Programa de monitoramento de defeitos congênitos: experiência do estudo colaborativo latino-americano de malformações congênitas no HCPA

OBJECTIVES: The authors show here the result of the registry analysis of the Birth Defects Surveillance Program, linked to the Latin American Study of Congenital Malformations (ECLAMC), from january 1993 to december 2000. This is a hospital-based registry, with a case-control design, which is carried out in 70 hospitals of Latin America. The importance of the development of registry programs of birth defects with the purpose of offering to government agencies the alternatives for the primary prevention of some congenital malformations. Some research projects, carried out in collaboration with ECLAMC, are also presented.MATERIALS AND METHODS: PMDC/ECLAMC was established in 1983 at Hospital das Clínicas de Porto Alegre (HCPA) and it has not been interrupted since then. All births that occurred from January 1993 to December 2000 were considered in this study. We included in the study all newborns weighing ³ 500g, either liveborn or stillborn. April and May 2000 represented only 2% of births in that year and were excluded due to technical problems, which did not have a significant influence on the final analysis. A database, based on the registers of malformed liveborns, controls and stillborns was created with Epinfo 6. These data were then analyzed, and they constitute the results of this study.RESULTS: Between January 1993 and December 2000, 31,680 children were born at HCPA, Among them, 31,090 were liveborns and 590 were stillborns. Birth defects were detected in 1632 (5.25%) of liveborns and in 72 (12.20%) of stillborns, totalizing 1,704 malformed children. When all birth defects are considered, it is possible to observe a time variation without epidemiological effect on the population. Twin pregnancy was identified as a risk factor for the occurrence of malformation, with OR=2.64 (CI: 1.30 – 5.47). The performance of prenatal follow-up and maternal age under 35 years were identified as protecting factors with OR=0.78 (CI: 0.64 – 0.96) and 0.84 (IC: 0.76 – 0.93), respectively.CONCLUSIONS: The establishment of similar programs in other maternities and the connection with institutions involved with research on birth defects would bring important benefits to families and regional population.OBJETIVOS: Os autores apresentam os resultados da análise dos registros do Programa de Monitoramento de Defeitos Congênitos, vinculado ao Estudo Colaborativo Latinoamericano de Malformações Congênitas (ECLAMC), no período de janeiro de 1993 a dezembro de 2000. Trata-se de um registro de base hospitalar, com delineamento tipo caso-controle, que funciona em aproximadamente 70 hospitais distribuídos em 10 países da América Latina. Discutem a importância do desenvolvimento de programas de registro de defeitos congênitos com o objetivo de oferecer aos órgãos governamentais a possibilidade de adotar políticas de saúde baseadas na prevenção primária de alguns destes defeitos.MATERIAIS E MÉTODOS: O PMDC/ECLAMC é um estudo que iniciou em 1983 no HCPA e está em andamento contínuo desde então. No presente trabalho foram considerados todos os nascimentos ocorridos entre janeiro de 1993 e dezembro de 2000. Foram incluídos todos os recém-nascidos com peso ³ 500g, nativivos a natimortos. Os meses de abril e novembro de 2000, representando apenas 2% dos nascimentos do ano foram excluídos por problemas técnicos, fato que não interferiu na análise final. A partir das fichas de nascidos vivos malformados, controles e natimortos, foi elaborado um banco de dados utilizando o Epinfo 6. Estes dados foram posteriormente analisados, vindo a constituir os resultados deste estudo. RESULTADOS: No período de janeiro de 1993 a dezembro de 2000, nasceram 31.680 crianças no HCPA, sendo 31.090 nascidos vivos e 590 natimortos. Foram detectados defeitos congênitos em 1632 (5,25%) dos RNV e em 72 (12,20%) dos NM, perfazendo um total de 1.704 malformados. Quando consideramos os defeitos congênitos agrupadamente, observa-se uma variação temporal sem efeito epidemiológico na população. Gemelaridade foi identificada como um fator de risco para a ocorrência de malformações, com um OR de 2,64 (IC: 1,30 – 5,47). A realização do acompanhamento de pré-natal e idade materna abaixo de 35 anos foram identificados como fatores protetores com um OR de 0,78 (IC: 0,64 – 0,96) e 0,84 (IC: 0,76 – 0,93) respectivamente.CONCLUSÕES: A implantação de programas semelhantes em outras maternidades e o vínculo com instituições voltadas à pesquisa sobre defeitos congênitos beneficiaria muito as famílias e a população regional

Síndrome de Down : características clínicas, perfil epidemiológico e citogenético em recém-nascidos no Hospital de Clínicas de Porto Alegre

Este trabalho tem como objetivo descrever as caracteristicas dos recém-nascidos com síndrome de Down no HCPA entre junho de 1988 e março de 1995 com relação à freqüência de achados fenotípicos, perfil citogenético e fatores de risco, usando controles contemporâneos. A incidência de Síndrome de Down no HCPA foi de 2,21 por 1.000 nascimentos. As características mais freqüentes foram: fendas palpebrais oblíquas, hipotonia muscular, perfil facial achatado, epicanto, clinodactilia e prega simiesca. Os casos foram significativamente diferentes dos controles com relação a peso ao nascer, idade da mãe e do pai e apresentação ao parto. Dos 39 casos que realizaram cariotipagem, 33 eram trissomias livres, 4 translocações e 2 mosaicos. Os dados da casuística do HCPA são condizentes com a literatura em relação ao perfil citogenético, caracteristicas fenotípicas e fatores associados. O conhecimento das características semiológicas mais freqüentes na população local é importante para realizar um rastreamento adequado.The aim of this study was to describe the profile of Down Syndrome children born in the Hospital de Clínicas de Porto Alegre between June/88 and March/95, regarding to the frequency of clinical traits, cytogenetic and risk factors, using contemporary controls. The incidence of Down syndrome in the Hospital was2,21 per 1,000 births. The most frequent traits were palpebral fissures slant down to the midline, muscular hypotonia, flat facial profile, epicanthal folds, clinodactyly and single palmar crease. The cases were statistically different from controls regarding to body weight at birth, maternal and paternal age, and presentation at parturition. Cytogenetic analysis was performed in 39 cases, 33 of which were 21 trissomy, 4 were translocation and 2 were mosaicism. The data from HCPA match the literature in respect to cytogenetics, physical traits and associated factors. The knowledge of most frequent traits in the local population is important to accomplish an adequate screening of the disease

Controversies on timing of sex assignment and surgery in individuals with disorders of sex development : a perspective

Appropriate management of disorders of sex development (DSD) has been a matter of discussion since the first guidelines were published in the 1950s. In the last decade, with the advent of the 2006 consensus, the classical methods, especially regarding timing of surgery and sex of rearing, are being questioned. In our culture, parents of DSD newborns usually want their children to undergo genital surgery as soon as possible after sexual assignment, as surgery helps them to confirm the assigned sex. Developmental psychology theories back this hypothesis. They state that anatomic differences between sexes initiate the very important process of identification with the parent of the same sex. Sex-related endocrinological issues also demand early care. For example, using dihydrotestosterone cream to increase penile length or growth hormone treatment to improve final height require intervention at young ages to obtain better results. Although the timing of surgery remains controversial, recent evidence suggests that male reconstruction should be performed between 6 and 18 months of age. Feminizing surgery is still somewhat controversial. Most guidelines agree that severe virilization requires surgical intervention, while no consensus exists regarding mild cases. Our perspective is that precocious binary sex assignment and early surgery is a better management method. There is no strong evidence for delays and the consequences can be catastrophic in adulthood

Clinical and molecular characterization of a brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations

Campomelic dysplasia (CD) is an autosomal, dominantly inherited, skeletal abnormality belonging to the subgroup of bent bone dysplasias. In addition to bowed lower limbs, CD typically includes the following: disproportionate short stature, flat face, micrognathia, cleft palate, bell-shaped thorax, and club feet. Up to three quarters of 46,XY individuals may be sex-reversed. Radiological signs include scapular and pubic hypoplasia, narrow iliac wings, spaced ischia, and bowed femora and tibiae. Lethal CD is usually due to heterozygous mutations in SOX9, a major regulator of chondrocytic development. We present a detailed clinical and molecular characterization of nine Brazilian CD patients. Infants were either stillborn (n = 2) or died shortly after birth and presented similar phenotypes. Sex-reversal was observed in one of three chromosomally male patients. Sequencing of SOX9 revealed new heterozygous mutations in seven individuals. Six patients had mutations that resulted in premature transcriptional termination, while one infant had a single-nucleotide substitution at the conserved splice-site acceptor of intron 1. No clear genotype-phenotype correlations were observed. This study highlights the diversity of SOX9 mutations leading to lethal CD, and expands the group of known genetic alterations associated with this skeletal dysplasia