In Utero Exposure to Metals and Birth Outcomes in an Artisanal and Small-Scale Gold Mining Birth Cohort in Madre de Dios, Peru.

BACKGROUND: Few birth cohorts in South America evaluate the joint effect of minerals and toxic metals on neonatal health. In Madre de Dios, Peru, mercury exposure is prevalent owing to artisanal gold mining, yet its effect on neonatal health is unknown. OBJECTIVES: We aimed to determine whether toxic metals are associated with lower birth weight and shorter gestational age independently of antenatal care and other maternal well-being factors. METHODS: Data are from the COhorte de NAcimiento de MAdre de Dios (CONAMAD) birth cohort, which enrolled pregnant women in Madre de Dios prior to their third trimester and obtained maternal and cord blood samples at birth. We use structural equation models (SEMs) to construct latent variables for the maternal metals environment (ME) and the fetal environment (FE) using concentrations of calcium, iron, selenium, zinc, magnesium, mercury, lead, and arsenic measured in maternal and cord blood, respectively. We then assessed the relationship between the latent variables ME and FE, toxic metals, prenatal visits, hypertension, and their effect on gestational age and birth weight. RESULTS: Among 198 mothers successfully enrolled and followed at birth, 29% had blood mercury levels that exceeded the U.S. Centers for Disease Control and Prevention threshold of 5.8µg/L and 2 mothers surpassed the former 5-µg/dL threshold for blood lead. The current threshold value is 3.5µg/dL. Minerals and toxic metals loaded onto ME and FE latent variables. ME was associated with FE (ß=0.24; 95% CI: 0.05, 0.45). FE was associated with longer gestational age (ß=2.31; 95% CI: -0.3, 4.51) and heavier birth weight. Mercury exposure was not directly associated with health outcomes. A 1% increase in maternal blood lead shortened gestational age by 0.05 d (ß=-0.75; 95% CI: -1.51, -0.13), which at the 5-µg/dL threshold resulted in a loss of 3.6 gestational days and 76.5g in birth weight for newborns. Prenatal care visits were associated with improved birth outcomes, with a doubling of visits from 6 to 12 associated with 5.5 more gestational days (95% CI: 1.6, 9.4) and 319g of birth weight (95% CI: 287.6, 350.7). DISCUSSION: Maternal lead, even at low exposures, was associated with shorter gestation and lower birth weight. Studies that focus only on harmful exposures or nutrition may mischaracterize the dynamic maternal ME and FE. SEMs provide a framework to evaluate these complex relationships during pregnancy and reduce overcontrolling that can occur with linear regression. https://doi.org/10.1289/EHP10557.

Risk of lead exposure from wild game consumption from cross-sectional studies in Madre de Dios, Peru.

Background: Studies have shown elevated blood lead levels (BLL) in residents of remote communities in the Amazon, yet sources of lead exposure are not fully understood, such as lead ammunition consumed in wild game. Methods: Data was collected during two cross-sectional studies that enrolled 307 individuals in 26 communities. Regression models with community random effects were used to evaluate risk factors for BLLs, including diet, water source, smoking, sex, age, and indigenous status. The All-Ages Lead Model (AALM) from the Environmental Protection Agency (EPA) was used to estimate background and dose from wild game consumption. Findings: Indigenous status and wild game consumption were associated with increased BLLs. Indigenous participants had 2.52 µg/dL (95% CI: 1.95-3.24) higher BLLs compared to non-indigenous. Eating wild game was associated with a 1.41 µg/dL (95% CI: 1.20-1.70) increase in BLLs. Two or more portions per serving were associated with increased BLLs of 1.66 µg/dL (95% CI: 1.10-2.57), compared to smaller servings. Using the AALM, we estimate background lead exposures to be 20 µg/day with consumption of wild game contributing 500 µg/meal. Lastly, we found a strong association between BLLs and mercury exposure. Interpretation: Consumption of wild game hunted with lead ammunition may pose a common source of lead exposure in the Amazon. Communities that rely on wild game and wild fish may face a dual burden of exposure to lead and mercury, respectively.

Efficacy of Hair Total Mercury Content as a Biomarker of Methylmercury Exposure to Communities in the Area of Artisanal and Small-Scale Gold Mining in Madre de Dios, Peru.

Total mercury content (THg) in hair is an accepted biomarker for chronic dietary methylmercury (MeHg) exposure. In artisanal and small-scale gold mining (ASGM) communities, the validity of this biomarker is questioned because of the potential for contamination from inorganic mercury. As mining communities may have both inorganic and organic mercury exposures, the efficacy of the hair-THg biomarker needs to be evaluated, particularly as nations begin population exposure assessments under their commitments to the Minamata Convention. We sought to validate the efficacy of hair THg for public health monitoring of MeHg exposures for populations living in ASGM communities. We quantified both THg and MeHg contents in hair from a representative subset of participants (N = 287) in a large, population-level mercury exposure assessment in the ASGM region in Madre de Dios (MDD), Peru. We compared population MeHg-THg correlations and %MeHg values with demographic variables including community location, sex, occupation, and nativity. We observed that hair MeHg-THg correlations were high (r > 0.7) for all communities, regardless of location or nativity. Specifically, for individuals within ASGM communities, 81% (121 of 150 total) had hair THg predominantly in the form of MeHg (i.e., >66% of THg) and reflective of dietary exposure to mercury. Furthermore, for individuals with hair THg exceeding the U.S. EPA threshold (1.0 µg/g), 88 out of 106 (83%) had MeHg as the predominant form. As a result, had urine THg solely been used for mercury exposure monitoring, approximately 59% of the ASGM population would have been misclassified as having low mercury exposure. Our results support the use of hair THg for monitoring of MeHg exposure of populations in ASGM settings where alternative biomarkers of MeHg exposure are not feasible.

CoNaMad-Cohorte de Nacimiento de Madre de Dios/Madre de Dios Birth Cohort to Study Effects of in-utero Trace Metals Exposure in the Southern Peruvian Amazon.

Background: In-utero exposure to mercury and other trace metals pose a significant threat to child health and development, but exposures and health impacts in artisanal and small-scale gold mining (ASGM) environments are poorly defined. Objectives: We describe the CONAMAD study design, a prospective birth cohort consisting of multiparous women (18 and over) living in rural and peri-urban Peruvian Amazon communities exposed to ASGM. Methods: Pregnant women are enrolled from health posts across four zones of Madre de Dios, Peru. Data are collected at enrollment, childbirth, and (planned) 36-48 months. At enrollment, hair samples for mercury assessment, demographic and clinical data are obtained. At birth, we obtain venous and cord blood, placenta, hair, toenails, and saliva. Findings: Two hundred seventy mothers were enrolled at an average 20 weeks gestational age with no differences in maternal characteristics across zones. Two hundred fifteen mothers were successfully followed at birth. We obtained 214 maternal and cord blood samples, 211 maternal and 212 infant hair samples, 212 placenta samples, 210 infant saliva samples, and 214 infant dried blood spots. Data collected will allow for testing our primary hypotheses of maternal malnutrition modifying ratios of cord:maternal blood total mercury (tHg), cord blood:maternal hair tHg, and infant:maternal hair tHg, and whether chemical mixtures (Hg, Pb, Cd) have synergistic effects on infant neurodevelopment. Conclusions: CONAMAD is designed to collect and store samples for future processing and hypothesis testing associated with in-utero mercury exposure and child development. We have completed the exposure assessments and will conduct a follow-up of mothers to evaluate early child development outcomes, including developmental delay and growth. These data offer insights into disease mechanisms, exposure prevention, and policy guidance for countries where ASGM is prevalent.

A population-based mercury exposure assessment near an artisanal and small-scale gold mining site in the Peruvian Amazon.

