Características ecográficas y anomalías congénitas en fetos con síndrome de Down / Ultrasound features and congenital anomalies in fetuses with Down syndrome

Resumen Objetivo: Describir y analizar los hallazgos ecográficos en 97 fetos portadores de síndrome de Down (SD) confirmado. Método: Se incluyeron todas las gestantes con diagnóstico prenatal de SD de nuestro centro, realizado por cariograma o reacción en cadena de la polimerasa cuantitativa fluorescente para aneuploidía. Se analizaron los informes genéticos y ecográficos, y se realizó un seguimiento posnatal. Resultados: De los 97 casos de SD, el 73% de los diagnósticos fueron entre las 11 y 14 semanas. El promedio de edad de las madres fue de 35,7 años. El 83% de los fetos con SD, evaluados a las 11-14 semanas, tuvieron una translucencia nucal ≥ 3,5 mm. Del total de los casos analizados, el 33% fueron portadores de una cardiopatía congénita, correspondiendo el 58% de estas a defectos mayores, principalmente anomalías del tabique auriculoventricular. Un 7,6% de los casos terminaron como mortinato, principalmente durante el tercer trimestre. Conclusiones: El ultrasonido es una herramienta muy sensible para la sospecha prenatal de SD y la detección de sus anomalías asociadas. Consideramos que la información aportada será útil para programar estrategias de pesquisa, organizar el control perinatal y precisar el consejo a los padres de fetos portadores de esta condición.

Abstract Objective: To describe and analyze the ultrasound findings in 97 fetuses with confirmed Down syndrome (DS). Method: All pregnant women with prenatal diagnosis of DS in our center, performed by karyotype or quantitative fluorescent polymerase chain reaction for aneuploidy, were included. Genetic and ultrasound reports were analyzed, as well as postnatal follow-up. Results: Of the 97 cases of DS, 73% of the diagnoses were between 11-14 weeks. The average age of the mothers was 35.7 years. 83% of our fetuses with DS, evaluated between 11-14 weeks, had a nuchal translucency ≥ 3.5 mm. Of the total of the fetuses analyzed, 33% were carriers of congenital heart disease, 58% of these correspond to a major defect, mainly anomalies of the atrioventricular septum. 7.6% of cases ended as stillbirth, mainly during the third trimester. Conclusions: Ultrasound is a very sensitive tool for prenatal suspicion of DS and the detection of its associated abnormalities. We believe that the information provided will be useful to program screening strategies, organize perinatal control and to counselling parents of fetuses carrying this condition.

Higroma quístico retronucal como marcador de anomalías cromosómicas en el primer trimestre de la gestación - Actualización

Objetivo. Evaluar la asociación del higroma quístico retronucal (HQR) y anomalías cromosómicas fetales. Métodos. Estudio observacional retrospectivo de 323 fetos del primer trimestre con riesgo para anomalías cromosómicas diagnosticados por ecografía entre las 11 y 13,6 semanas. Resultados. De 323 fetos con riesgo para anomalías cromosómicas, se encontró 132 casos de anomalías cromosómicas (40,9%). Se identificaron 145 casos de HQR; en 64 (56,6%) se realizó biopsia de vellosidades coriales y en 81 (43,5%) amniocentesis, hallándose cariotipo anómalo en 82 (56,6%). De 88 fetos con HQR aislado, 33 casos (37,5%) tuvieron alguna anomalía cromosómica; en 58 fetos con HQR asociado a otros hallazgos anormales, se encontró que en 43 fetos (74,1%) hubo anomalías cromosómicas, y de ellos 24 (41,4%) tenían onda de flujo (OVF) anormal del ductus venoso, 17 (29,3%) tenían edema generalizado, 8 casos (13,8%) con cardiopatía, 7 (12,1%) ausencia del hueso nasal. Los valores predictivos del HQR fueron: sensibilidad (S) 62,1%, especificidad (E) 67%, valor predictivo positivo (VPP) 56,6%, valor predictivo negativo (VPN) 71,9%, p<0,001, OR: 3,3. El HQR asociado a otros hallazgos anormales, tuvo los siguientes valores predictivos: S 52,4%, E 76,2%, VPP 76,2%, OR: 3,5, LR+: 2,2, p<0,000. El edema generalizado y el ductus venoso anormal tuvieron los valores predictivos más altos: VPP 88,2% y 83,3%, respectivamente. Las anomalías cromosómicas encontradas con mayor frecuencia fueron: T21 (53,7%), monosomía X (18,3%), T18 (15,9%), T13 (6,1%). Conclusiones. El higroma quístico retronucal es un marcador de riesgo con alto valor predictivo para anomalías cromosómicas, siendo mayor cuando está asociado a otros hallazgos ecográficos anormales. La identificación ecográfica del HQR en el tamizaje prenatal del primer trimestre debería ser indicación para recomendar una prueba diagnóstica para anomalías cromosómicas.

Objective: To evaluate the association of retronucal cystic hygroma (RCH) and fetal chromosomal abnormalities. Methods: Retrospective observational study of 323 first trimester fetuses at risk for chromosomal abnormalities diagnosed by ultrasound between 11 and 13.6 weeks. Results: Of 323 fetuses at risk for chromosomal abnormalities, 132 cases of chromosomal abnormalities were found (40.9%). A total of 145 cases of RCH were identified; chorionic villus biopsy was performed in 64 (56.6%) and amniocentesis in 81 (43.5%); an abnormal karyotype was found in 82 (56.6%). Of 88 fetuses with isolated RCH, 33 (37.5%) had some chromosomal abnormality. In 58 fetuses with RCH associated with other abnormal findings, chromosomal abnormalities were found in 43 fetuses (74.1%) and of these 24 (41.4%) had abnormal ductus venosus flow wave (DVF), 17 (29.3%) had generalized edema, 8 cases (13.8%) with cardiopathy, 7 (12,1%) with absent nasal bone. The predictive values of RCH were sensitivity (S) 62.1%, specificity (Sp) 67%, positive predictive value (PPV) 56.6%, negative predictive value (NPV) 71.9%, p<0.001, OR: 3.3. RCH associated with other abnormal findings were S 52.4%, Sp 76.2%, PPV 76.2%, OR: 3.5, LR+: 2.2, p<0.000. Generalized edema and abnormal ductus venosus had the highest predictive values: PPV 88.2% and 83.3%, respectively. The most frequently found chromosomal abnormalities were T21 (53.7%), monosomy X (18.3%), T18 (15.9%), T13 (6.1%). Conclusions: Retronucal cystic hygroma is a risk marker with high predictive value for chromosomal abnormalities, being higher when associated with other abnormal ultrasound findings. Ultrasonographic identification of RCH in first trimester prenatal screening should be an indication to recommend diagnostic testing for chromosomal abnormalities.

Higroma quístico y la importancia de su diagnóstico prenatal: a propósito de un caso / Cystic hygroma and the importance of the prenatal diagnosis: about a case

RESUMEN El higroma quístico es la malformación del sistema linfático que más frecuentemente se observa en el período prenatal y que se ubica principalmente en el cuello y/o la nuca. Su tasa de detección ha aumentado desde la implementación de la translucencia nucal fetal (TN) en el primer trimestre de embarazo, y su presencia se ha relacionado con anomalías congénitas, aneuploidías, pérdida del embarazo y trastornos en el desarrollo. El objetivo de la presentación de este caso es resaltar la importancia del diagnóstico antenatal del higroma quístico, con el fin de realizar una intervención precoz y evitar la muerte fetal. Se recibe para estudio anatomopatológico, feto de sexo indeterminado producto del primer embarazo de una madre de 19 años de edad sin previos controles prenatales, con presencia de una gran masa quística que se extiende desde el rostro hasta la nuca. Mediante el estudio histológico se confirma el diagnóstico de higroma quístico. Al carecer de análisis de cariotipo no fue posible establecer la preexistencia de alguna anomalía genética. El también conocido como linfangioma quístico, es un tumor vascular benigno cuyo diagnóstico antenatal mediante la ultrasonografía resulta fundamental en la evolución y pronóstico de la enfermedad. Desafortunadamente en nuestro caso, la falta de controles prenatales y la ausencia de estudios ultrasonográficos que permitieran conocer las características de este linfangioma, pudo impactar significativamente en el desenlace fatal.

ABSTRACT The cystic hygroma is the malformation of the lymphatic system that is most frequently observed in the prenatal period and is located mainly in the neck and/or the nape of the neck. Its detection rate has increased since the implementation of fetal nuchal translucency (NT) in the first trimester of pregnancy and its presence has been associated with congenital abnormalities, aneuploidies, pregnancy loss, and developmental disorders. The aim of this case is to highlight the importance of antenatal diagnosis of cystic hygroma in order to perform early intervention and avoid fetal death. It is received, for anatomopathological study, a fetus of undetermined sex product of the first pregnancy of a 19 year-old mother without previous prenatal controls, with the presence of a large cystic mass that extends from the face to the neck. The histological study confirms the diagnosis of cystic hygroma. As there was no karyotype analysis, it was not possible to establish the preexistence of any genetic abnormality. Also known as cystic lymphangioma, is a benign vascular tumor whose antenatal diagnosis by ultrasonography is essential in the evolution and prognosis of the disease. Unfortunately in our case, the lack of prenatal controls and the absence of ultrasonographic studies that would allow knowing the characteristics of this lymphangioma, could significantly impact in the fatal outcome.

