Background The association between exposure to perfluorinated compounds (PFCs) and attention deficit hyperactivity disorder (ADHD) diagnosis has been sparsely investigated in humans and the findings are inconsistent. Objectives A matched case-control study was conducted to investigate the association between fetal exposure to PFCs and ADHD diagnosis in childhood. Methods The study base comprised children born in Malm？, Sweden, between 1978 and 2000 that were followed up until 2005. Children with ADHD (n = 206) were identified at the Department of Child and Adolescent Psychiatry. Controls (n = 206) were selected from the study base and were matched for year of birth and maternal country of birth. PFC concentrations were measured in umbilical cord serum samples. The differences of the PFC concentrations between cases and controls were investigated using Wilcoxon's paired test. Possible threshold effects (above the upper quartile for perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) and above limit of detection [LOD] for perfluorononanoic acid (PFNA)) were evaluated by conditional logistic regression. Results The median umbilical cord serum concentrations of PFOS were 6.92 ng/ml in the cases and 6.77 ng/ml in the controls. The corresponding concentrations of PFOA were 1.80 and 1.83 ng/ml. No associations between PFCs and ADHD were observed. Odds ratios adjusted for smoking status, parity, and gestational age were 0.81 (95% confidence interval [CI] 0.50 to 1.32) for PFOS, 1.07 (95% CI 0.67 to 1.7) for PFOA, and 1.1 (95% CI 0.75 to 1.7) for PFNA. Conclusions The current study revealed no support for an association between fetal exposure to PFOS, PFOA, or PFNA and ADHD.
References
[1]
Fromme H, Tittlemier SA, Volkel W, Wilhelm M, Twardella D (2009) Perfluorinated compounds—exposure assessment for the general population in Western countries. Int J Hyg Environ Health 212: 239–270. doi: 10.1016/j.ijheh.2008.04.007
[2]
Kissa E (2001) Fluorinated Surfactants and Repellants. NY, USA: Marcel Dekker Inc.
Butt CM, Berger U, Bossi R, Tomy GT (2010) Levels and trends of poly- and perfluorinated compounds in the arctic environment. Sci Total Environ 408: 2936–2965. doi: 10.1016/j.scitotenv.2010.03.015
[5]
Giesy JP, Kannan K (2001) Global distribution of perfluorooctane sulfonate in wildlife. Environ Sci Technol 35: 1339–1342. doi: 10.1021/es001834k
[6]
Giesy JP, Kannan K (2002) Perfluorochemical surfactants in the environment. Environ Sci Technol 36: 146A–152A. doi: 10.1021/es022253t
[7]
Kannan K, Corsolini S, Falandysz J, Fillmann G, Kumar KS, et al. (2004) Perfluorooctanesulfonate and Related Fluorochemicals in Human Blood from Several Countries. Environmental Science & Technology 38: 4489–4495. doi: 10.1021/es0493446
[8]
Olsen GW, Huang H-Y, Helzlsouer KJ, Hansen KJ, Butenhoff JL, et al. (2005) Historical Comparison of Perfluorooctanesulfonate, Perfluorooctanoate, and Other Fluorochemicals in Human Blood. Environmental Health Perspectives 113: 539–545. doi: 10.1289/ehp.7544
[9]
Beesoon S, Webster GM, Shoeib M, Harner T, Benskin JP, et al. (2011) Isomer profiles of perfluorochemicals in matched maternal, cord, and house dust samples: manufacturing sources and transplacental transfer. Environ Health Perspect 119: 1659–1664. doi: 10.1289/ehp.1003265
[10]
Inoue K, Okada F, Ito R, Kato S, Sasaki S, et al. (2004) Perfluorooctane Sulfonate (PFOS) and Related Perfluorinated Compounds in Human Maternal and Cord Blood Samples: Assessment of PFOS Exposure in a Susceptible Population during Pregnancy. Environmental Health Perspectives 112: 1204–1207. doi: 10.1289/ehp.6864
[11]
Ode A, Rylander L, Lindh CH, Kallen K, Jonsson BA, et al. (2013) Determinants of maternal and fetal exposure and temporal trends of perfluorinated compounds. Environ Sci Pollut Res Int 20: 7970–7978. doi: 10.1007/s11356-013-1573-5
Austin ME, Kasturi BS, Barber M, Kannan K, MohanKumar PS, et al. (2003) Neuroendocrine Effects of Perfluorooctane Sulfonate in Rats. Environmental Health Perspectives 111: 1485–1489. doi: 10.1289/ehp.6128
[14]
Butenhoff JL, Ehresman DJ, Chang SC, Parker GA, Stump DG (2009) Gestational and lactational exposure to potassium perfluorooctanesulfonate (K+PFOS) in rats: developmental neurotoxicity. Reprod Toxicol 27: 319–330. doi: 10.1016/j.reprotox.2008.12.010
