Research | Children’s Health Lead Exposure and Behavior among Young Children in Chennai, India Ananya Roy,1 David Bellinger,2,3 Howard Hu,1,2,4 Joel Schwartz,2,4 Adrienne S. Ettinger,1,2,4 Robert O. Wright,2,4,5 Maryse Bouchard,2 Kavitha Palaniappan,6 and Kalpana Balakrishnan 6 1Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA; 2Depart- ment of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA; 3Department of Neurology, Children’s Hospital Boston, Boston, Massachusetts, USA; 4Channing Laboratory, Brigham and Women’s Hospital, Boston, Massachusetts, USA; 5Department of Medicine, Children’s Hospital Boston, Boston, Massachusetts, USA; 6Department of Environmental Health Engineering, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India Bdnuorgkca : Lead exposure has long been associated with deficits in IQ among children. However, few studies have assessed the impact of lead on specific domains of behavior and cognition. o Bjectiv : We evaluated the associations between lead and different domains of neurobehavior and their relative sensitivity to lead. Msdohte : We determined blood lead levels using a LeadCare instrument in 756 children 3–7 years of age attending pre- and elementary schools in Chennai, India. Anxiety, social problems, inatten- tion, hyperactivity, and attention deficit hyperactivity disorder (ADHD), as well as executive function were assessed in children by their schoolteachers using Conners’ Teacher Rating Scales-39, Conners’ ADHD/Diagnostic and Statistical Manual for Mental Disorders, 4th Edition Scales (CADS), and the Behavior Rating Inventory of Executive Function questionnaires, with higher scores denoting worse behavior. Analyses were carried out using multivariate generalized estimating equations with com- parisons of outcome Z-scores to assess the relative strengths of the associations between log-blood lead and the different domains of behavior. r tluse : Mean blood lead level was 11.4 ± 5.3 µg/dL. Blood lead was associated with higher anxiety (β = 0.27, p = 0.01), social problems (β = 0.20, p = 0.02), and higher scores in the ADHD index (β = 0.17; p = 0.05). The effect estimate was highest for global executive function (β = 0.42; p < 0.001). c onclusi : Higher blood lead levels in this population of young children is associated with increased risk of neurobehavioral deficits and ADHD, with executive function and attention being particularly vulnerable domains to the effects of lead. k ey words : ADHD, anxiety, blood lead, children, executive function, India, sociability. Environ Health Perspect 117:1607–1611 (2009). doi:10.1289/ehp.0900625 available via http://dx.doi.org/ [Online 26 June 2009] The removal of lead from sources in the environment, such as gasoline and residential paint, have resulted in declines in blood lead levels in many countries [Centers for Disease Control and Prevention (CDC) 1997, 2005a]. In India, leaded gasoline was phased out in early 2001. Nichani et al. (2006) reported that 37% of children in Mumbai in 2002 had blood lead levels > 10 µg/dL, the CDC level of concern for blood lead (CDC 2005b), down from 60% in 1997. Other studies describe continued elevations in blood lead levels among children in other parts of the country (Ahamed et al. 2006; Bellinger et al. 2005). Many studies have shown that lead exposure is associated with significant defi- cits in intelligence quotient (IQ) of children (Lanphear et al. 2005). However, IQ is a global construct of cognition, and fewer studies have assessed the impact of lead on specific domains of behavior and cognition, such as executive function (Canfield et al. 2003, 2004; Froehlich et al. 2007), attention (Bellinger et al. 1994; Stiles and Bellinger 1993), and internaliz- ing behaviors. Recent evidence suggests that increased lead exposure is associated with atten- tion deficit hyperactivity disorder (ADHD) (Braun et al. 2006; Nigg 2008) and conduct disorder (Needleman et al. 2002; Nevin 2000). Currently, relatively little is known about the shape of the dose–response relationships or the relative sensitivity of behavioral domains to lead toxicity. Only one study has reported on the relationship between lead exposure and behav- ior, as well as other cognitive outcomes among children in India (Bellinger et al. 2005). The objective of this study was to explore the associations between lead and specific neurobehavioral outcomes such as ADHD- like behaviors, executive function, and inter- nalizing problems (anxiety and sociability) in a cohort of children 3–7 years of age in Chennai, India. In addition, we investigated the shape of the dose–response relationships and the relative sensitivity of the different behavioral outcomes to lead exposure. Methods Study population. This cross-sectional study of 814 children was carried out during 2005–2006 in Chennai, India. Four traffic and industry zones were selected on the basis of industrial zoning information provided by the Tamil Nadu State Pollution Control Board and the Chennai traffic police department. Children 3–7 years of age were recruited from 12 schools (three schools within each zone). Informed consent was obtained from each child’s primary caregiver. Venous blood was collected from each child, and questionnaires Environmental Health Perspectives • volume 117 | number 10 | October 2009 were administered in Tamil (the regional lan- guage) to the teachers and primary caregivers (usually the mothers) of the children. A semi- quantitative food frequency questionnaire was used to assess nutritional status. Information was collected on a family’s average monthly income, educational attainment and occupa- tion of the parents, and type of housing. Data on family size, maternal age at birth of child, and child’s age, birth weight, and birth rank were also collected. This investigation was conducted as part of a collaborative study between the Harvard School of Public Health (HSPH), Boston, Massachusetts (USA), and Sri Ramachandra Medical College and Research Institute (SRMC), Chennai, India, on lead genetics and neurotoxicity. The study was approved by institutional review boards at HSPH, SRMC, the University of Michigan, and the Indian Council for Medical Research, New Delhi, India, and complied with U.S. federal and Indian regulations and laws regarding research on human subjects. Blood lead measurement. Blood was col- lected from the cubital vein of each child into lead-free tubes (royal blue top tubes #369736; Becton-Dickinson, Franklin Lakes, NJ, USA) by a trained phlebotomist during a school day. The blood was transferred to the laboratory at SRMC, and blood lead was measured using Anodic Stripping Voltammetry by a LeadCare Analyzer (ESA Laboratories, Chelmsford, MA, USA), which is a well-validated field instru- ment with sensitivity of 1 µg/dL blood lead (Shannon and Rifai 1997). Duplicates and controls were run with every 20 samples, every new batch, and kit lot. Fifty-eight children Address correspondence to A. Roy, University of Michigan School of Public Health, Department of Environmental Health Sciences, 109 South Observatory St., Building 1, Ann Arbor, MI 48109 USA. Telephone: (617) 642-1376. Fax: (734) 936- 7283. E-mail: aroyk@umich.edu This study was supported by U.S. National Institutes of Health (NIH) grants 1R03TW005914 and R01ES007821. This work was carried out as a part of the Sc.D. thesis of A.R. at the Harvard School of Public Health, where she was supported by the training core of NIH P42-ES05947. The contents of this study are solely the responsi- bility of the authors and do not necessarily represent the official views of the NIH. The authors declare they have no competing financial interests. Received 28 January 2009; accepted 26 June 2009. 1607