Prenatal Arsenic Exposure and Birth Outcomes among a Population Residing near a Mining-Related Superfund Site

Birgit Claus Henn, Adrienne S Ettinger, Marianne R Hopkins, Rebecca Jim, Chitra Amarasiriwardena, David C Christiani, Brent A Coull, David C Bellinger, Robert O Wright, Birgit Claus Henn, Adrienne S Ettinger, Marianne R Hopkins, Rebecca Jim, Chitra Amarasiriwardena, David C Christiani, Brent A Coull, David C Bellinger, Robert O Wright

Abstract

Background: Limited epidemiologic data exist on prenatal arsenic exposure and fetal growth, particularly in the context of co-exposure to other toxic metals.

Objective: We examined whether prenatal arsenic exposure predicts birth outcomes among a rural U.S. population, while adjusting for exposure to lead and manganese.

Methods: We collected maternal and umbilical cord blood samples at delivery from 622 mother-infant pairs residing near a mining-related Superfund site in Northeast Oklahoma. Whole blood arsenic, lead, and manganese were measured using inductively coupled plasma mass spectrometry. We modeled associations between arsenic concentrations and birth weight, gestational age, head circumference, and birth weight for gestational age.

Results: Median (25th-75th percentile) maternal and umbilical cord blood metal concentrations, respectively, were as follows: arsenic, 1.4 (1.0-2.3) and 2.4 (1.8-3.3) μg/L; lead, 0.6 (0.4-0.9) and 0.4 (0.3-0.6) μg/dL; manganese, 22.7 (18.8-29.3) and 41.7 (32.2-50.4) μg/L. We estimated negative associations between maternal blood arsenic concentrations and birth outcomes. In multivariable regression models adjusted for lead and manganese, an interquartile range increase in maternal blood arsenic was associated with -77.5 g (95% CI: -127.8, -27.3) birth weight, -0.13 weeks (95% CI: -0.27, 0.01) gestation, -0.22 cm (95% CI: -0.42, -0.03) head circumference, and -0.14 (95% CI: -0.24, -0.04) birth weight for gestational age z-score units. Interactions between arsenic concentrations and lead or manganese were not statistically significant.

Conclusions: In a population with environmental exposure levels similar to the U.S. general population, maternal blood arsenic was negatively associated with fetal growth. Given the potential for relatively common fetal and early childhood arsenic exposures, our finding that prenatal arsenic can adversely affect birth outcomes is of considerable public health importance.

Citation: Claus Henn B, Ettinger AS, Hopkins MR, Jim R, Amarasiriwardena C, Christiani DC, Coull BA, Bellinger DC, Wright RO. 2016. Prenatal arsenic exposure and birth outcomes among a population residing near a mining-related Superfund site. Environ Health Perspect 124:1308-1315; http://dx.doi.org/10.1289/ehp.1510070.

Conflict of interest statement

Within the last 3 years, D.C.B. has provided paid expert witness testimony in several civil litigation cases involving exposure to neurotoxicants. D.C.B. has also provided expert witness testimony in a criminal case on behalf of the Capital Punishment Project of the American Civil Liberties Union. and is a paid member of the Biology and Medicine Panel of the Research Grants Council of Hong Kong. R.J. is employed by Local Environmental Action Demanded (L.E.A.D.) Agency, Inc., Vinita, OK, a 501 c 3 organization. The goals of L.E.A.D. are to educate the community on environmental concerns in Northeast Oklahoma, including conducting environmental workshops and seminars; to counter environmental hazards that put local communities at risk; and to partner with other environmental organizations throughout Oklahoma and the nation to address environmental hazards.

The other authors declare they have no actual or potential competing financial interests.

