represents body [prenatal or
newborn] concentration of the chemical of interest.” She asked panel members to consider the
availability of each specimen (cord and newborn spot blood), ease and cost of collection, the
ability to compare and interpret results with other studies and reference groups, the capacity
to conduct additional analyses with the same specimen, and laboratory quality assurance and
validity issues.
Jean then asked the panel to take a vote in the following question:
Which specimen type should MDH collect for ongoing biomonitoring of mercury in newborns to
meet the 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
In funding EHTB’s biomonitoring program in 2013-14, she explained, the Minnesota
legislature’s intent was for MDH to follow up on the findings of the Mercury in Newborns in the
Lake Superior Basin 4 project to learn whether other populations were similarly exposed in other
parts of the state. Newborn bloodspots analyzed in the Lake Superior project indicated that
10% of Minnesota newborns tested in the study had total mercury levels over 5.8µg/L, the
Environmental Protection Agency’s reference limit for methylmercury exposure. In addition,
the high levels peaked in the summer months, which suggested that the source was probably
methylmercury in fish that the mothers had eaten.
Jean also reminded panel members of a new barrier to using newborn bloodspots in similar
studies. Under recent legislation in Minnesota, storing and using newborn bloodspots for any
purpose other than newborn screening now requires the mother’s consent within 71 days of
the birth.
3
Minn. Stats. 144-995-144-998.
Mercury in Newborns in the Lake Superior Basin, conducted by MDH’s Fish Consumption Advisory Program and
funded by the Environmental Protection Agency (EPA), with additional support from MDH’s Environmental Health
Tracking and Biomonitoring (EHTB) Program.
4
11
Discussion
The panel’s discussion revolved around the issues below:
•
•
•
•
•
Ability to obtain consent from participants
Ability to report results to parents, crucial for newborns with elevated mercury levels
Ability to collect and analyze specimens with limited finances
Potential to contribute to better scientific understanding
Potential for public health assessment of exposure (to measure the extent to which
newborns in different parts of the state are exposed to potentially harmful levels of
mercury during prenatal development)
Ability to obtain consent from participants
Panel members discussed Minnesota’s data practices requirements first, turning to Assistant
Commissioner Aggie Leitheiser to learn more about the 2006 legislation and its effects on public
health practice. Aggie explained that MDH’s newborn screening program tests newborn
bloodspots to identify congenital disorders that could pose health and developmental
challenges if they are not addressed early in a child’s life. The 2006 law followed a lawsuit that
claimed that MDH was collecting newborn spots and using them for research without consent.
This legislation has raised barriers to using newborn spots for such projects as tracking mercury
exposure in newborns. The requirements allow the newborn spots to be stored for 71 days,
after which they are destroyed. During the 71 day period, the spots cannot be used for any
purpose other than newborn screening, except with special consent. Test results can be stored
for two years before they are destroyed. Spots retained with consent to allow research may be
retained for 18 years or “until I request otherwise,” but to date, few mothers (< 1%) have been
approached for consent and agreed to that long period of time.
Jean Johnson suggested that staff could obtain consent prenatally, or that staff could send out
letters shortly after births to obtain consent within the 71-day period. Jean wasn’t optimistic
about the likelihood of getting consents within that window of time and meeting recruitment
goals. Pat McCann, principal investigator of the Mercury in Newborns in the Lake Superior Basin
project, said that the Lake Superior Basin study’s requests for consent to use newborn spots
were returned about five weeks after the consent request (or 8 weeks after the birth).
Lisa Yost asked whether some event had occasioned this lawsuit, but Aggie answered, no. MDH
complies with federal definitions of public health surveillance v. research, she said, but a group
of people, concerned that babies’ genetic information could be used inappropriately by the
government, filed the lawsuit. Obtaining consent can be expensive and difficult, Aggie
commented. Alan Bender noted that requiring consent for collecting public health data on the
population could make it difficult to do effective surveillance.
12
Currently, MDH is writing a report arguing for longer storage and research options in future
newborn screening spots, and expects to need informed consent from the mothers for these
options.
