Biological, Environmental, and Physical Effects Panel Part 2 Navajo - - PowerPoint PPT Presentation

Biological, Environmental, and Physical Effects Panel –Part 2

Navajo Birth Cohort Study, DiNEH Project, and Native EH Equity Center

Debra MacKenzie, Research Assistant Professor, Community Environmental Health Program, Department of Pharmaceutical Sciences, UNM David Begay, Research Assistant Professor, Community Environmental Health Program, UNM Maria Welch-Research Field Staff (NBCS), Southwest Research and Information Center (SRIC) Abigail Sanders - Cohort Clinical Liaison (NBCS), Tuba City Regional Health Center

Overview of projects addressing health effects of uranium exposure

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DINEH Project

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Active and Legacy Exposure

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Older population (average age 55)

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Exposure data includes surveys and biomonitoring data

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Navajo Birth Cohort Study

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Legacy Exposure

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Younger adult population (average age 27)

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Extensive exposure data (surveys, home environmental assessments, biomonitoring, existing agency & research data – e.g., NURE, NTUA, previous water quality measurement data)

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Native Environmental Health Equity Center (EH Equity)

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Mixed metal exposure in three Tribal communities (Cheyenne River Sioux, Crow Nation and Navajo Nation)

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Immunologic and Mechanistic studies with community members and model systems

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ECHO-Environmental influences on Child Health Outcomes

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Follow NBCS cohort up to 5 years of age

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Immunologic and developmental outcomes, continued biomonitoring and mechanistic studies

DINEH PROJECT RESULTS (AVERAGE AGE 55):

ACTIVE-MINING ERA EXPOSURES (WORKERS AND FAMILY) INCREASED RISK OF KIDNEY DISEASE

Active-mining related exposures were estimated from self-reported survey data

A: Washed the clothes of a uranium worker (22%) B: Worked in a uranium mine (10%)* C: Lived in a mining camp (4%) D: Worked in a uranium mill (2%)* E: Worked on a uranium mine or mill reclamation or hauled uranium ore or tailings in a pickup truck (2%)

*Many workers have already died from lung cancer, cohort had more family members than workers

Hund et al., 2015, Journal of Royal Statistical Society, Series A, Statistics in Society

DINEH RESULTS (AVERAGE AGE 55):

ON GOIN G EN V IRONMENTA L LEGA CY EXPOSU RES à IN CREA SED RISK FOR HYPERTEN SION, A U TOIMMU NE DISEA SE & DEV ELOPMENT OF ON E OR MORE CHRON IC DISEA SES IN CLU DING KIDN EY DISEA SE, DIA BETES, HYPERTEN SION

Exposures to legacy uranium mine and mill waste estimated from: 1) Integrated proximity of each resident’s home* to all of the 100 abandoned uranium mine and mill waste features 2) Reported activities resulting in contact with uranium mine and mill wastes A: Used materials from abandoned uranium mine or mill (17%) B: Herded livestock next to uranium mine, mill or waste dump (13%) C: Drunk or contacted uranium mine waste water (13%) D: Played on a uranium tailings pile or waste dump (13%) E: Played outdoors near a uranium mine, mill, or waste dump (12%) F: Sheltered livestock in an abandoned uranium mine (2%) *Note: Median length of residence in current homes was 33 years Hund et al., 2015, Journal of Royal Statistical Society, Series A, Statistics and Society

(B) (A) (C) (D) and (E) (F)

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• ~30% of Navajo population lack access to

regulated drinking water (14% of tribal population nationally; 0.6 of US population)

• Water quality in ~500 unregulated sources

shows 18-20% exceed arsenic MCL; 15% exceed uranium MCL, often colocated (Hoover et al., submitted)

• In contrast to previous studies, only 5.5% of

NBCS participants report drinking from unregulated sources

• 10.3% drinking from PWSs out of compliance

with As &/or U

Drinking water, hauling, and co-exposure concerns

Arsenic in Navajo Nation Water Sources Uranium in Navajo Nation Water Sources

Uranium in Waste Also Mobile in Water

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Wetland and reservoir downstream

• f Jackpile Mine

Elevated U and co-occurring metals in abandoned mine wastes (Blake et al., ES&T, 2015)

Uranium in water sources used for drinking by humans and livestock exceed drinking water standards by 5 - >20 fold

Supported by funding from NSF EPSCOR

Navajo Birth Cohort Study

• Multi-agency, prospective study to assess pregnancy
• utcomes and child development in relation to

uranium waste exposures among Navajo mother- infant pairs

• Cohort characterized with respect to mobility,

exposures, co-exposures, demographic and cultural characteristics that may influence birth and developmental outcomes

• Extensive public outreach, communication of results
• NBCS is only cohort study exclusively studying

environmental impacts on development in Native American children in the U.S.

• Approved by Institutional Review Boards of the

Navajo Nation, UNM, and CDC/ATSDR, and by federal Office of Management and Budget

http://www.nativeamericanlinks.co m/postcards.htm

Growing in Beauty

(developmental disabilities services provider)

USEPA Region 9

Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Navajo Area Indian Health Service (NAIHS) Navajo Nation

Department of Health

DiNEH Project Team

• UNM Community Environmental

Health Program (CEHP)

• UNM Pediatrics Department, Center

for Development and Disability

• Southwest Research and Information

Center (SRIC)

• Consultants

Birth Cohort

Navajo mothers, fathers and babies; other community members; chapters

With Help From

PL93-638 Facilities

(Tséhootsooí, Tuba City)

Other Navajo Nation Agencies

Environmental Protection Agency, WIC, Health Education, Office of Uranium Workers

Navajo Birth Cohort Study Cooperating Organizations

NBCS Enrollment

Updated: July 18, 2016

Participant # Enrolled as of 7/18/16 Mothers 704 Fathers 211 Babies 574 TOTALS 1,489

NBCS Enrollment (Mothers, Fathers, and Babies)

Service Unit # Enrolled as of 7/18/16 Chinle 310 Gallup 105 Kayenta 23 Shiprock* 49 Tséhootsooí* 52 Tuba City 165 TOTALS 704

*New enrollments ceased at Shiprock and Tséhootsooí in September 2015.

Mother Enrollments by Service Unit Hospital

Enrollment Map (July 2016)

Map by Joseph Hoover, PhD

Event Staffing Timing Content Enrollment Survey

CHERS (photos at L), RFS Prenatal period Participant and family lifetime uranium exposures,

• ccupations, water & land use, health histories,

demographics

Home Environmental Assessment (HEA)

RFS (photos below) Prenatal period preferred Outdoor & indoor gamma radiation screenings; indoor radon; metals on dust wipe samples from 2 locations; drinking water use (Analyses of dust wipes, water samples

@ USEPA-9 lab)

Biomonitoring

CCLs Pre- and post-natal Blood, serum, urine for 36 metals, metalloids, micronutrients;meconium for alcoholmetabolites

(Biomonitoring analyses at CDC lab, Atlanta, GA)

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NBCS field staff (CHERS, RFS, CCLs) conduct surveys, collect environmental and biological data to assess exposure and health outcomes

All photos above by C. Shuey. L: Enrollment survey; middle: HEA; R: blood sample processing in hospital lab

Nikki Begay Qeturah Anderson Melissa Samuel Roxanne Thompson

Research Field Staff (RFS) – from left, Lynda Lasiloo, Teddy Nez, Sandy Ramone, Maria Welch. At left, Community Health and Environmental Research Specialists (CHERS)

Child Developmental Assessments: Ages and Stages Questionnaire-Inventory (ASQ-I) Birth outcomes, immunity, and overall health to Age 1

— ASQ-I’s are performed when babies’ are 2, 6, 9 and 12

months old -- establish Navajo specific normative values.

— Medical record abstractions performed — Data analysis will look for how outcome measures are

associated with exposure data

Home Environmental Assessments

Purpose: To ascertain participants’ exposures to contaminants in and around their homes. Major contaminant categories are gamma radiation, radon, metals in dust and contaminants in drinking water. All exposure pathways considered.

