Progress of research on clinical use of non-invasive prenatal screening for special groups of pregnant women / 中华医学遗传学杂志

As a prenatal testing for chromosomal abnormalities, non-invasive prenatal testing (NIPT) has been integrated into prenatal healthcare service. NIPT has shown a high sensitivity and specificity for screening fetal trisomies 13, 18 and 21, and has attained excellent clinical results. With the propagation of the NIPT screening, international organizations have issued guidelines and comments for its clinical utility with regular updating. China has also developed guidelines for NIPT in 2016. NIPT guidelines in various countries have provided valuable guidance for its target diseases and suitable patient groups, but there has been few research data on its clinical application for special groups of patients. Based on the guidelines and comments of various professional bodies and published data on the clinical utility of NIPT, in addition with consideration of the conditions in China, clinical utility of NIPT for particular groups of pregnant women, including those with advanced maternal age, obesity, twin pregnancy and fetal ultrasonographic anomalies, are reviewed. The value of genetic counseling for NIPT is also emphasized, which is critical for the clinical application of NIPT.

Value of chromosomal microarray analysis for the prenatal diagnosis of pregnancy with high risk signaled by non-invasive prenatal testing / 中华医学遗传学杂志

OBJECTIVE@#To explore the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with high risk signaled by non-invasive prenatal testing (NIPT).@*METHODS@#From June 2017 to August 2019, 628 pregnant women with high risk signaled by NIPT underwent invasive prenatal diagnosis. Amniotic fluid or cord blood samples were subjected to chromosomal karyotyping analysis or CMA. Pregnancy outcome and postnatal conditions of the fetuses were followed up.@*RESULTS@#The positive predictive value for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidy, other rare trisomies and copy number variants (CNVs) among the 628 women were 86.4% (127/147), 41.7% (30/72), 12.9% (4/31), 43.7% (101/231), 16.5% (14/85) and 52.2% (35/67), respectively. In 218 samples with normal karyotype, 5.5% (12/218) of additional pathogenic CNVs and 2.3% (5/218) of loss of heterozygosity were detected by CMA.@*CONCLUSION@#CMA combined with karyotyping analysis can be used as first-tier test for prenatal diagnosis for women with high-risk signaled by NIPT.

Results of non-invasive prenatal testing for 2473 women with twin pregnancy / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of non-invasive prenatal testing (NIPT) for the detection of fetal chromosomal aneuploidies in women with twin pregnancy.@*METHODS@#A total of 2473 women with twin pregnancy underwent the NIPT test to assess the risk for fetal chromosomal aneuploidies from January 2016 to September 2019. Those with a high risk by NIPT were confirmed by amniocentesis or chorionic villus sampling. All cases were followed up to evaluate the positive prediction value of NIPT for twin pregnancies.@*RESULTS@#Among the 2473 women, the NIPT test has identified 31 cases (1.25%) with a high risk for fetal chromosomal aneuploidies, which included 5 cases of trisomy 21, 1 case of chromosome 21 deletion, 4 cases of trisomy 18, 7 cases of sex chromosome abnormality and 14 cases of microdeletion and microduplication. By invasive prenatal diagnosis or chromosomal karyotyping analysis of neonates, 5 cases of trisomy 21, 3 cases of trisomy 18, 1 case of sex chromosome abnormality, and 2 cases of microdeletion and microduplication were confirmed, which yielded a positive predictive value of 100%, 75%, 25% and 25%, respectively.@*CONCLUSION@#NIPT can be used for the screening of fetal chromosomal aneuploidies in women with twin pregnancy with high accuracy. The method is non-invasive, safe and effective for the screening of fetal chromosomal aneuploidies, in particular trisomy 21.

Analysis of the efficacy of non-invasive prenatal testing in the system of prenatal screening and diagnosis / 中华医学遗传学杂志

OBJECTIVE@#To evaluate the efficacy of non-invasive prenatal testing (NIPT) in the prenatal screening and its role in the system of prenatal diagnosis.@*METHODS@#A total of 22 649 singleton pregnant women who were registered and finally delivered or had induced labor at Beijing Obstetrics and Gynecology Hospital of Capital Medical University were enrolled. The routes of prenatal screening were analyzed to evaluate the efficacy of prenatal screening. Meanwhile, 9268 pregnant women who underwent invasive prenatal diagnosis procedure were enrolled. The indications and results of prenatal diagnosis were analyzed to evaluate the effectiveness of prenatal screening.@*RESULTS@#60.24% of singleton pregnant women have opted for Down syndrome screening, and their age was mainly under 35. The proportion of women opted for NIPT was 34.74%, and were mainly between 35 and 39. The overall diagnostic rate of trisomy 21, 18 and 13 trisomy for those with high risk by NIPT was 0.89%, which yielded a positive predictive value of 75.71%. For those with moderate risk by serum screening, 0.30% was predicted with a high risk by NIPT. Among women undergoing prenatal diagnosis, 63.04% and 21.22% had the indication of advanced age or high risk by serum screening, and the positive predictive values were 5.1% and 5.13%, respectively. By contrast, 2.30% of women undergoing prenatal diagnosis had a high risk by NIPT, which yielded a positive predictive value of 54.46%.@*CONCLUSION@#With the change of the age composition of pregnant women and increase in the complexity of pregnancy in China, to build a prenatal screening system based on NIPT will be helpful to improve the efficiency of the current system of prenatal screening and diagnosis.

Is it necessary to choose NIPT-plus for pregnant women who opt for non-invasive prenatal testing? A study of 50 cases / 中华医学遗传学杂志

OBJECTIVE@#To explore whether it is necessary to choose NIPT-plus for the prenatal screening of pregnant women.@*METHODS@#The results of NIPT and NIPT-plus sequencing data, fetal DNA concentration, prenatal diagnosis and pregnancy outcome of 50 pregnant women were compared.@*RESULTS@#Compared with NIPT, NIPT-plus attained similar fetal DNA concentration and a 4.4-fold increase in sequencing data. NIPT was able to detect 4 cases of 21-trisomy, 2 cases of 18-trisomy, and 9 cases of sex chromosome aneuploidies (SCAs) signaled by NIPT-plus, but missed one 18-trisomy, and failed to detect rare chromosome aneuploidies (RCAs) and microdeletion/microduplication syndromes (MMS). The PPVs of NIPT-plus for 21-trisomy, 18-trisomy, SCAs, MMS and RCAs were 100%, 100%, 44.4%, 30.4% and 0%, respectively. And those of NIPT for 21-trisomy, 18-trisomy, and SCAs were 100%, 100%, and 44.4%, respectively.@*CONCLUSION@#It is necessary for pregnant women to select NIPT-plus to improve the detection rate of common trisomies, SCAs and disease-specific MMS, therefore reduce the occurrene of birth defect.

Trisomía 9, trisomía 13 y trisomía 18: resultados del análisis citogenético prenatal, Hospital Clínico Universidad de Chile, años 2000-2017 / Trisomy 9, trisomy 13 and trisomy 18: results of the prenatal cytogenical analysis, Hospital Clínico Universidad de Chile, years 2000-2017

INTRODUCCIÓN: En Chile, la norma técnica de la Ley N° 21.030 de 2017 considera tres aneuploidías como letales; las trisomías 9, 13 y 18, cuyo diagnóstico se confirma con un cariograma. No existe a la fecha registro nacional de frecuencia prenatal de estas patologías. OBJETIVO: Determinar la frecuencia de trisomías 9, 13 y 18 en los estudios citogenéticos prenatales en muestras de células obtenidas con amniocentesis y cordocentesis, procesados en el Laboratorio de Citogenética del Hospital Clínico Universidad de Chile. MATERIALES Y MÉTODOS: Estudio descriptivo y retrospectivo de los resultados de cariograma de líquido amniótico (LA) y sangre fetal (SF), procesados desde enero de 2000 a diciembre de 2017. RESULTADOS: Se incluyeron 2.305 muestras (402 de SF y 1.903 de LA), de ellas 442 (19%) fueron trisomías letales (TL), dentro de ellas fueron TL libres 416 (95%), TL estructurales 15 (2,7%) y mosaicos 11 (2,3%). La trisomía 18 fue en ambos tipos de muestra la más frecuente (73,5%), seguida de trisomía 13 (24,2%) y trisomía 9 (2,3%). Se desglosan resultados conforme al tipo de TL, muestra, motivo de derivación, edad materna y edad gestacional. CONCLUSIONES: El cariograma confirma el diagnóstico de aneuploidías y aporta datos relevantes para el consejo genético. La cromosomopatía letal más frecuente fue la trisomía 18. Se observó que uno de cada cinco cariogramas referidos por anomalías congénitas y/o marcadores de aneuploidía revelaban una TL.

INTRODUCTION: In Chile, the technical standard of Law No. 21,030 of 2017 considers three aneuploidies as lethal; trisomies 9, 13 and 18, whose diagnosis is confirmed with a Karyotype. To date there is not a national registry of prenatal frequency of these pathologies. OBJECTIVE: To determine the frequency of trisomies 9, 13 and 18 in prenatal cytogenetic studies in samples of cells obtained with amniocentesis and cordocentesis, processed in the Cytogenetics Laboratory of the Universidad de Chile Clinical Hospital. MATERIALS AND METHODS: Descriptive and retrospective study of the results of karyotypes of amniotic fluid (LA) and fetal blood (SF) processed from January 2000 to December 2017. Results: 2,305 samples (402 of SF and 1,903 of LA) were included, of which 438 (19%) were lethal trisomies (TL), corresponding to free TL 416 (95%), structural TL 12 (2,7%) and mosaics 10 (2.3%). Trisomy 18 was the most frequent in both types of sample (73,5 %), followed by trisomy 13 (24,2%) and trisomy 9 (2.3%). RESULTS are shown according to the type of TL, sample, reason for referral, maternal age and gestational age. CONCLUSIONS: The karyotype confirms the diagnosis of aneuploidies and provides relevant data for genetic counseling. The most frequent lethal chromosomopathy was trisomy 18. It was observed that one in five karyotypes referred for congenital anomalies and / or aneuploidy markers revealed a TL.

Placenta mórbidamente adherente asociada a malformaciones congénitas: reporte de caso / Morbidly adherent placenta associated with congenital malformations: a case report

INTRODUCCIÓN: Las alteraciones en la placentación son causa importante de morbilidad materna y neonatal y, en ocasiones, de mortalidad. La literatura científica menciona la posible asociación entre acretismo placentario y alteraciones en los parámetros bioquímicos para aneuploidía, sin descripciones de casos en que coincidan estos dos hallazgos. OBJETIVO: Este es un reporte de caso de una gestante con placenta percreta y producto con trisomía 13 REPORTE DE CASO: Gestante de 34 años, gesta 4 cesáreas 2, abortos 1, vivos 2, con embarazo de 20.4 semanas, sin antecedentes de importancia, con hallazgos en ecografía de iii nivel de alteraciones morfológicas en el sistema nervioso central, onfalocele, malformación cardiaca y deformidades en miembros. Con doppler de placenta que evidencia placenta mórbidamente adherida variedad percreta; hallazgos ecográficos confirmados con el estudio anatomopatológico. CONCLUSIONES: La trisomía 13 es una condición genética que debido a las múltiples malformaciones asociadas se considera incompatible con la vida, la placenta mórbidamente adherida se ha asociado con morbimortalidad neonatal y fetal, la no evidencia en la literatura de estas dos condiciones asociadas puede ser debido a la interrupción temprana de las gestaciones en las que se confirma el primer diagnóstico.

BACKGROUND: Alterations in placentation are an important cause of maternal and neonatal morbidity and, sometimes, deaths. The scientific literature mentions the possible association between placental accreta and alterations in the biochemical parameters for aneuploidy, without descriptions of cases in which these two findings coincide. OBJECTIVE: This is a case report of a pregnant woman with placenta percreta and trisomy 13, in which an ultrasound and pathological analysis were made. The use of keywords, in different databases, did not yield information that directly comply with these associations. CASE REPORT: A 34-year-old pregnant woman, G4C2A1V2 with a 20.4-week pregnancy, without significant medical records, with findings at III level ultrasound of morphological alterations of the central nervous system, omphalocele, cardiac malformation and limb deformities. Also, with placental Doppler that evidences morbidly adhered placenta variety percreta; ultrasound findings confirmed with the pathological study. CONCLUSION: The morbidly adhered placenta has been associated with neonatal and fetal mortality, in which some of the identified causes of fetal death are congenital anomalies. This way this case report allows for the first time to describe the association of placental accreta with aneuploidy, type trisomy 13, demonstrated by the morphological alterations of the pathological and karyotype study.

A case study of Mosaic Trisomy 13 in a 2-year-old Filipino child

@#Mosaic trisomy 13 is estimated to occur in 5% of all trisomy 13 cases. Presentation of trisomy 13 mosaicism is highly variable, with cases that may present with a normal phenotype and intellectual function, to cases with grossly abnormal features and profound developmental delays. We present a 2-year-old female with trisomy 13 mosaicism, who presented with small for gestational age (SGA), polydactyly, ventricular septal defect (VSD), and poor oral feeding.

Mirror syndrome assocciated with patau syndrome: A case report / Síndrome de espelho associada a uma síndrome de Patau: um relato de caso

Abstract Mirror syndrome is an unusual pathological condition in which maternal edema in pregnancy is seen in association with severe fetal and/or placental hydrops. The disease can be life-threatening for both the mother and the fetus. The pathogenesis is poorly understood, and may be confused with preeclampsia, even though distinguishing features can be identified. We report a rare case of mirror syndrome with maternal pulmonary edema associated with fetal hydrops due to Patau syndrome.

Resumo A síndrome de espelho é uma patologia invulgar na qual o edemamaterno é observado em associação com hidropsia fetal e/ou placentária graves. Esta doença pode ser fatal paraamãe e para o feto. A sua patogênese émal compreendida, e pode ser confundida compré-eclâmpsia,mesmo comcaracterísticas distintivas identificadas. Relatamos um caso raro de síndrome de espelho com edema pulmonar materno associado a hidropsia fetal devido a síndrome de Patau.

Anesthesia in a child operated for cleft lip associated with Patau's syndrome / Anestesia em criança operada para lábio leporino associado à síndrome de Patau

Abstract Patients with Patau's syndrome (Trisomy 13) have multiple craniofacial, cardiac, neurological and renal anomalies with very less life expectancy. Among craniofacial anomalies cleft lip and palate are common. These craniofacial and cardiac anomalies present difficulties with anesthesia. We therefore describe the anesthetic management in the case of a Trisomy 13 child for operated for cleft lip at 10 months of age.

Resumo Os pacientes com síndrome de Patau (trissomia 13) apresentam várias anomalias craniofaciais, cardíacas, neurológicas e renais, com expectativa de vida bem menor. Entre as anomalias craniofaciais, o lábio leporino e a fenda palatina são comuns. Essas anomalias craniofaciais e cardíacas apresentam dificuldades na anestesia. Portanto, descrevemos o manejo anestésico em uma criança de 10 meses com trissomia 13 submetida à cirurgia de lábio leporino.

Result of prenatal diagnosis for 151 high-risk women by noninvasive prenatal screening based on high-throughput sequencing / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the value of combined fetal karyotyping and chromosomal microarray analysis (CMA) for the verification of high-risk pregnancy signaled by noninvasive prenatal screening (NIPS) based on high-throughput sequencing.</p><p><b>METHODS</b>One hundred and fifty-one pregnant women with high risks for aneuploidies of chromosomes 13, 18, 21, X and Y or pathological copy number variations (CNVs) by NIPS were subjected to amniocytic karyotyping and CMA analysis.</p><p><b>RESULTS</b>One hundred and forty-two women were found to have a high risk for fetal chromosomal aneuploidies, which included 83 cases of trisomy 21, 17 cases of trisomy 18, 2 cases of trisomy 13, and 40 cases of sex chromosome aneuploidies. Amniocytic karyotyping and CMA analysis has confirmed 81 cases of trisomy 21, 15 cases of trisomy 18, 10 cases of 47,XXY, 4 cases of 47,XXX, 2 cases of 47,XYY and 1 case of 46,X,del(X)(q26.1). Two trisomy 21, two trisomy 18, 2 trisomy 13, and 23 cases of sex chromosomal aneuploidies were verified as false positives. For 9 women with pathological fetal CNVs detected by NIPS, combined fetal karyotyping and CMA has confirmed 1 case of chromosome 13 microdeletion, 1 case of chromosome 18 microduplication, and 1 case of chromosome 18 deletion. For a case with 30 Mb duplication of chromosome 2 and 25 Mb duplication of chromosome 8, CMA analysis had no positive finding, while fetal umbilical cord blood karyotyping has yielded a 46,XX,dup(2)(p23.1p25.3)[13]/46,XX[87] karyotype. The remaining 5 cases were confirmed as false positive results.</p><p><b>CONCLUSION</b>Combined fetal karyotyping and CMA has provided a powerful tool for verifying high-risk fetuses signaled by NIPS.</p>

Intrauterine death in singleton pregnancies with trisomy 21, 18, 13 and monosomy X / Óbito fetal em gestações únicas com diagnóstico de trissomias dos cromossomos 21, 18, 13 e monossomia do X

Summary A retrospective study from November 2004 to May 2012, conducted at the Obstetric Clinic of Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HC-FMUSP), which included 92 singleton pregnancies with prenatal diagnosis of trisomy of chromosome 21 (T21), 18, 13 (T13/18) and monosomy X (45X), with diagnosis performed until the 26th week of pregnancy. The aim of the study was to describe the frequency and to investigate predictors of spontaneous fetal death (FD). Diagnosis (T21, n=36; T13/18, n=25; 45X, n=31) was made at a mean gestational age of 18.3±3.7 weeks, through chorionic villus biopsy (n=22,24%), amniocentesis (n=66, 72%) and cordocentesis (n=4, 4%). Major malformations were present in 45 (49%); with hydrops in 32 (35%) fetuses, more frequently in 45X [n=24/31, 77% vs. T21 (n=6/36, 17%) and T13/18 (n=2/25, 8%), p<0.001]. Specialized fetal echocardiography was performed in 60% (55/92). Of these, 60% (33/55) showed changes in heart morphology and/or function. Fetuses with T13/18 had a higher incidence of cardiac anomalies [60 vs. 25% (T21) and 29% (45X), p= 0.01]. FD occurred in 55 (60%) gestations, being more frequent in 45X [n=26/31, 84% vs. T21 (n=13/36, 36%) and T13/18 (n=16/25, 64%), p<0.01]. Stepwise analysis showed a correlation between hydrops and death in fetuses with T21 (LR= 4.29; 95CI=1.9-8.0, p<0.0001). In fetuses with 45X, the presence of echocardiographic abnormalities was associated with lower risk of FD (LR= 0.56; 95CI=0.27- 0.85, p=0.005). No predictive factors were identified in the T13/18 group. Intra- uterine lethality of aneuploid fetuses is high. Occurrence of hydrops increases risk of FD in pregnancies with T21. In pregnancies with 45X, the occurrence of echocardiographic changes reduces this risk.

Resumo Estudo retrospectivo, de novembro de 2004 a maio de 2012, na Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, incluindo 92 gestações únicas com diagnóstico pré-natal de trissomia dos cromossomos 21 (T21), 18, 13 (T13/18) e monossomia do X (45X), realizado até a 26a semana, com o objetivo de descrever a frequência e investigar preditores do óbito fetal espontâneo (OF). O diagnóstico (T21: n=36; T13/T18: n=25; 45X: n=31) foi realizado em idade gestacional média de 18,3±3,7 semanas, por biópsia de vilo corial (n=22; 24%), amniocentese (n=66; 72%) e cordocentese (n=4; 4%). Malformação major presente em 45 (49%) fetos e hidropisia em 32 (35%), mais frequente no grupo 45X [n=24/31, 77% vs. T21 (n=6/36, 17%) e T13/18 (n=2/25, 8%); p<0,001]. Ecocardiografia fetal especializada foi realizada em 60% (55/92). Destes, 60% (33/55) tinham alterações na morfologia e/ou na função cardíaca. Fetos com T13/18 apresentaram incidência maior de anomalias cardíacas [60 vs. 25% (T21) e 29% (45X); p=0,01]. Ocorrência de OF em 55 (60%) gestações e mais frequente no grupo 45X [n=26/31, 84% vs. T21 (n=13/36, 36%) e T13/18 (n=16/25, 64%); p<0,01]. Análise stepwise demonstrou associação entre hidropisia e óbito em fetos com T21 (LR=4,29; IC95%=1,9-8,0; p<0,0001). Em fetos com 45X, a presença de alterações ecocardiográficas esteve associada com menor risco de OF (LR=0,56; IC95%=0,27-0,85; p=0,005). Não foram identificados fatores preditores no grupo T13/18. A letalidade intrauterina de fetos aneuploides é elevada. A presença de hidropisia aumenta o risco de OF em gestações com T21. Em gestações com 45X, a ocorrência de alterações ecocardiográficas reduz esse risco.

Prevalência das malformações congênitas identificadas em fetos com trissomia dos cromossomos 13, 18 e 21 / Prevalence of congenital abnormalities identified in fetuses with 13, 18 and 21 chromosomal trisomy

OBJETIVO: Descrever a prevalência das malformações encontradas nos fetos com trissomia dos cromossomos 13, 18 e 21, identificando as mais frequentes em cada condição. MÉTODOS: Estudo transversal retrospectivo, com análise dos casos de trissomias dos cromossomos 13, 18 e 21 que foram diagnosticados pelo cariótipo fetal obtido por amniocentese/cordocentese, entre outubro de 1994 e maio de 2014, em um Hospital de Ensino da região Sul do Brasil. Foram descritas as malformações identificadas no exame ultrassonográfico morfológico e, posteriormente, confirmadas em exames do recém-nascido e/ou por necropsia fetal. Os resultados foram analisados por meio do teste de Fisher e da análise de variância (ANOVA). O nível de significância empregado foi 5% (p=0,05). RESULTADOS: Em 840 exames realizados, foram diagnosticados 69 casos de trissomias; nove deles foram excluídos por desfecho ocorrido fora do Hospital de Clínicas de Porto Alegre ou prontuário incompleto, restando 60 casos (nove de trissomia do cromossomo 13, 26 do cromossomo 18 e 25 do cromossomo 21). As cardiopatias ocorreram, na maioria dos casos, nos três grupos; a comunicação interventricular foi mais prevalente, em 66,7% do grupo da trissomia 13. As anomalias gastrintestinais aconteceram mais no grupo da trissomia 18, principalmente a onfalocele (38,5%; p<0,01). As anomalias geniturinárias foram significativamente mais frequentes no grupo da trissomia 13 (pielectasia com 55,6% - p<0,01; genitália ambígua com 33,3% - p=0,01). Defeitos do sistema nervoso central foram identificados em todos os casos de trissomia 13. Fendas faciais foram mais prevalentes dentre os fetos com trissomia 13 (66,7%; p<0,01). Malformações nas mãos e nos pés tiveram diferenças estatísticas entre os grupos de trissomia. Os defeitos nas mãos ocorreram em 50% dos casos de trissomia 18 e em 44,4% dos casos de 13 (p<0,01); pé torto congênito foi mais comum no grupo da trissomia 18, descrito em 46,2% dos ...

PURPOSE: To describe the prevalence of malformations found in fetuses with trisomy of chromosomes 13, 18 and 21 by identifying the most frequent within each condition. METHODS: A retrospective cross-sectional study with the analysis of trisomy cases of chromosomes 13, 18 and 21 diagnosed through fetal karyotype obtained by amniocentesis/cordocentesis, between October 1994 and May 2014, at a Teaching Hospital in Brazil Southern Region. Malformations identified through morphological ultrasonography were described and, subsequently, confirmed in newborn examinations and/or fetal autopsy. The results were analyzed using Fisher's test and analysis of variance (ANOVA), with a 5% level of significance (p=0.05). RESULTS: Sixty-nine cases of trisomy were diagnosed among 840 exams; nine were excluded due to outcome outside Hospital de Clínicas de Porto Alegre or incomplete records, remaining 60 cases (nine cases of chromosome 13 trisomy, 26 of chromosome 18, and 25 of chromosome 21). In all three groups, heart disease occurred in most cases; the ventricular septal defect was more prevalent and occurred in 66.7% of the trisomy 13 group. Gastrointestinal abnormalities were more prevalent in the trisomy 18 group, especially omphalocele (38.5%; p<0.01). Genitourinary anomalies were more significantly frequent in the trisomy 13 group (pyelectasis, 55.6% - p<0.01; ambiguous genitalia, 33.3% - p=0.01). Central nervous system defects were identified in all cases of trisomy 13. Facial cracks were significantly more prevalent among fetuses with trisomy 13 (66.7%; p<0.01). Hand and feet malformations significantly differed among the trisomy groups. Hand defects occurred in 50% of trisomy 18 cases, and in 44.4% of all trisomy 13 cases (p<0.01); congenital clubfoot was more common in the trisomy 18 group, being detected in 46.2% of fetuses (p<0.01). The abnormalities were found in 50.9, 27.3 and 21.7% of trisomy 18, 13 and 21 cases respectively. ...