Review Prenatal Exposure to Polychlorinated Biphenyls: A Neuropsychologic Analysis Olivier Boucher,1,2 Gina Muckle,1,2 and Célyne H. Bastien1,3 1École de psychologie, Université Laval, Québec, Canada; 2Unité de recherche en santé publique, Centre de recherche du CHUQ-CHUL, Québec, Canada; 3Laboratoire de neurosciences comportementales humaines, Centre de recherche Université Laval-Robert Giffard, Québec, Canada o Bjectivs : A large body of literature documents the effects of prenatal exposure to polychlori- nated biphenyls (PCBs) on cognitive development of children. Despite this fact, no integrative synthesis has been published yet to identify the cognitive functions that are particularly affected. Our aim is to review this literature in an attempt to identify the cognitive profile associated with prenatal PCB exposure. d at aspects of cognition. : Studies were identified by searching the PubMed database for articles published source before June 2008. We reviewed data from nine prospective longitudinal birth cohorts for different xetracion d at : Associations between indicators of prenatal PCB exposure and performance on cognitive tasks reported in the selected studies are summarized and classified as general cognitive abilities, verbal or visual–spatial skills, memory, attention, and executive functions. d at : The most consistent effects observed across studies are impaired executive func- synthei tioning related to increased prenatal PCB exposure. Negative effects on processing speed, verbal abilities, and visual recognition memory are also reported by most studies. Converging results from different cohort studies in which exposure arises from different sources make it unlikely that co- exposure with another associated contaminant is responsible for the observed effects. c onclusi : Prenatal PCB exposure appears to be related to a relatively specific cognitive profile of impairments. Failure to assess functions that are specifically impaired may explain the absence of effects found in some studies. Our findings have implications in the selection of cognitive assess- ment methods in future studies. words k ey : attention, children, cognitive development, executive functions, memory, neuro- psychologic profile, neurotoxicity, polychlorinated biphenyls, processing speed, review. Environ Health Perspect 117:7–16 (2009). doi:10.1289/ehp.11294 available via http://dx.doi.org/ [Online 14 August 2008] Polychlorinated biphenyls (PCBs) are syn­ thetic organochlorine compounds that were produced large scale from the early 1930s. Because of their unique physical and chemical properties, they were used largely in indus­ try, notably as capacitor and transformer oils, hydraulic fluids, lubricating oils, and in plasti­ cizers (Brinkman and De Kok 1980). Toward the end of the 1970s, their persistence in the environment was recognized, and their pro­ duction was banned in most industrialized countries. More than 20 years after the prohi­ bition of their production in North America, PCBs were still detectable in the environment because of inadvertent spills, careless disposal, their chemical stability, and resistance to bio­ degradation (Safe 1994). Currently, one of the major nonaccidental sources of exposure to PCBs is fish consump­ tion (Schwartz et al. 1983). Concentrations of PCBs are particularly high in predatory species, because their long halfl­ife and strong lipophilicity cause their bioamplification in the food chain (Dewailly et al. 1993; Jensen 1987). PCB exposure in young children occurs first during prenatal development via placental transfer and then after birth from breastf­eeding (Masuda et al. 1978; Patandin et al. 1997) and through contaminated food intake. Fetuses, infants, and children are especially vulnerable to environmental contaminants, more so than adults (Chance and Harmsen 1998), because of physiologic, anatomic, and behavioral features associated with development (e.g., fast brain growth and underdeveloped immune system). The developmental neurotoxicity of PCBs was first recognized after large­ scale poison­ ing episodes in Japan in 1968 and in Taiwan in 1979. The poisoning was associated with the intake of rice oil contaminated by PCB during production processes. Thousands of people displayed clinical signs of intoxication (Hsu et al. 1985). Children exposed in utero, whose mothers ingested contaminated rice oil prior to or during pregnancy, were the most affected. Many of them presented growth retardation, nail malformations, delays in cognitive development, and behavioral prob­ lems (Guo et al. 2004). Since these poisoning episodes, birth cohort studies to identify the effects of prenatal and perinatal exposure to background levels of PCBs from environ­ mental sources on child cognition have been conducted in various countries. These studies usually reported associations between bio­ logic markers of PCB exposure and child performance on various neuropsychological tests. Although most of these results have been summarized elsewhere (Schantz et al. 2003), no integrative synthesis aimed at por­ traying a profile of cognitive impairments Environmental Health Perspectives • volume 117 | number 1 | January 2009 from these results has been published yet. Earlier reports compared results by focusing on methodologic aspects such as exposure measurement. Albeit important and quite pertinent, these comparisons did not offer a comprehensive and detailed profile of specific assessed outcomes. Because of inconsistency among studies, some reviewers recently con­ cluded that the effects of prenatal exposure to background levels of PCBs on child cogni­ tion are still not clearly established (Cicchetti et al. 2004; Ross 2004). Actually, it may well be that PCB exposure affects only certain cognitive functions rather than all aspects of cognitive functioning. Because neuropsycho­ logical assessment differs from one study to the other, part of the apparent inconsistency may result from the absence of theory­based comparisons between the cognitive outcomes of the different studies. The main goal of the present literature review is to determine whether a distinctive cognitive profile associated with prenatal PCB exposure from environmental sources emerges from the studies conducted to date and if it does, to characterize it. Implications for future studies, notably in the selection of neuro­ psychological tests, will then be discussed. Methods We searched the PubMed database (http:// www.ncbi.nlm.nih.gov/sites/entrez? db= pubmed) for articles published up to June 2008. We included longitudinal prospec­ tive birth cohort studies with biologic mark­ ers of prenatal PCB exposure and indicators of cognition from infancy to childhood, and we report results pertaining to associa­ tions between PCB exposure and cognition. Associations between PCB exposure and cog­ nition were considered statistically significant Address correspondence to G. Muckle, Unité de recherche en santé publique, Centre de recherche du CHUL­ CHUQ, Édifice Delta 2, Bureau 600, 2875, boulevard Laurier, 6e étage, Sainte­ Foy (Qc), Canada, G1V 2M2. Telephone: 1 418 656 4141, ext. 46199. Fax: 1 418 654 2726. E­ mail address: gina.muckle@psy.ulaval.ca. We thank F. Doré, P. Jackson, and the reviewers of this article for their judicious advice, and J. Jacobson and S. Jacobson for their valuable collaboration. This review was accomplished with the finan­ cial support from Canadian Institutes of Health Research and the Nasivvik Center for Inuit Health and Changing Environments. The authors declare they have no competing financial interests. Received 26 January 2008; accepted 14 August 2008. 7