[15]
Cui L, Zhou QF, Liao CY, Fu JJ, Jiang GB (2009) Studies on the toxicological effects of PFOA and PFOS on rats using histological observation and chemical analysis. Arch Environ Contam Toxicol 56: 338–349. doi: 10.1007/s00244-008-9194-6
[16]
Greaves AK, Letcher RJ, Sonne C, Dietz R (2013) Brain region distribution and patterns of bioaccumulative perfluoroalkyl carboxylates and sulfonates in east greenland polar bears (Ursus maritimus). Environ Toxicol Chem 32: 713–722. doi: 10.1002/etc.2107
[17]
Johansson N, Fredriksson A, Eriksson P (2008) Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes neurobehavioural defects in adult mice. Neurotoxicology 29: 160–169. doi: 10.1016/j.neuro.2007.10.008
[18]
Slotkin TA, MacKillop EA, Melnick RL, Thayer KA, Seidler FJ (2008) Developmental neurotoxicity of perfluorinated chemicals modeled in vitro. Environ Health Perspect 116: 716–722. doi: 10.1289/ehp.11253
[19]
Johansson N, Eriksson P, Viberg H (2009) Neonatal exposure to PFOS and PFOA in mice results in changes in proteins which are important for neuronal growth and synaptogenesis in the developing brain. Toxicol Sci 108: 412–418. doi: 10.1093/toxsci/kfp029
Gizer IR, Ficks C, Waldman ID (2009) Candidate gene studies of ADHD: a meta-analytic review. Hum Genet 126: 51–90. doi: 10.1007/s00439-009-0694-x
[22]
Faraone SV, Khan SA (2006) Candidate gene studies of attention-deficit/hyperactivity disorder. J Clin Psychiatry 67 Suppl 813–20.
[23]
Gustafsson P, Thernlund G, Ryding E, Rosen I, Cederblad M (2000) Associations between cerebral blood-flow measured by single photon emission computed tomography (SPECT), electro-encephalogram (EEG), behaviour symptoms, cognition and neurological soft signs in children with attention-deficit hyperactivity disorder (ADHD). Acta Paediatr 89: 830–835. doi: 10.1111/j.1651-2227.2000.tb00391.x
[24]
Faraone SV, Biederman J, Mick E (2006) The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med 36: 159–165. doi: 10.1017/s003329170500471x
[25]
Lara C, Fayyad J, de Graaf R, Kessler RC, Aguilar-Gaxiola S, et al. (2009) Childhood predictors of adult attention-deficit/hyperactivity disorder: results from the World Health Organization World Mental Health Survey Initiative. Biol Psychiatry 65: 46–54. doi: 10.1016/j.biopsych.2008.10.005
Thapar A, Cooper M, Jefferies R, Stergiakouli E (2012) What causes attention deficit hyperactivity disorder? Arch Dis Child 97: 260–265. doi: 10.1136/archdischild-2011-300482
[28]
Braun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP (2006) Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect 114: 1904–1909. doi: 10.1289/ehp.9478
[29]
Eubig PA, Aguiar A, Schantz SL (2010) Lead and PCBs as risk factors for attention deficit/hyperactivity disorder. Environ Health Perspect 118: 1654–1667. doi: 10.1289/ehp.0901852
[30]
Hoffman K, Webster TF, Weisskopf MG, Weinberg J, Vieira VM (2010) Exposure to polyfluoroalkyl chemicals and attention deficit/hyperactivity disorder in U.S. children 12-15 years of age. Environ Health Perspect 118: 1762–1767. doi: 10.1289/ehp.1001898
[31]
Stein CR, Savitz DA (2011) Serum perfluorinated compound concentration and attention deficit/hyperactivity disorder in children 5–18 years of age. Environ Health Perspect 119: 1466–1471. doi: 10.1289/ehp.1003538
[32]
Gump BB, Wu Q, Dumas AK, Kannan K (2011) Perfluorochemical (PFC) exposure in children: associations with impaired response inhibition. Environ Sci Technol 45: 8151–8159. doi: 10.1021/es103712g
[33]
Fei C, McLaughlin JK, Lipworth L, Olsen J (2008) Prenatal exposure to perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) and maternally reported developmental milestones in infancy. Environ Health Perspect 116: 1391–1395. doi: 10.1289/ehp.11277
[34]
Fei C, Olsen J (2011) Prenatal exposure to perfluorinated chemicals and behavioral or coordination problems at age 7 years. Environ Health Perspect 119: 573–578. doi: 10.1289/ehp.1002026
[35]
Pastor PN, Reuben CA (2008) Diagnosed attention deficit hyperactivity disorder and learning disability: United States, 2004–2006. Vital Health Stat 10: 1–14.