Síndrome de Down y su pesquisa durante el primer trimestre de la gestación / Down Syndrome and Screening During Pregnancy First Trimester

RESUMEN Introducción: La pesquisa prenatal de anomalías cromosómicas, mediante el uso de marcadores epidemiológicos y ecográficos del primer trimestre permite identificar gestantes con riesgo incrementado de síndrome de Down. Objetivos: Analizar la edad materna, la translucencia nucal, el ductus venoso y el hueso nasal, durante el cribaje del primer trimestre, en las gestantes que se realizaron diagnóstico prenatal citogenético, con el fin de evaluar la efectividad del mismo en la detección temprana del síndrome Down y su utilidad para la reducción del número de pruebas invasivas. Métodos: Se realizó un estudio descriptivo retrospectivo de corte transversal y se analiza una muestra de 3439 gestantes a las que se realizó el estudio citogenético indicado en el Centro Provincial de Genética Médica de La Habana, en el período comprendido entre el 3 de enero de 2006 y el 30 de diciembre de 2008. Resultados: La edad materna avanzada mostró una sensibilidad de un 87 por ciento del test y una tasa de falsos positivos de 99 por ciento. La translucencia nucal se comportó con una sensibilidad de 10 por ciento. El hueso nasal no mostró asociación con los cariotipos positivos para síndrome de Down. Al no realizarse sistemáticamente la presencia del ductus venoso, no se pudo establecer una asociación estadística. La estimación de riesgo de síndrome de Down basada únicamente en la edad materna avanzada determina una alta tasa de falsos positivos. Por lo que este marcador, unido a la evaluación de los marcadores ecográficos del primer trimestre para recalcular el riesgo individual, puede aumentar la efectividad en el diagnóstico y disminuir el número de pruebas invasivas. Conclusiones: La estimación de riesgo de síndrome de Down basada únicamente en la edad materna avanzada determina una alta tasa de falsos positivos. Por lo que este marcador, unido a la evaluación de los marcadores ecográficos del primer trimestre para recalcular el riesgo individual, puede aumentar la efectividad en el diagnóstico y disminuir el número de pruebas invasivas(AU)

ABSTRACT Introduction: The prenatal investigation of chromosomal abnormalities through the use of epidemiological and echographic markers on the first trimester, allows to identify pregnant women with an increased risk of Down syndrome. Objectives: To analyze maternal age, nuchal translucency, venous ductus and nasal bone, during the first trimester screening, in pregnant women who underwent prenatal cytogenetic diagnosis, in order to evaluate effectiveness in early detection of Down syndrome and the value for reducing the number of invasive tests. Methods: A descriptive retrospective cross-sectional study was carried out and a sample of 3439 pregnant women was studied. The cytogenetic study ordered at Havana Provincial Center for Medical Genetics was carried out from January 3, 2006 to December 30, 2008. Results: Advanced maternal age showed 87 percent sensitivity and 99 percent of false positive rate. Nuchal translucency accounted 10 percent of sensitivity. The nasal bone showed no association with positive karyotypes for Down syndrome. A statistical association of the venous ductus presence could not be established since the search was not systematically. Conclusions: The estimation of Down syndrome risk based solely on advanced maternal age determines high false positive rate. Therefore, this marker, together with the evaluation of the first trimester ultrasound markers for recalculating the individual risk, can increase the diagnostic effectiveness and decrease the number of invasive tests(AU)

Pronóstico de la translucencia nucal fetal ≥ 5,5 mm en Lima, Perú

Introduction: First trimester screening has been performed for over 19 years in Peru, but there is no information on the outcomes. Objective: To determine the prognosis of an increased fetal nuchal thickness (NT). Patients: Ultrasound assessment of fetal nuchal thickness in 10 340 consecutive fetuses, 11 to 13 weeks gestation. Interventions. Fetal screening was performed by nine sonographers accredited by the Fetal Medicine Foundation (FMF); the FMF recommendations were followed. Data were recorded using Astraia software. Results: Thirty-seven (0.36%) fetuses presented NT ≥ 5.5mm. Eight patients were lost to follow up. The remaining 29 cases were included in this report. Prenatal karyotyping was performed in 18 cases; 17 of them were abnormal and presented trisomy 21 (7), trisomy 18 (4), monosomy X (5), and trisomy 22 (1). Four of the seven cases of trisomy 21 were born at term without major anomalies. Eleven did not have prenatal testing; one of them was a healthy newborn at term, the remaining 10 died in utero. Seventeen of the 19 known karyotypes were abnormal, which significantly differs from Kagan's results (89% vs 64%, p<0.05) Conclusion: Fetuses with nuchal translucency ≥ 5.5mm in our institution presented a worse prognosis in significantly more cases, compared to other reports.

