Risk factors for epilepsy: A population-based case–control study in Kerala, southern India Sudheeran Kannoth, Janardhanan P. Unnikrishnan, T. Santhosh Kumar, P. Sankara Sarma, Kurupath Radhakrishnan * R. Madhavan Nair Center for Comprehensive Epilepsy Care, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India article info Article history: Received 19 May 2009 Revised 25 June 2009 Accepted 10 July 2009 Available online 5 August 2009 Keywords: Case–control study Epidemiology Epilepsy Risk factors abstract We undertook a community-based case–control study on persons with active epilepsy residing in Kerala, southern India. Using a standardized questionnaire, we collected information from 362 cases and 362 controls. In the final multivariate model, family history of epilepsy (odds ratio = 7.8, 95% confidence inter- val = 3.2–18.8, P = 0.000), antecedent history of febrile seizures (7.7, 4.3–14.0, 0.000), birth by compli- cated delivery (6.8, 2.1–21.8, 0.001), and neonatal seizures (7.8, 1.7–35.4, 008) emerged as strong independent predictors of epilepsy, followed in decreasing order by mental retardation, prematurity, maternal age P 30, perinatal distress, and incomplete immunization. There were more similarities than differences in the distribution of risk factors between generalized and localization-related epilepsy syn- dromes. Our findings suggest interplay between genetic and acquired factors in the pathogenesis of epi- lepsies, and underscore the need for improvement in obstetric and neonatal care to minimize the epilepsy burden in low-income countries. Ó 2009 Elsevier Inc. All rights reserved. 1. Introduction According to the World Health Organization, of 50 million peo- ple with epilepsy worldwide, 80% reside in developing countries [1]. Despite modern diagnostic techniques, the cause of epilepsy remains unknown in more than two-thirds of patients [2]. Identi- fying risk factors for epilepsy will help not only in understanding its pathogenesis, but also in implementing appropriate preventive strategies. Case–control study design is a well-established method of detecting and quantifying disease–risk factor associations [3]. Dur- ing the last three decades, several case–control studies on epilepsy have been undertaken both in high-income [4–9] and in low-in- come countries [10–13]. Although these studies have identified a variety of risk factors associated with epilepsy, the results have varied widely between studies. In addition to general methodolog- ical problems inherent to case–control design such as different strategies used in the selection of cases and controls and risk factor ascertainment, and recall bias [14], the results of epilepsy–risk fac- tor association studies are influenced by following disease-specific issues. As epilepsy comprises a group of heterogeneous disorders with widely variable etiopathogenesis, risk factors for generalized and localization-related epilepsies and those for pediatric and adult-onset epilepsies are expected to differ. Whereas cerebrovas- cular and degenerative causes are likely to be more frequently encountered in the aging population of high-income countries, perinatal insults, infections, and parasitic infestations prevail in re- source-poor countries [2,15]. The state of Kerala, situated along the southwest coast of the In- dian peninsula, is distinguished from the rest of India by the high level of literacy and health awareness of its population [16]. Cysti- cercosis is nonexistent in Kerala [17]. The age-adjusted prevalence ratio of active epilepsy in Kerala is 4.7 per 1000 population [17]. These characteristics are similar to those of developed regions. With this background, we designed this community-based case–control study to ascertain the risk factors for epilepsy among the people of central Kerala, southern India. 2. Methods 2.1. Study area and population characteristics In a previous epidemiological study on epilepsy during 1996– 1997, we conducted a door-to-door survey in 10 panchayats in the central part of Kerala, covering the entire population of 238,102 residing in 43,681 households [17]. The principal charac- teristics of this semiurban/rural population from a tropical region, 1525-5050/$ - see front matter Ó 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2009.07.019 * Corresponding author. Address: Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695011, Kerala, India. Fax: + 91 471 2446433. E-mail address: krk@sctimst.ac.in (K. Radhakrishnan). Epilepsy & Behavior 16 (2009) 58–63 Contents lists available at ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh