Grantee Research Project Results

2011 Progress Report: An Epidemiologic Study of Time Trends and Health Effects of Persistent Organic Pollutants, Mercury and Micronutrients

EPA Grant Number: R833705
Title: An Epidemiologic Study of Time Trends and Health Effects of Persistent Organic Pollutants, Mercury and Micronutrients
Investigators: Berner, James E.
Institution: Alaska Native Tribal Health Consortium
EPA Project Officer: Aja, Hayley
Project Period: June 1, 2009 through May 31, 2013 (Extended to May 31, 2015)
Project Period Covered by this Report: June 1, 2011 through May 31,2012
Project Amount: $948,121
RFA: Issues in Tribal Environmental Research and Health Promotion: Novel Approaches for Assessing and Managing Cumulative Risks and Impacts of Global Climate Change (2007) RFA Text |  Recipients Lists
Research Category: Environmental Justice , Climate Change , Tribal Environmental Health Research , Human Health

Objective:

1. Determine current maternal blood levels of persistent organic pollutants (POP), heavy metals and micronutrients, and compare these levels to previous cohorts of pregnant women in 1999-2002, 2004-2006.
2. Look for associations between levels of POPs, heavy metals and micronutrients and positive and negative health outcomes in mothers and infants.
3. Measure blood pressure in children born to mothers recruited in 1999-2004 to determine any relationship of prenatal Hg exposure of childhood blood pressure.
4. Measure tissue levels of POPs, heavy metal in Pacific salmon caught in the Yukon and Kuskokwim Rivers to compare at time trends in the Bering Sea and the North Pacific Ocean contaminant levels, by comparison with a study in 2001, possibly influenced by climate-induced changes in Asian river flow.

Progress Summary:

Research Objective 1

Recruitment reached 160 Yupik women and has stopped. Rising costs of travel for recruitment and costs of human blood analysis, since the original grant budget was approved, mean that the cohort size will be limited to 160 women and their infants. The last pregnant woman to enter the cohort is scheduled to deliver in February 2013, and her infant will reach 12 months of age in February 2014.

The prior two cohorts, 1999-2002 and 2004-2006, have undergone additional data review; review of most of the charts that were missing from earlier reviews have been done. Preliminary data are included in this report, and will be discussed in this section and in Research Objective 2. Preliminary descriptive statistical analyses have been performed on late data, including brominated flame retardants and fluorinated compounds.
Brominated and fluorinated compounds are not included in this report, as the data were completed well after the legacy POPs and metals data. Salmon tissue levels have not been returned from the U.S. Fish and Wildlife Service (USFWS) contract laboratory yet, but are expected this fall. Only 95 fatty acid analyses have been performed on maternal blood from the first two cohorts, and comparative data with a cohort of Inupiat mothers is presented in this report.

Correlative data from legacy POPs, omega-3 fatty acids (O-3FAs) and Hg are presented in Table 3. The remainder of the fatty acid specimens will be processed with the samples in the current cohort.

Results:
The demographic data from the initial two cohorts of Yupik pregnant women are shown in Table 1 below.

Table 1 - Maternal Demographics; Cohort I, 1999-2002 and Cohort II, 2004-2007

Data for all moms N=418
Age Group*	n	%
14-18	31	7.6%
19-25	180	43.9%
26-35	160	39.0%
36-45	38	9.3%
45+	1	0.2%
Location
A - Bethel	354	84.7%
B - Barrow	57	13.6%
C – A/P Islands	7	1.7%
Medical Abstracts
Y	371	88.8%
N	47	11.2%
Data below is for moms with medical abstracts N=371
Birth Outcomes
Live Birth	332	89.5%
Missing/Unknown	23	6.2%
Spontaneous Abortion	13	3.5%
Stillborn	3	0.8%
Breastfeeding
Not Available	93	25.1%
No	48	12.9%
Yes	230	62.0%
Alcohol use
Not Available	57	15.4%
No	258	69.5%
Yes	56	15.1%
Smoke at home
Don’t know	154	41.5%
No	95	25.6%
Yes	122	32.9%
Pregnancy abnormality
Not Available	29	7.8%
No	136	36.7%
Yes	206	55.5%
Delivery abnormality
Not Available	62	16.5%
No	197	53.2%
Yes	112	30.3%
Illicit drugs
Not Available	71	19.1%
No	271	73.0%
Yes	29	7.8%
Therapeutic Drugs
Not Available	60	16.2%
No	173	46.6%
Yes	138	37.2%

*Age data not available for eight (8) of the mothers

Initial data from this cohort on risk factors, including tobacco and alcohol, are shown but at this time, data on underlying disease and pregnancy associated conditions have not been added, as that has not yet been reviewed. Compared to the U.S. all races population data, the Yupik women are younger and have more children.

Comparisons of geometric mean blood levels of legacy POPs between the first two Yupik cohorts are shown in Table 2.

 

Table 2. Geometric mean levels (lipid adjusted) selected POPs detected in at least 60% of the serum samples collected from a population of Alaska Native women – 1999 - 2006, residing in the Yukon-Kuskokwim Delta.

Analyte	Total		Cohort 1 1999 - 2202		Cohort 2 2003 -2006
	N	Geo Mean	N	Geo Mean	N	Geo Mean
Persistent pesticides
p,p’,-DDE	339	125.97	136	129.66	203	123.56
Hexachlorobenzene	329	20.52	127		202	21.91
Mirex	339		136		203
Oxychlordane	329	13.40	133	14.82	196	12.51
B-Hexachlorocyclohexane	332	7.64	133	10.51	199	6.17
y-Hexachlorocyclohexane	332		133		199
o,p’-DDT	341		136		205
p,p’-DDT	337		133		204
trans-Nonachlor	335	20.55	133	19.30	202	21.42
Polychlorinated biphenyls
138/158	344	15.30	142	17.08	202	14.16
153	345	27.86	142	33.92	203	24.15
180	345	11.24	142	13.18	203	10.06

 

Care in interpreting any differences between the two groups should be exercised, as there appear to be differences between residents of coastal villages compared to riverine villages, which may reflect the greater intake of top predator sea mammals in coastal communities, and thus higher levels of both POPs and Hg. Further analysis will be carried out on these two categories of residents when the currently recruited cohort data are available.

Comparisons of Yupik women from the first two cohorts and other pregnant circumpolar populations in the AMAP Maternal Blood Monitoring Program are shown in Figure 1 below.

As can be seen, Yupik women are very similar in blood levels of legacy POPs to most other populations, and are most similar to western Canadian Inuit women.

Results of the preliminary correlations between POPs, O-3 FAs, and blood levels of Hg are shown in Table 3, shown below.

 

Table 3. Pearson Correlation Coefficients for Maternal Contaminant and micronutrient values Cohorts I and II Prob>[r] under H0: Rho=0 Number of Observations

	PP_DDE	PP_DDT	T_NONA	PCB	THG	C22_6w3	C18_2w6	C183w6	C20_4w6	Screening OGT	Birth Wt. Grams
PP_DDE PP_DDE	1.00000 306	0.65006 <.0001 303	0.70876 <.0001 303	0.77699 <.0001 306	0.30373 <.0001 294	0.27114 0.0082 94	0.23397 0.0225 95	0.08369 0.4226 94	0.07755 0.4551 95	0.02293 0.7980 127	-0.12537 0.0576 230
PP_DDT PP_DDT	0.65006 <.0001 303	1.00000 303	0.61184 <.0001 303	0.58892 <.0001 303	0.38919 <.0001 291	0.34373 0.0009 91	0.32580 0.0015 92	0.25241 0.0158 91	0.22401 0.0318 92	0.14939 0.0937 127	-0.12483 0.0604 227
T_NONA T_NONA	0.70876 <.0001 303	0.61184 <.0001 303	1.00000 303	0.85264 <.0001 303	0.42018 <.0001 291	0.50092 <.0001 91	0.31984 0.0019 92	0.10068 0.3423 91	0.19635 0.0607 92	0.06693 0.4547 127	-0.10290 0.1221 227
PCB PCB153	0.77699 <.0001 306	0.58892 <.0001 303	0.85264 <.0001 303	1.00000 306	0.43228 <.0001 294	0.43866 <.0001 94	0.20217 0.0494 95	-0.01647 0.8748 94	0.08225 0.4281 95	0.05415 0.5454 127	-0.08770 0.1851 230
THG THG	0.30373 <.0001 294	0.38919 <.0001	0.42018 <.0001 291	0.43228 <.0001 294	1.00000 294	0.65845 <.0001 94	0.00275 0.9789 95	-0.18426 0.0754 94	0.25018 0.0145 95	0.06655 0.4702 120	-0.08466 0.2079 223
C22_6w3 C22:6w3	0.27114 0.0082 94	0.34373 0.0009 91	0.50092 <.0001 91	0.43866 <.0001 94	0.65845 <.0001 94	1.00000 94	0.37976 0.0002 94	0.01562 0.8819 93	0.51424 <.0001 94	0	-0.08727 0.4385 81
C18_2w6 C18:2w6	0.23397 0.0225 95	0.32580 0.0015 92	0.31984 0.0019 92	0.20217 0.0494 95	0.00275 0.9789 95	0.37976 0.0002 94	1.00000 95	0.48841 <.0001 94	0.22701 0.0269 95	0	-0.21431 0.0532 82
C18_3w6 C18:3w6	0.08369 0.4226 94	0.25241 0.0158 91	0.10068 0.3423 91	-0.01645 0.8748 94	-0.18426 0.0754 94	0.01562 0.8819 93	0.48841 <.0001 94	1.00000 94	-0.02434 0.8159 94	0	-0.30732 0.0050 82
C20_4w6 C20:4w6	0.07755 0.4551 95	0.22401 0.0318 92	0.19635 0.0607 92	0.08225 0.4281 95	0.25018 0.0145 95	0.51424 <.0001 94	0.22701 0.0269 95	-0.02434 0.8159 94	1.00000 95	0	0.03474 0.7567 82
Screening OGT	0.02293 0.7980 127	0.14939 0.0937 127	0.06693 0.4547 127	0.05415 0.5454 127	0.06655 0.4702 120	0	0	0	0	1.00000 127	0.08825 0.4002 93
Birth Weight Grams	-0.12537 0.0576 230	-0.12483 0.0604 227	-0.10290 0.1221 227	-0.08770 0.1851 230	-0.08466 0.2079 223	-0.08727 0.4385 81	-0.21431 0.0532 82	-.30732 0.0050 82	0.03474 0.7567 82	0.08825 0.4002 93	1.00000 230
Prepreg Weight_lb	-0.10439 0.0857 272	0.05695 0.3522 269	-0.05309 0.3858 269	-0.08261 0.1743 272	-0.04878 0.4326 261	-0.12397 0.2702 81	-0.00173 0.9877 82	-0.03210 0.7760 81	0.10606 0.3430 82	0.12825 0.1701 116	0.26822 <.0001 209

These data demonstrate several interesting findings:

1. There is a strong positive correlation between the blood levels of legacy POPs, indicating that exposure is from a common source, in this case, marine fish (mostly salmon) and marine mammals.
2. There is a similarly strong positive correlation between blood Hg level and legacy POPs, indicating that Hg exposure is from the same source as POPs.
3. There is a strong positive correlation between O3-FAs, Hg, and POPs, indicative of this valuable micronutrient being found in the same subsistence food sources as Hg and POPs.

The data for any correlations of brominated flame retardants (BFRs) and polyfluorinated compounds have not been statistically examined yet, but levels in specimens from the first two cohorts show levels of BFRs similar to U.S. NHANES data in pregnant women, and far higher than levels in Europe. These are shown in Figure 2 below.

This analysis will be completed this fall. Because these compounds also are found in most residences, exposure to these may, or may not, be related to subsistence foods. Data from the salmon tissue also will provide evidence for, or against, marine sources for these compounds.

Research Objective 2

An analysis of prenatal and neonatal health metrics has been performed and a list has tentatively been selected based on prevalence in the first two cohorts. At present, the health metrics include spontaneous abortion, preterm delivery, length of pregnancy, birth weight, hypertensive disorders in pregnancy, results of oral glucose challenge screening and congenital anomalies. Neonatal metrics include hospitalizations due to infection, growth abnormalities, and developmental abnormalities. Other metrics and outcomes also will be examined, and possibly added to the analysis, depending on the statistical characteristics of the metric.

Of interest is a significant negative association of urine Hg levels in mothers, with infant birth weight, and head circumference. These data are not included in Table 3, but will be a part of the MOM Study paper that is in preparation. This association has never been previously observed, and it will be important to add the current cohort numbers to those already analyzed to see if the association persists.

Research Objective 3

This objective will be accomplished in the final 6 months of the grant, as the youngest children in Cohort 2 will have reached the age of 7 years and BP obtained at that age, or older, will replicate the ages of the Faroe Island cohort of children in whom the association between BP and prenatal mercury exposure was first documented. This will entail chart reviews, as travel to the small villages in the Yukon-Kuskokwim Delta has become very expensive.

Research Objective 4

Salmon tissue samples for this objective now are in the USFWS contract laboratory, and the results will be available this fall, according to the USFWS. These results will be examined for any significant changes from the 2001 samples, done in the same species, from the same rivers, at the same locations, by the same laboratory. The salmon results will be compared to human tissue levels, for organochlorines, brominated and fluorinated compounds, and metals.

Future Activities:

Year 4 will concentrate on completion of the fatty acid analyses and the POP and heavy metal analyses from the current cohort of mothers and infants. Continuing efforts to complete the data from charts of prior cohorts will continue, with presentations to tribal groups in Alaska on the initial results of both human and salmon tissue analyses; IRB, agency and tribal approval of papers from the analyses; and submission of the papers to journals. In addition, chart reviews of the current cohort will begin this fall for the mothers and infants already having reached 1 year of age. The collaborators at the National Institutes of Health will work with the PI to determine if any single contaminant, or group of contaminants, is associated with risk of an abnormal response to the prenatal oral glucose challenge. The salmon tissue levels of brominated flame retardants and fluorinated compounds will be examined for any evidence that they are related to human tissue levels of those compounds, as both are found in indoor environments as well. The evaluation of cord blood will need to wait until collection is complete and the results are analyzed, and then these data will undergo evaluation for association with infant outcomes.

It will take an additional year to complete the activities of the grant, for the reasons outlined above. The grant will have sufficient funding for the extension year’s activities, by our current calculations.

ANTHC would like to request a 12 month no-cost extension to ensure that all of the grant activities are completed. The PI will undertake to complete any remaining work after that time with in-kind resources.

Journal Articles:

No journal articles submitted with this report: View all 54 publications for this project

Supplemental Keywords:

Micronutrients, salmon, gestational diabetes mellitus, persistent organic pollutants, heavy metals

Progress and Final Reports:

Original Abstract

2009 Progress Report

2010 Progress Report

2012 Progress Report

2013

Final Report