Descriptive Analysis of High Birth Prevalence Rate Geographical Clusters of Congenital Anomalies in South America Juan Antonio Gili* 1 , Fernando Adri  an Poletta 1,2 , Lucas Gabriel Gim  enez 1 , Mariela Soledad Pawluk 1 , Hebe Campa ~ na 1 , Eduardo Enrique Castilla 1,2 , and Jorge Santiago L  opez-Camelo 1,2 Background: The birth prevalence rate (BPR) of congenital anomalies (CAs) is heterogeneous and exhibits geographical and sociocultural variations throughout the world. In South America (SA), high birth prevalence regions of congenital anomalies have been observed. The aim of this study was to identify, describe, and characterize geographical clusters of congenital anomalies in SA. Methods: This observational descriptive study is based on clinical epidemiological data registered by the Latin-American Collaborative Study of Congenital Malformations network. Between 1995 and 2012, a total of 25,082 malformed newborns were ascertained from 2,557,424 births at 129 hospitals in SA. The spatial scan statistic was used to determine geographical regions with high BPR of CAs. The BPR was obtained with a Poisson regression model. Odds ratios were estimated for several risk factors inside the geographical clusters. Results: We confirmed the existence of high BPR regions of CAs in SA. Indicators of low socioeconomic conditions, such as a low maternal education, extreme age childbearing, infectious diseases, and medicine use during pregnancy were detected as risk factors inside these regions. Native and African ancestries with high frequency of consanguineous marriages could explain partially these high BPR clusters. Conclusion: The recognition of clusters could be a starting point in the identification of susceptibility genes associated with the occurrence of CA in high BPR regions. Birth Defects Research (Part A) 106:257–266, 2016. V C 2016 Wiley Periodicals, Inc. Key words: South America; ECLAMC; congenital anomalies; birth prevalence rate Introduction The birth prevalence rate (BPR) of congenital anomalies (CAs) is heterogeneous and exhibits geographical and soci- ocultural variations throughout the world (L opez-Camelo and Orioli, 1996; Gili et al., 2015; ICBDSR). The ECLAMC (Latin-American Collaborative Study of Congenital Malfor- mations) network (Castilla and Orioli, 2004; Poletta et al., 2014) has studied CAs in South America for over 40 years. Previously, the ECLAMC has observed heterogeneous rates of CA across countries (L opez Camelo and Orioli, 1996). Recently, with a different approach (spatial scan analysis), this network has established geographical clusters of CAs in regions of South America (Poletta et al., 2007; Gili et al., 2015). Spatial scan analysis (Kulldorff and Nagarwalla, 1995; Kulldorff, 1997) allows to identifying areas of high BPR independent of political boundaries. This makes this approach useful for identifying etiologic factors and gener- ating causal hypotheses regarding these geographic areas. Populations on this continent have been described as having different ethnic origins (i.e., due to European, Afri- can, and Asian migrations) and broad sociocultural and environmental diversity (L opez Camelo et al., 1996; Sal- zano and Sans, 2014). Because genetic, sociocultural, and environmental factors influence BPR of CAs, a cluster detection and its epidemiological characterization may be an efficient approach to identify environmental and/or genetic factors causing birth defects (Poletta et al., 2007; Gili et al., 2015). The aim of this study was to identify, describe, and characterize geographical clusters of CAs in South America. Materials and Methods SAMPLE This observational descriptive study is based on clinical epidemiological data registered by the ECLAMC network (Castilla and Orioli, 2004; Poletta et al., 2014; http://www. eclamc.org/). A total of 25,082 malformed newborns were ascertained among 2,557,424 births (stillbirths weighing  500 g and livebirths) occurring between 1995 and 2012 in 129 maternity hospitals throughout nine South Ameri- can countries. The hospitals were distributed throughout Argentina (48 hospitals), Bolivia (5), Brazil (25), Chile (16), Colombia (9), Ecuador (11), Paraguay (3), Uruguay Supported by Agencia Nacional de Promoci on Cient  ıfica y Tecnol ogica (ANP- CyT), Argentina; Consejo Nacional de Investigaciones Cient  ıficas y T ecnicas (CONICET), Argentina.. 1 Estudio Colaborativo Latinoamericano de Malformaciones Cong enitas- ECLAMC, Laboratorio de Epidemiologia Gen etica, Direcci on de Investigaci on, CEMIC-CONICET, Buenos Aires, Argentina 2 Estudio Colaborativo Latinoamericano de Malformaciones Cong enitas- ECLAMC, Instituto Nacional de Gen etica M edica Populacional, Rio de Janeiro, Brazil *Correspondence to: Juan Antonio Gili, Direcci on de Investigaci on - Hospital Universitario CEMIC, Galv an 4102 (C1431FWO) Buenos Aires, Argentina.E- mail: jagili79@gmail.com Published online 17 February 2016 in Wiley Online Library (wileyonlinelibrary. com). Doi: 10.1002/bdra.23481 V C 2016 Wiley Periodicals, Inc.