Risk factors and demographics for microtia in South America: a case-control analysis

BACKGROUND: The etiopathogenesis of microtia is still unknown in the majority of the cases, particularly for individuals presenting with isolated microtia. Our aim was to evaluate potential risk factors for this condition using a case–control approach. METHODS: We analyzed data from 1,194 live births with isolated microtia enrolled in the ECLAMC study (Estudio Colaborativo Latino Americano de Malformaciones Congénitas) from 1982 to 2011 and their respective controls. Odds ratios (ORs) were estimated with logistic regression models along with 95% confidence intervals for the resulting OR estimates controlling for the effects of potential confounders (sex, maternal age, hospital, and year of birth) for an adjusted OR (aOR). RESULTS: Multiparity was associated with a higher risk of microtia compared with primiparity (aOR, 1.5; 95% confidence interval [CI], 1.2–1.8), with women who had eight or more prior pregnancies having the highest risk (aOR, 2.8; 95% CI, 1.6–5.2). Women who presented with cold-like symptoms were at higher risk for microtia (aOR, 2.2; 95% CI, 1.2–3.9) as well as those that used tobacco or alcohol during pregnancy (aOR, 1.7; 95% CI, 1.1–2.6 and aOR, 1.4; 95% CI, 0.9–2.1, respectively). The association with alcohol use appeared to be limited to those women who reported binge drinking during pregnancy (aOR, 1.4; 95% CI, 0.7–3.1). Cases from hospitals at low altitude (<2500 m) tended to have more severe types of microtia than those from hospitals at high altitude. CONCLUSION: These results support the hypothesis that, in addition to teratogens, other nongenetic risk factors contribute to the occurrence of isolated microtia.Fil: Luquetti, Daniela. University of Washington; Estados Unidos. Seattle Children; Estados UnidosFil: Saltzman, Babette S.. Seattle Children; Estados UnidosFil: López Camelo, Jorge Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; ArgentinaFil: Dutra, Maria da Graça. Instituto Oswaldo Cruz; BrasilFil: Castilla, Eduardo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; Argentina. Instituto Nacional de Genética Médica Populacional; Brasi

Preferential associated anomalies in 818 cases of microtia in South america

The etiology of microtia remains unknown in most cases. The identification of patterns of associated anomalies (i.e., other anomalies that occur with a given congenital anomaly in a higher than expected frequency), is a methodology that has been used for research into the etiology of birth defects. We conducted a study based on cases of microtia that were diagnosed from more than 5 million live (LB)- and stillbirths (SB) examined in hospitals participating in ECLAMC (Latin American Collaborative Study of Congenital Malformations) between 1967 and 2009. We identified 818 LB and SB with microtia and at least one additional non-related major congenital anomaly (cases) and 15,969 LB and SB with two or more unrelated major congenital anomalies except microtia (controls). A logistic regression analysis was performed to identify the congenital anomalies preferentially associated with microtia. Preferential associations were observed for 10 congenital anomalies, most of them in the craniofacial region, including facial asymmetry, choanal atresia, and eyelid colobomata. The analysis by type of microtia showed that for anomalies such as cleft lip and palate, macrostomia, and limb reduction defects, the frequency increased with the severity of the microtia. In contrast, for other anomalies the frequency tended to be the same across all types of microtia. Based on these results we will integrate data on the developmental pathways related to preferentially associated congenital anomalies for future studies investigating the etiology of microtia.Fil: Luquetti, Daniela V.. University of Washington; Estados Unidos. Seattle Children’s Research Institute; Estados UnidosFil: Cox, Thimoty C.. Monash University; Australia. University of Washington; Estados UnidosFil: López Camelo, Jorge Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; ArgentinaFil: Dutra, Maria da Graça. Instituto Oswaldo Cruz; BrasilFil: Cunningham, Michael L.. University of Washington; Estados Unidos. Seattle Children’s Research Institute; Estados UnidosFil: Castilla, Eduardo Enrique. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina. Instituto Oswaldo Cruz; Brasil. Instituto Nacional de Genética Médica Populacional; Brasi

Preferential associated anomalies in 818 cases of microtia in South America

The etiology of microtia remains unknown in most cases. The identification of patterns of associated anomalies (i.e., other anomalies that occur with a given congenital anomaly in a higher than expected frequency), is a methodology that has been used for research into the etiology of birth defects. We conducted a study based on cases of microtia that were diagnosed from more than 5 million live (LB)- and stillbirths (SB) examined in hospitals participating in ECLAMC (Latin American Collaborative Study of Congenital Malformations) between 1967 and 2009. We identified 818 LB and SB with microtia and at least one additional non-related major congenital anomaly (cases) and 15,969 LB and SB with two or more unrelated major congenital anomalies except microtia (controls). A logistic regression analysis was performed to identify the congenital anomalies preferentially associated with microtia. Preferential associations were observed for 10 congenital anomalies, most of them in the craniofacial region, including facial asymmetry, choanal atresia, and eyelid colobomata. The analysis by type of microtia showed that for anomalies such as cleft lip and palate, macrostomia, and limb reduction defects, the frequency increased with the severity of the microtia. In contrast, for other anomalies the frequency tended to be the same across all types of microtia. Based on these results we will integrate data on the developmental pathways related to preferentially associated congenital anomalies for future studies investigating the etiology of microtia.Instituto Multidisciplinario de Biología Celula

Evaluation of ICD-9-CM codes for craniofacial microsomia

Craniofacial microsomia (CFM) is a congenital condition characterized by microtia and mandibular underdevelopment. Healthcare databases and birth defects surveillance programs could be used to improve knowledge of CFM. However, no specific ICD-9-CM code exists for this condition, which makes standardized data collection challenging. Our aim was to evaluate the validity of existing ICD-9-CM codes to identify individuals with CFM

Damaging variants in FOXI3 cause microtia and craniofacial microsomia

Q1Q1Pacientes con Microtia y Microsomía craneofacialPurpose: Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown. Methods: We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro. Results: We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3. Conclusion: Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.https://orcid.org/0000-0003-3822-7780https://orcid.org/0000-0002-0729-6866Revista Internacional - IndexadaA1N

Diretriz da Sociedade Brasileira de Cardiologia sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas

This guideline aimed to update the concepts and formulate the standards of conduct and scientific evidence that support them, regarding the diagnosis and treatment of the Cardiomyopathy of Chagas disease, with special emphasis on the rationality base that supported it.&nbsp; Chagas disease in the 21st century maintains an epidemiological pattern of endemicity in 21 Latin American countries. Researchers and managers from endemic and non-endemic countries point to the need to adopt comprehensive public health policies to effectively control the interhuman transmission of T. cruzi infection, and to obtain an optimized level of care for already infected individuals, focusing on diagnostic and therapeutic opportunistic opportunities. &nbsp; Pathogenic and pathophysiological mechanisms of the Cardiomyopathy of Chagas disease were revisited after in-depth updating and the notion that necrosis and fibrosis are stimulated by tissue parasitic persistence and adverse immune reaction, as fundamental mechanisms, assisted by autonomic and microvascular disorders, was well established. Some of them have recently formed potential targets of therapies.&nbsp; The natural history of the acute and chronic phases was reviewed, with enhancement for oral transmission, indeterminate form and chronic syndromes. Recent meta-analyses of observational studies have estimated the risk of evolution from acute and indeterminate forms and mortality after chronic cardiomyopathy. Therapeutic approaches applicable to individuals with Indeterminate form of Chagas disease were specifically addressed. All methods to detect structural and/or functional alterations with various cardiac imaging techniques were also reviewed, with recommendations for use in various clinical scenarios. Mortality risk stratification based on the Rassi score, with recent studies of its application, was complemented by methods that detect myocardial fibrosis.&nbsp; The current methodology for etiological diagnosis and the consequent implications of trypanonomic treatment deserved a comprehensive and in-depth approach. Also the treatment of patients at risk or with heart failure, arrhythmias and thromboembolic events, based on pharmacological and complementary resources, received special attention. Additional chapters supported the conducts applicable to several special contexts, including t. cruzi/HIV co-infection, risk during surgeries, in pregnant women, in the reactivation of infection after heart transplantation, and others.&nbsp; &nbsp;&nbsp; Finally, two chapters of great social significance, addressing the structuring of specialized services to care for individuals with the Cardiomyopathy of Chagas disease, and reviewing the concepts of severe heart disease and its medical-labor implications completed this guideline.Esta diretriz teve como objetivo principal atualizar os conceitos e formular as normas de conduta e evidências científicas que as suportam, quanto ao diagnóstico e tratamento da CDC, com especial ênfase na base de racionalidade que a embasou. A DC no século XXI mantém padrão epidemiológico de endemicidade em 21 países da América Latina. Investigadores e gestores de países endêmicos e não endêmicos indigitam a necessidade de se adotarem políticas abrangentes, de saúde pública, para controle eficaz da transmissão inter-humanos da infecção pelo T. cruzi, e obter-se nível otimizado de atendimento aos indivíduos já infectados, com foco em oportunização diagnóstica e terapêutica. Mecanismos patogênicos e fisiopatológicos da CDC foram revisitados após atualização aprofundada e ficou bem consolidada a noção de que necrose e fibrose sejam estimuladas pela persistência parasitária tissular e reação imune adversa, como mecanismos fundamentais, coadjuvados por distúrbios autonômicos e microvasculares. Alguns deles recentemente constituíram alvos potenciais de terapêuticas. A história natural das fases aguda e crônica foi revista, com realce para a transmissão oral, a forma indeterminada e as síndromes crônicas. Metanálises recentes de estudos observacionais estimaram o risco de evolução a partir das formas aguda e indeterminada e de mortalidade após instalação da cardiomiopatia crônica. Condutas terapêuticas aplicáveis aos indivíduos com a FIDC foram abordadas especificamente. Todos os métodos para detectar alterações estruturais e/ou funcionais com variadas técnicas de imageamento cardíaco também foram revisados, com recomendações de uso nos vários cenários clínicos. Estratificação de risco de mortalidade fundamentada no escore de Rassi, com estudos recentes de sua aplicação, foi complementada por métodos que detectam fibrose miocárdica. A metodologia atual para diagnóstico etiológico e as consequentes implicações do tratamento tripanossomicida mereceram enfoque abrangente e aprofundado. Também o tratamento de pacientes em risco ou com insuficiência cardíaca, arritmias e eventos tromboembólicos, baseado em recursos farmacológicos e complementares, recebeu especial atenção. Capítulos suplementares subsidiaram as condutas aplicáveis a diversos contextos especiais, entre eles o da co-infecção por T. cruzi/HIV, risco durante cirurgias, em grávidas, na reativação da infecção após transplante cardíacos, e outros.&nbsp;&nbsp;&nbsp; Por fim, dois capítulos de grande significado social, abordando a estruturação de serviços especializados para atendimento aos indivíduos com a CDC, e revisando os conceitos de cardiopatia grave e suas implicações médico-trabalhistas completaram esta diretriz.&nbsp

Assessment of quality of information on congenital anomalies of the information system on live births

Made available in DSpace on 2011-05-04T12:42:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2009Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Rio de Janeiro, RJ, Brasil.Este estudo teve como objetivo avaliar a qualidade da informação sobre anomalias congênitas no Sistema de Informações sobre Nascidos Vivos em oito hospitais distribuídos em sete municípios do Brasil. Foi avaliada a cobertura, validade de critério e confiabilidade da codificação dos diagnósticos de anomalias congênitas em 2004 e, posteriormente, esta cobertura e validade foi comparada para o ano de 2007. Foram utilizados os bancos de dados do SINASC de 2004 e 2007 destes hospitais, consistindo de 27.945 e 25.905 nascidos vivos respectivamente. Para a validade de critério utilizou-se como padrão-ouro o ECLAMC (Estudo Colaborativo Latino Americano de Malformações Congênitas) e para a análise deconfiabilidade um profissional capacitado do SINASC. Ademais, foram descritas as intervenções realizadas pelos hospitais e suas respectivas Secretarias Municipais de Saúde(SMS) e pelo Ministério da Saúde (MS) no mesmo período. Na análise de 2004, os resultados mostraram uma elevada sub notificação das anomalias congênitas, tanto de anomalias menores como de maiores, pelo SINASC, variando entre 33,5 por cento e 88,6 por cento. A sensibilidade variou de11,4 por cento a 66,5 por cento, a especificidade, valores preditivos positivo e negativo foram maiores que80 por cento. Observou-se uma elevada concordância entre os diagnósticos descritos na declaração de nascido vivo e no ECLAMC. A confiabilidade da codificação, calculada pelo índice kappa, variou de 0,61 a 1,00 para três dígitos da CID-10 e de 0,41 a 0,78 para quatro dígitos. Na comparação entre 2004 e 2007, observou-se a persistência da baixa cobertura em todos os hospitais, exceto por um, com sub notificação de pelo menos 40 por cento das anomalias congênitas. Além disso, verificou-se piora da notificação em dois hospitais. Intervenções foram realizadas em quatro hospitais e duas SMS. Foram realizados cursos de capacitação no diagnóstico e codificação das anomalias congênitas por uma SMS. Concluiu-se que a informação sobre anomalias congênitas no SINASC, tanto em 2004 como em 2007, apresentou baixa cobertura e validade de critério, restringindo o seu uso na determinação das prevalências destas condiçõesno Brasil. A confiabilidade da codificação, apesar de apresentar valores moderados, representauma limitação importante para os estudos epidemiológicos. Poucas intervenções estão sendo realizadas objetivando a melhora da qualidade das informações sobre anomalias congênitas. Com base nos resultados deste estudo recomendamos ações urgentes pelo MS e SMS para o preenchimento deste campo no SINASC, principalmente referente à capacitação dos profissionais, assim como avaliações periódicas da qualidade.This study aimed to evaluate the birth defects data from the Brazilian birth certificate in eight hospitals distributed in seven municipalities. We evaluated the case ascertainment, criterion validity and coding reliability of birth defect cases in 2004, and afterwards, the case ascertainment and validity was compared to the year 2007. The birth certificate databases of these hospitals, from 2004 and 2007, were used, consisting of 27,945 e 25,905 live-births, respectively. For the criterion validity we used Latin-American Collaborative Study of Congenital Malformations (ECLAMC) as the gold-standard and for the reliability analysis a trained professional from the birth certificate information system. Besides, the interventions performed by the hospitals and the corresponding Municipal Departments of Health (MDOH) and the Ministry of Health (MOH), in the same period, were described. In the 2004 analysis, minor as well as major birth defects were underreported by the birth certificate, varying from 33.5% to 88.6%.The sensitivity varied from 11.4% to 66.5%, the specificity, positive and negative predictive values were all above 80%. We observed a high concordance between the birth defects diagnosis described in the birth certificate and ECLAMC. The coding reliability, calculated by kappa, varied from 0.61 to 1.00 for three digits- and from 0.41 to 0.78 for four digits of the ICD-10. In the comparison between 2004 and 2007, we observed a persistence of the low case ascertainment in all hospitals, except for one, with underreporting of at least 40% of the birth defects. In addition, we verified a significant decrease in reporting in two of the hospitals. Interventions were performed in four hospitals and two MDOHs. Training courses on birth defects diagnosis and coding were only realized by one MDOH. We concluded that the information on birth defects in the birth certificate, in 2004 as well as in 2007, presented low case ascertainment and criterion validity, restraining its use in the determination of the prevalence of these conditions in Brazil. The coding reliability, even if it presented moderate values, represents an important limitation for epidemiologic studies. Few interventions are being performed aiming the improvement of the birth defects information quality. Considering the results from this study, we recommend urgent initiatives by the MOH and MDOHs for the birth defects data in the birth certificate, especially regarding professional training, as well as periodic quality evaluations

Quality of reporting on birth defects in birth certificates: case study from a Brazilian reference hospital

The aim of this study was to evaluate the coverage, validity and reliability of Brazil's Information System on Live Births (SINASC) for birth defects in a hospital in the city of Campinas (São Paulo State). The study population consisted of 2,823 newborn infants delivered in 2004 at the Women's Integrated Health Care Center (CAISM). A birth defect registry (ECLAMC) was used as the gold-standard. All birth defect cases reported at CAISM in 2004 (92 cases) were selected from SINASC data files. All 168 birth defect cases from the same city and year registered at ECLAMC were also retrieved. An underreporting of 46.8% was observed for all birth defects, and 36.4% when considering only the major birth defects. The ascertained sensitivity and specificity were, respectively, 54.2% and 99.8%. The reliability of three and four-digit ICD-10 coding for birth defects was 0.77 and 0.55 respectively (kappa statistic). These results suggest that information provided by birth certificates in Campinas still presents limitations when seeking to ascertain accurate estimates of the prevalence of birth defects, hence indicating the need for improvements in the SINASC database to enable it to portray birth defect prevalence at birth in this city

Healthcare and psychosocial experiences of individuals with craniofacial microsomia: Patient and caregivers perspectives

© 2018 Elsevier B.V. Objective: Craniofacial microsomia (CFM) is primarily characterized by underdevelopment of the ear and mandible, with several additional possible congenital anomalies. Despite the potential burden of care and impact of CFM on multiple domains of functioning, few studies have investigated patient and caregiver perspectives. The objective of this study was to explore the diagnostic, treatment-related, and early psychosocial experiences of families with CFM with the aim of optimizing future healthcare delivery. Methods: Forty-two caregivers and nine adults with CFM responded to an online mixed-methods survey. Descriptive statistics and qualitative methods were used for the analysis. Results: Survey respondents reported high rates of subspecialty evaluations, surgeries, and participation in therapies. Some participants reported receiving inaccurate or incomplete information about CFM and experienced confusion about etiology. Communication about CFM among family members included mostly positive messages. Self-awareness of facial differences began at a mean age of three years and teasing at mean age six, with 43% of individuals four years or older reporting teasing. Teasing often involved name-calling and frequent reactions were ignoring and negative emotional responses. Participants ranked “understanding diagnosis and treatment” as a top priority for future research and had the most questions about etiology and treatment guidance. Conclusions: The survey results on the healthcare and psychosocial experiences from birth through adulthood of individuals with CFM reinforce the need for ongoing psychological assessment and intervention. Healthcare provision could be improved through establishing diagnostic criteria and standardized treatment guidelines, as well as continued investigation of CFM etiology