Introducción. El tamizaje ecográfico del primer trimestre se realiza en el Perú desde hace 19 años, pero se carece de información del seguimiento de las pacientes evaluadas. Objetivos. Determinar el pronóstico de una translucencia nucal (TN) muy aumentada en el feto. Diseño. Estudio retrospectivo observacional. Pacientes. Se evaluó 10 340 fetos consecutivos entre las 11 y 13 semanas, en madres que llegaron al servicio de ecografía. Intervenciones. Evaluación por nueve ecografistas acreditados por la Fetal Medicine Foundation (FMF) siguiendo las recomendaciones de la FMF. Los resultados fueron registrados en el software Astraia. Resultados. Treintaisiete (0,36%) pacientes tuvieron TN ≥ 5,5 mm; ocho no regresaron a la institución y se desconoce el desenlace de su embarazo, por lo que no fueron considerados en el análisis posterior. De los 29 reportados, en 18 se realizó cariotipo prenatal, 17 de ellos fueron anormales (7 trisomías 21; 4 trisomías 18; 5 monosomías X; una trisomía 22). Cuatro de los 7 fetos con trisomía 21 nacieron a término sin malformaciones importantes; uno falleció durante el embarazo, otro embarazo fue interrumpido en el extranjero y se desconoce el desenlace de un caso. De los 11 que no se realizaron cariotipo prenatal, uno (3,2%) nació vivo y sano y los otros 10 fallecieron durante el embarazo. Diecisiete cariotipos de 19 conocidos fueron anormales, lo que difiere significativamente de los resultados de Kagan (89% vs 64%, p<0,05). Conclusiones. El pronóstico de los fetos con TN ≥5,5 mm en nuestra institución fue significativamente peor que el publicado en la literatura.

Tamizaje prenatal de trisomía 21 en el Perú por medio del test combinado ampliado contingente en el primer trimestre / Prenatal screening of trisomy 21 in Peru through the first-trimester contingent combined plus screening test

Introduction. The combined first-trimester screening test is the international recommendation for prenatal screening of trisomy 21. The combined plus screening test adds one or more ultrasound markers (ductus venosus, tricuspid flow, nasal bone). The contingent test is a two-step protocol of risk assessment that considers all markers only as a contingency in the group with an inconclusive result. Objective: Assessment of the performance of the Kagan biochemical contingent protocol in our population. Methods. All pregnant women between 11 and 13 weeks attended in our unit were assessed with the first-trimester combined plus screening test. We followed the Fetal Medicine Foundation published quality criteria and the International Society of Ultrasound in Obstetrics and Gynaecology guidelines. Results 2 578 single pregnancies were assessed; the foetuses were classified by an initial ultrasound evaluation; 37 (1,4%) presented high risk (≥ 1/50), 1 888 low risk (<1/1 000) and 653 intermediate risk (between 1/51 and 1/1 000). Contingent PAPP-a and free beta-hCG were recommended to pregnant women with intermediate risk. 46 (1,8%) other foetuses were classified at high risk for trisomy 21 following biochemical testing. All trisomy 21 foetuses in our cohort were among them. Pregnant women over the age of 36 (at ultrasound date) or 38 (at term) were considered with basal high risk (BHR basal risk ≥ 1/200), since all of them needed biochemical testing. Conclusions: Our results validated Kagan's protocol. The false positive rate and the size of the intermediate risk subgroup would depend on the maternal age distribution.

Introducción. El tamizaje combinado es la recomendación internacional para el tamizaje prenatal de trisomía 21 en el primer trimestre. El test combinado ampliado agrega uno o más marcadores ecográficos (ducto venoso, flujo tricuspídeo y osificación del hueso nasal). La variedad contingente consiste en dividir la evaluación en dos etapas y usar todos los marcadores solo como contingencia en el grupo con resultado dudoso. Objetivo. Demostrar la efectividad del protocolo de bioquímica contingente propuesto por Kagan. Métodos. Se aplicó el test combinado ampliado en variedad contingente a todas las gestantes con embarazos únicos que acudieron al servicio entre las semanas 11 y 13. Se siguió los criterios publicados por la Fetal Medicine Foundation y la International Society of Ultrasound in Obstetrics and Gynecology. Resultados. Se evaluó 2 578 fetos de embarazos únicos. La evaluación ecográfica inicial identificó 37 (1,4%) fetos con riesgo de 1/50 o mayor (riesgo alto), 1 888 fetos con riesgo menor a 1/1 000 (riesgo bajo) y 653 fetos con riesgo entre 1/51 y 1/1 000 (riesgo intermedio). Como contingencia, al grupo de fetos con riesgo intermedio se les indicó las pruebas bioquímicas (PAPP-a y hCG) que seleccionaron otros 46 (1,8%) fetos con riesgo alto de trisomía 21. Los seis fetos con trisomía 21 en la cohorte estuvieron en el grupo de riesgo alto. Se identificó una población de riesgo basal alto (RBA) (mayores de 36 o 38 años, dependiendo si el riesgo es evaluado en el momento de la ecografía o a término) de trisomía 21, en las cuales no es aplicable el modelo contingente, ya que todas requieren las pruebas bioquímicas. Conclusiones. Nuestros resultados validan el modelo propuesto por Kagan. La tasa de falsos positivos y el tamaño del grupo de riesgo intermedio dependerá de la distribución de la edad materna.