Human exposure to mercury is a leading public health problem. Artisanal and small-scale gold mining (ASGM) is a major source of global mercury emissions. Although occupational mercury exposure to miners (via mercury vapor inhalation) is known, chronic mercury exposure to nearby residents that are not miners (via mercury-contaminated fish consumption) is poorly characterized. We conducted a population-based mercury exposure assessment in 23 communities (19 rural, 4 urban) around the Amarakaeri Communal Reserve, which is bordered on the east by heavy ASGM activity. We measured total mercury in hair (N = 2083) and blood (N = 476) from March-June 2015 and performed follow-up measurements (N = 723 hair and N = 290 blood) from February-April 2016. Mercury exposure risk was highest in communities classified as indigenous, or native, regardless of proximity to mining activity. Residence in a native community (vs. non-native) was associated with mercury levels 1.9 times higher in hair (median native 3.5 ppm vs. median non-native 1.4 ppm total mercury) and 1.6 times higher in blood (median native 7.4 ng/mL vs median non-native 3.2 ng/mL total mercury). Unexpectedly, proximity to mining was not associated with exposure risk. These findings challenge common assumptions about mercury exposure patterns and emphasize the importance of population-representative studies to identify high risk sub-populations.

Evaluation of Peruvian Government Interventions to Reduce Childhood Anemia.

Background: In Peru, anemia has been a persistent health problem that is known to lead to irreversible cognitive and developmental deficits in children. The Peruvian government has recently made anemia a primary health concern by passing legislation in 2017 that makes anemia an intersectoral priority. This new legislation fortifies previous programs while creating new programs that target specific age groups. Objectives: Evaluate the effectiveness of government programs in Madre de Dios, Peru to reduce anemia prevalence and increase hemoglobin levels among children ages 2-11 years old. Methods: Propensity scores are used to match 688 children enrolled in 2018, after the legislation, and 2,140 children enrolled in previous studies our team conducted in the region between 2014 and 2017, based on sex, age (years), intervention status (prior/post), community income, presence of a health post in the community (yes/no), community type (indigenous, non-indigenous rural, non-indigenous urban) and road access (fraction of the number of months out of the year with road access). A pseudo matched case-control analysis to evaluate changes in anemia prevalence and hemoglobin was conducted using t-tests and multivariate models. Program effectiveness is evaluated overall, by age groups (2-4, 5-7 and 8-11 years old), and community type (indigenous vs. urban). Findings: The adjusted odds ratio indicated lower odds of anemia (OR = 0.31, 95%CI 0.17-0.54) for children exposed to the anemia prevention programs vs. those not exposed. The effect was not significantly different across age groups; however, the intervention effects significantly differed by community type among children 8-11 years old, with urban children less likely to benefit from anemia interventions (OR = 0.69, 95% CI 0.38-1.25) compared to indigenous children (OR = 0.21, 95% CI 0.08-0.56). Conclusion: Government programs to reduce anemia in Madre de Dios were found to be associated with reduced anemia prevalence in the study communities. However, the lack of program monitoring precludes the attribution of anemia decline to specific interventions or program components. In addition, regional anemia prevalence remains high according to the 2019 Demographic and Health Survey, suggesting impaired population impact. Program monitoring and evaluation is a key component of health interventions to improve program implementation effectiveness.

Deforestation Due to Artisanal and Small-Scale Gold Mining Exacerbates Soil and Mercury Mobilization in Madre de Dios, Peru.

Artisanal and small-scale gold mining (ASGM) is a significant contributor of mercury (Hg) contamination and deforestation across the globe. In the Colorado River watershed in Madre de Dios, Peru, mining and deforestation have increased exponentially since the 1980s, resulting in major socioeconomic shifts in the region and two national state of emergency (2016 and 2019) in response to concerns for wide-scale mercury poisoning by these activities. This research employed a watershed-scale soil particle detachment model and environmental field sampling to estimate the role of land cover change and soil erosion on river transport of Hg in a heavily ASGM-impacted watershed. The model estimated that observed decreases in forest cover increased soil mobilization by a factor of two in the Colorado River watershed during the 18 year period and by 4-fold in the Puquiri subwatershed (the area of most concentrated ASGM activity). If deforestation continues to increase at its current exponential rate through 2030, the annual mobilization of soil and Hg may increase by an additional 20-25% relative to 2014 levels. While, the estimated total mass of Hg transported by rivers is substantially less than the estimated tons of Hg used with ASGM in Peru, this research shows that deforestation associated with ASGM is an additional mechanism for mobilizing naturally occurring and anthropogenic Hg from terrestrial landscapes to aquatic environments in the region, potentially leading to bioaccumulation in fish and exposure to communities downstream.

Predictors of mitochondrial DNA copy number and damage in a mercury-exposed rural Peruvian population near artisanal and small-scale gold mining: An exploratory study.

Mitochondrial DNA (mtDNA) copy number (CN) and damage in circulating white blood cells have been proposed as effect biomarkers for pollutant exposures. Studies have shown that mercury accumulates in mitochondria and affects mitochondrial function and integrity; however, these data are derived largely from experiments in model systems, rather than human population studies that evaluate the potential utility of mitochondrial exposure biomarkers. We measured mtDNA CN and damage in white blood cells (WBCs) from 83 residents of nine communities in the Madre de Dios region of the Peruvian Amazon that vary in proximity to artisanal and small-scale gold mining. Prior research from this region reported high levels of mercury in fish and a significant association between food consumption and human total hair mercury level of residents. We observed that mtDNA CN and damage were both associated with consumption of fruit and vegetables, higher diversity of fruit consumed, residential location, and health characteristics, suggesting common environmental drivers. Surprisingly, we observed negative associations of mtDNA damage with both obesity and age. We did not observe any association between total hair mercury or, in contrast to previous results, age, with either mtDNA damage or CN. The results of this exploratory study highlight the importance of combining epidemiological and laboratory research in studying the effects of stressors on mitochondria, suggesting that future work should incorporate nutritional and social characteristics, and caution should be taken when applying conclusions from epidemiological studies conducted in the developed world to other regions, as results may not be easily translated. Environ. Mol. Mutagen. 60: 197-210, 2019. © 2018 Wiley Periodicals, Inc.

Hair Mercury Level is Associated with Anemia and Micronutrient Status in Children Living Near Artisanal and Small-Scale Gold Mining in the Peruvian Amazon.

Anemia has been widely studied in global health contexts because of severe nutritional deficiency, and more recently, inflammatory status, but chemical exposures are rarely considered. Until recently, "anemia" was used synonymously with "iron deficiency anemia (IDA)" in global health settings. However, only 50% of anemia cases worldwide are IDA. Environmental toxicology studies of anemia risk have generally focused on populations in developed countries, albeit with high exposure to environmental toxicants, such as lead or cadmium. In the developing world, toxicant exposures commonly coexist with other risk factors for anemia. In particular, artisanal and small-scale gold mining (ASGM) communities are at risk for dietary methylmercury exposure through contaminated fish consumption, and for anemia due to food insecurity and infectious and chronic diseases. Here, we report analysis of total hair mercury content, hemoglobin, and serum micronutrient levels in children < 12 years of age (N = 83) near ASGM in the Peruvian Amazon. Forty-nine percent (N = 29/59) of those aged < 5 years were anemic (< 11 g/dL) and 52% (N = 12/23) of those aged 5-11 years (< 11.5 g/dL). Few children were stunted, wasted, or micronutrient deficient. Median total hair mercury was 1.18 µg/g (range: 0.06-9.70 µg/g). We found an inverse association between total mercury and hemoglobin (ß = -0.12 g/dL, P = 0.06) that persisted (ß = -0.14 g/dL, P = 0.04) after adjusting for age, sex, anthropometrics, and vitamin B12 in multivariate regression. This study provides preliminary evidence that methylmercury exposure is associated with anemia, which is especially relevant to children living near ASGM.