==== Front Rev Bras Ginecol Obstet Rev Bras Ginecol Obstet 10.1055/s-00030576 RBGO Gynecology & Obstetrics 0100-7203 1806-9339 Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil 32330960 10.1055/s-0040-1709692 190091 Original Article Fetal Medicine Frequency of Congenital Anomalies in the Brazilian Midwest and the Association with Maternal Risk Factors: Case-control Study Frequência das anomalias congênitas no centro-oeste brasileiro e a associação com fatores de risco materno: estudo caso-controlehttp://orcid.org/0000-0003-0755-0753 Moraes Carolina Leão de 1 http://orcid.org/0000-0001-9981-7085 Melo Natália Cruz e 2 http://orcid.org/0000-0002-0824-1138 Amaral Waldemar Naves do 1 1 Faculty of Medicine, Department of Obstetrics and Gynecology, Hospital das Clínicas, Universidade Federal de Goiás, Goiânia, GO, Brazil 2 Escola Paulista de Medicina, Universidade Federal de São Paulo, SP, Brazil Address for correspondence Carolina Leão de Moraes, MSc Universidade Federal de GoiásGoiânia, GOBrasilcarolina.leao.moraes@gmail.com 4 2020 1 4 2020 42 4 188193 27 3 2019 02 3 2020 https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective To evaluate the frequency of structural congenital anomalies (CAs) in the midwest of Brazil and its association with maternal risk factors. Methods This was a prospective, observational, case-control study based on a hospital population. Pregnant women attended at a fetal medicine service in Brazil were analyzed in the period from October 2014 to February 2016.A total of 357 pregnant women were included, 223 of whom had fetuses with structural anomalies (group case), and 134 of whom had structurally normal fetuses (control group). The clinical history was made previous to prenatal consultation, and the diagnosis of the structural CA was performed through ultrasound. Results A frequency of 64.27% (n = 223) of pregnant women with fetuses with structural anomalies was observed. The most frequent structural CAs were those of the central nervous system (30.94%), followed by anomalies of the genitourinary system (23.80%), and, finally, by multiple CAs (16.60%). The background of previous children with CAs (odds ratio [OR]: 3.85; p = 0.022), family history (OR: 6.03; p = < 0.001), and consanguinity between the progenitors (OR: 4.43; p = 0.034) influenced the occurrence of structural CA. Conclusion The most frequent CAs are those of the central nervous system, followed by those of the genitourinary system, and then multiple anomalies. The maternal risk factors that may have influenced the occurrence of structural CA were previous children with CA, family history, and consanguinity among the parents. Resumo Objetivo Avaliar a frequência de anomalias congênitas (ACs) estruturais no centro-oeste brasileiro e a associação com fatores de risco maternos. Métodos Estudo prospectivo, observacional, caso-controle, baseado em uma população hospitalar. Foram analisadas gestantes atendidas em um serviço de medicina fetal no Brasil, no período de outubro de 2014 a fevereiro de 2016. Foram analisadas 357 gestantes, dentre as quais 223 tiveram fetos com ACs estruturais (grupo controle) e 134 tiveram fetos estruturalmente normais (grupo controle). A história clínica foi feita antes da consulta de pré-natal, e o diagnóstico da AC estrutural foi realizado por ultrassonografia. Resultados Observou-se uma frequência de 64,27% (n = 223) de gestantes com fetos com ACs estruturais. As ACs estruturais mais frequentes foram as do sistema nervoso central (30,94%), seguidas das anomalias do sistema gênito-urinário (23,80%), e, por fim, das ACs múltiplas (16,60%). Antecedentes de crianças com AC (razão de probabiliade [RP]: 3,85; p = 0,022), antecedentes familiares (RP: 6,03; p = < 0,001), e consanguinidade entre os grupos progenitores (RP: 4,43; p = 0,034) influenciaram a ocorrência de AC estrutural. Conclusão As ACs mais frequentes foram as do sistema nervoso central, as do sistema gênito-urinário, e as ACs múltiplas. Os fatores de risco maternos que podem ter influenciado a ocorrência de AC estrutural foram antecedentes de crianças com AC, história familiar, e a consanguinidade entre os pais. Keywords congenital anomalies ultrasound prenatal