First-trimester combined screening test for aneuploidies in brazilian unselected pregnancies: diagnostic performance of fetal medicine foundation algorithm / Rastreio combinado do primeiro trimestre para aneuploidias em gestantes brasileiras não selecionadas: desempenho diagnóstico do algoritmo da Fetal Medicine Foundation

Abstract Objective The main objective of this study was to examine the diagnostic performance of the first-trimester combined test for aneuploidies in unselected pregnancies from Rio de Janeiro and compare it with the examples available in the literature. Methods We investigated 3,639 patients submitted to aneuploidy screening from February 2009 to September 2015. The examination is composed of the Fetal Medicine Foundation risk evaluation based on nuchal translucency evaluation, mother's age, presence of risk factors, presence of the nasal bone and Doppler of the ductus venous in addition to biochemical analysis of pregnancy-associated plasma protein A (PAPP-A) and beta-human chorionic gonadotropin (β-hCG) markers. The cut-off point for high risk for aneuploidies was defined as greater than 1:100, with intermediate risk defined between 1:100 and 1:1,000, and low risk defined as less than 1:1,000. The variable aneuploidy was considered as a result not only of trisomy of chromosome 21 but also trisomy of chromosomes 13 and 18. Results Excluding the losses, the results of 2,748 patients were analyzed. The firsttrimester combined test achieved 71.4% sensitivity with a 7.4% false-positive (FP) rate, specificity of 92.6%, positive predictive value (PPV) of 6.91% and negative predictive value (NPV) of 99.76%, when the cut-off point considered was greater than 1:1,000. Through a receiving operating characteristics (ROC) curve, the cut-off point that maximized the sensitivity and specificity for the diagnosis of aneuploidies was defined as 1:1,860. When we adjusted the false-positive (FP) rate to 5%, the detection rate for this analysis is 72.7%, with a cut-off point of 1:610. Conclusion The combined test of aneuploidy screening showed a detection rate inferior to those described in the literature for a higher FP rate.

Resumo Objetivo O objetivo principal deste estudo foi examinar o desempenho diagnóstico do rastreio combinado de aneuploidias do primeiro trimestre em gestações não selecionadas do Rio de Janeiro e compará-lo com os exemplos disponíveis na literatura. Métodos Investigamos 3.639 pacientes submetidas à triagem para aneuploidia, de fevereiro de 2009 a setembro de 2015. O exame é composto pela avaliação do risco da FetalMedicine Foundation combase na avaliação da translucência nucal, idade da mãe, presença de fatores de risco, presença de osso nasal e Doppler do ducto venoso, além da análise bioquímica dos marcadores proteína A plasmática associada à gravidez (PAPP-A) e gonadotrofina coriônica humana-beta (β-hCG). O ponto de corte para alto risco de aneuploidias foi definido como superior a 1:100, para risco intermediário foi definido entre 1: 100 e 1: 1.000 e para baixo risco foi definido como inferior a 1:1.000. A variável aneuploidia foi considerada não apenas como resultado da trissomia do cromossomo 21, mas também da trissomia dos cromossomos 13 e 18. Resultados Excluindo as perdas, foram analisados os resultados de 2.748 pacientes. O teste combinado do primeiro trimestre alcançou 71,4% de sensibilidade com uma taxa de falsos positivos (FPs) de 7,4%, especificidade de 92,6%, (valor preditivo positivo) VPP de 6,91% e (valor preditivo negativo) VPN de 99,76%, quando o ponto de corte considerado foi maior que 1:1.000. Através de uma curva de característica de operação do receptor (COR), o ponto de corte que maximizou a sensibilidade e especificidade para o diagnóstico de aneuploidias foi de 1:1.860. Quando corrigimos a taxa de FP para 5%, a taxa de detecção para esta análise é de 72,7%, com um ponto de corte de 1:610. Conclusão O rastreio combinado de aneuploidia mostrou uma taxa de detecção inferior à descrita na literatura para uma maior taxa de FP.

