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Authors
Abstract(s)
Introdução: O rastreio combinado do primeiro trimestre atualmente em vigor resulta
num elevado número de falsos positivos que, consequentemente, são sujeitos a testes
invasivos para determinação do cariótipo fetal, com os respetivos riscos implícitos a estas
técnicas. O teste pré-natal não invasivo por análise de ADN livre fetal (NIPT) trouxe, pela
primeira vez nas técnicas de diagnóstico pré-natal, a oportunidade de conhecer o genoma
fetal através de um procedimento não invasivo, permitindo uma deteção mais fidedigna de
patologias genéticas do feto. No entanto, em Portugal, a Direção-Geral de Saúde não o
contempla ainda nas normas de rastreio pré-natal.
Objetivos: O presente estudo pretende verificar se o NIPT poderia substituir com
segurança o rastreio combinado do primeiro trimestre atualmente utilizado, sem
comprometer o diagnóstico de cromossomopatias, ou se traz mais vantagens enquanto teste
de segunda linha nos casos de rastreio combinado positivo. Propõe-se também a determinar
o impacto que a sua adoção poderá ter no número de procedimentos diagnósticos invasivos
necessários.
Métodos: Neste estudo observacional transversal retrospetivo, foram incluídas todas as
grávidas que realizaram, além do rastreio combinado do primeiro trimestre, um teste
pré-natal não invasivo por análise de ADN livre fetal no decurso do acompanhamento da
sua gestação no Centro Hospitalar Universitário Cova da Beira desde fevereiro de 2016 até
março de 2022. A determinação da presença de anomalia cromossómica foi feita usando
como gold-standard o cariótipo ou, em alternativa, o estudo do fenótipo do recém-nascido
no exame físico à nascença. Foi analisado o desempenho do rastreio combinado e do NIPT
na amostra, recorrendo-se a análise descritiva e análise estatística com o teste
qui-quadrado, teste de Fisher, teste de McNemar e curvas ROC.
Resultados: Entre as 197 gestações existiram 4 casos de aneuploidia. O NIPT foi capaz de
detetar 3 delas, sendo a restante uma alteração não identificável através de NIPT (triploidia
69,XXX). Comparando o uso do NIPT como rastreio de primeira linha com a sua adoção
em segunda linha, após os casos identificados pelo rastreio combinado como sendo de risco
elevado e intermédio, obteve-se respetivamente: especificidade de 98.45% e 100%, falsos
positivos de 1.52% e 0, valor preditivo positivo 50% e 100%, e valor preditivo negativo de
100% em ambas as situações. Se usado como primeira linha, comparativamente ao rastreio
atual, o NIPT reduziria os testes invasivos necessários em 57.14%. Se usado em segunda
linha, seria possível uma redução de 92.86% das amniocenteses. Conclusão: O NIPT apresentaria mais vantagens se fosse introduzido como rastreio de
segunda linha perante um rastreio combinado do primeiro trimestre positivo. Esta opção
não comprometeria a deteção de aneuploidias e, simultaneamente, permitiria diminuir o
número de testes invasivos necessários de forma significativa.
Introduction: The first trimester combined screening currently in place results in a high number of false positives that consequently undergo invasive tests for fetal karyotyping, with the respective risks implicit in these techniques. The non-invasive prenatal testing by cell-free fetal DNA analysis (NIPT) has brought, for the first time in prenatal diagnosis, the opportunity to know the fetal genome through a non-invasive procedure, allowing a more reliable detection of genetic pathologies of the fetus. However, in Portugal, the Directorate-General for Health doesn’t include it yet in the norms for prenatal screening. Objectives: This study aims to investigate if the NIPT could safely replace the first trimester combined screening currently in use, without compromising the diagnosis of chromosomal defects, or whether it has more advantages as a second-line test in cases of positive combined screening. It is also intended to determine the impact that its adoption may have on the number of invasive diagnostic procedures required. Methods: This retrospective cross-sectional observational study includes all pregnant women who performed, in addition to the first trimester combined screening, a non-invasive prenatal test by cell-free fetal DNA during the follow-up of their pregnancy at the Cova da Beira University Hospital Center since February 2016 until March 2022. The determination of the presence of chromosomal abnormality was made using as gold-standard the karyotype or, alternatively, the study of the newborn's phenotype in the physical examination at birth. The performance of the combined screening and NIPT in the sample was analyzed using descriptive and statistical analysis with the chi-square test, Fisher's test, McNemar's test, and ROC curves. Results: Among the 197 pregnancies there were 4 cases of aneuploidy. NIPT was able to detect 3 of them, the remaining one being a disorder not identifiable through NIPT (triploidy 69,XXX). Comparing the use of the NIPT as a first-line screening with its adoption as a second-line after the cases identified as high and intermediate risk by the combined screening, we obtained respectively: specificity of 98.45% and 100%, false positives of 1.52% and 0, positive predictive value of 50% and 100%, and negative predictive value of 100% in both situations. If used as first-line, compared to the current screening, the NIPT would reduce the invasive tests needed by 57.14%. If used as a second-line, a 92.86% reduction in amniocentesis would be possible. Conclusion: NIPT would have more advantages if it were introduced as a second-line screening after a positive first trimester combined screening. This option would not compromise the detection of aneuploidies and would at the same time significantly decrease the number of invasive tests needed.
Introduction: The first trimester combined screening currently in place results in a high number of false positives that consequently undergo invasive tests for fetal karyotyping, with the respective risks implicit in these techniques. The non-invasive prenatal testing by cell-free fetal DNA analysis (NIPT) has brought, for the first time in prenatal diagnosis, the opportunity to know the fetal genome through a non-invasive procedure, allowing a more reliable detection of genetic pathologies of the fetus. However, in Portugal, the Directorate-General for Health doesn’t include it yet in the norms for prenatal screening. Objectives: This study aims to investigate if the NIPT could safely replace the first trimester combined screening currently in use, without compromising the diagnosis of chromosomal defects, or whether it has more advantages as a second-line test in cases of positive combined screening. It is also intended to determine the impact that its adoption may have on the number of invasive diagnostic procedures required. Methods: This retrospective cross-sectional observational study includes all pregnant women who performed, in addition to the first trimester combined screening, a non-invasive prenatal test by cell-free fetal DNA during the follow-up of their pregnancy at the Cova da Beira University Hospital Center since February 2016 until March 2022. The determination of the presence of chromosomal abnormality was made using as gold-standard the karyotype or, alternatively, the study of the newborn's phenotype in the physical examination at birth. The performance of the combined screening and NIPT in the sample was analyzed using descriptive and statistical analysis with the chi-square test, Fisher's test, McNemar's test, and ROC curves. Results: Among the 197 pregnancies there were 4 cases of aneuploidy. NIPT was able to detect 3 of them, the remaining one being a disorder not identifiable through NIPT (triploidy 69,XXX). Comparing the use of the NIPT as a first-line screening with its adoption as a second-line after the cases identified as high and intermediate risk by the combined screening, we obtained respectively: specificity of 98.45% and 100%, false positives of 1.52% and 0, positive predictive value of 50% and 100%, and negative predictive value of 100% in both situations. If used as first-line, compared to the current screening, the NIPT would reduce the invasive tests needed by 57.14%. If used as a second-line, a 92.86% reduction in amniocentesis would be possible. Conclusion: NIPT would have more advantages if it were introduced as a second-line screening after a positive first trimester combined screening. This option would not compromise the detection of aneuploidies and would at the same time significantly decrease the number of invasive tests needed.
Description
Keywords
Adn Livre Fetal Cromossomopatias Diagnóstico Pré-Natal Rastreio Pré-Natal Teste Pré-Natal Não Invasivo