Ability to report results to parents
Bruce Alexander asked whether MDH would be able to contact parents of babies who were
found to have high mercury exposures. If we measure mercury in cord or newborn bloodspots,
he said, we will find high mercury levels in some babies. Would that concern influence the
decision to choose cord blood v. newborn spots? Aggie Leitheiser replied that MDH tests
newborn spots in routine newborn screening now and has a protocol for contacting parents.
Ruby Nguyen said that the MDH-UMN study reported the cord blood results to the parents and
also enabled parents concerned about their child’s exposure to consult with MDH’s
environmental health physician. Jean Johnson added that, so far, MDH has not reported any
newborn blood spot results to the parents.
Lisa Yost asked, isn’t that because you found only one baby with a high mercury level in the
MDH-UMN study? Yes, said Jean, but 10% of the babies tested in the Lake Superior Basin
project had high mercury levels in their newborn spots. Because the Lake Superior study
anonymized the spots, 5 MDH was unable to contact the parents of babies born with high
mercury levels. Lisa noted that part of the reason for anonymizing the spots was that, at the
time, we didn’t know what the laboratory report might mean.
Utah’s state health department is doing a surveillance study of cadmium, lead, and mercury
levels in newborn bloodspots, Jean said, but MDH does not know whether the department is
sending the results to the parents. But in any future project, whether in newborn spots or in
cord blood, MDH would notify the parents. Any baby with a mercury level of 5.8µg/L and
above should have follow up. Alan Bender agreed, saying that it’s hard to believe that MDH
would conduct a public health assessment of exposure in newborns without contacting the
parents if we identified a problem. If you find an elevated reading, he added, aren’t the results
from either of the two specimens just indicators for further follow up with the participants? In
either case, finding an elevated mercury level in a newborn requires follow up.
Ability to collect and analyze specimens with limited finances
Both David DeGroote and Jill Heins-Nesvold asked about the differences in cost between cord
blood collection and analysis v. newborn spot collection and analysis. MDH will have to
consider both costs. Pat McGovern noted that the cost of cord blood collection would depend
on whether hospitals bill for the collection. Sometimes, she said, hospitals interested in doing
research will collect the cord blood as an in-kind contribution to a study; others may not. Betsy
Edhlund said that it is cheaper to measure metals in cord blood than in spots. Speciating
mercury 6 in the cord blood raises the analysis cost, but the longer time to prepare and run
5
6
The laboratory technique for mercury in newborn spots was considered experimental at the time.
Speciation identifies the proportion of methylmercury v. inorganic mercury.
13
bloodspots through the lab instrument costs more than measuring metals in whole blood (cord
blood). Overall, however, she thinks the two analyses may be fairly comparable in cost.
Aggie Leitheiser asked, how many mercury projects do you envision? Jean Johnson replied that
EHTB has $268,000 each year for mercury assessment for Fiscal Years 2014—2015. Assessing
mercury exposure in Minnesota newborns is only one project, but will need to be carried out in
multiple sites. David asked whether staff had any sense of the number of samples needed to
address the question of newborn spots versus cord blood samples. Jean replied that the
program had budgeted for 600 newborn spots.
Potential for better scientific understanding v. public health assessment
The discussion then turned to the scientific and public health value that each kind of specimen
offered. Pat McGovern urged the staff to keep pushing the science to determine whether the
newborn spots provide a robust, valid, reliable index. She said that more research with
matched cord blood: newborn spot pairs would help to clarify this question. Bruce Alexander
argued for using newborn bloodspots to assess mercury exposure in newborns across
Minnesota. Long-term, this would build a framework for tracking routine measurements of
mercury exposure in Minnesota newborns. In the end, the decision hinged on the purpose of
the project and on the populations of interest.
Arguments for cord blood focused on two factors.
•
•
First, hospital staff can collect 4 to 40 ml of cord blood. The amount of blood is enough
to allow the laboratory to speciate mercury, measure other analytes, such as cadmium,
lead, and manganese, and to use the blood to further test the results found in the MDHUMN study.
Second, cord blood has been used to assess mercury in many studies of newborns, so
MDH can compare its results with those of published results.