Efectividad de la translucencia nucal aumentada en la detección de embarazos con riesgo de cromosomopatías / Effectiveness of Increased Nuchal Translucency in Detecting Pregnancies at Risk for Chromosomal Abnormalities

Fundamento: la evaluación mediante ultrasonido de la anatomía embrionaria desde edades precoces permite la detección de embarazos con riesgo de cromosomopatías, con importante valor agregado pues la edad materna avanzada aislada como único indicador de riesgo no es suficiente. Objetivo: evaluar resultados de la medición de translucencia nucal en el ultrasonido del primer trimestre de gestación como marcador sonográfico de cromosomopatías. Métodos: se estudió un universo de 29 334 embarazadas, desde septiembre de 2006 hasta diciembre de 2010. Se evaluó el comportamiento general del marcador sonográfico considerando los años y la edad materna. Se determinó la efectividad de la translucencia nucal aumentada en la detección indirecta de productos con cromosomopatías mediante los parámetros habituales. Resultados: con los años disminuyó el número neto de translucencias nucales aumentadas y la cantidad absoluta de cariotipos prenatales realizados pero aumentó su proporción y la de los cariotipos prenatales positivos entre las mujeres con translucencia nucal aumentada. Entre los 71 fetos con aumento de la translucencia nucal, fueron confirmados por otros elementos del programa prenatal siete cromosomopatías, con una sensibilidad de la translucencia aumentada aislada para su detección de 14,6 %; especificidad de 99,8 %; los valores predictivos positivos fueron de 18,4 % y los negativos de 99,9 %. Se obtuvieron tasas de falsos positivos muy bajos.Conclusiones: la elevada especificidad la reafirma como un buen marcador precoz de riesgo de cromosomopatías, sobre todo síndrome de Down y trisomía 18, que conlleva a una tasa mínima de indicación de procedimientos obstétricos invasivos e incremento extra en la detección de defectos fetales.

Background: assessment of embryonic anatomy by ultrasound since early ages leads to the detection of pregnancies at risk for chromosomal abnormalities. Advanced maternal age alone is not enough. Objective: to assess the results of the nuchal translucency measurement at the first trimester ultrasound as a sonographic marker of chromosomal abnormalities.Methods: a sample of 29 334 pregnant women was studied from September 2006 to December 2010. General performance of the sonographic marker was assessed taking into account the years and maternal age. Effectiveness of increased nuchal translucency in the indirect detection of chromosomal abnormalities was determined using the common parameters. Results: the net number of increased nuchal translucencies diminished over the years, as well as the absolute amount of prenatal karyotypes performed; but its proportion increased along with the positive prenatal karyotypes among women with increased nuchal translucency. Among the 71 fetuses with increased translucency, seven cases of chromosomal abnormalities were confirmed by other elements of the prenatal program. The sensitivity of the isolated nuchal translucency was 14.6%; specificity was high (99.8%); positive and negative predictive values were 18.4% and 99.9%, respectively. Rates of false positives were very low. Conclusions: high specificity reaffirms nuchal translucency as a good early marker of risk for chromosomal abnormalities, particularly Down syndrome and Trisomy 18, with a minimum rate of indications for invasive testing and an extra increase in the detection of fetal defects.

Experiencia en la aplicación del algoritmo de la Fundación de Medicina Fetal en el tamizaje de aneuploidías entre las 11-13+6 semanas

Objetivos: Evaluar nuestra experiencia en la aplicación del algoritmo de la Fundación de Medicina Fetal (FMF) en el tamizaje prenatal de aneuploidías en el primer trimestre en una población no seleccionada. Diseño: Estudio descriptivo, retrospectivo, transversal. Institución: Servicio de Medicina Fetal, Clínica Santa Isabel, Lima, Perú. Participantes: Gestantes y sus fetos. Intervenciones: Entre el 1 de marzo de 2012 y el 24 de setiembre de 2012, en 324 pacientes con 11 a 13+6 semanas de edad gestacional y fetos con longitud corona nalga (LCC) de 45 a 84 mm, se logró medir la translucencia nucal (TN) mediante ecografía transabdominal. Principales medidas de resultados: Factibilidad de la aplicación del algoritmo de la FMF en el tamizaje de 11 a 13+6 semanas. Resultados: La curva observada de los valores de la TN en relación a la LCC se ajustó a la ecuación cuadrática descrita por la FMF, y la distribución de las medidas presentó una disposición normal, teniendo la mediana una desviación de 0,2 mm respecto al esperado. El porcentaje de valores por encima de la mediana fue 43,3%. Se observó una TN >percentil 95 en 4,6% de casos y TN ≥ 3,5 mm en 1,2%. Se encontró un valor de riesgo por encima del punto de corte de 1:100 en 10 casos para T21 y en un caso para T13. Los resultados del estudio citogenético en tres pacientes fueron un cariotipo femenino normal, una trisomía 18 y una trisomía extra-estructural (47XY+mar). Conclusiones: Nuestros resultados concuerdan con lo comunicado en la literatura y muestran que es factible la aplicación del algoritmo de la FMF en el tamizaje de 11 a 13+6 semanas en un entorno de práctica clínica, en nuestro medio.

