A reação em cadeia da polimerase fluorescente quantitativa (QF-PCR) é um método molecular de diagnóstico que se baseia na amplificação de pequenas sequências repetitivas do genoma (Short Tandem Repeats - STRs). Este método pode ser empregado para a detecção de aneuploidias durante a triagem pré-natal, porém, no Brasil, ainda não é utilizado nas instituições públicas. O objetivo do presente estudo foi avaliar a eficácia da QF-PCR em comparação com a citogenética na detecção de aneuploidias. Foram avaliadas 162 amostras de líquido amniótico de gestantes com risco fetal de aneuploidia aumentado. As amostras foram coletadas no Ambulatório de Obstetrícia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. O DNA fetal, para a análise do QF-PCR, foi extraído do líquido amniótico e foram utilizados 24 marcadores moleculares fluorescentes para a amplificação de genes presentes nos cromossomos 13, 18, 21, X e Y. A interpretação foi baseada na análise quantitativa dos fragmentos obtidos na amplificação. A análise citogenética foi realizada segundo metodologia convencional. A QF-PCR foi realizada às cegas, sem o conhecimento do resultado citogenético. A concordância entre os resultados obtidos pela citogenética e pela QF-PCR foi de 93,2% (151/162), com sensibilidade total de 90% e especificidade de 97,2%. Quando analisado apenas os resultados passíveis de detecção pela QF-PCR, sem os rearranjos, a concordância atinge 98,1% com sensibilidade de 98,7% e especificidade de 97,2%. O presente estudo demonstra que a QF-PCR é um método eficiente e confiável para triagem pré-natal de aneuploidias. Para a investigação de alterações cromossômicas estruturais a avaliação citogenética é necessária / Quantitative fluorescence polymerase chain reaction (QF-PCR) is a molecular diagnostic method based on the amplification of short tandem repeats (STRs) present in genome. This method is widely used to detect aneuploidies in prenatal screening, but, in Brazil, it is not used in public services. We investigated the accuracy of QF-PCR for the prenatal recognition of common aneuploidies and compared these results with cytogenetic results in our laboratory. A total of 162 amniotic fluid samples of pregnancies with high risk of fetus aneuploid were collected at the Obstetric Ambulatory of Hospital das Clínicas - Universidade de São Paulo, São Paulo, Brazil. Fetal DNA was extracted and analyzed by multiplex QF-PCR kit, which contains 24 primer pairs located on chromosomes 13, 18, 21, X and Y. Cytogenetic analysis was performed based on conventional method. The results of cytogenetics test was not known while QF-PCR assay was performed. QF-PCR results were consistent with the results of cytogenetic analysis in 93.2% of all samples (151/162), with 90% total sensitivity and 97.2% specificity. When only possible results detected by QF-PCR are analyzed, without rearrangements samples, the agreement between both tests increases to 98.1%, with 98.7% sensitivity and 97.2% specificity. The present study demonstrates that QF-PCR was efficient and reliable for prenatal aneuploidy screening. This study suggests that QF-PCR can be used as a rapid diagnostic method; however, to structural chromosomal abnormalities cytogenetic analysis must be used

A reação em cadeia da polimerase fluorescente quantitativa (QF-PCR) é um método molecular de diagnóstico que se baseia na amplificação de pequenas sequências repetitivas do genoma (Short Tandem Repeats - STRs). Este método pode ser empregado para a detecção de aneuploidias durante a triagem pré-natal, porém, no Brasil, ainda não é utilizado nas instituições públicas. O objetivo do presente estudo foi avaliar a eficácia da QF-PCR em comparação com a citogenética na detecção de aneuploidias. Foram avaliadas 162 amostras de líquido amniótico de gestantes com risco fetal de aneuploidia aumentado. As amostras foram coletadas no Ambulatório de Obstetrícia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. O DNA fetal, para a análise do QF-PCR, foi extraído do líquido amniótico e foram utilizados 24 marcadores moleculares fluorescentes para a amplificação de genes presentes nos cromossomos 13, 18, 21, X e Y. A interpretação foi baseada na análise quantitativa dos fragmentos obtidos na amplificação. A análise citogenética foi realizada segundo metodologia convencional. A QF-PCR foi realizada às cegas, sem o conhecimento do resultado citogenético. A concordância entre os resultados obtidos pela citogenética e pela QF-PCR foi de 93,2% (151/162), com sensibilidade total de 90% e especificidade de 97,2%. Quando analisado apenas os resultados passíveis de detecção pela QF-PCR, sem os rearranjos, a concordância atinge 98,1% com sensibilidade de 98,7% e especificidade de 97,2%. O presente estudo demonstra que a QF-PCR é um método eficiente e confiável para triagem pré-natal de aneuploidias. Para a investigação de alterações cromossômicas estruturais a avaliação citogenética é necessária / Quantitative fluorescence polymerase chain reaction (QF-PCR) is a molecular diagnostic method based on the amplification of short tandem repeats (STRs) present in genome. This method is widely used to detect aneuploidies in prenatal screening, but, in Brazil, it is not used in public services. We investigated the accuracy of QF-PCR for the prenatal recognition of common aneuploidies and compared these results with cytogenetic results in our laboratory. A total of 162 amniotic fluid samples of pregnancies with high risk of fetus aneuploid were collected at the Obstetric Ambulatory of Hospital das Clínicas - Universidade de São Paulo, São Paulo, Brazil. Fetal DNA was extracted and analyzed by multiplex QF-PCR kit, which contains 24 primer pairs located on chromosomes 13, 18, 21, X and Y. Cytogenetic analysis was performed based on conventional method. The results of cytogenetics test was not known while QF-PCR assay was performed. QF-PCR results were consistent with the results of cytogenetic analysis in 93.2% of all samples (151/162), with 90% total sensitivity and 97.2% specificity. When only possible results detected by QF-PCR are analyzed, without rearrangements samples, the agreement between both tests increases to 98.1%, with 98.7% sensitivity and 97.2% specificity. The present study demonstrates that QF-PCR was efficient and reliable for prenatal aneuploidy screening. This study suggests that QF-PCR can be used as a rapid diagnostic method; however, to structural chromosomal abnormalities cytogenetic analysis must be used

Duzentas amostras de DNA obtidas de voluntários brasileiros não aparentados foram triadas para SNPs em uma região de 4079 pares de bases do gene PLAC4 através de reação em cadeia da polimerase (PCR) - utilizando o kit Taq Platinum DNA polymerase (Invitrogen, USA) ciclada em termociclador Eppendorf Mastercycle Gradient (Eppendorf, Germany); e posterior sequenciamento - utilizando o kit Big Dye Terminator Cycle Sequencing v3.1 (Applied Biosystems, USA) corrida em sequenciador ABI 3100 DNA Sequencer (Applied Biosystems, USA). Sete fragmentos foram amplificados utilizando pares de iniciadores desenhados com o auxílio do programa Primer 3 baseado em uma sequência do gene PLAC4 obtida do GenBank. Dez SNPs com taxa de heterozigozidade superior a 25% foram identificados, localizados em seis dos sete fragmentos estudados, que fazem a cobertura de 93% da população brasileira. Um painel combinando estes 10 SNPs apresenta potencial utilidade clínica em um teste pré-natal não invasivo da síndrome de Down fetal baseado na abordagem SNP/mRNA / Two hundred DNA samples obtained from unrelated Brazilian individuals were screened for SNPs in a region of 4079 bp of the exon of PLAC4 gene by polymerase chain reaction (PCR) - using Taq Platinum DNA polymerase kit (Invitrogen, USA) cycled on Eppendorf Mastercycle Gradient thermocycle (Eppendorf, Germany); and subsequent sequencing using Big Dye Terminator Cycle Sequencing v3.1 kit (Applied Biosystems, USA) on ABI 3100 DNA Sequencer (Applied Biosystems, USA). Seven fragments were amplified using primer pairs designed by primer 3 software based on PLAC4 sequence obtained from GenBank. Ten SNPs with heterozigosity rate above 25% were identified, located in six of the seven fragments studied, that covers up to 93% of Brazilian population. A panel combining this 10 SNPs show potential utility in clinical setting for a noninvasive prenatal diagnostic test for Down syndrome based in the SNP/mRNA approach

A reação em cadeia da polimerase fluorescente quantitativa (QF-PCR) é um método molecular de diagnóstico que se baseia na amplificação de pequenas sequências repetitivas do genoma (Short Tandem Repeats - STRs). Este método pode ser empregado para a detecção de aneuploidias durante a triagem pré-natal, porém, no Brasil, ainda não é utilizado nas instituições públicas. O objetivo do presente estudo foi avaliar a eficácia da QF-PCR em comparação com a citogenética na detecção de aneuploidias. Foram avaliadas 162 amostras de líquido amniótico de gestantes com risco fetal de aneuploidia aumentado. As amostras foram coletadas no Ambulatório de Obstetrícia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. O DNA fetal, para a análise do QF-PCR, foi extraído do líquido amniótico e foram utilizados 24 marcadores moleculares fluorescentes para a amplificação de genes presentes nos cromossomos 13, 18, 21, X e Y. A interpretação foi baseada na análise quantitativa dos fragmentos obtidos na amplificação. A análise citogenética foi realizada segundo metodologia convencional. A QF-PCR foi realizada às cegas, sem o conhecimento do resultado citogenético. A concordância entre os resultados obtidos pela citogenética e pela QF-PCR foi de 93,2% (151/162), com sensibilidade total de 90% e especificidade de 97,2%. Quando analisado apenas os resultados passíveis de detecção pela QF-PCR, sem os rearranjos, a concordância atinge 98,1% com sensibilidade de 98,7% e especificidade de 97,2%. O presente estudo demonstra que a QF-PCR é um método eficiente e confiável para triagem pré-natal de aneuploidias. Para a investigação de alterações cromossômicas estruturais a avaliação citogenética é necessária / Quantitative fluorescence polymerase chain reaction (QF-PCR) is a molecular diagnostic method based on the amplification of short tandem repeats (STRs) present in genome. This method is widely used to detect aneuploidies in prenatal screening, but, in Brazil, it is not used in public services. We investigated the accuracy of QF-PCR for the prenatal recognition of common aneuploidies and compared these results with cytogenetic results in our laboratory. A total of 162 amniotic fluid samples of pregnancies with high risk of fetus aneuploid were collected at the Obstetric Ambulatory of Hospital das Clínicas - Universidade de São Paulo, São Paulo, Brazil. Fetal DNA was extracted and analyzed by multiplex QF-PCR kit, which contains 24 primer pairs located on chromosomes 13, 18, 21, X and Y. Cytogenetic analysis was performed based on conventional method. The results of cytogenetics test was not known while QF-PCR assay was performed. QF-PCR results were consistent with the results of cytogenetic analysis in 93.2% of all samples (151/162), with 90% total sensitivity and 97.2% specificity. When only possible results detected by QF-PCR are analyzed, without rearrangements samples, the agreement between both tests increases to 98.1%, with 98.7% sensitivity and 97.2% specificity. The present study demonstrates that QF-PCR was efficient and reliable for prenatal aneuploidy screening. This study suggests that QF-PCR can be used as a rapid diagnostic method; however, to structural chromosomal abnormalities cytogenetic analysis must be used

Mitochondrien haben eine entscheidende Rolle im Zellmetabolismus, da sie den Hauptort der ATP-Produktion darstellen. Störungen des mitochondrialen Metabolismus sind mit einem weiten Spektrum von Erkrankungen assoziiert. Das Gehirn und die Muskulatur sind aufgrund ihres hohen Energiebedarfs dabei oft betroffen (Epilepsie, Ataxie, Myopathie). Diese Arbeit beschreibt die Klonierung von nukleären Genen des Komplexes I der mitochondrialen Atmungskette. Besonderes Augenmerk wird dabei auf die 51 kDa Untereinheit (NDUFV1) gerichtet, da sie mit ihrer Bindungsstelle für NADH2 die Eintrittspforte in den Komplex I darstellt. In dieser Untereinheit werden die ersten Mutationen beschrieben, die bei Kindern zu schwerer Entwicklungsretardierung, Leukenzephalopathie und Muskelhypotonie führen. Im weiteren werden Patienten mit isoliertem Komplex III Mangel molekulargenetisch untersucht und klassifiziert. Bei einem Patienten war ein isolierter Komplex III-Mangel und eine Mutation im mitochondrialen Cytochrom b-Gen mit einer septo-optischen Dysplasie vergesellschaftet. Am Ende beschreibt die Arbeit die Probleme der pränatalen Diagnostik mitochondrialer Erkrankungen und die Besonderheiten der genetischen Beratung betroffener Familien. / Mitochondria have a crucial role in the energy metabolism of the cell, since they constitute the main place for ATP-production. Defects in the mitochondrial metabolism are associated with a wide spectrum of diseases. Due to their high energy demand brain and muscles are regularly affected (epilepsy, ataxia, myopathy). This work describes the cloning of nuclear encoded genes of complex I of the mitochondrial respiratory chain. The main interest is directed towards the 51 kDa subunit (NDUFV1) since, due to its NADH2-binding domain, it constitutes the entry port into complex I. Therein the first mutations are described, which lead to severe developmental delay, leukencephalopathy and muscular hypotonia in infants. Additionally patients with isolated complex III-deficiency are examined molecularly and are classified according to their clinical symptoms. In one patient isolated complex III deficiency and a mutation in the mitochondrial cytochrome b-gene are associated with septo-optic dysplasia. At the end problems with prenatal diagnosis of mitochondrial diseases and the peculiarities of genetic counselling of affected families are discussed.

Η αναζήτηση και επινόηση νέων προσεγγίσεων για την προγεννητική διάγνωση χρωμοσωμικών συνδρόμων, που να συνδυάζουν ταχύτητα, αξιοπιστία και ασφάλεια για την μητέρα και το έμβρυο, είναι πάντοτε επίκαιρη και επιτακτική, ιδιαίτερα στην εποχή μας, όπου η πρόοδος της μοριακής βιολογίας και η αποκρυπτογράφηση του ανθρώπινου γονιδιώματος, προσφέρουν νέα γνώση και εργαλεία για την προσπάθεια αυτή. Στην παρούσα εργασία τυποποιήθηκε η μεθοδολογία της ποσοτικής φθορίζουσας αλυσιδωτής αντίδρασης της πολυμεράσης (Quantitative Fluorescence Polymerase Chain Reaction, QF-PCR) σε συνδυασμό με τη συμβατική PCR για την ανίχνευση ανευπλοειδιών και φύλου σε δείγματα αμνιακών κυττάρων, σε βλαστομερίδια προεμβρύου και κυρίως σε ελεύθερο εμβρυϊκό DNA από την μητρική κυκλοφορία καθώς και σε ούρα της εγκύου, για την καθιέρωση μη επεμβατικής μεθοδολογίας προγεννητικής διάγνωσης. Είναι σαφές από τα αποτελέσματα της παρούσας ερευνητικής εργασίας ότι οι συγκεκριμένες μεθοδολογίες μπορούν να χρησιμοποιηθούν συμπληρωματικά στο συμβατικό χρωμοσωμικό έλεγχο και παράλληλα να αξιοποιηθούν όσον αφορά την ανάλυση του ελεύθερου εμβρυϊκού DNA στο πλάσμα της μητέρας για την ασφαλή διάγνωση του φύλου του εμβρύου στα πρώτα στάδια της κύησης. Επιπλέον, επινοήθηκαν πειράματα προσομοίωσης μητρικού πλάσματος με σκοπό τον προσδιορισμό του ποσοστού του εμβρυϊκού DNA στη μητρική κυκλοφορία σε όλη τη διάρκεια της κύησης. Τα αποτελέσματα έδειξαν ότι στα δείγματα μας το εμβρυϊκό DNA μπορεί να διαχωριστεί από το DNA της μητέρας, ανιχνεύοντας μοναδικά εμβρυϊκά αλληλόμορφα πολυμορφικών περιοχών STR (Short Tandem Repeats) πατρικής προέλευσης με QF-PCR. Αυτά τα αλληλόμορφα χρησιμοποιήθηκαν για τον υπολογισμό του ποσοστού του εμβρυϊκού DNA στο μητρικό πλάσμα. Έτσι βρέθηκε ότι σε φυσιολογικές κυήσεις, το εμβρυϊκό DNA είναι της τάξεως του 7% (διακύμανση 0-20%) του ολικού ελεύθερου DNA στη μητρική κυκλοφορία. Με βάση την ανάλυση των μοντέλων προσομοίωσης προσδιορίσθηκε με QF-PCR ο αριθμός των αντιγράφων των εμβρυϊκών χρωμοσωμάτων συγκρίνοντας τις αναλογίες των αλληλομόρφων δεικτών STR στα χρωμοσώματα 21, 18, 13, Χ και Υ. Τα αποτελέσματα έδειξαν ότι για φυσιολογικά έμβρυα και σε περιπτώσεις όπου το ποσοστό του εμβρυϊκού DNA στο μητρικό πλάσμα είναι ≥15%, ο λόγος των αναλογιών των αλληλομόρφων δύο δεικτών STR σε διαφορετικά χρωμοσώματα προσεγγίζει τη μονάδα. Η ανάλυση δειγμάτων μητρικού πλάσματος από φυσιολογικές κυήσεις και μετά από εμπλουτισμό τους στο ελεύθερο εμβρυϊκό DNA επιβεβαίωσε τα αποτελέσματα των μοντέλων προσομοίωσης. Αντίστοιχα μοντέλα προσομοίωσης δειγμάτων πλάσματος εγκύων με τρισωμικά έμβρυα για το χρωμόσωμα 21 έδειξαν ότι ο λόγος της αναλογίας των αλληλομόρφων ενός δείκτη STR σε ένα αυτοσωμικό χρωμόσωμα (π.χ. 18 ή 13) προς την αναλογία των αλληλομόρφων ενός δείκτη STR στο χρωμόσωμα 21, διαφέρει από τη μονάδα και εξαρτάται από την προέλευση, πατρική ή μητρική, του επιπλέον εμβρυϊκού χρωμοσώματος 21 στο δείγμα (0.5 έναντι 1.3 αντιστοίχως). Τα αποτελέσματα αυτά μπορούν, εφόσον επαληθευθούν σε ικανό αριθμό δειγμάτων να αξιοποιηθούν ως επιπλέον δείκτες προγεννητικού ελέγχου και ενδεχομένως να συμβάλλουν στην τυποποίηση αποτελεσματικής μεθοδολογίας μη επεμβατικής χρωμοσωμικής διάγνωσης. / The quest and devise of new approaches for the prenatal diagnosis of chromosomal syndromes that combine rapid analysis robustness and safety for mother and embryo are always in demand especially in the post-genome era with new tools and methods in our disposition. In the present study, the methodology of quantitative fluorescent polymerase chain reaction (QF-PCR) has been developed and standardized in conjunction with conventional PCR for the detection of aneuploidies and sex in amniotic cells, blastomeres and most importantly in free fetal DNA isolated from maternal peripheral blood and urine, for the establishment of non-invasive methods of prenatal diagnosis. It has become evident that the methodology we have followed can complement conventional prenatal chromosome analysis and in addition can be exploited for the analysis of fetal DNA in maternal plasma for fetal sex determination at the first stages of gestation. Moreover, simulation experiments have been devised in order to determine the percentage of fetal DNA in maternal circulation throughout pregnancy. Our results showed that free fetal DNA can be distinguished from the mother’s DNA in maternal plasma by identifying unique paternally inherited fetal polymorphisms, such as short tandem repeat (STR) alleles, with QF-PCR. These alleles were used to calculate the percentage of fetal DNA in maternal plasma. Fetal DNA was found to be present on an average of 7% (range 0-20%) of the total free DNA in maternal circulation, in normal pregnancies. QF-PCR analysis was also used to determine the copy number of fetal chromosomes by comparing the allelic ratios for chromosomes 21, 18, 13 X and Y. It appears that in informative cases where free fetal DNA is 15% or more and originates from normal embryos, the value of the allelic ratio of a STR marker on one chromosome divided by the value of the allelic ratio of another STR marker on a different chromosome is equal to 1. Analysis of DNA samples isolated from the plasma of pregnant women bearing normal embryos confirmed the results of the simulation models. Comparison of the above data with new analyses simulating DNA from the plasma of pregnant women carrying trisomic for chromosome 21 embryos have shown that the value of the allelic ratio of a STR marker on an autosomal chromosome (e.g. 18 or 13), divided by the allelic ratio of a STR marker on chromosome 21, is different from 1 and it depends on the origin, paternal or maternal, of the extra copy of chromosome 21 in the embryo, with values of 0.5 in paternal compared to 1.3 in maternal trisomies respectively. These results differentiate between normal and trisomic cases and after further evaluation may provide a new indication marker for prenatal diagnosis. In the long term, they may also provide the basis of a non-invasive procedure for early prenatal chromosomal analysis.

Univ., Diss.-2005 u.d.T.: Fumagalli, Manuel Angelo: Die immanenten Schranken des pränatalen Familienrechtsverhältnisses--Hamburg, 2004. / Literaturverz. S. 303 - 328.

OBJETIVO: Analisar as freqüências de malformações congênitas detectadas ao nascimento no Rio Grande do Sul, enfocando especialmente aquelas passíveis de Diagnóstico Pré-Natal através do Estudo Morfológico Fetal, para sugerir, ao final, uma rotina mínima de exame ultra-sonográfico fetal. MÉTODOS: Inicialmente realizou-se um estudo descritivo de base populacional dos bancos de dados oficiais do Rio Grande do Sul referentes aos defeitos congênitos no estado. Foi delimitado o período de 2001 a 2005, sendo incluídos todos recém-nascidos vivos que foram registrados ao nascimento como portadores de uma ou mais anomalias congênitas na Declaração de Nascidos Vivos. Foram incluídos também os nascidos vivos falecidos com menos de um ano, com causa mortis atribuída a um defeito congênito e os óbitos fetais cuja Declaração de Óbito registrou defeitos congênitos. Para fins deste estudo, foram analisados 25 defeitos ou grupos de defeitos, levando em conta suas prevalências relatadas na literatura, gravidade, possibilidade de diagnóstico pré-natal ou no exame do recém-nascido. A seguir foram estudadas as possibilidades de Diagnóstico Pré-Natal dos principais defeitos congênitos através da ultra-sonografia, tendo como base na literatura atual e buscando-se elaborar uma rotina mínima de exame fetal. RESULTADOS: Os 25 defeitos ou grupos de defeitos representaram 81,74% do total dos 6.236 recém nascidos com defeitos identificados no nascimento. No período de 2001-2005 nasceram no estado 765.230 bebês, com média anual de 153.046. A ocorrência geral de defeitos diagnosticados no nascimento no período foi de 0,81%, sendo relatadas as freqüências específicas daqueles 25 defeitos. Identificou-se que 787 casos de defeitos congênitos que faleceram no 1º ano de vida não foram diagnosticados ao nascimento. Calculou-se que para cada caso de cardiopatia diagnosticado no nascimento cerca de 3 casos não foram percebidos e faleceram no 1º ano de vida. Estes cálculos foram expressivos também para trissomias do 13 e 18 (3:1) e sistema nervoso central (1,28:1). CONCLUSÕES: A análise das freqüências de defeitos congênitos no Rio Grande do Sul mostrou que 25 defeitos ou grupo de defeitos representam mais de 80% do total das ocorrências no estado. Alguns defeitos congênitos registrados ao nascimento no Campo 34 da Declaração de Nascidos Vivos parecem estar subestimados, especialmente aqueles cujo diagnóstico necessita de exames especializados, como as cardiopatias congênitas. Este estudo sugere que com a avaliação ultra-sonográfica de 18 planos da anatomia fetal se pode rastrear a maioria dos defeitos congênitos do nosso meio. / OBJECTIVE: To analyze the frequency of congenital defects detected at birth in Rio Grande do Sul, focusing mainly on those that can be diagnosed prenatally by a Fetal Morphological Ultrasound Study, and finally, to suggest a minimum routine for fetal ultrasonographic examination. METHODS: Initially a population-based descriptive study was performed of the Rio Grande do Sul (RS) state official database referring to congenital defects in the state. The period from 2001 to 2005 was delimited, and all livebirths recorded in the Declaration of Livebirths as having one or more congenital anomalies were included. Babies born alive who died at less that one year of age were also included if their cause of death was attributed to a congenital defect, and the fetal deaths when the Death Declaration recorded congenital defects. For the purposes of this study, 25 defects or groups of defects were analyzed, taking into account their prevalence reported in the literature, severity, possibility of prenatal diagnosis or diagnosis during the examination of the newborn. Next the possibilities of Prenatal Diagnosis of the main congenital defects by ultrasound were studied based on the current literature and trying to create a minimum routine for a fetal examination. RESULTS: The 25 defects or groups of defects were 81.74% of the total of 6,236 newborns with defects identified at birth. During the 2001-2005 period, 765,230 babies were born in the state, with an annual mean of 153,046. The overall occurrence of defects diagnosed at birth during the period was 0.81%, and the specific frequencies of those 25 defects were reported. It was found that 787 cases with congenital defects that died in the first year of life were not diagnosed at birth. It was calculated that for each case of cardiopathy diagnosed at birth, about 3 cases were not perceived, and died during the 1st year of life. These calculations were also important for trisomies 13 and 18 (3:1) and the central nervous system (1.28:1). CONCLUSIONS: The analysis of frequencies of congenital defects or groups of defects that represents more than 80% of them. Some congenital defects recorded in the Declaration of Livebirths at field number 34 seams to be underestimates, like the congenital cardiopathies. This study suggest that with the ultrasonographic evaluation of 18 planes of fetal anatomy the majority of congenital defects can be traced.

OBJETIVO: Analisar as freqüências de malformações congênitas detectadas ao nascimento no Rio Grande do Sul, enfocando especialmente aquelas passíveis de Diagnóstico Pré-Natal através do Estudo Morfológico Fetal, para sugerir, ao final, uma rotina mínima de exame ultra-sonográfico fetal. MÉTODOS: Inicialmente realizou-se um estudo descritivo de base populacional dos bancos de dados oficiais do Rio Grande do Sul referentes aos defeitos congênitos no estado. Foi delimitado o período de 2001 a 2005, sendo incluídos todos recém-nascidos vivos que foram registrados ao nascimento como portadores de uma ou mais anomalias congênitas na Declaração de Nascidos Vivos. Foram incluídos também os nascidos vivos falecidos com menos de um ano, com causa mortis atribuída a um defeito congênito e os óbitos fetais cuja Declaração de Óbito registrou defeitos congênitos. Para fins deste estudo, foram analisados 25 defeitos ou grupos de defeitos, levando em conta suas prevalências relatadas na literatura, gravidade, possibilidade de diagnóstico pré-natal ou no exame do recém-nascido. A seguir foram estudadas as possibilidades de Diagnóstico Pré-Natal dos principais defeitos congênitos através da ultra-sonografia, tendo como base na literatura atual e buscando-se elaborar uma rotina mínima de exame fetal. RESULTADOS: Os 25 defeitos ou grupos de defeitos representaram 81,74% do total dos 6.236 recém nascidos com defeitos identificados no nascimento. No período de 2001-2005 nasceram no estado 765.230 bebês, com média anual de 153.046. A ocorrência geral de defeitos diagnosticados no nascimento no período foi de 0,81%, sendo relatadas as freqüências específicas daqueles 25 defeitos. Identificou-se que 787 casos de defeitos congênitos que faleceram no 1º ano de vida não foram diagnosticados ao nascimento. Calculou-se que para cada caso de cardiopatia diagnosticado no nascimento cerca de 3 casos não foram percebidos e faleceram no 1º ano de vida. Estes cálculos foram expressivos também para trissomias do 13 e 18 (3:1) e sistema nervoso central (1,28:1). CONCLUSÕES: A análise das freqüências de defeitos congênitos no Rio Grande do Sul mostrou que 25 defeitos ou grupo de defeitos representam mais de 80% do total das ocorrências no estado. Alguns defeitos congênitos registrados ao nascimento no Campo 34 da Declaração de Nascidos Vivos parecem estar subestimados, especialmente aqueles cujo diagnóstico necessita de exames especializados, como as cardiopatias congênitas. Este estudo sugere que com a avaliação ultra-sonográfica de 18 planos da anatomia fetal se pode rastrear a maioria dos defeitos congênitos do nosso meio. / OBJECTIVE: To analyze the frequency of congenital defects detected at birth in Rio Grande do Sul, focusing mainly on those that can be diagnosed prenatally by a Fetal Morphological Ultrasound Study, and finally, to suggest a minimum routine for fetal ultrasonographic examination. METHODS: Initially a population-based descriptive study was performed of the Rio Grande do Sul (RS) state official database referring to congenital defects in the state. The period from 2001 to 2005 was delimited, and all livebirths recorded in the Declaration of Livebirths as having one or more congenital anomalies were included. Babies born alive who died at less that one year of age were also included if their cause of death was attributed to a congenital defect, and the fetal deaths when the Death Declaration recorded congenital defects. For the purposes of this study, 25 defects or groups of defects were analyzed, taking into account their prevalence reported in the literature, severity, possibility of prenatal diagnosis or diagnosis during the examination of the newborn. Next the possibilities of Prenatal Diagnosis of the main congenital defects by ultrasound were studied based on the current literature and trying to create a minimum routine for a fetal examination. RESULTS: The 25 defects or groups of defects were 81.74% of the total of 6,236 newborns with defects identified at birth. During the 2001-2005 period, 765,230 babies were born in the state, with an annual mean of 153,046. The overall occurrence of defects diagnosed at birth during the period was 0.81%, and the specific frequencies of those 25 defects were reported. It was found that 787 cases with congenital defects that died in the first year of life were not diagnosed at birth. It was calculated that for each case of cardiopathy diagnosed at birth, about 3 cases were not perceived, and died during the 1st year of life. These calculations were also important for trisomies 13 and 18 (3:1) and the central nervous system (1.28:1). CONCLUSIONS: The analysis of frequencies of congenital defects or groups of defects that represents more than 80% of them. Some congenital defects recorded in the Declaration of Livebirths at field number 34 seams to be underestimates, like the congenital cardiopathies. This study suggest that with the ultrasonographic evaluation of 18 planes of fetal anatomy the majority of congenital defects can be traced.

OBJETIVO: Analisar as freqüências de malformações congênitas detectadas ao nascimento no Rio Grande do Sul, enfocando especialmente aquelas passíveis de Diagnóstico Pré-Natal através do Estudo Morfológico Fetal, para sugerir, ao final, uma rotina mínima de exame ultra-sonográfico fetal. MÉTODOS: Inicialmente realizou-se um estudo descritivo de base populacional dos bancos de dados oficiais do Rio Grande do Sul referentes aos defeitos congênitos no estado. Foi delimitado o período de 2001 a 2005, sendo incluídos todos recém-nascidos vivos que foram registrados ao nascimento como portadores de uma ou mais anomalias congênitas na Declaração de Nascidos Vivos. Foram incluídos também os nascidos vivos falecidos com menos de um ano, com causa mortis atribuída a um defeito congênito e os óbitos fetais cuja Declaração de Óbito registrou defeitos congênitos. Para fins deste estudo, foram analisados 25 defeitos ou grupos de defeitos, levando em conta suas prevalências relatadas na literatura, gravidade, possibilidade de diagnóstico pré-natal ou no exame do recém-nascido. A seguir foram estudadas as possibilidades de Diagnóstico Pré-Natal dos principais defeitos congênitos através da ultra-sonografia, tendo como base na literatura atual e buscando-se elaborar uma rotina mínima de exame fetal. RESULTADOS: Os 25 defeitos ou grupos de defeitos representaram 81,74% do total dos 6.236 recém nascidos com defeitos identificados no nascimento. No período de 2001-2005 nasceram no estado 765.230 bebês, com média anual de 153.046. A ocorrência geral de defeitos diagnosticados no nascimento no período foi de 0,81%, sendo relatadas as freqüências específicas daqueles 25 defeitos. Identificou-se que 787 casos de defeitos congênitos que faleceram no 1º ano de vida não foram diagnosticados ao nascimento. Calculou-se que para cada caso de cardiopatia diagnosticado no nascimento cerca de 3 casos não foram percebidos e faleceram no 1º ano de vida. Estes cálculos foram expressivos também para trissomias do 13 e 18 (3:1) e sistema nervoso central (1,28:1). CONCLUSÕES: A análise das freqüências de defeitos congênitos no Rio Grande do Sul mostrou que 25 defeitos ou grupo de defeitos representam mais de 80% do total das ocorrências no estado. Alguns defeitos congênitos registrados ao nascimento no Campo 34 da Declaração de Nascidos Vivos parecem estar subestimados, especialmente aqueles cujo diagnóstico necessita de exames especializados, como as cardiopatias congênitas. Este estudo sugere que com a avaliação ultra-sonográfica de 18 planos da anatomia fetal se pode rastrear a maioria dos defeitos congênitos do nosso meio. / OBJECTIVE: To analyze the frequency of congenital defects detected at birth in Rio Grande do Sul, focusing mainly on those that can be diagnosed prenatally by a Fetal Morphological Ultrasound Study, and finally, to suggest a minimum routine for fetal ultrasonographic examination. METHODS: Initially a population-based descriptive study was performed of the Rio Grande do Sul (RS) state official database referring to congenital defects in the state. The period from 2001 to 2005 was delimited, and all livebirths recorded in the Declaration of Livebirths as having one or more congenital anomalies were included. Babies born alive who died at less that one year of age were also included if their cause of death was attributed to a congenital defect, and the fetal deaths when the Death Declaration recorded congenital defects. For the purposes of this study, 25 defects or groups of defects were analyzed, taking into account their prevalence reported in the literature, severity, possibility of prenatal diagnosis or diagnosis during the examination of the newborn. Next the possibilities of Prenatal Diagnosis of the main congenital defects by ultrasound were studied based on the current literature and trying to create a minimum routine for a fetal examination. RESULTS: The 25 defects or groups of defects were 81.74% of the total of 6,236 newborns with defects identified at birth. During the 2001-2005 period, 765,230 babies were born in the state, with an annual mean of 153,046. The overall occurrence of defects diagnosed at birth during the period was 0.81%, and the specific frequencies of those 25 defects were reported. It was found that 787 cases with congenital defects that died in the first year of life were not diagnosed at birth. It was calculated that for each case of cardiopathy diagnosed at birth, about 3 cases were not perceived, and died during the 1st year of life. These calculations were also important for trisomies 13 and 18 (3:1) and the central nervous system (1.28:1). CONCLUSIONS: The analysis of frequencies of congenital defects or groups of defects that represents more than 80% of them. Some congenital defects recorded in the Declaration of Livebirths at field number 34 seams to be underestimates, like the congenital cardiopathies. This study suggest that with the ultrasonographic evaluation of 18 planes of fetal anatomy the majority of congenital defects can be traced.