Clusters of rare disorders and congenital anomalies in South America.

Objective: To map geographic clusters of rare disorders and congenital anomalies reported in South America. Methods: Qualitative systematic review conducted in Medline/PubMed, Lilacs, and Scielo electronic databases to identify studies meeting eligibility criteria. The strategy resulted in 1 672 unique articles, from which 164 were selected for full reading by a pair of reviewers. Results: Fifty-five articles reported at least one cluster of genetic disorders or congenital anomalies in South American territory. From these papers, 122 clusters were identified, of which half (61) were related to autosomal recessive disorders. Sixty-five (53.3%) of the clusters were located in Brazil. Conclusions: The results of the review reinforce that rare diseases and congenital anomalies can occur in a non-random way in space, which is discussed in the perspective of the complex history of formation, social organization, and genetic structure of the South American population. Mapping clusters in population medical genetics can be an important public health tool, given that such places concentrate cases of rare diseases that frequently require multiprofessional, specialized care. Therefore, these results can support important agendas in public health related to rare diseases and congenital anomalies, such as health promotion and surveillance.

Clusters of rare disorders and congenital anomalies in South America

[ABSTRACT]. Objective. To map geographic clusters of rare disorders and congenital anomalies reported in South America. Methods. Qualitative systematic review conducted in Medline/PubMed, Lilacs, and Scielo electronic data- bases to identify studies meeting eligibility criteria. The strategy resulted in 1 672 unique articles, from which 164 were selected for full reading by a pair of reviewers. Results. Fifty-five articles reported at least one cluster of genetic disorders or congenital anomalies in South American territory. From these papers, 122 clusters were identified, of which half (61) were related to autoso- mal recessive disorders. Sixty-five (53.3%) of the clusters were located in Brazil. Conclusions. The results of the review reinforce that rare diseases and congenital anomalies can occur in a non-random way in space, which is discussed in the perspective of the complex history of formation, social organization, and genetic structure of the South American population. Mapping clusters in population medical genetics can be an important public health tool, given that such places concentrate cases of rare diseases that frequently require multiprofessional, specialized care. Therefore, these results can support important agendas in public health related to rare diseases and congenital anomalies, such as health promotion and surveillance.

[RESUMEN]. Objetivo. Trazar los conglomerados geográficos de los trastornos y las malformaciones congénitas poco frecuentes notificados en América del Sur. Métodos. Se realizó una revisión sistemática cualitativa en las bases de datos electrónicas Medline/PubMed, Lilacs y Scielo para encontrar los estudios que cumplieran con los criterios de selección. Se encontraron 1672 artículos originales, de los que se seleccionaron 164 para su lectura completa por un par de revisores. Resultados. En 55 artículos se informó de al menos un conglomerado de trastornos genéticos o malforma- ciones congénitas en América del Sur. A partir de estos artículos, se encontraron 122 conglomerados, de los cuales la mitad (61) se asociaron con trastornos autosómicos recesivos. Sesenta y cinco (53,3%) de los conglomerados se ubicaron en Brasil. Conclusiones. Los resultados de la revisión confirman que las enfermedades raras y las malformaciones congénitas pueden presentarse de una forma no aleatoria en el espacio, lo que se comenta desde la per- spectiva de la complejidad histórica del proceso de formación, organización social y estructura genética de la población de América del Sur. Definir geográficamente los conglomerados en la genética médica pobla- cional puede ser una importante herramienta de salud pública, ya que en esos lugares se concentran casos de enfermedades raras que suelen requerir una atención especializada y multidisciplinaria. Por lo tanto, estos resultados pueden servir de apoyo a importantes programas de salud pública relacionados con las enferme- dades raras y las malformaciones congénitas como, por ejemplo, la promoción de la salud y la vigilancia.

