title: Neurological and neuropsychological functions in adults with a history of developmental arsenic poisoning from contaminated milk powder.
abstract: During the summer of 1955, mass arsenic poisoning of bottle-fed infants occurred in the western part of Japan due to contaminated milk powder, and more than 100 died; some childhood victims were later found to suffer from neurological sequelae in adolescence. This unique incident enabled us to explore infancy as a critical period of arsenic exposure in regard to developmental neurotoxicity and its possible persistence through adulthood. The purpose of this work is to evaluate the association between developmental arsenic exposure and the neurological outcomes more than 50 years later. We conducted a retrospective cohort study during the period from April 2012 to February 2013 in two hospitals in Okayama Prefecture, Japan. The study sample consisted of 50 individuals: 27 known poisoning victims from Okayama Prefecture, and 23 non-exposed local controls of similar age. In addition to neurological examination, we adapted a battery of neurophysiological and neuropsychological tests to identify the types of brain functions affected by early-life arsenic exposure. While limited abnormalities were found in the neurophysiological tests, neuropsychological deficits were observed. Except for Finger tapping, all test scores in the exposed group--Vocabulary and Block Design from Wechsler Adults Intelligent Scale III, Design memory subtest from Wide Range Assessment of Memory and Learning 2, and Grooved pegboard test--were substantially below those obtained by the unexposed. The exposed group showed average performance at least 1.2 standard deviations below the average for the controls. Exposed participants performed less well than controls, even after exclusion of subjects with recognized disabilities or those with a high level of education. Adults who had suffered arsenic poisoning during infancy revealed neuropsychological dysfunctions, even among those subjects not recognized as having disabilities. Developmental neurotoxicity due to arsenic likely results in permanent changes in brain functions.
authors.affiliation: Department of Human Ecology, Graduate School of Environmental and Life Science, Okayama University, Okayama, 700-8530, Japan. Electronic address: yorichan@md.okayama-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yorifuji
authors.affiliation: Department of Social Science, National Center for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Tsuguhiko
authors.initials: T
authors.lastname: Kato
authors.affiliation: Mizushima Kyodo Hospital, Kurashiki, Okayama 712-8567, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohta
authors.affiliation: Department of Neurology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Environmental Health, Harvard T.H.Chan School of Public Health, Boston, MA 02215, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Bellinger
authors.affiliation: Mizushima Kyodo Hospital, Kurashiki, Okayama 712-8567, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Department of Environmental Health, Harvard T.H.Chan School of Public Health, Boston, MA 02215, USA; Department of Environmental Medicine, University of Southern Denmark, DK-5000, Odense, Denmark.
authors.forename: Philippe
authors.initials: P
authors.lastname: Grandjean
mesh_terms: D000161:Acoustic Stimulation; D000368:Aged; D000818:Animals; D020261:Arsenic Poisoning / Q000150:complications*; D003072:Cognition Disorders / Q000139:chemically induced*; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000502:physiology; D005260:Female; D005506:Food Contamination; D006801:Humans; D007361:Intelligence Tests; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008892:Milk; D009422:Nervous System Diseases / Q000139:chemically induced*; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D012189:Retrospective Studies
keywords: Arsenic; Food contamination; Milk substitute; Neurological examinations; Neurophysiological monitoring; Neuropsychological tests