Lisa Yost suggested that cord blood might be more reliable for a targeted study of vulnerable
populations. Alan Bender agreed that cord blood is the standard. If the program must choose,
and if we are unsure of what the data mean, he said, the specimen should be cord blood. Lisa
advised the program to look at other studies and to decide which of the two specimens to use
based on which populations would be more willing to consent to one specimen or the other.
Pat McGovern suggested that the program could go forward with cord blood in the Metro and
then address the question of the relationship between cord v. newborn spots in two years. Lisa
suggested that staff focus on groups that are likely to be exposed. Although cord blood is more
reliable, she said, if we ask for consent, we may be able to get both cord blood and newborn
bloodspots. Jean Johnson said that, with Ruby Nguyen’s help, we can reach diverse populations
in the Metro area to determine which are being exposed. Pat added, given the health
disparities in minority and disadvantaged populations, this is important.
14
Geary Olsen asked, what target populations would be recruited in these projects, and how
would EHTB staff recruit them? Jean said that staff would present target populations at the
next Advisory Panel meeting, in February. In the meantime, staff would talk with hospital staff
and find out where we would have viable partners. Geary also asked for clarification on the
question the project would address. Jean said to answer the legislature’s question: Are
newborns being exposed to mercury in regions of Minnesota other than the Lake Superior
Basin? Alan Bender reminded panel members of legislative intent— to determine whether
mercury is a problem in Minnesota with the best use of the resources you have.
Arguments for newborn bloodspots depended on four major factors clarified in the discussion:
•
•
•
•
First, newborn screening bloodspots are collected from almost all babies in Minnesota.
Second, both the Public Health Laboratory’s experience and the results of the MDHUMN project indicate that newborn bloodspots give reliable results at and above the
EPA reference limit for methylmercury, 5.8µg/L of blood.
Third, although MDH must obtain consent for collecting either cord blood or newborn
bloodspots, the newborn spot collection is a routine request and less expensive.
Last, the legislature funded MDH to assess mercury exposure in Minnesota to learn
whether mercury is a problem in parts of the state other than the Lake Superior Basin.
Twice during the earlier discussions, both Jean Johnson and Mary Manning, assistant director of
the Health Promotion & Chronic Disease division, had turned to the Public Health Laboratory to
ask about their confidence in the results of mercury measurements in newborn bloodspots.
Both times, the laboratory staff affirmed that they were confident of the validity of the
newborn blood spot results. These answers, plus the close correlation between cord blood
mercury and newborn spot mercury seen in the MDH-UMN study, led panel members to return
to considering the role of newborn bloodspots.
Bruce Alexander pointed out that MDH already has a system for collecting newborn bloodspots.
He asked: Can MDH make use of this newborn screening system for routine public health
surveillance? Are we setting up a surveillance system across the state that would be able to
detect and report high mercury levels in newborns? Is this [a decision] for a long-term plan?
Pat McGovern suggested that the question of interest might determine the specimen:
surveillance v. targeted study, with cord blood in some populations, newborn spots in others.
David DeGroote said the issue is a question of analytics—should we use cord blood because it
offers better science v. how can we best answer the legislature’s question: Is mercury a
problem in Minnesota? David encouraged the panel to think beyond the Metro area. He
pointed out that St. Cloud is near the state’s largest coal-fired power plant, the Sherco
Generating Plant, which in the past released much more mercury than the other, smaller, coalfired plants in Minnesota. [Note: The Sherco Plant is reducing its mercury emissions in
cooperation with the Minnesota Pollution Control Agency.] St. Cloud Hospital has a strong
research arm and serves a large population of Somali and Hmong residents who may be
affected by mercury, he added, so staff might want to contact St. Cloud Hospital.
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Bruce Alexander concurred with the need for a more statewide sample. Newborn bloodspots,
rather than cord blood, may be a better way to answer the legislators’ question: Are newborns
exposed to high levels of mercury exposure in other regions of Minnesota? Spots could give a
more efficient sample from a larger portion of the state. Even given the hurdle of having to
obtain informed consent, he said, I still think the legislature’s question about the distribution of
high mercury exposure in Minnesota will be answered better by measuring newborn
bloodspots. Collecting cord blood would involve far more work, from recruiting and consent to
collection, storage, and shipping from outstate Minnesota.
Lisa Yost asked, am I right that the spots have a detection limit that’s adequate to detect 5.8
µg/L and above? Jean Johnson answered that bloodspots reliably identify newborn exposure at
the 5.8 µg/L limit and above, and results above 5.8 µg/L should have follow up. In that case,
Lisa said, the spots serve the purpose of identifying babies with a mercury problem. A wider
distribution of data may not be needed for this purpose. In addition, both cord blood and
newborn spot samples involve a consent issue, but if what you want to get a better picture of
the overall state population, the availability of the bloodspots is very attractive.
Ruby Nguyen suggested that new projects could use either leftover newborn screening spots or
ask for consent to collect an extra spot with the standard newborn screening spots. In the
MDH-UMN collaboration, staff asked pregnant women to consent to the collection of an extra
blood spot on special filter paper. The advantage was that the collection was done through the
normal newborn screening process, with the addition of an extra spot. She also noted that
some leftover spots might be on contaminated filter paper.
Geary Olsen suggested that the best access to cord blood is [likely to be] local and suggested
that the program collect and analyze cord blood locally and newborn bloodspots statewide. Pat
McGovern suggested that the program might collect cord blood in a subsection of the newborn
spot study to answer the scientific question at the same time. But Bruce Alexander disagreed,
saying that adding cord blood to the 600 newborn spot samples would likely be too expensive.
Lisa Yost joined Bruce in arguing for using newborn bloodspots. With either specimen, she said,
you need to spend the funds to get consents that are representative of Minnesota populations.
I think we know that bloodspots are good enough to use [for a statewide study]. The real
barrier is the consent. The bloodspots under-predict the exposure, but not dramatically, and
bloodspots are both valid and cheaper. Moreover, Alan Bender pointed out, if the project limits
the inferences it can draw, the data would be sound for the purpose.
After first asking panel members which specimen they thought would best answer the
legislature’s question, Pat McGovern asked panel members for a motion and a vote. Bruce
Alexander proposed the motion: Staff should pursue the use of newborn bloodspots to answer
the legislature’s question: Is mercury exposure in newborns a problem in Minnesota [outside of
the Lake Superior Basin]? Pat McGovern seconded it, and the vote was unanimous in favor.
16
After the vote, Bruce proposed that it would be useful to pursue the cord blood: newborn
bloodspot validation in some arena. Pat seconded that motion, saying that the program could
look for external resources with the support of the panel. She asked for a vote on the motion,
If resources exist, the program should further explore the cord: newborn blood spot correlation
in a new study. This vote, too, was unanimous in favor.
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, Washington, and Wisconsin. The Summit provided a
platform for sharing the program’s accomplishments since Minnesota’s EHTB program began in
2007, and for learning from other states’ experiences and envisioning the future.
In the afternoon sessions, participants were asked to consider questions about the
sustainability of Minnesota’s Biomonitoring Program. The 2007 legislation that created the
EHTB program had based the program’s funding on an ongoing appropriation. In 2011 and
again in 2013, the legislature changed that appropriation to funding for specific, limited
projects over each two-year period (FY 2011-12 and FY 2014-15), with no assurance for
continuing state support beyond FY 2015. As speakers from other states made clear in their
own presentations, this situation is not unusual.
Barbara Deming, a consultant from Minnesota Management and Budget’s Management
Analysis Division, reported on the outcomes of the Summit and on EHTB’s proposed
sustainability planning. She noted that the 2007 legislation that established the program had
directed MDH to plan and implement an ongoing biomonitoring program for the state of
Minnesota. The program’s 2013 Report to the Legislature (EHTB 2013 Report to the
Legislature) put forward a vision and strategies (see p. 32, AP background book) that included
protecting future generations by focusing resources on biomonitoring populations that are
most vulnerable to chemical exposures, including pregnant women, their babies, children, and
disadvantaged communities.
At the Summit, Barbara reported, participants demonstrated a high level of interest, both in the
state and among other states. Participants said that the Summit showed the value of
biomonitoring through progress in identifying exposures and addressing public health concerns.
They saw biomonitoring as a tool to be used in identifying and understanding health disparities
and social determinants of health, and as a tool to help us understand where to focus our
public health interventions. The overall message from participants was that the program meets
a need in public health and needs to develop financial sustainability. Barbara then presented
the next steps: a three-part plan for addressing the program’s sustainability:
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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.
Barbara introduced Kris Van Amber, another consultant from MAD who will work closely with
staff and will lead the biomonitoring task force. Kris said her role is to work with a task force
from the panel to identify funding and develop strategies to sustain the program.
Panel members were invited to discuss and comment on the Summit Report and recommended
strategies, and to 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?
Discussion
Pat McGovern applauded the strategy, saying that the three tasks—funding, evaluation, and
communication are right. “I think you nailed it with these three issues.” The funding is the key
factor, but knowing how to frame your message with strong communications must have a role.
Alan Bender’s view was that some of these strategies are out of our hands. We need to capture
people’s imagination. Stories will help keep the program going—stories capture people’s
imagination. Jill Heins-Nesvold said, I think the question is too big – it starts with, what’s the
plan for addressing sustainability. Sustainability of what? Are we talking about the data portal,
special research projects, or are we looking at public health surveillance? I think we’re looking
at too large a question. We need to break it down into sub-questions and then determine what
the strategies are to sustain the program’s components.
Kris Van Amber answered that the work of this group will be doing some of that discovery,
understanding what kind of financially sustainable programs and models are out there. Also, is
this a specific issue of funding? Part of this is exploring sources of funding, but we also need to
understand who the stakeholders are.
Bruce Alexander said that the funding strategy would be huge, so the program will have to
develop it piecemeal. But the communications, public relations, and marketing—getting
resources for that – may be the way to begin. Think about the process for getting consent, for
example. If health providers aren’t aware of this program and why it is valuable, and if they
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don’t know why they should advise their patients to consent, we need to educate them. We
should do that by using Alan’s good stories… why biomonitoring is important to individuals. A
good story is better able to communicate importance than a long report with data and
statistics. Jean Johnson replied that Mary Jeanne Levitt, who handles communications and
marketing for the tracking program, will also be working with the biomonitoring program.
Before this, we’ve never taken a marketing approach with biomonitoring.
Pat McGovern wondered whether the program could identify a family or person or community
whose health behaviors or health changed because of biomonitoring. Lisa Yost suggested that
the program might create something interesting and accessible. She suggested that staff might
make a UTube video explaining public health tracking and biomonitoring.
Kris Van Amber agreed, saying you need to show the intrinsic benefit. But we will also need to
be looking at other funding as well.
Pat McGovern asked about the demands on time and the amount of work for panel members
who would work on the task force. Kris Van Amber said that, initially, task force members
would come together to look at the process, assess what the time demands might be, define
the goals, and suggest ways to accomplish them. Barbara Deming added, we could ask staff to
do some research and bring ideas and possibilities to the meetings, so more work could be
done outside of the meetings for staff, but not for panel members.
Jean Johnson summed up the dilemma: our vision is long-term surveillance, and our funding is
for a short-term project. The other states with biomonitoring programs have the same
problem. Everyone is just kind of piecing it together.
PFC3: Draft Protocol for East Metro PFC Biomonitoring III
After the 2004 discovery of contamination of East Metro drinking water supplies with PFCs,
MDH and the MPCA carried out public health interventions to reduce residents’ exposure to
PFCs in their drinking water. MDH then carried out two biomonitoring projects, in 2008 and
2010, to assess PFC exposure in long-term residents in the area. The first round of
biomonitoring documented that the residents had higher body burdens of the PFCs compared
to the general U.S. population; the second (PFC Follow-Up Project) documented declines in the
PFCs in the same group. 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.
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Christina Rosebush and Jessica Nelson presented a draft protocol for the third round of PFC
biomonitoring. The study will test two hypotheses, said Christina.
•
•
Blood levels of PFOS, PFOA, and PFHxS will have declined from 2010 - 2014 in the
original cohort.
Blood levels of PFOS, PFOA, and PFHxS in new Oakdale residents will not be significantly
different than PFC levels in the US general population.