HEAs Conducted by Service Unit, 2013-2016 (thru 7/15/16) Contaminants exceeding screening guidelines and percentage of homes having detectable levels of uranium in indoor dust (results through 7/15/16)

220 71 21 47 40 129 50 100 150 200 250 Chinle Gallup Kayenta Shiprock Ft. Defiance Tuba City

• Purpose: Obtain biological specimens for exposure assessment while

maintaining routine standard of care

• Specifics on samples from baby:

Ø Cord blood Ø Meconium when possible Ø Blood from baby at 2-6 months (well-baby visits) and 12 months Ø Urine collected at birth and well-baby clinic visit Blood Urine Meconium Mother

Ø Enrollment Ø Delivery Ø Enrollment Ø Delivery

Father

Ø Enrollment Ø Enrollment

Baby

Ø Birth (cord blood) Ø 2-6 months of age Ø 12 months of age Ø Birth Ø 2-6 months of age Ø 12 months of age Ø Birth

Biological sample collection in NBCS

Biomonitoring for the NBCS samples

• To understand relationships between uranium

exposures and birth outcomes and early developmental delays

• Why are we looking at so many metals?

Ø

To fully understand uranium exposures on health

— U wastes are a combination of a wide range of metals — Metals often interact through similar toxicity pathways

(arsenic and antimony, arsenic and uranium)

Ø

To identify other metals of potential health concern on the Navajo Nation

Ø

Metals from other than mining wastes sources

Biomonitoring results:

Urine-uranium among NBCS participants shifted to the right of the US NHANES average

• 21% of study participants have

urine uranium concentrations greater than the US 95th percentile

Ø

NHANES national averages, 2011-12

Ø

95th percentile is 0.031 micrograms per liter

• Father enrollment:

36%

• Mother enrollment:

24%

• Mother delivery:

17%

• Babies

Ø Birth:

0.6%

Ø 6 months:

17%

Ø 12 months:

24%

Babies show continual increase

• ver the first year of life.

Babies Parents

95th percentile

Urine total arsenic distribution for NBCS mothers, fathers and infants has lower mean and 95th percentile levels than the US population (NHANES). This finding is surprising because arsenic is ►component of mine wastes ►prevalent in home dust ►most frequent contaminant exceeding MCL in water sources However, arsenic below the 95th percentile may be harmful over time Similarly, blood lead (not depicted in graph here) for NBCS mothers, fathers and infants is lower than the mean and 95th percentile for the US population. Lead is the most frequently occurring metal exceeding its screening value in indoor dust.

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Babies Parents

US 95th percentile

Arsenic and Lead

“Bean” chart by Joe Hoover, UNM-CEHP

Other metals for which NBCS distribution is greater than mean levels in US adults, based on NHANES data

Metal Attributes Manganese

• Higher than expected in babies (blood and urine)
• Neurotoxicant
• Among more frequently occurring metals exceeding screening values in indoor dust

Mercury (inorganic and total)

• Of concern due to coal burning in regional power plants and in homes
• Known neurotoxicant
• Elevated above US population for moms, dads, babies at birth

Antimony

• Replaced cadmium in solder; used in semiconductors, alloys, hardens lead in batteries, used

as fire retardant

• Toxicity to lungs, skins, liver, cardiovascular system reported, potential carcinogen
• Similar mechanism of action to arsenic -- increased DNA damage; hypothesized to inhibit

repair enzymes

• Among more frequently occurring metals exceeding screening values in indoor dust
• Elevated in moms, dads, babies

Tungsten

• Used in bullets, fishing weights, darts, golf clubs, grinding wheels, cutting tools, light bulbs
• Used to replace depleted uranium in armour penetrating weapons, lead in bullets
• Often alloyed with nickel, copper – toxicity not well studied for metal or alloys
• Only elevated in babies at birth!

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Iodine insufficiency

— Iodine used as a population-level

biomarker; daily variability exists

— Key for organogenesis and

neurodevelopment

— ~ 40% below WHO sufficiency level — Dietary sources of iodine – fish,

dairy, wheat – low in Colorado Plateau soils

WHO sufficiency level

Zinc (Zn) insufficiency

• 364 of 595 NBCS Mothers

(61.1%) below WHO Zn sufficiency level

• Important in DNA repair (As and U

toxicity), coenzyme

• Tends to be lower in pregnant

women, particularly mothers of several children

• Prenatal vitamins seem unrelated
• We have a new study to check

function, not just level in serum

WHO sufficiency level

Nutrient Status During Pregnancy

Supported by pilot funding from UNM-CTSC

Copper Calcium Iron Niacin Pantothenic Acid Riboflavin Sodium Thiamin Total Folate Vitamin B12 Vitamin B6 Vitamin C Vitamin D Vitamin E Vitamin K Zinc 50 100 150 200 % RDA

Median Nutrient Intakes

NBCS (n=101) 1981 Study (n=22)

100% RDA 60% RDA Zinc of particular concern due to ability to protect against DNA damage – nearly 50% are zinc insufficient

• Nutrient status generally improved over what was reported

in 1981 (last published study on 22 pregnant Navajo women’s nutritional status)

• Some key nutrients (e.g. folate, vitamin D) still lower than

recommended for good fetal development

• NOTE: Still missing many delivery weights, so normalization not yet

complete

Native Environmental Health Equity Research Center

DISTRIBUTION OF ABANDONED URANIUM MINES IN WESTERN US

CROW NATION

(DRAINAGE FROM PRYOR & BIG HORN MTNS) >50 mines, ~500 features)

CHEYENNE RIVER SIOUX TRIBE

(DRAINAGE FROM BLACK HILLS)

NAVAJO NATION

(~500 mines, 1100 features)

NATIVE EH EQUITY

The Questions

— ARE EXPOSURE à TOXICITY RELATIONSHIPS CONSISTENT ACROSS

COMMUNITIES?

— If not – why

— mixture of metals? — form of metals? — route or pathway of exposure? — cultural/traditional practice differences? — nutritional differences — disparities in SES, background health status

Compare individuals within tribes over a range of exposures/variables Examine effects across tribes

NATIVE EH EQUITY

Potential health effects we see in specific tribes with metal mixture exposures (mine waste)

— Navajo

— Community exposures to uranium waste (Uranium/arsenic dominated)

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Unrepaired damage to DNA (average age 55, and 26),

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increased antibodies to “self” (autoantibodies – even at 26),

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increased evidence of uranium exposure in biomonitoring (elderlies, parents, infants)

— increased U in infants at birth

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Increased cytokines in babies associated with prenatal U exposure

— Cheyenne River Sioux Tribe

— Increased autoantibodies related to fish consumption and living near arsenic deposits

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Mercury in fish related to airborne deposition (power plants in airshed release > 1T/yr)

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Arsenic released from Homestake goldmine in Black Hills

— major inventory remains upriver

(Ong et al., Autoimmune Disease, 2014)

Clinicians working in all P50 tribes have noted immune insufficiency and increased autoimmune disease

NATIVE EH EQUITY

Research Projects

Two studies to examine the common concerns of poor immune function and increased autoimmune disease I. DNA Damage: Examine how metal mixtures affect DNA damage and repair ii. Autoimmunity & Immune Dysfunction: Determine whether exposures increase antibodies to self (ANA), alter inflammation (cytokine profiles)and cell types in the immune system (T & B lymphocyte profiles)

Studies start with people and their environment, go to lab to investigate mechanisms, and look for potential intervention and or prevention strategies

NATIVE EH EQUITY

ECHO-Environmental Influence's on Child Health Outcomes

Consortium of pediatric cohorts from diverse racial, geographic and socioeconomic backgrounds across US (n=50,000). For Navajo – specifically

• Follow children from the NBCS to 5 years of age (vs 12 months).
• Investigate pre- and postnatal exposures to metal mixtures and their effect on

development (immunologic, neurobehavioral, and overall health).