[36]
Gustafsson P, Kallen K (2011) Perinatal, maternal, and fetal characteristics of children diagnosed with attention-deficit-hyperactivity disorder: results from a population-based study utilizing the Swedish Medical Birth Register. Dev Med Child Neurol 53: 263–268. doi: 10.1111/j.1469-8749.2010.03820.x
[37]
Lindh CH, Rylander L, Toft G, Axmon A, Rignell-Hydbom A, et al. (2012) Blood serum concentrations of perfluorinated compounds in men from Greenlandic Inuit and European populations. Chemosphere 88: 1269–1275. doi: 10.1016/j.chemosphere.2012.03.049
[38]
Apelberg BJ, Goldman LR, Calafat AM, Herbstman JB, Kuklenyik Z, et al. (2007) Determinants of fetal exposure to polyfluoroalkyl compounds in Baltimore, Maryland. Environ Sci Technol 41: 3891–3897. doi: 10.1021/es0700911
[39]
Carballo JJ, Garcia-Nieto R, Alvarez-Garcia R, Caro-Canizares I, Lopez-Castroman J, et al. (2013) Sibship size, birth order, family structure and childhood mental disorders. Soc Psychiatry Psychiatr Epidemiol 48: 1327–1333. doi: 10.1007/s00127-013-0661-7
[40]
Chu SM, Tsai MH, Hwang FM, Hsu JF, Huang HR, et al. (2012) The relationship between attention deficit hyperactivity disorder and premature infants in Taiwanese: a case control study. BMC Psychiatry 12: 85. doi: 10.1186/1471-244x-12-85
[41]
Desrosiers C, Boucher O, Forget-Dubois N, Dewailly E, Ayotte P, et al. (2013) Associations between prenatal cigarette smoke exposure and externalized behaviors at school age among Inuit children exposed to environmental contaminants. Neurotoxicol Teratol 39C: 84–90. doi: 10.1016/j.ntt.2013.07.010
[42]
Fei C, McLaughlin JK, Tarone RE, Olsen J (2007) Perfluorinated chemicals and fetal growth: a study within the Danish National Birth Cohort. Environ Health Perspect 115: 1677–1682. doi: 10.1289/ehp.10506
[43]
Kotimaa AJ, Moilanen I, Taanila A, Ebeling H, Smalley SL, et al. (2003) Maternal smoking and hyperactivity in 8-year-old children. J Am Acad Child Adolesc Psychiatry 42: 826–833. doi: 10.1097/01.chi.0000046866.56865.a2
[44]
Langley K, Holmans PA, van den Bree MB, Thapar A (2007) Effects of low birth weight, maternal smoking in pregnancy and social class on the phenotypic manifestation of Attention Deficit Hyperactivity Disorder and associated antisocial behaviour: investigation in a clinical sample. BMC Psychiatry 7: 26. doi: 10.1186/1471-244x-7-26
[45]
Perricone G, Morales MR, Anzalone G (2013) Neurodevelopmental outcomes of moderately preterm birth: precursors of attention deficit hyperactivity disorder at preschool age. Springerplus 2: 221. doi: 10.1186/2193-1801-2-221
[46]
Washino N, Saijo Y, Sasaki S, Kato S, Ban S, et al. (2009) Correlations between prenatal exposure to perfluorinated chemicals and reduced fetal growth. Environ Health Perspect 117: 660–667. doi: 10.1289/ehp.11681
[47]
George L, Granath F, Johansson AL, Cnattingius S (2006) Self-reported nicotine exposure and plasma levels of cotinine in early and late pregnancy. Acta Obstet Gynecol Scand 85: 1331–1337. doi: 10.1080/00016340600935433
[48]
Gutzkow KB, Haug LS, Thomsen C, Sabaredzovic A, Becher G, et al. (2012) Placental transfer of perfluorinated compounds is selective—a Norwegian Mother and Child sub-cohort study. Int J Hyg Environ Health 215: 216–219. doi: 10.1016/j.ijheh.2011.08.011
[49]