Figures

Figure 1
Figure 1
Effect estimates and 95% confidence intervals for quartiles of maternal blood arsenic with birth weight (BW), gestational age (GA), weight for gestational age (BW for GA), and head circumference (HC). Generalized additive models include maternal blood lead and manganese (smoothed), maternal age at delivery (smoothed), infant sex, race/ethnicity, parity, smoking during pregnancy, maternal education, prenatal vitamin use, and maternal hemoglobin at delivery (n = 596 for BW, GA, BW for GA; n = 574 for HC). Dashed horizontal line represents null association.
Figure 2
Figure 2
Effect estimates and 95% confidence intervals for quartiles of cord blood arsenic with birth weight (BW), gestational age (GA), weight for gestational age (BW for GA), and head circumference (HC). Generalized additive models include cord blood lead and manganese (smoothed), maternal age at delivery (smoothed), infant sex, race/ethnicity, parity, smoking during pregnancy, maternal education, prenatal vitamin use, and maternal hemoglobin at delivery (n = 588 for BW, GA, BW for GA; n = 565 for HC). Dashed horizontal line represents null association.

References

    1. ACOG (American College of Obstetricians and Gynecologists) Committee opinion no 611: method for estimating due date. Obstet Gynecol. 2014;124:863–866.
    1. Ahmed S, Ahsan KB, Kippler M, Mily A, Wagatsuma Y, Hoque AM, et al. In utero arsenic exposure is associated with impaired thymic function in newborns possibly via oxidative stress and apoptosis. Toxicol Sci. 2012;129:305–314.
    1. Ahmed S, Mahabbat-e Khoda S, Rekha RS, Gardner RM, Ameer SS, Moore S, et al. 2011. Arsenic-associated oxidative stress, inflammation, and immune disruption in human placenta and cord blood. Environ Health Perspect 119 258 264, doi:10.1289/ehp.1002086
    1. American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 95: anemia in pregnancy. Obstet Gynecol. 2008;112(1):201–207.
    1. Bailey KA, Fry RC. Arsenic-associated changes to the epigenome: what are the functional consequences? Curr Environ Health Rep. 2014;1:22–34.
    1. Bevington PR, Robinson DK. New York: McGraw Hill; 2003. Data Reduction and Error Analysis for the Physical Sciences. 3rd ed.
    1. Bloom MS, Surdu S, Neamtiu IA, Gurzau ES. Maternal arsenic exposure and birth outcomes: a comprehensive review of the epidemiologic literature focused on drinking water. Int J Hyg Environ Health. 2014;217:709–719.
    1. Calderón J, Navarro ME, Jimenez-Capdeville ME, Santos-Diaz MA, Golden A, Rodriguez-Leyva I, et al. Exposure to arsenic and lead and neuropsychological development in Mexican children. Environ Res. 2001;85:69–76.
    1. CDC (Centers for Disease Control and Prevention) Recommendations to Prevent and Control Iron Deficiency in the United States. MMWR. 1998;47(RR-3):1–36. Available: [accessed 28 June 2016]
    1. Chen KL, Amarasiriwardena CJ, Christiani DC. Determination of total arsenic concentrations in nails by inductively coupled plasma mass spectrometry. Biol Trace Elem Res. 1999;67:109–125.
    1. Chen L, Ding G, Gao Y, Wang P, Shi R, Huang H, et al. Manganese concentrations in maternal-infant blood and birth weight. Environ Sci Pollut Res Int. 2014;21:6170–6175.
    1. Cochran WG, Carroll SP. A sampling investigation of the efficiency of weighting inversely as the estimated variance. Biometrics. 1953;9:447–459.
    1. Concha G, Vogler G, Lezcano D, Nermell B, Vahter M. Exposure to inorganic arsenic metabolites during early human development. Toxicol Sci. 1998;44:185–190.