The study populations will include two different groups: one is the original group of adults
whose blood was measured for PFCs; 183 people are eligible. The second group will be 200
newer adult residents who moved to Oakdale after the municipal water was treated to reduce
PFC contamination. These people are eligible if they moved to Oakdale and started their water
service on or after November 1, 2006.
In the original group of people, the PFC analysis will measure the same 7 PFCs of interest in the
original pilot project, plus PFNA. The 2014 blood levels will be compared to the earlier levels
seen in 2008 and 2010. In the new residents, MDH will compare the participants’ PFC blood
levels to those seen in the general population as measured in the Centers for Disease Control’s
National Health and Nutrition Examination Survey (NHANES).
Christina also reviewed the proposed questionnaire topics that the PFC3 project will use to
learn more about participants’ exposure to PFCs. The questionnaire will ask about a range of
possible exposures, including drinking water, diet, occupation, and product use.
Then, Jessica Nelson listed the limitations of the study of new residents:
•
We can’t compare new residents to the original cohort. The original participants were
long-term residents, and they are older (mean, 60 years) than the new residents.
Greater age is associated with higher levels of PFCs.
•
The new sample does not include private well users, Cottage Grove/Lake Elmo
residents, or additional long-term residents in Oakdale.
•
While NHANES provides a very valuable U.S. reference population, there are some
limitations. One is timing: we will have NHANES data from samples collected in 20112012, while the MDH samples will be collected in 2014. As levels of some PFCs are
declining in the general population, this time lag could affect the comparison.
•
Sociodemographic and other differences between people studied in NHANES and the
new resident population studied in the East Metro may also be an issue. In NHANES,
PFCs are positively associated with higher income, and it is likely that the East Metro
population differs from the NHANES population in this respect.
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The proposed protocol was the approach we thought would give the clearest answer to the key
questions that people have about PFC exposures in the East Metro. Then Jessica described two
alternative approaches that staff had considered and rejected (Table 7, below):
Table 7. Alternative Approaches
Approach
Stratified random sample of
Oakdale residents by length of
residence (n=100 new residents
and n=100 long-term residents)
•
•
Pro
Will be sure to get sufficient
number of new residents
Age match will enable valid
comparison between new
and long-term residents
•
•
•
Random sample of new
Oakdale residents (n=100) and
new residents of a reference
East Metro community (n=100)
•
•
Can compare new Oakdale
residents to similar MN
reference population w/o
exposure history
Avoid limitations of NHANES
comparison
•
•
Con
Recruiting more long-term
residents not a priority; have
answered the question of
more PFCs associated with
longer residence
Will be hard to recruit older
new residents
More complicated to explain
to public
Given need for minimum
residency requirement, new
resident window of eligibility
very narrow (~3 years)
If we have no minimum
residency requirement, may
not have power to look at
length of residence in
Oakdale residents
Christina then asked the panel members to consider the following questions:
•
•
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?
Discussion
David DeGroote asked about the proposed size of the new resident population. Do you know
how many people have moved here since November 1, 2006? Christina Rosebush responded
that the Oakdale population is around 20,000 adults, and in any given year, about 10% of
residents are new to their home. We will know more about the size of the Oakdale new
resident pool when we get water records from the city.
You plan to send out 500 letters to get 200 participants, David continued. Will that size of
population be enough—is this a good statistical sample size? Christina answered, yes, our
power calculations show that 200 people will be sufficient to answer our primary question: Are
PFC levels in the new resident population different from those in the US general population?
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Bruce Alexander said there is an issue about people moving into and out of Oakdale and other
parts of the East Metro and then moving into Oakdale again. Are there ways to track those
people who might have lived there before? Christina said that “no residence in Oakdale before
11/1/06” is an eligibility requirement, and we will be sure to ask this in the household survey.
We will also ask about all past East Metro addresses in the questionnaire, so we will have
residential history information for other towns as well.
Bruce asked, why did you exclude Cottage Grove residents on private wells? Christina
answered that it would be difficult to get a representative sample of Cottage Grove residents
who are both municipal water and private well users. Jessica Nelson added that focusing on
the Oakdale population answers the question most directly because so many people are on city
water, and there is one clear intervention date when the city water filters were changed.