[RESUMO]. Objetivo. Mapear agrupamentos geográficos de doenças raras e anomalias congênitas relatados na América do Sul. Métodos. Revisão sistemática qualitativa realizada nas bases de dados eletrônicos Medline/PubMed, Lilacs e Scielo para identificar estudos que atendessem aos critérios de elegibilidade. A estratégia resultou em 1.672 artigos únicos, dos quais 164 foram selecionados para leitura completa por uma dupla de revisores. Resultados. Cinquenta e cinco artigos relataram pelo menos um agrupamento de distúrbios genéticos ou anomalias congênitas no território sul-americano. A partir desses artigos, foram identificados 122 agrupamen- tos, dos quais metade (61) estava relacionada a doenças autossômicas recessivas. Sessenta e cinco (53,3%) dos agrupamentos estavam localizados no Brasil. Conclusões. Os resultados da revisão reforçam a observação de que doenças raras e anomalias congênitas podem ocorrer de forma não aleatória no espaço, o que é discutido na perspectiva da complexa história de formação, organização social e estrutura genética da população sul-americana. O mapeamento de agrupa- mentos em genética médica populacional pode ser uma importante ferramenta de saúde pública, visto que esses locais concentram casos de doenças raras que frequentemente requerem atendimento multiprofissional especializado. Portanto, esses resultados podem apoiar importantes agendas de saúde pública relacionadas a doenças raras e anomalias congênitas, como a vigilância e a promoção da saúde.

Clusters of rare disorders and congenital anomalies in South America / Conglomerados de trastornos y malformaciones congénitas poco frecuentes en América del Sur / Agrupamentos de doenças raras e anomalias congênitas na América do Sul

ABSTRACT Objective. To map geographic clusters of rare disorders and congenital anomalies reported in South America. Methods. Qualitative systematic review conducted in Medline/PubMed, Lilacs, and Scielo electronic databases to identify studies meeting eligibility criteria. The strategy resulted in 1 672 unique articles, from which 164 were selected for full reading by a pair of reviewers. Results. Fifty-five articles reported at least one cluster of genetic disorders or congenital anomalies in South American territory. From these papers, 122 clusters were identified, of which half (61) were related to autosomal recessive disorders. Sixty-five (53.3%) of the clusters were located in Brazil. Conclusions. The results of the review reinforce that rare diseases and congenital anomalies can occur in a non-random way in space, which is discussed in the perspective of the complex history of formation, social organization, and genetic structure of the South American population. Mapping clusters in population medical genetics can be an important public health tool, given that such places concentrate cases of rare diseases that frequently require multiprofessional, specialized care. Therefore, these results can support important agendas in public health related to rare diseases and congenital anomalies, such as health promotion and surveillance.

RESUMEN Objetivo. Trazar los conglomerados geográficos de los trastornos y las malformaciones congénitas poco frecuentes notificados en América del Sur. Métodos. Se realizó una revisión sistemática cualitativa en las bases de datos electrónicas Medline/PubMed, Lilacs y Scielo para encontrar los estudios que cumplieran con los criterios de selección. Se encontraron 1672 artículos originales, de los que se seleccionaron 164 para su lectura completa por un par de revisores. Resultados. En 55 artículos se informó de al menos un conglomerado de trastornos genéticos o malformaciones congénitas en América del Sur. A partir de estos artículos, se encontraron 122 conglomerados, de los cuales la mitad (61) se asociaron con trastornos autosómicos recesivos. Sesenta y cinco (53,3%) de los conglomerados se ubicaron en Brasil. Conclusiones. Los resultados de la revisión confirman que las enfermedades raras y las malformaciones congénitas pueden presentarse de una forma no aleatoria en el espacio, lo que se comenta desde la perspectiva de la complejidad histórica del proceso de formación, organización social y estructura genética de la población de América del Sur. Definir geográficamente los conglomerados en la genética médica poblacional puede ser una importante herramienta de salud pública, ya que en esos lugares se concentran casos de enfermedades raras que suelen requerir una atención especializada y multidisciplinaria. Por lo tanto, estos resultados pueden servir de apoyo a importantes programas de salud pública relacionados con las enfermedades raras y las malformaciones congénitas como, por ejemplo, la promoción de la salud y la vigilancia.