• Investigate the association of maternal autoimmune responses and/or inflammatory

status with neurodevelopment Collaborators-University of California-San Francisco, Southwest Research and Information Center (SRIC) and Navajo Nation Department of Health.

Acknowledgement of Funding

Disclaimer This publication was developed under Assistance Agreement No. 83615701 awarded by the U.S. Environmental Protection Agency to the University of New Mexico Health Sciences Center. It has not been formally reviewed by EPA. The views expressed in this document are solely those of the authors and do not necessarily reflect those of the Agency. EPA does not endorse any products or commercial services mentioned in this publication. Research reported in this publication was supported by the National Institute Of Environmental Health Sciences of the National Institutes of Health under Award Number P50ES026102. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All human research reported here is monitored and approved by UNM, Navajo Nation, and/or other institutional and tribal IRB’s as appropriate for the scope of the study.

DiNEH project – grant support: NIEHS, RO1 ES014565; R25 ES013208; P30 ES-012072; USEPA/ERRG pass through contract; with support from DHHS/NIH/NCRR #1UL1RR031977-01. Navajo Birth Cohort Study (UNM) - UO1 TS000135 CDC/ATSDR P50 Native EH Equity Center-funded jointly by grants from NIEHS & NIMHD ((1P50ES026102) & USEPA (#83615701) ECHO Center Funding: NIEHS 1UG3OD023344-01

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The NBCSTeam:

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With thanks to the many others who have contributed to and supported this work!

The people of the Navajo Nation:

• 2000 Navajo families
• 110 chapters
• HEHSC, Tribal and Agency Councils,

Executive Branch, NNEPA, GIB

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Funding:

• NIEHS (16 yrs)
• CDC/ATSDR (5 yrs)
• USEPA Region 9 Superfund Emergency

Response (4yrs)

• NIMHHD (4 yrs)
• NNEPA (1 yr)
• NIAAA (3 yrs)
• NIGMS K12 (2 yrs)

Current DiNEH & NBCS Teams UNM-HSC Johnnye Lewis, Ph.D. David Begay, Ph.D. Curtis Miller, Ph.D. Eszter Erdei, Ph.D. Courtney Burnette, Ph.D. Laurie Hudson, Ph.D. Debra MacKenzie, Ph.D. Lauren Hund, Ph.D. Karen Cooper, Ph.D. Matt Campen, Ph.D. Jim Liu, Ph.D. Chris Vining, MS, SLP Becky Smith Carla Chavez Miranda Cajero Bernadette Pacheco Jennifer Ong Shea McClain CJ Laselute Malcolm Benally Elena O’Donald, Ph.D. Molly Harmon Joseph Hoover, Ph.D. Vanessa De La Rosa, Ph.D. Erica Dashner, Ph.D. Ji-Hyun Lee Li Luo Ruofei Du SRIC Chris Shuey, MPH Lynda Lasiloo Sandy Ramone Teddy Nez Maria Welch CDC/ATSDR/DLS/IRAT Angela Ragin-Wilson, Ph.D. Candis Hunter, MSPH Elizabeth Irvin-Barnwell, Ph.D. Kathleen Caldwell, Ph.D. Cynthia Weekfall NAIHS Doug Peter, M.D. Johnna Rogers, RN Ursula Knoki-Wilson, CNM, MSN Charlotte Swindal, CNM, RN Diedre Sam Lorraine Barton Lisa Kear, RN Marcia Tapaha Francine Begay Myra Francisco PL-638 HOSPITALS Delila Begay Abigail Sanders Navajo Nation NNDOH Mae-Gilene Begay Anna Rondon Qutarah Anderson Roxanne Thompson Melissa Samuel Doris Tsinnijinnie Josey Watson Nikki Begay NNEPA Stephen Etsitty Yolanda Barney Freida White Chandra Manandhar Vivian Craig Eugenia Quintana CONSULTANTS Perry Charley Adrienne Ettinger, Ph.D. USEPA – Region 9 Clancy Tenley Linda Reeves Harry Allen Rich Bauer