    1. Delves HT, Clayton BE, Bicknell J. Concentration of trace metals in the blood of children. Br J Prev Soc Med. 1973;27:100–107.
    1. Engström KS, Vahter M, Johansson G, Lindh CH, Teichert F, Singh R, et al. Chronic exposure to cadmium and arsenic strongly influences concentrations of 8-oxo-7,8-dihydro-2’-deoxyguanosine in urine. Free Radic Biol Med. 2010;48:1211–1217.
    1. Ettinger AS, Zota AR, Amarasiriwardena CJ, Hopkins MR, Schwartz J, Hu H, et al. 2009. Maternal arsenic exposure and impaired glucose tolerance during pregnancy. Environ Health Perspect 117 1059 1064, doi:10.1289/ehp0800533
    1. Fei DL, Koestler DC, Li Z, Giambelli C, Sanchez-Mejias A, Gosse JA, et al. 2013. Association between in utero arsenic exposure, placental gene expression, and infant birth weight: a US birth cohort study. Environ Health 12 58, doi:10.1186/1476-069X-12-58
    1. Flora SJ. Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med. 2011;51:257–281.
    1. Fry RC, Navasumrit P, Valiathan C, Svensson JP, Hogan BJ, Luo M, et al. 2007. Activation of inflammation/NF-κB signaling in infants born to arsenic-exposed mothers. PLoS Genet 3 e207, doi:10.1371/journal.pgen.0030207
    1. Gilbert-Diamond D, Cottingham KL, Gruber JF, Punshon T, Sayarath V, Gandolfi AJ, et al. Rice consumption contributes to arsenic exposure in US women. Proc Natl Acad Sci USA. 2011;108:20656–20660.
    1. Gossai A, Lesseur C, Farzan S, Marsit C, Karagas MR, Gilbert-Diamond D. Association between maternal urinary arsenic species and infant cord blood leptin levels in a New Hampshire pregnancy cohort. Environ Res. 2015;136:180–186.
    1. Graziano JH, Popovac D, Factor-Litvak P, Shrout P, Kline J, Murphy MJ, et al. Determinants of elevated blood lead during pregnancy in a population surrounding a lead smelter in Kosovo, Yugoslavia. Environ Health Perspect. 1990;89:95–100.
    1. Guan H, Piao F, Zhang X, Li X, Li Q, Xu L, et al. Prenatal exposure to arsenic and its effects on fetal development in the general population of Dalian. Biol Trace Elem Res. 2012;149:10–15.
    1. Guan H, Wang M, Li X, Piao F, Li Q, Xu L, et al. Manganese concentrations in maternal and umbilical cord blood: related to birth size and environmental factors. Eur J Public Health. 2014;24:150–157.
    1. Harder T, Roepke K, Diller N, Stechling Y, Dudenhausen JW, Plagemann A. Birth weight, early weight gain, and subsequent risk of type 1 diabetes: systematic review and meta-analysis. Am J Epidemiol. 2009;169:1428–1436.
    1. Hattersley AT, Tooke JE. The fetal insulin hypothesis: an alternative explanation of the association of low birthweight with diabetes and vascular disease. Lancet. 1999;353:1789–1792.
    1. Hopenhayn C, Ferreccio C, Browning SR, Huang B, Peralta C, Gibb H, et al. Arsenic exposure from drinking water and birth weight. Epidemiology. 2003;14:593–602.
    1. Hu H, Shine J, Wright RO. The challenge posed to children’s health by mixtures of toxic waste: the Tar Creek Superfund Site as a case-study. Pediatr Clin North Am. 2007;54:155–175.
    1. Huyck KL, Kile ML, Mahiuddin G, Quamruzzaman Q, Rahman M, Breton CV, et al. Maternal arsenic exposure associated with low birth weight in Bangladesh. J Occup Environ Med. 2007;49:1097–1104.
    1. Intarasunanont P, Navasumrit P, Waraprasit S, Chaisatra K, Suk WA, Mahidol C, et al. 2012. Effects of arsenic exposure on DNA methylation in cord blood samples from newborn babies and in a human lymphoblast cell line. Environ Health 11 31, doi:10.1186/1476-069X-11-31
    1. Jackson BP, Taylor VF, Karagas MR, Punshon T, Cottingham KL. 2012. Arsenic, organic foods, and brown rice syrup. Environ Health Perspect 120 623 626, doi:10.1289/ehp.1104619
    1. Joselow MM, Tobias E, Koehler R, Coleman S, Bogden J, Gause D. Manganese pollution in the city environment and its relationship to traffic density. Am J Public Health. 1978;68:557–560.
    1. Kippler M, Wagatsuma Y, Rahman A, Nermell B, Persson LÅ, Raqib R, et al. Environmental exposure to arsenic and cadmium during pregnancy and fetal size: a longitudinal study in rural Bangladesh. Reprod Toxicol. 2012;34:504–511.
    1. Kordas K, Ettinger AS, Lamadrid-Figueroa H, Tellez-Rojo MM, Hérnandez-Avila M, Hu H, et al. Methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and G1793A genotypes, and the relationship between maternal folate intake, tibia lead and infant size at birth. Br J Nutr. 2009;102:907–914.
    1. Krachler M, Rossipal E, Micetic-Turk D. Trace element transfer from the mother to the newborn—investigations on triplets of colostrum, maternal and umbilical cord sera. Eur J Clin Nutr. 1999;53:486–494.
    1. Mantzoros CS, Rifas-Shiman SL, Williams CJ, Fargnoli JL, Kelesidis T, Gillman MW. Cord blood leptin and adiponectin as predictors of adiposity in children at 3 years of age: a prospective cohort study. Pediatrics. 2009;123:682–689.
    1. Misra DP, Nguyen RH. Environmental tobacco smoke and low birth weight: a hazard in the workplace? Environ Health Perspect. 1999;107(suppl 6):897–904.
    1. Molin M, Ulven SM, Meltzer HM, Alexander J. Arsenic in the human food chain, biotransformation and toxicology—review focusing on seafood arsenic. J Trace Elem Med Biol. 2015;31:249–259.
    1. Navas-Acien A, Silbergeld EK, Pastor-Barriuso R, Guallar E. Arsenic exposure and prevalence of type 2 diabetes in US adults. JAMA. 2008;300:814–822.
    1. NRC (National Research Council) Washington, DC: National Academies Press; 1999. Arsenic in Drinking Water. Subcommittee on arsenic in drinking water.
    1. Oken E, Kleinman KP, Olsen SF, Rich-Edwards JW, Gillman MW. Associations of seafood and elongated n-3 fatty acid intake with fetal growth and length of gestation: results from a US pregnancy cohort. Am J Epidemiol. 2004;160:774–783.
    1. Oken E, Kleinman KP, Rich-Edwards J, Gillman MW. 2003. A nearly continuous measure of birth weight for gestational age using a United States national reference. BMC Pediatr 3 6, doi:10.1186/1471-2431-3-6
    1. Ong KK, Ahmed ML, Sherriff A, Woods KA, Watts A, Golding J, et al. Cord blood leptin is associated with size at birth and predicts infancy weight gain in humans. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. J Clin Endocrinol Metab. 1999;84:1145–1148.
    1. Pollack AZ, Perkins NJ, Mumford SL, Ye A, Schisterman EF. Correlated biomarker measurement error: an important threat to inference in environmental epidemiology. Am J Epidemiol. 2013;177:84–92.
    1. Pomroy C, Charbonneau SM, McCullough RS, Tam GK. Human retention studies with 74As. Toxicol Appl Pharmacol. 1980;53:550–556.
    1. Quansah R, Armah FA, Essumang DK, Luginaah I, Clarke E, Marfoh K, et al. 2015. Association of arsenic with adverse pregnancy outcomes/infant mortality: a systematic review and meta-analysis. Environ Health Perspect 123 412 421, doi:10.1289/ehp.1307894
    1. R Core Team. Vienna, Austria: R Foundation for Statistical Computing; 2008. R: A Language and Environment for Statistical Computing. Available: [accessed 31 October 2014]