prenatal diagnosis risk factors Palavras-chave anomalias congênitas ultrassom pré-natal diagnóstico pré-natal fatores de risco ==== Body pmcIntroduction Congenital anomalies (CAs) are among the main causes of death in children under 5 years of age.1 It is estimated that between 3 and 7% of children are born with birth defects worldwide,2 and that ∼ 270,000 newborns die during the first 28 days of life every year.2 3 In developed countries, CA is the leading cause of death in children, while in developing countries, mortality by CA is still not considered a public health problem.4 However, with the control of infections and diseases of nutritional deficiency, there is a tendency to reduce infant mortality for these reasons; thus, congenital malformations have become important causes of perinatal mortality in countries such as Brazil.5 6 Currently, ∼ 60% of the etiology of CAs in human beings are not elucidated. However, in around 25% of CAs, the causes seem to be multifactorial, reflecting a complex interaction of known and unknown genetic and environmental factors, including sociocultural, racial, and ethnic variables.7 In Brazil, there is a shortage of data on the incidence of CA and the associated maternal risk factors. The absence of comprehensive studies on CAs in Brazil justifies a prospective study case control that aims to describe the frequency of structural CAs and the characteristics of pregnant women to determine possible risk factors associated with the structural CA. The results presented herein can help in the development of strategies to improve the management, genetic counseling, and rehabilitation of patients with CA as well as the taking of public health measures to determine risk factors. Methods This was a prospective, observational, case-control study based on a hospital population. Pregnant women attended at a fetal medicine service in Brazil were analyzed in the period from October 2014 to February 2016.The research ethics committee of the institution approved the research with the number 808.377. Participants who responded to the questions asked during the interview and performed all the prenatal follow-up at the institution were included in the study. The collection of data was obtained through interview of the pregnant women, using a preform that contained personal and family history (maternal age, maternal ethnicity, previous children with CA, CA family history, and consanguinity) data. Data on previous obstetric history (number of previous pregnancies and prior abortions) were also verified. The presence of structural CA and its classification was confirmed by prenatal ultrasound evaluation by a fetal medicine specialist in. After the monitoring of ultrasounds, the pregnant women were categorized in the case or control groups. The case group was made up of pregnant women of fetuses with structural anomalies, and the control group by pregnant women whose fetuses did not have structural abnormalities. The pregnant women in the case group were accompanied by the main researcher in all the consultations performed after the diagnosis of CA. Thus, it was possible to update the information concerning the development of the fetus. The results of childbirth and newborns with structural anomaly were obtained by telephone contact with the pregnant women, in the computerized reports system, and, in the cases of childbirth performed in the hospital where the study was conducted, by consulting the medical file. The data were analyzed through descriptive statistics (average, standard deviation [SD], absolute frequency, relative frequency, median, confidence interval [CI]), Chi-squared tests, odds ratio, and the IBM SPSS Statistics for Windows version 22.0 software (IBM Corp., Armonk, NY, USA). Values of p < 0.05 were considered statistically significant. Results In the investigation period, 357 pregnant women were sent for attendance at the institution. Of these, 62.46% (223/357) were pregnant with fetuses with structural anomalies (case group), and 37.54% (134/357) were pregnant with structurally normal fetuses (control group). The average age of pregnant women in the case group was 25.73 years, and, in the control group, it was 25.39 years. Table 1 describes the study population in detail. Table 1 Description of sociodemographic and obstetric data of pregnant women Variables Population Case Control n % n % Maternal age  ≤ 18 32 14.34% 19 14.18%  19–24 70 31.40% 46 34.33%  25–30 69 30.94% 34 25.37%  31–36 41 18.39% 26 19.40%  ≥ 37 11 4.93% 9 6.72% Ethnicity  White 46 20.62% 45 33.58%  Brown 128 57.40% 62 46.27%  Black 45 20.20% 27 20.15%  Indigenous 4 1.80% 0 – Nr. of gestations  Primigravida 92 41.26% 46 34.33%  Multigravida 131 58.74% 88 65.67%  One previous gestation 68 51.91% 42 47.73%  Two previous gestations 38 29.00% 33 37.50%  ≥ Three previous gestations 25 19.09% 13 14.77% History of abortion  No 180 80.72% 120 89.55%  Yes 43 19.28% 14 10.45%  Previous gestation 12 27.91% 5 35.72%  In one of two previous pregnancies 18 41.86% 2 14.28%  In one of ≥ three previous pregnancies 13 30.23% 7 50.00% Children with CA  No 205 91.93% 131 97.76%  Yes 18 8.07% 3 2.24%  Previous gestation 2 11.11% 2 66.67%  In one of two previous pregnancies 10 55.56% 0 –  In one of ≥ three previous pregnancies 6 33.33% 1 33.33% Family history of CA  No 148 66.37% 124 91.94%  Yes 75 33.63% 10 8.06%  Parents with CA 7 9.33% 1 10.00%  Brothers or grandmothers with CA 23 30.67% 4 40.00%  Uncles and grandmothers with CA 10 13.33% 0 -  Uncles, grandmothers, and cousins with CA 22 29.33% 5 50.00%  CA in several relatives 13 17.33% 0 - Consanguinity  No 209 93.72% 132 98.51%  Yes 14 6.28% 2 1.49% Total 223 100% 134 100% Abbreviations: %, frequency; CA, congenital anomaly; mean, arithmetic mean; n, sample. The most frequently diagnosed CAs were anomalies of the central nervous system (CNS) (30.94%; n = 69), followed by anomalies of the genitourinary system (GUSs) (23.80%; n = 53), and, finally, by multiple congenital anomalies (MCAs) (16.60%; n = 37). Table 2 demonstrates the distribution of major structural CAs, according to topography and type of lesion. In addition, other abnormalities, such as abdominal (8.52%; n = 19), cardiovascular (6.30%; n = 14), and lymphatic system (5.82%; n = 13), among others (8.02%; n = 18), were observed. Table 2 Distribution of main structural congenital anomalies according to topography and type of lesion Congenital anomalies n % Central nervous system  Hydrocephalus 23 33.33%  Anencephaly 16 23.20%  Meningocele 7 10.14%  Others 23 33.33%  Total 69 100% Genitourinary system  Renal dysplasia 20 37.73%  Hydronephrosis 13 24.53%  Pyelectasis 12 22.64%  Others 8 15.10%  Total 53 100% Multiple anomalies  Craniofacial and limbs 13 35.14%  Craniofacial and cardiac 9 24.32%  Craniofacial and digestive 6 16.22%  Others 9 24.32%  Total 37 100% Abbreviations: %, frequency; n, sample. When comparing the case group with the control group, the data analysis revealed a statistically significant difference in relation to the CA family history (p < 0.001, CI: 3.12–12.67), indicating that pregnant women with relatives who have structural CAs have 6.03 more chance of develop fetuses with structural CAs. Patients with previous children with CAs (p = 0.022) and consanguinity (p = 0.034) also showed a statistically significant difference between the groups (Table 3). Table 3 Distribution of cases of fetal evaluation according to the characteristics of pregnant women attended at a fetal medicine service Variables Population Case Control OR 95%CI p-value n % n % Maternal age  < 35 21 90.42% 12 80.96% – 0.50–2.22 0.884  ≥ 35 202 90.58% 122 91.04% Nr. of gestations  Primigravida 92 41.26% 46 34.33% – 0.86–2.10 0.193  Multigravida 131 58.74% 88 65.67% Previous children with CA  Yes 18 8.07 3 2.24% 3.85 1.11–13.27 0.022  No 205 91.93 131 97.76% Family history of CA  Yes 75 33.63% 10 8.06% 6.03 3.12–12.67 < 0.001  No 148 66.37% 124 91.94% Consanguinity  Yes 14 6.28% 2 1.49% 4.43 0.99–19.76 0.034  No 209 93.72% 132 98.51%  Total 223 100% 134 100% Abbreviations: %, frequency; 95%CI, 95% confidence interval; CA, congenital anomaly; n, sample; OR, odds ratio. Discussion During the investigation period, a frequency of 62.46% of pregnant women with fetuses carrying structural anomalies was observed. The CNS, GUS, and MC anomalies were the most frequent ones. Indian studies showed similar results.8 9 10 Differently, other studies report higher frequency of CAs of the cardiovascular system.5 11 12 13 On the other hand, the higher frequency of CNS has been reported in several studies in Iran,14 Japan,15 Pakistan,16 17 China,18 Nigeria,19 Tanzania,20 and India.8 9 10 The etiology of CNS anomalies is multifactor and involves complex interactions between genetic and environmental factors, constituting one of the most common congenital defects.9 21 22 Among the anomalies of the CNS observed in this study, hydrocephalus and anencephaly were the most reported changes, which is similar to other studies that also reported hydrocephalus8 14 17 23 and the anencephaly8 15 17 24 among the most common malformations. The data in this study indicated that the occurrence of fetal malformation in one or more family members is associated with the development of CAs in the current gestation. Pregnant women who have a family history of CAs are 6.03 times more likely to develop fetuses with some structural anomaly. the literature data already highlighted this association.8 23 Correia et al25 revealed that 16% of families with registered cases of fetal malformations in Portugal had one or more family members with CAs. In addition, studies indicate that some specific CAs, such as those of the kidney and heart, have the potential to aggregate into families.26 27 In this study, the pregnant women who have had children with some CA presented 3.85 times more chance of having other children with malformations. These data are similar to the results of Lie et al,28 which showed that mothers who already had a child with CA would have a 2.4 times greater risk of having a second gestation affected when compared with a pregnant woman without a history of CA occurrence. Marwah et al8 observed higher frequency of malformations in pregnant women who had already had children with CA. Thus, possibly, there is a strong tendency of recurrence of specific defects in the same family, indicating the persistence of a causal factor. Regarding consanguinity, it was verified that consanguineous parents presented 4.43 times more chance of having children with anomalies than parents with no degree of kinship. These data are concordant with other studies that show a positive association between CA and consanguineous parents.8 9 11 23 29 However, Hatibaruah and Hussain30 found no relation between consanguinity and CA, and Neira et al31 did not observe cases of consanguinity among the parents of malformed newborns. Maternal age is considered an important parameter in the birth of a fetus with CA and patients aged <20 or >40 years old may showed increased risk of having children with certain birth defects.32 However, in our study, the correlation between maternal age and CA was not evident (p = 0.884). Similar to our findings, the study by Francine et al.11 et al also did not report the occurrence of this association. Despide, some studies have reported the association of increased maternal age and the occurrence of CA.8 15 There are few studies in the literature that evaluate number of pregnancies as a risk factor for the occurrence of CA. Our study found no differences between the occurrence of AC between and multigravida and primigravida. But, we can verify a higher frequency of CA in multigravida and this result is in agreement with other data in the literature.8 16 30 While, other studies have reported a higher frequency of CA in primigravida.9 30 31 32 33 Thus, the data still do not conclude how parity can influence the occurrence of CA. The differences between studies can be reflected in different racial, ethnic, and social factors in various regions of the world. Other justifications for these variations include the different study methodologies used for sampling, accessibility, and use of advanced diagnostic techniques, which improve the early and correct detection of CAs.14 The current study presents some limitations. First of all, the collected data were from a fetal medicine service, and the prevalence showed may be greater than that of the general population. Because genetic tests are not offered by the institution, tests such as karyotype, that could prove the influence of parental genetics in the occurrence of structural CA, were not performed. However, we recognize the importance of such tests. Despite the aforementioned limitations, we emphasize the importance of this work, mainly because it is prospective and because it presents the reality from the midwest of Brazil. Conclusion In the present study's population, a higher frequency of CNS, GUS, and MC anomalies was observed. The maternal risk factors that may have influenced the occurrence of structural CAs were previous children with CA, family history, and consanguinity. The results related here are important for the development of strategies to improve the management, genetic counseling, and rehabilitation of patients with CA as well as for the taking of public health measures for risk factors. Acknowledgments We appreciate the financial support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for providing a PhD scholarship for Melo NC. and Moraes CL. Contributions Conflicts of Interest The authors have no conflicts of interest to declare. Moraes C. L.: project development, data collection or management, data analysis, and manuscript writing/editing. Melo N. C.: data collection or management, data analysis, and manuscript writing/editing. Amaral W. N.: project development, manuscript writing, and critical review. ==== Refs References 1 Kyu H H Pinho C Wagner J A Brown J C Bertozzi-Villa A Charlson F J GBD 2013 Collaboration. Global and national burden of diseases and injuries among children and adolescents between 1990 and 2013: findings from the Global Burden of Disease 2013 Study JAMA Pediatr 2016 170 03 267 287. Doi: 10.1001/jamapediatrics.2015.427626810619 2 Singh G Sidhu K Bad obstetric history: a prospective study Med J Armed Forces India 2010 66 02 117 120. Doi: 10.1016/S0377-1237(10)80121-227365723 3 Sekhobo J P Druschel C M An evaluation of congenital malformations surveillance in New York State: an application of Centers for Disease Control and Prevention (CDC) guidelines for evaluating surveillance systems Public Health Rep 2001 116 04 296 305. Doi: 10.1093/phr/116.4.29612037258 4 Penchaszadeh V B Preventing congenital anomalies in developing countries Community Genet 2002 5 01 61 69. Doi: 10.1159/00006463214960901 5 Bhide P Gund P Kar A Prevalence of congenital anomalies in an Indian Maternal Cohort: healthcare, prevention, and surveillance implications PLoS One 2016 11 11 e0166408. Doi: 10.1371/journal.pone.016640827832123 6 Liu L Johnson H L Cousens S Perin J Scott S Lawn J E Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000 Lancet 2012 379 (9832):2151 2161. Doi: 10.1016/S0140-6736(12)60560-122579125 7 Adeboye M Abdulkadir M B Adegboye O A Saka A O Oladele P D Oladele D M A prospective study of spectrum, risk factors and immediate outcome of congenital anomalies in Bida, North Central Nigeria Ann Med Health Sci Res 2016 6 06 380 384. Doi: 10.4103/amhsr.amhsr_108_1328540107 8 Marwah S Sharma S Kaur H Gupta M Goraya S PS Surveillance of congenital malformations and their possible risk factors in a teaching hospital in Punjab Int J Reprod Contracept Obstet Gynecol 2014 3 01 162 167. Doi: 10.5455/2320-1770.ijrcog20140332 9 Sunitha T Prasoona K R Kumari T M Srinadh B Deepika M LN Aruna R Jyothy A Risk factors for congenital anomalies in high risk pregnant women: a large study from South India Egypt J Med Hum Genet 2017 18 01 79 85. Doi: 10.1016/j.ejmhg.2016.04.001 10 Prashar N Gupta S Thakur R Sharma P Sharma G A study of incidence of congenital anomalies in newborn: a hospital-based study Int J Res Med Sci 2016 4 06 2050 2053. Doi: 10.18203/2320-6012.ijrms20161758 11 Francine R Pascale S Aline H Congenital anomalies: prevalence and risk factors Univers J Public Health 2014 2 02 58 63. Doi: 10.13189/ujph.2014.020204 12 Jain S R Naik J D Dhakne B R Prabhu P M Kamble S V Mathurkar M P Pattern of congenital malformations in newborn: a hospital-based study Int J Res Med Sci 2016 4 02 524 528. Doi: 10.18203/2320-6012.ijrms20160308 13 Egbe A Uppu S Lee S Stroustrup A Ho D Srivastava S Congenital malformations in the newborn population: a population study and analysis of the effect of sex and prematurity Pediatr Neonatol 2015 56 01 25 30. Doi: 10.1016/j.pedneo.2014.03.01025267275 14 Mashhadi Abdolahi H Kargar Maher M H Afsharnia F Dastgiri S Prevalence of congenital anomalies: a community-based study in the northwest of iran ISRN Pediatr 2014 2014 920940. Doi: 10.1155/2014/92094024995131 15 Chen B Y Hwang B F Guo Y L Epidemiology of congenital anomalies in a population-based birth registry in Taiwan, 2002 J Formos Med Assoc 2009 108 06 460 468. Doi: 10.1016/S0929-6646(09)60093-019515626 16 Hussain S Asghar I Sabir M U Chattha M N Tarar S H Mushtaq R Prevalence and pattern of congenital malformations among neonates in the neonatal unit of a teaching hospital J Pak Med Assoc 2014 64 06 629 634 25252479 17 Gul F Jabin M Khan A S Frequency of congenital malformations and associated risk factors at Liaqat Memorial Hospital, Kohat Khyber Med Univ J 2012 4 03 119 124 18 Zhang Y P Liu X H Gao S H Wang J M Gu Y S Zhang J Y Risk factors for preterm birth in five Maternal and Child Health hospitals in Beijing PLoS One 2012 7 12 e52780. Doi: 10.1371/journal.pone.005278023300774 19 Ekanem B Bassey I E Mesembe O E Eluwa M A Ekong M B Incidence of congenital malformation in 2 major hospitals in Rivers state of Nigeria from 1990 to 2003 East Mediterr Health J 2011 17 09 701 705 22259922 20 Mashuda F Zuechner A Chalya P L Kidenya B R Manyama M Pattern and factors associated with congenital anomalies among young infants admitted at Bugando medical centre, Mwanza, Tanzania BMC Res Notes 2014 7 195. Doi: 10.1186/1756-0500-7-19524679067 21 Li K Wahlqvist M L Li D Nutrition, one-carbon metabolism and neural tube defects: a review Nutrients 2016 8 11 741. Doi: 10.3390/nu811074127886045 22 Singh N Kumble Bhat V Tiwari A Kodaganur S G Tontanahal S J Sarda A A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in an Indian family Hum Mol Genet 2017 26 06 1104 1114. Doi: 10.1093/hmg/ddx02028087737 23 El Koumi M A Al Banna E A Lebda I Pattern of congenital anomalies in newborn: a hospital-based study Pediatr Rep 2013 5 01 e5. Doi: 10.4081/pr.2013.e523667734 24 Parker S E Mai C T Canfield M A Rickard R Wang Y Meyer R E Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006 Birth Defects Res A Clin Mol Teratol 2010 88 12 1008 1016. Doi: 10.1002/bdra.2073520878909 25 Correia S Machado A Braz P Rodrigues A P Matias-Dias C Absence of prenatal ultrasound surveillance: Data from the Portuguese congenital anomalies registry Birth Defects Res A Clin Mol Teratol 2016 106 06 489 493. Doi: 10.1002/bdra.2353027301562 26 Øyen N Poulsen G Boyd H A Wohlfahrt J Jensen P KA Melbye M Recurrence of congenital heart defects in families Circulation 2009 120 04 295 301. Doi: 10.1161/CIRCULATIONAHA.109.85798719597048 27 Dias T Sairam S Kumarasiri S Ultrasound diagnosis of fetal renal abnormalities Best Pract Res Clin Obstet Gynaecol 2014 28 03 403 415. Doi: 10.1016/j.bpobgyn.2014.01.00924524801 28 Lie R T Wilcox A J Skjaerven R A population-based study of the risk of recurrence of birth defects N Engl J Med 1994 331 01 1 4. Doi: 10.1056/NEJM1994070733101018202094 29 Tayebi N Yazdani K Naghshin N The prevalence of congenital malformations and its correlation with consanguineous marriages Oman Med J 2010 25 01 37 40. Doi: 10.5001/omj.2010.922125696 30 Hatibaruah A Hussain S AM A study on prevalence of birth defects and its association with risk factors in Fakhrudhin Ali Ahmed Medical College and Hospital J Evid Based Med Health 2015 2 30 4336 4343. Doi: 10.18410/jebmh/2015/614 31 Neira F C Garay R C Luzuriaga I T Cañizares J N Vega L P Estudio descriptivo : malformaciones congénitas en recién nacidos del Servicio de Neonatología del Hospital “José Carrasco Arteaga”. 2012–2014 Rev Méd HJCA 2015 7 02 128 133 32 Gill S K Broussard C Devine O Green R F Rasmussen S A Reefhuis J ; National Birth Defects Prevention Study. Association between maternal age and birth defects of unknown etiology: United States, 1997-2007 Birth Defects Res A Clin Mol Teratol 2012 94 12 1010 1018. Doi: 10.1002/bdra.2304922821755 33 Fontoura F C Cardoso M VLML Association between congenital malformation and neonatal and maternal variables in neonatal units of a Northeast Brazilian city Texto Contexto Enferm 2014 23 04 907 914. Doi: 10.1590/0104-07072014002320013