Objectives: To determine our experience in applying the Fetal Medicine Foundation (FMF) algorithm for first trimester aneuploidy screening in an unselected population. Design: Descriptive, retrospective, cross-sectional study. Setting: Fetal Medicine Service, Clinica Santa Isabel, Lima, Peru. Participants: Pregnant women and their fetuses. Interventions: Between March 1 and September 24 2012, nuchal translucency (NT) was measured by transabdominal ultrasound in 324 women with 11-13+6 weeks pregnancies and crown-rump length (CRL) between 45.0-84.0 mm. Main outcome measures: Factibility of FMF algorithm in 11-13+6 weeks screening. Results: NT curve in relation to CRLs was consistent with the quadratic equation described by FMF, and measurements followed a normal distribution with median deviation 0.2 mm lower than expected. The percentage of values above the median was 43.3%. A TN >95th percentile was observed in 4.6% of cases and TN ≥3.5 mm in 1.2%. A risk value above the 1:100 cut-off was found in 10 cases for T21 and in one case for T13. Cytogenetic study was performed in 3 patients; results were one normal female karyotype, one trisomy 18 and one extra-estructural trisomy (47XY+mar). Conclusions: Results agree with literature reports and show feasibility of FMF algorithm application in 11-13+6 weeks screening in a clinical practice setting in our country.

Evolução perinatal e pediátrica de crianças com translucência nucal aumentada e cariótipo normal / Perinatal and pediatric follow up of children with increased nuchal translucency and normal karyotype

OBJETIVOS: Analisar o desfecho perinatal e pediátrico de fetos que apresentaram translucência nucal (TN) acima do percentil 95 (P95) e cariótipo normal a fim de obter dados que permitam um melhor aconselhamento materno pré-natal. METÓDOS: Análise de fetos em um serviço terciário de obstetrícia apresentaram TN acima do P95 e cariótipo normal entre os anos 2005 e 2011. Analisamos o seguimento ultrassonográfico gestacional, ecocardiografia (ECO) fetal e pós-natal, peso, comprimento e escore de Apgar ao nascimento, além do desenvolvimento neuropsicomotor por meio do Ages and Stages Questionnaire (ASQ) até julho de 2012. RESULTADOS: Durante esse período, foram 116 casos de translucência nucal acima do P95, sendo que em 79 (68%) foi realizado cariótipo fetal. Das análises, 43 foram normais (54,4%) e 36, alteradas (45,6%). Nos fetos com cariótipo normal, houve um abortamento na 15ª semana gestacional com pentalogia de Cantrel, um óbito na 24ª semana com diversas anomalias estruturais, um óbito neonatal sem causa definida e dois casos de comunicação intraventricular (CIV) detectados no ECO fetal. Na avaliação ecocardiográfica pós-natal, persistiu um caso de CIV e foi diagnosticado um caso de comunicação interatrial (CIA) e persistência do canal arterial (PCA). Entre os 40 casos sobreviventes, apenas 1 criança apresentou atraso no desenvolvimento da fala e outra apresentou quadro de autismo. Os demais casos resultaram em desenvolvimento neuropsicomotor normal. CONCLUSÃO: No acompanhamento dos fetos com TN aumentada e cariótipo normal, os pais podem ser mais bem aconselhados de que, frente a um exame morfológico-ecocardiográfico do 2º trimestre sem alterações, a probabilidade de a criança nascer viva e bem é alta (93,5%).

PURPOSE: To analyze the perinatal and pediatric outcome of fetuses that showed nuchal translucency (NT) above the 95th percentile (P95) and a normal karyotype in order to obtain data allowing better maternal prenatal counseling. METHODS: fetuses from a tertiary obstetric service with an NT above P95 and a normal karyotype were analyzed between 2005 and 2011. We analyzed gestational ultrasound follow-up, fetal and postnatal echocardiography (ECHO), weight, length and Apgar score at birth, and neuropsychomotor development by the Ages and Stages Questionnaire (ASQ) up to July 2012. RESULTS: During this period, there were 116 cases of nuchal translucency above the 95th percentile, and the fetal karyotype was determined in 79 of them (68%). Forty-three analyses were normal (54.4%) and 36 were altered (45.6%). Among the fetuses with a normal karyotype, one was miscarried at 15 weeks of gestation with Cantrel pentalogy and one died at 24 weeks with several structural abnormalities. There was one neonatal death of unknown cause and two cases of intraventricular communication (IVC) detected by fetal ECHO. Postnatal echocardiography revealed the persistence of IVC in one case and one case of atrial septal defect (ASD) and patent ductus arteriosus (PDA). Of the 40 surviving children, only 1 showed delayed speech development and another presented autism. The remaining cases resulted in normal neurodevelopment. CONCLUSION: During the monitoring of fetuses with increased NT and a normal karyotype, parents can be best advised that when a 2nd trimester morphological-echocardiography ultrasound study is normal, the probability of the child being born alive and well is high (93.5%).