RESUMO Objetivo. Mapear agrupamentos geográficos de doenças raras e anomalias congênitas relatados na América do Sul. Métodos. Revisão sistemática qualitativa realizada nas bases de dados eletrônicos Medline/PubMed, Lilacs e Scielo para identificar estudos que atendessem aos critérios de elegibilidade. A estratégia resultou em 1.672 artigos únicos, dos quais 164 foram selecionados para leitura completa por uma dupla de revisores. Resultados. Cinquenta e cinco artigos relataram pelo menos um agrupamento de distúrbios genéticos ou anomalias congênitas no território sul-americano. A partir desses artigos, foram identificados 122 agrupamentos, dos quais metade (61) estava relacionada a doenças autossômicas recessivas. Sessenta e cinco (53,3%) dos agrupamentos estavam localizados no Brasil. Conclusões. Os resultados da revisão reforçam a observação de que doenças raras e anomalias congênitas podem ocorrer de forma não aleatória no espaço, o que é discutido na perspectiva da complexa história de formação, organização social e estrutura genética da população sul-americana. O mapeamento de agrupamentos em genética médica populacional pode ser uma importante ferramenta de saúde pública, visto que esses locais concentram casos de doenças raras que frequentemente requerem atendimento multiprofissional especializado. Portanto, esses resultados podem apoiar importantes agendas de saúde pública relacionadas a doenças raras e anomalias congênitas, como a vigilância e a promoção da saúde.

Prevalence of Congenital Anomaly and Its Relationship with Maternal Education and Age According to Local Development in the Extreme South of Brazil.

Congenital anomalies (CA) contribute to disabilities and health conditions throughout life. Furthermore, they can cause emotional distress to the mothers and children, who may also experience limitations in individual and social development. This study investigated the prevalence of CA and the relationship with maternal education and age according to local development in the extreme south of Brazil. This is a retrospective observational study with birth data from the Live Birth Information System from 2000 to 2017. The association between age and maternal education with the presence of CA was verified using multiple Poisson regression for robust variances in models adjusted for those variables with a preliminary significant association. A total of 5131 (1.5%) had some CA identified at birth between 2000 and 2017. Only advanced age (≥36 years) was associated with CA regardless of macro-region development (p ≤ 0.001). The highest risk was observed in regions with medium development (RR = 1.60; 95% CI 1.30−1.97). Maternal education (<8 years of study) was associated with CA only in mothers from macro-regions with very high development (RR = 1.27; 95% CI 1.03−1.54). These analyses confirmed that women of advanced age are at greater risk of having children with a CA regardless of maternal education and local development, but social characteristics can also have an influence, as regions with higher development had lower prevalence of CA.

Anomalías congénitas frecuentes en Uruguay entre 2011 y 2014: importancia de un registro para la evaluación de las necesidades de salud / Frequent congenital anomalies in Uruguay in 2011-2014; importance of a medical record for health assessment / Anomalias congênitas frequentes no Uruguai entre 2011-2014, importância de um registro para avaliação das necessidades de saúde

Introducción: las anomalías congénitas (AC) son un problema de salud pública con impacto en la infancia, la mortalidad infantil (MI) y la discapacidad. En Uruguay, así como en otros países desarrollados, las AC y la prematuridad son las principales causas de MI. Objetivos: el objetivo de este trabajo fue analizar las anomalías más frecuentes en el país entre 2011 y 2014, y evaluar los factores de riesgo. Material y método: los datos se obtuvieron del Registro Nacional de Defectos Congénitos y Enfermedades Raras y Estadísticas Vitales del Ministerio de Salud Pública. Resultados: se determinó que prácticamente la mitad de los casos fueron: cardiopatías congénitas, síndrome de Down y defectos del tubo neural (anencefalia, encefalocele y mielomeningocele), representando 0,42% (812/191.820) y 2,85% (38/1334) de los nacidos vivos (NV) y de los óbitos fetales respectivamente. Las prevalencias por 10.000 NV y OF fueron: 38,52 y 149,93 para cardiopatías congénitas; 3,6 y 7,5 para síndrome de Down; 2,1 y 127,4 para defectos del tubo neural. La edad materna avanzada fue el principal factor de riesgo de síndrome de Down. Los factores de riesgo observados en las tres anomalías seleccionadas fueron: prematurez, depresión neonatal y bajo peso al nacer. Conclusiones: las anomalías congénitas en general y las seleccionadas en este trabajo en particular, constituyen una causa relevante de morbimortalidad en el período neonatal e infantil, plausibles de prevención. El diagnóstico temprano es fundamental para planificar servicios de salud especializados. Los resultados aquí presentados se pueden utilizar como línea de base para medir el impacto de las acciones de salud a nivel nacional.

Introduction: congenital anomalies (CA) are a public health problem with an impact on childhood, infant mortality (IM) and disability. In Uruguay, as well as in other developed countries, CA and prematurity are the main causes of IM. Objectives: analyze the most frequent anomalies in the country in 2011-2014 and evaluate risk factors. Material and methods: the data were obtained from the National Record of Congenital Defects and Rare Diseases and health statistics from the Ministry of Public Health. Results: it was determined that practically half of the cases were: congenital heart disease, Down syndrome and Neural Tube Defects (anencephaly, encephalocele and myelomeningocele), accounting for 0.42% (812/191,820) and 2.85% (38/1334) of live births and stillbirths respectively. The prevalence per 10,000 NV and stillbirths were: 38.52 and 149.93 for Congenital Heart Disease; 3.6 and 7.5 for Down Syndrome; 2.1 and 127.4 for neural tube defects. Advanced maternal age was the main risk factor for Down syndrome. The risk factors observed in the three selected anomalies were: prematurity, neonatal depression and low birth weight. Conclusions: congenital anomalies in general, and those selected in this study in particular, are a relevant cause of morbidity and mortality in newborns and infants, likely to be prevented. Early diagnosis is essential for planning specialized health services. The results presented in the present paper can be used as a baseline to measure the impact of health actions at national level.

Introdução: as anomalias congênitas (AC) são um problema de saúde pública com impacto na infância, na mortalidade infantil (MI) e na deficiência. No Uruguai, assim como em outros países desenvolvidos as AC e prematuridade são as principais causas de MI. Objetivos: analisar as anomalias mais frequentes no país, entre 2011-2014 e avaliar os fatores de risco. Material e métodos: os dados foram obtidos do Registro Nacional de Defeitos Congênitos e Doenças Raras e estatísticas vitais do Ministério da Saúde Pública. Resultados: determinou-se que praticamente a metade dos casos eram: cardiopatias congênitas, Síndrome de Down e Defeitos do tubo neural (anencefalia, encefalocele e mielomeningocele), representando 0,42% (812/191.820) e 2,85% (38/1334) de nascidos vivos-NV e natimortos, respectivamente. As prevalências por 10.000 NV e natimortos foram: 38,52 e 149,93 para Cardiopatia Congênita; 3,6 e 7,5 para Síndrome de Down; 2,1 e 127,4 para defeitos do tubo neural. A idade materna avançada foi o principal fator de risco para a síndrome de Down. Os fatores de risco observados nas três anomalias selecionadas foram: prematuridade, depressão neonatal e baixo peso ao nascer. Conclusões: as anomalias congênitas em geral e as selecionadas neste estudo em particular, constituem causa relevante de morbimortalidade no período neonatal e infantil, possível de ser prevenida. O diagnóstico precoce é fundamental para o planejamento de serviços de saúde especializados. Os resultados aqui apresentados podem ser usados como base para medir o impacto das ações de saúde realizadas a nível nacional.

Site Occupancy by Aedes aegypti in a Subtropical City is Most Sensitive to Control during Autumn and Winter Months.

The Aedes aegypti mosquito inhabits most tropical and subtropical regions of the globe, where it transmits arboviral diseases of substantial public health relevance, such as dengue fever. In subtropical regions, Ae. aegypti often presents an annual abundance cycle driven by weather conditions. Because different population states may show varying responses to control, we are interested in studying what time of the year is most appropriate for control. To do so, we developed two dynamic site-occupancy models based on more than 200 weeks of mosquito trapping data from nearly 900 sites in a subtropical Brazilian city. Our phenomenological, Markovian models, fitted to data in a Bayesian framework, accounted for failure to detect mosquitoes in two alternative ways and for temporal variation in dynamic rates of local extinction and colonization of new sites. Infestation varied from nearly full cover of the city area in late summer, to between 10% and 67% of sites occupied in winter depending on the model. Sensitivity analysis reveals that changes in dynamic rates should have the greatest impact on site occupancy during autumn and early winter months, when the mosquito population is declining. We discuss the implications of this finding to the timing of mosquito control.

Fetal Alcohol Spectrum Disorders: Health Needs Assessment in Brazil.

BACKGROUND: Fetal alcohol syndrome (FAS) is a disorder caused by alterations in embryo-fetal development due to prenatal alcohol exposure. It is estimated that between 0.5 and 2 per 1,000 individuals are born with FAS every year. In Brazil, there are few studies addressing the extent of the problem of FAS/fetal alcohol spectrum disorders (FASD); these studies are confined to limited geographic areas. Therefore, we decided to perform a health needs assessment for FAS/FASD in Brazil. METHODS: To estimate the prevalence of FAS and FASD in Brazil, we used information from the literature, which estimates between 0.5 and 2/1,000 births per year for FAS and 10 to 50/1,000 for FASD. RESULTS: We estimated that approximately 1,500 to 6,000 children are born with FAS every year. Considering the whole population, the prevalence would be 95,377 to 380,000 affected people. However, when we consider FASD as a whole, we estimate that between 1,900,000 and 9,500,000 Brazilians might suffer the more severe consequences of alcohol exposure during pregnancy and be living with FASD. CONCLUSION: The results of the current study indicate that FAS and FASD are prevalent disorders in Brazil, and more policies targeting alcohol intake during pregnancy must be developed.

Self-assessment of color categories and its relationship with HLA profiling in Brazilian bone marrow donors.

The Brazil Ministry of Health maintains a Registry of Bone Marrow Donors that corresponds to approximately 12% of the Bone Marrow Donors Worldwide registry. This registry contains information on ethnicity (by self-assessment of color) and HLA-A, -B, and -DRB1 type. The self-assessment of color tool has been extensively used for admixed population characterization. In this context, Brazil represents a highly admixed population, resulting from 5 centuries of colonization and interbreeding, mainly, but not exclusively, among Native Americans, Europeans, and Africans. Here we evaluated self-assessed skin color and HLA genetic information from 71,291 bone marrow donors of southern Brazil to verify how likely is the HLA profiling correspondence within and between self-assessed color groups. We found that HLA itself was a better ancestry indicator than was self-assessed color. Therefore, self-assessment of color in highly admixed populations, such as that of Brazil, is not indicative of higher correspondence in the HLA profiles within skin color groups.

Implications of the admixture process in skin color molecular assessment.

The understanding of the complex genotype-phenotype architecture of human pigmentation has clear implications for the evolutionary history of humans, as well as for medical and forensic practices. Although dozens of genes have previously been associated with human skin color, knowledge about this trait remains incomplete. In particular, studies focusing on populations outside the European-North American axis are rare, and, until now, admixed populations have seldom been considered. The present study was designed to help fill this gap. Our objective was to evaluate possible associations of 18 single nucleotide polymorphisms (SNPs), located within nine genes, and one pseudogene with the Melanin Index (MI) in two admixed Brazilian populations (Gaucho, N = 352; Baiano, N = 148) with different histories of geographic and ethnic colonization. Of the total sample, four markers were found to be significantly associated with skin color, but only two (SLC24A5 rs1426654, and SLC45A2 rs16891982) were consistently associated with MI in both samples (Gaucho and Baiano). Therefore, only these 2 SNPs should be preliminarily considered to have forensic significance because they consistently showed the association independently of the admixture level of the populations studied. We do not discard that the other two markers (HERC2 rs1129038 and TYR rs1126809) might be also relevant to admixed samples, but additional studies are necessary to confirm the real importance of these markers for skin pigmentation. Finally, our study shows associations of some SNPs with MI in a modern Brazilian admixed sample, with possible applications in forensic genetics. Some classical genetic markers in Euro-North American populations are not associated with MI in our sample. Our results point out the relevance of considering population differences in selecting an appropriate set of SNPs as phenotype predictors in forensic practice.

Health needs assessment for congenital anomalies in middle-income countries: Examining the case for neural tube defects in Brazil.

Recent economic improvement in Brazil has been reflected in better maternal-child health indicators, with decreases in infant and perinatal mortality. However, under-five mortality due to congenital disorders remained unchanged, and congenital disorders have become the second leading cause of infant mortality. In the present study, we used the PHG Foundation Health Needs Assessment (HNA) Toolkit with the objective of first assessing the burden of disease caused by neural tube defects (NTDs) in Brazil and the impact of interventions already put in place to address the burden, and second to evaluate and prioritize further interventions and policies required for its prevention and treatment. The results from these two components of the HNA process are described in this paper. The published literature was reviewed to identify studies of NTDs (prevalence; morbidity; prenatal, perinatal, and postnatal mortality; treatment or prevention). Data on indicators of maternal and child health were obtained directly from the Brazilian Ministry of Health, through the online Live Births Information System (SINASC) and from the Mortality Information System (SIM). Descriptive analyses included reports of the rates of NTD in liveborns, fetal, and infant deaths. Differences between folic acid flour pre-fortification (2001-2004) and post-fortification (2006-2010) periods were expressed as prevalence rate ratios. Around 20 % of fetal deaths were related to congenital disorders with approximately 5 % of those being NTDs. For infant mortality, congenital disorders were notified in approximately 15 % of cases, with NTDs present in 10 % of the malformed children. Although statistically significant, the prevalence rate ratio (PRR) for spina bifida in live births was only 0.937 (95 % confidence interval (CI) 0.884-0.994), a decrease of 6.3 % when comparing the pre and post-fortification periods. The impact of fortification seemed to be more visible in fetal deaths due to anencephaly (PRR = 0.727, 95 % CI 0.681-0.777) and for spina bifida (PRR = 0.700, 95 % CI 0.507-0.967) with associated decreases of 27.3 and 30 %. The lower impact of folic acid fortification in Brazil, compared to other Latin-American countries, can be due to differences in dietary habits, concentration of folic acid in flour, as well as characteristic population ethnic composition. The HNA led to the identification of the needs to be addressed in Brazil, including the improvement of reporting congenital disorders within the nationwide birth certification system, and revision of the policy of flour folic acid fortification.

Clinical genetics and public policies: how should rare diseases be managed?

The implementation of a specific policy for rare diseases in the Brazilian Unified Health System presents challenges in terms of its rationale. Recognizing the importance of rarity in the context of public health means understanding genetics as one of the dimensions of disease and accepting that Brazil is undergoing a period of transition in health indicators. Although most rare diseases lack pharmacological treatment and genetic counseling constitutes the best strategy for their prevention, the cost of "orphan drugs" and their consequent lack of cost-effectiveness are still claimed as hurdles to the implementation of public policies in this field. Epidemiological aspects should not be used as isolated criteria for prioritization in public policies

Maternal drinking behavior and Fetal Alcohol Spectrum Disorders in adolescents with criminal behavior in southern Brazil.

Prenatal alcohol exposure can have serious and permanent adverse effects. The developing brain is the most vulnerable organ to the insults of prenatal alcohol exposure. A behavioral phenotype of prenatal alcohol exposure including conduct disorders is also described. This study on a sample of Brazilian adolescents convicted for criminal behavior aimed to evaluate possible clinical features of Fetal Alcohol Syndrome (FAS). These were compared to a control group of school adolescents, as well as tested for other environmental risk factors for antisocial behavior. A sample of 262 institutionalized male adolescents due to criminal behavior and 154 male students aged between 13 and 21 years comprised the study population. Maternal use of alcohol was admitted by 48.8% of the mothers of institutionalized adolescents and by 39.9% of the school students. In this sample of adolescents we could not identify individual cases with a clear diagnosis of FAS, but signs suggestive of FASD were more common in the institutionalized adolescents. Social factors like domestic and family violence were frequent in the risk group, this also being associated to maternal drinking during pregnancy. The inference is that in our sample, criminal behavior is more related to complex interactions between environmental and social issues including prenatal alcohol exposure.

Population prevalence of hereditary breast cancer phenotypes and implementation of a genetic cancer risk assessment program in southern Brazil.

In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort) was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA) program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.9%) reported a family history of cancer. Of the 902 women who attended GCRA, 55 (8%) had an estimated lifetime risk of breast cancer ≥ 20% and 214 (23.7%) had pedigrees suggestive of a breast cancer predisposition syndrome; an unexpectedly high number of these fulfilled criteria for Li-Fraumeni-like syndrome (122 families, 66.7%). The overall prevalence of a hereditary breast cancer phenotype was 6.2% (95%CI: 5.67-6.65). These findings identified a problem of significant magnitude in the region and indicate that genetic cancer risk evaluation should be undertaken in a considerable proportion of the women from this community. The large proportion of women who attended GCRA (72.3%) indicates that the program was well-accepted by the community, regardless of the potential cultural, economic and social barriers.

Population prevalence of hereditary breast cancer phenotypes and implementation of a genetic cancer risk assessment program in southern Brazil

In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort) was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA) program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.9 percent) reported a family history of cancer. Of the 902 women who attended GCRA, 55 (8 percent) had an estimated lifetime risk of breast cancer ³ 20 percent and 214 (23.7 percent) had pedigrees suggestive of a breast cancer predisposition syndrome; an unexpectedly high number of these fulfilled criteria for Li-Fraumeni-like syndrome (122 families, 66.7 percent). The overall prevalence of a hereditary breast cancer phenotype was 6.2 percent (95 percentCI: 5.67-6.65). These findings identified a problem of significant magnitude in the region and indicate that genetic cancer risk evaluation should be undertaken in a considerable proportion of the women from this community. The large proportion of women who attended GCRA (72.3 percent) indicates that the program was well-accepted by the community, regardless of the potential cultural, economic and social barriers.

Reproductive risk factors related to socioeconomic status in pregnant women in southern Brazil.

To evaluate patterns of drug use during pregnancy and other potential reproductive risks in pregnant women, we applied a standard questionnaire to 412 pregnant women classified as low socioeconomic status (SES) or as middle/high SES, in two cities of South Brazil. 77% of the women used at least one medication during pregnancy. We observed significant differences, when comparing low SES and middle/high SES groups, for the following variables: teenage pregnancies (28.4 vs. 12.4%); self-medication (21.8 vs. 13.1%); smoking habits (21.5 vs. 5.1%); unplanned pregnancies (69.5 vs. 51.8%); unwanted pregnancies (31.3 vs. 10.9%), and abortion attempts (13.1 vs. 5.8%). The average number of drugs consumed, however, was not different between low SES and middle/high SES. We believe that better education and conditions for family planning are key points to improve this scenario.