Private wells are complicated because they may be treated with different kinds of filters. Geary
Olsen added that many people in Lake Elmo are now on municipal water, so new residents
there might be available for a larger population.
Geary Olsen then asked, why are you measuring PFPeA and PFHxA again? They weren’t
detected in the earlier projects, so do we need to keep testing for them? PFHxA has a halflife of
30 days, and the 4-carbon chain PFBA has a halflife of 3 days, so PFPeA will likely have a halflife
between 30 days and 3 days. It may be reasonable to keep PFHxA, as this is the chemistry that
companies are now using, but it’s not going to be in the water and will be coming from other
sources. Levels in the water have not been changing. Christina responded that staff will think
more about this in the next phase of planning.
Geary also noted that the NHANES 2011-2012 sample included participants from Washington
County. Because that may affect the overall results, he suggested that MDH may want to check
with NHANES to see if they will provide information on the number of people involved. Jessica
said she thought that this will be important to check. Jean Johnson said that the NHANES
Washington County data would be a very useful reference to have.
Next, Geary referred to two sentences in the October Advisory Panel background book that
read “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.” He asked, why is MDH trying to
correlate exposure to PFCs in water to blood levels in people? The water levels are below the
Health Risk Limits (HRLs), and MDH says they’re safe for drinking for a lifetime. And when
water levels are very low, ambient environmental exposures—non-water source exposures—
can become more important. Jessica Nelson answered that we see our mandate as a question
about new residents’ exposures—are there any water exposures that might be accumulating in
the body?
Geary then asked how the variation in water levels over time will be taken into account. Jessica
explained that we are using length of residence as a proxy for low-level exposure; we are not
actually using water values in any models. Low-level exposure means living in a community for
22
a longer time and presumably drinking water that has varying levels while you live there. Bruce
pointed out that there are limitations to this, e.g., you assume that everybody drinks water in
the same amount and from the same source. David added, I assume the questionnaire gets at
those questions and that you will analyze those variables along with the laboratory data.
Jessica agreed that the assumption that everyone is getting the same water all the time is a big
one. Jean said that staff will change the wording in the project protocol to clarify that the
analysis will not involve water concentrations, but will use length of residence as a proxy for
water exposure.
Geary commented that the decline we saw in blood levels from 2008 to 2010 followed the
pharmacokinetic data well, and that the third time point should do the same. For each
individual in the original cohort, he suggested that staff predict ahead of time what blood
values will be in 2014 based on pharmacokinetic data. Then, when we have the results, we can
compare these predictions to the actual measured values. If past water exposure is still the
main source, you should be able to predict the participants’ levels closely.
Pat McGovern pointed out that the time was up, and suggested that the discussion could
continue by email or phone. But staff asked the panel to agree that, on the whole, with the
small changes noted above, the project can move forward. Panel members agreed.
Biomonitoring Updates
Members had no questions or comments.
Administrative Item
Because time was limited, Pat McGovern moved on to the next item: request for applications
from panel members whose terms end on December 31, 2013. Barbara Scott Murdock named
those whose terms would end on that date and handed out copies of the requirements for
applications to the Office of the Secretary of State (OSS). The OSS will post the open positions
on the panel on November 4; applications should be submitted by November 26, 2013.
Tracking Updates
Matthew Montesano gave a short presentation of new work on the data portal—Community
Environmental Health Profiles. This new web function will offer users an overview of
environmental health issues in their community (e.g., data by location for multiple indicators on
the state/grantee/national portals). It would allow users, such as local public health officials,
to see all the county-level data, compare the data to statewide averages, and use it for making
graphs and tables. Data users are now asking for community-level data, saying that countylevel data are nice, but we need more detailed community data, so MDH staff are beginning to
develop a system for these data as well. After giving a brief demonstration of examples,
Matthew concluded by noting that the project is underway and a little ahead of CDC.
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Discussion
Bruce Alexander asked, are you able to export data broken out by other categories? Matthew
replied that people can integrate the data with other queries, carry out a more in-depth query,
and crunch the data by smaller categories.
Adjournment
Pat McGovern adjourned the meeting. The next Advisory Panel meeting will be held on
February 11, 2014, from 1:00–4:00 PM, at the American Lung Association.
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