    1. Rahman A, Vahter M, Smith AH, Nermell B, Yunus M, El Arifeen S, et al. Arsenic exposure during pregnancy and size at birth: a prospective cohort study in Bangladesh. Am J Epidemiol. 2009;169:304–312.
    1. Remy S, Govarts E, Bruckers L, Paulussen M, Wens B, Den Hond E, et al. 2014. Expression of the sFLT1 gene in cord blood cells is associated to maternal arsenic exposure and decreased birth weight. PLoS One 9 e92677, doi:10.1371/journal.pone.0092677
    1. Sanders AP, Flood K, Chiang S, Herring AH, Wolf L, Fry RC. 2012. Towards prenatal biomonitoring in North Carolina: assessing arsenic, cadmium, mercury, and lead levels in pregnant women. PLoS One 7 e31354, doi:10.1371/journal.pone.0031354
    1. Shi X, Ayotte JD, Onda A, Miller S, Rees J, Gilbert-Diamond D, et al. Geospatial association between adverse birth outcomes and arsenic in groundwater in New Hampshire, USA. Environ Geochem Health. 2015;37:333–351.
    1. Silverman BL, Rizzo T, Green OC, Cho NH, Winter RJ, Ogata ES, et al. Long-term prospective evaluation of offspring of diabetic mothers. Diabetes. 1991;40(suppl 2):121–125.
    1. Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy metal toxicity and the environment. EXS. 2012;101:133–164.
    1. Vandorsten JP, Dodson WC, Espeland MA, Grobman WA, Guise JM, Mercer BM, et al. NIH consensus development conference: diagnosing gestational diabetes mellitus. NIH Consens State Sci Statements. 2013;29:1–31.
    1. WHO (World Health Organization) Nutritional anaemias. Report of a WHO scientific group. WHO Technical Report Series, No. 405. 1968 Available: [accessed 28 June 2016]
    1. Wigle DT, Arbuckle TE, Walker M, Wade MG, Liu S, Krewski D. Environmental hazards: evidence for effects on child health. J Toxicol Environ Health B Crit Rev. 2007;10:3–39.
    1. Wilson D, Hooper C, Shi X. Arsenic and lead in juice: apple, citrus, and apple-base. J Environ Health. 2012;75:14–20.
    1. Xie X, Ding G, Cui C, Chen L, Gao Y, Zhou Y, et al. The effects of low-level prenatal lead exposure on birth outcomes. Environ Pollut. 2013;175:30–34.
    1. Xu L, Yokoyama K, Tian Y, Piao FY, Kitamura F, Kida H, et al. Decrease in birth weight and gestational age by arsenic among the newborn in Shanghai, China. Nihon Koshu Eisei Zasshi. 2011;58:89–95.
    1. Xu X, Yang H, Chen A, Zhou Y, Wu K, Liu J, et al. Birth outcomes related to informal e-waste recycling in Guiyu, China. Reprod Toxicol. 2012;33:94–98.
    1. Yang CY, Chang CC, Tsai SS, Chuang HY, Ho CK, Wu TN. Arsenic in drinking water and adverse pregnancy outcome in an arseniasis-endemic area in northeastern Taiwan. Environ Res. 2003;91:29–34.
    1. Zheng G, Zhong H, Guo Z, Wu Z, Zhang H, Wang C, et al. Levels of heavy metals and trace elements in umbilical cord blood and the risk of adverse pregnancy outcomes: a population-based study. Biol Trace Elem Res. 2014;160:437–444.
    1. Zhu M, Fitzgerald EF, Gelberg KH, Lin S, Druschel CM. 2010. Maternal low-level lead exposure and fetal growth. Environ Health Perspect 118 1471 1475, doi:10.1289/ehp.0901561
    1. Zota AR, Ettinger AS, Bouchard M, Amarasiriwardena CJ, Schwartz J, Hu H, et al. Maternal blood manganese levels and infant birth weight. Epidemiology. 2009;20:367–373.
    1. Zota AR, Schaider LA, Ettinger AS, Wright RO, Shine JP, Spengler JD. Metal sources and exposures in the homes of young children living near a mining-impacted Superfund site. J Expo Sci Environ Epidemiol. 2011;21:495–505.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi