Utilização de ácidos nucleicos fetais livres no plasma materno para o diagnóstico pré-natal: realidade do Brasil neste cenário / Use of cell-free fetal nucleic acids in maternal blood for prenatal diagnosis: the reality of this scenario in Brazil

A descoberta de ácidos nucleicos fetais livres no plasma de gestantes possibilitou o desenvolvimento de novos testes de diagnóstico pré-natal não invasivo para a determinação do sexo e do Rh fetal. Esses testes foram implantados no sistema de saúde pública de diversos países da Europa há mais de cinco anos. As novas possibilidades de aplicação diagnóstica dessas tecnologias são a detecção de aneuploidias cromossômicas fetais, de doenças monogênicas fetais e de distúrbios relacionados com a placenta, temas pesquisados intensivamente por diversos grupos ao redor do mundo. O objetivo deste estudo é expor a situação brasileira no âmbito de pesquisa e utilização clínica dos testes disponíveis comercialmente que utilizam esses marcadores moleculares plasmáticos, ressaltando as vantagens, tanto econômicas quanto de segurança, que os testes não invasivos têm em relação aos atualmente utilizados em nosso sistema de saúde pública.

The discovery of cell-free fetal nucleic acids in the plasma of pregnant women has allowed the development of new, noninvasive prenatal diagnostic tests for the determination of fetal gender and Rh. These tests have been implemented in the public health system in several countries of Europe for over five years. The new possibilities for diagnostic use of these technologies are the detection of fetal chromosomal aneuploidies, monogenic fetal disorders, and placental-related disorders, subjects that have been intensively studied by several groups around the world. The aim of this review was to assess the Brazilian research and clinical scenarios regarding the utilization of commercially available tests that use these plasma markers, stressing the advantages, both economic and safety-related, that non-invasive tests have when compared to those currently used in the Brazilian public health system.

Cost-effectiveness in establishing hemophilia carrier detection and prenatal diagnosis services in a developing country with limited health resources.

The cost-effectiveness of carrier detection and prenatal diagnosis for hemophilia at the International Hemophilia Training Center, Bangkok, Thailand was studied. From 1991 to 2002, 209 females from 124 families with hemophilia A and B were included. There were 180 hemophilia A carriers and 29 hemophilia B carriers which could be classified into 78 obligate and 131 possible carriers. The phenotypic analysis for possible carriers involved the determination of levels of factor VIII or IX clotting activity (FVIII:C, FIX:C) and the ratio of FVIII:C and von Willebrand factor antigen. The result revealed that 49 females (37.4%) were diagnosed as carriers, 65 females (49.6%) were normal and 17 females (13%) were undetermined. Additional genotypic analysis was provided to 46 families with 74 females with obligate, proven or undetermined carriers within the reproductive life. The polymorphisms associated with factor VIII and IX genes were used including Bcl I for the factor VIII gene and combined use of Mse I, Sal I, Nru I, Hha I and Dde I for the factor IX gene. The informative rate was 59.4% (44/74). Consequently, 12 prenatal diagnoses for fetus at risk were performed. Sex determination was initially determined and followed by the diagnosis of hemophilia through informative gene tracking and/or the measurement of fetal levels of FVIII:C or FIX:C. The result revealed that 3 male fetuses were affected. The total cost of carrier detection and prenatal diagnosis that the families had to pay in the government hospital was 238,600 Baht (US dollars 5,965). It was compared to the estimated cost of minimal replacement therapy using lyophilized cryoprecipitate for the survival time of 30 years in one patient with hemophilia of 1,012,500 Baht (US dollars 25,312.5). The cost of prevention was much less than the replacement therapy. In conclusion, it is cost-effective to establish the service for carrier detection and prenatal diagnosis for hemophilia especially in developing countries with limited health resources.