Di NEH and NBCS Resear c h i s r evi ewed and moni to r e d by Navaj o Nati on Huma n Resear c h Revi ew Boar d

(Navajo Team Members-Bold)

Community Environmental Health Program

Native EH Equity Team

University of New Mexico (UNM)

Co-PIs: Johnnye Lewis, Ph.D. and Melissa Gonzales, Ph.D. Debra MacKenzie, Ph.D. Laurie Hudson, Ph.D. Eszter Erdei, Ph.D. Jose Cerrato, Ph.D. Lucia Rodriguez-Friere, Ph.D. Joe Hoover, Ph.D. Vanessa De La Rosa, Ph.D. Ji-Hyun Lee, Ph.D. Li Luo, Ph.D. Rufei Du, Ph.D. Miranda Cajero Elena O’Donald CJ Lasalute

Montana State University (MSU)

Deborah Keil, Ph.D. Jean Pfau, Ph.D. Mari Eggers, Ph.D.

Apsaalooke (Crow)

John Doyle (MSU, Little Big Horn College & Crow Environmental Health Steering Committee) Emery Three Irons (MSU)

Cheyenne River Sioux Lakota

Carlyle Ducheneaux (CRST Department of the Environment and Natural Resources - DENR) Misti Hebb (CRST DENR)

Southwest Research and Information Center (SRIC)

Chris Shuey, MPH

Missouri Breaks Industries

Marcia O’Leary, RN

Navajo

David Begay, Ph.D. (UNM) Clarita Lefthand-Begay, Ph.D. (U Washington) Cherie DeVore (UNM) Malcolm Benally (UNM) Ranalda Tsosie, (University of Montana)

EAC

Randolph Runs After (Lakota) Derrith Watchman-Moore (Navajo) Myra Lefthand (Apsaalooke) Michael Pollard, Ph.D. (Scripps) Ana Navas-Acien, Ph.D. (Columbia) NATIVE EH EQUITY

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Updated duties and responsibilities of NBCS field personnel

CHERS

(Community Environmental Health Research Specialist)

Navajo Division of Health (5)

CCL

(Cohort Clinical Liaison)

NAIHS and PL-638 facilities (5)

RFS

(Research Field Staff)

SRIC (5)

n recruit participants n conduct outreach to increase public

awareness;

n report outreach activities in REDCap n participate in weekly regional meetings with

CCLs, RFS

n use REDCap to administer eligibility survey

and consents/HIPAAs

n schedule and administer enrollment surveys n verify enrollments n enter survey data in REDCap n assist with home environmental

assessments, as needed

n administer post-birth developmental surveys

& assessments in REDCap

n hand out, account for incentives n liaison with CCLs and DiNEH Team n recruit participants, report outreach activities in

REDCap tracking log

n coordinate in weekly CCL calls n coordinate weekly regional meetings n administer eligibility survey in REDCap n administer consents & HIPAA in clinic n confirm pregnancy; complete enrollment n ensure all biological samples collected for mother,

father, baby

n coordinate storage, tracking, processing, shipping

& CofC of biological samples

n administer food frequency questionnaire (FFQ) at

36-week prenatal visit

n abstract participant medical records; enter data in

REDCap

n track deliveries promptly in REDCap n hand out, account for incentives n monitor participants to identify and report

unanticipated problems, adverse events

n be point-of-contact for clinicians n regularly communicate with OB/GYN, L&D and lab

staffs

n recruit participants n conduct outreach to increase public

awareness;

n report outreach activities in

REDCap

n participate in weekly regional

meetings with CCLs, CHERSs

n conduct staff trainings; n use REDCap to administer

eligibility survey and consents/HIPAA in clinic

n use Navajo language and cultural

experience, expertise;

n maintain regular contact with

NNEPA, other partner agencies to ensure consistency of training, survey administration, in-home assessments;

n coordinate scheduling and conduct

home environmental assessments

n enter home environmental

assessment data in REDCap

n administer post-birth

developmental surveys & assessments in REDCap