Needham LL, Grandjean P, Heinzow B, Jorgensen PJ, Nielsen F, et al. (2011) Partition of environmental chemicals between maternal and fetal blood and tissues. Environ Sci Technol 45: 1121–1126. doi: 10.1021/es1019614
[50]
Kim S, Choi K, Ji K, Seo J, Kho Y, et al. (2011) Trans-placental transfer of thirteen perfluorinated compounds and relations with fetal thyroid hormones. Environ Sci Technol 45: 7465–7472. doi: 10.1021/es202408a
[51]
Kim SK, Lee KT, Kang CS, Tao L, Kannan K, et al. (2011) Distribution of perfluorochemicals between sera and milk from the same mothers and implications for prenatal and postnatal exposures. Environ Pollut 159: 169–174. doi: 10.1016/j.envpol.2010.09.008
[52]
Liu J, Li J, Liu Y, Chan HM, Zhao Y, et al. (2011) Comparison on gestation and lactation exposure of perfluorinated compounds for newborns. Environ Int 37: 1206–1212. doi: 10.1016/j.envint.2011.05.001
Lee HG, Lee YJ, Yang JH (2012) Perfluorooctane sulfonate induces apoptosis of cerebellar granule cells via a ROS-dependent protein kinase C signaling pathway. Neurotoxicology 33: 314–320. doi: 10.1016/j.neuro.2012.01.017
[55]
Trudel D, Horowitz L, Wormuth M, Scheringer M, Cousins IT, et al. (2008) Estimating consumer exposure to PFOS and PFOA. Risk Anal 28: 251–269. doi: 10.1111/j.1539-6924.2008.01017.x
[56]
Skounti M, Philalithis A, Galanakis E (2007) Variations in prevalence of attention deficit hyperactivity disorder worldwide. Eur J Pediatr 166: 117–123. doi: 10.1007/s00431-006-0299-5
[57]
Lahey BB, Applegate B, McBurnett K, Biederman J, Greenhill L, et al. (1994) DSM-IV field trials for attention deficit hyperactivity disorder in children and adolescents. Am J Psychiatry 151: 1673–1685.
[58]
Biederman J, Faraone SV, Weber W, Russell RL, Rater M, et al. (1997) Correspondence between DSM-III-R and DSM-IV attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 36: 1682–1687. doi: 10.1097/00004583-199712000-00016
[59]
Baumgaertel A, Wolraich ML, Dietrich M (1995) Comparison of diagnostic criteria for attention deficit disorders in a German elementary school sample. J Am Acad Child Adolesc Psychiatry 34: 629–638. doi: 10.1097/00004583-199505000-00015
[60]
Hamm MP, Cherry NM, Chan E, Martin JW, Burstyn I (2010) Maternal exposure to perfluorinated acids and fetal growth. J Expo Sci Environ Epidemiol 20: 589–597. doi: 10.1038/jes.2009.57
[61]
Calafat AM, Wong LY, Kuklenyik Z, Reidy JA, Needham LL (2007) Polyfluoroalkyl chemicals in the U.S. population: data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and comparisons with NHANES 1999–2000. Environ Health Perspect 115: 1596–1602. doi: 10.1289/ehp.10598
[62]
Harada K, Koizumi A, Saito N, Inoue K, Yoshinaga T, et al. (2007) Historical and geographical aspects of the increasing perfluorooctanoate and perfluorooctane sulfonate contamination in human serum in Japan. Chemosphere 66: 293–301. doi: 10.1016/j.chemosphere.2006.05.010
[63]
Haug LS, Thomsen C, Becher G (2009) Time trends and the influence of age and gender on serum concentrations of perfluorinated compounds in archived human samples. Environ Sci Technol 43: 2131–2136. doi: 10.1021/es802827u
[64]
Olsen GW, Ellefson ME, Mair DC, Church TR, Goldberg CL, et al. (2011) Analysis of a homologous series of perfluorocarboxylates from American Red Cross adult blood donors, 2000-2001 and 2006. Environ Sci Technol 45: 8022–8029. doi: 10.1021/es1043535