Higroma quístico y translucencia nucal aumentada como marcadores de anomalías cromosómicas

Objetivos: Determinar la importancia del espacio retronucal en fetos entre las 11 y 13+6 semanas, identificando sus características, la asociación con anomalías cromosómicas y las posibles diferencias entre higroma quístico y translucencia nucal aumentada. Diseño: Estudio transversal prospectivo. Institución: Instituto Latinoamericano de salud Reproductiva, Lima, Perú. Participantes: Gestantes y sus fetos con diagnóstico citogenético prenatal. Intervenciones: Entre el año 2007 y junio 2012, se revisó 266 casos con diagnóstico citogenético prenatal, que correspondieron a 230 amniocentesis realizadas después de las 14 semanas y 36 biopsias de vellosidades coriales (BVC), entre las 11 a 13 semanas. Principales medidas de resultados: Marcadores ecográficos prenatales. Resultados: Se detectó 106 casos de anomalías cromosómicas (39,9%). El higroma quístico (HQ) fue el marcador que con más frecuencia, en relación al aumento de la translucencia de la nuca (TN) (30,8% versus 11,3%), se asoció a anomalías cromosómicas (68,3% versus 31%), correspondiendo al HQ una sensibilidad (S) de 45%, valor predictivo positivo (VPP) de 62%, ratio de probabilidad+ (LR+) de 2,4, y para la TN aumentada S 11%, VPP 40%, LR+ 1. El HQ se asoció en 35,7% a monosomía X, la TN aumentada a trisomías. Conclusiones: El HQ fue el marcador de anomalías cromosómicas más frecuente encontrado entre las 11 y 13+6 semanas y tuvo mayor valor predictivo que la TN aumentada. Ambas serían dos entidades distintas, siendo necesaria su diferenciación.

Objectives: To determine the importance of nuchal translucence in fetuses 11 to 13 +6 weeks, identifying characteristics, association with chromosomal anomalies and differences between cystic hygroma and increased nuchal translucency. Design: Prospective cross-sectional study. Setting: Instituto Latinoamericano de Salud Reproductiva, Lima, Peru. Participants: Pregnant women and their fetuses with prenatal cytogenetic diagnosis. Interventions: Between 2007 and June 2012, 266 cases with prenatal cytogenetic diagnosis had 230 amniocentesis after 14 gestational weeks and 36 chorionic villi biopsy (CVS) between 11-13 gestational weeks. Main outcome measures: Prenatal ultrasound markers. Results: One hundred and six cases of chromosomal abnormalities (39.9%) were found. Cystic hygroma (CH) was more often found than nuchal translucency (NT) (30.8% versus 11.3%) associated with chromosomal abnormalities (68.3% versus 31%), corresponding to HQ sensitivity (S) 45%, positive predictive value (PPV) 62%, likehood ratio+ (LR+) 2.4, and for increased TN S 11%, PPV 40%, LR+ 1. CH was associated in 35.7% to monosomy X, and NT to trisomy. Conclusions: CH was the most common chromosomal abnormalities marker found between 11 and 13 +6 weeks and had greater predictive value than increased NT. Each would represent separate entities requiring differentiation.

Análise do rastreamento combinado no primero trimestre da gestação para detecção de anomalias cromossômicas / Analysis of the combined first trimester screening for chromosomal abnormalities

OBJETIVO: avaliar o desempenho do rastreamento combinado do primeiro trimestre da gestação na detecção de anomalias cromossômicas em um grupo da população brasileira. MÉTODO: estudo retrospectivo envolvendo gestantes com feto único, referidas ao setor de medicina fetal para a realização do teste de rastreamento do primeiro trimestre da gestação pela combinação da idade materna, a medida da translucência nucal e dois marcadores bioquímicos do soro materno: free B-hCG e PAPP-A. Para avaliar o desempenho do teste foram calculados a sensibilidade, especificidade, valores preditivos positivos e negativos e as taxas de falso positivo, considerando como risco elevado valores superiores a 1:300. RESULTADOS: foram incluídas 456 gestantes submetidas ao teste. A idade materna avançada, acima de 35 anos, ocorreu em 36,2 por cento dos casos. A incidência de cromossomopatia na população estudada foi de 2,2 por cento. Vinte e uma das gestantes (4,6 por cento) apresentou risco elevado ao teste (superior a 1:300). Usando-se este ponto de corte, a sensibilidade do teste foi de 70 por cento para as cromossomopatias em geral e 83,3 por cento para os casos de trissomia do cromossomo 21, com taxa de falso positivo de 3,1 por cento. CONCLUSÃO: o rastreamento combinado do primeiro trimestre foi eficaz na detecção das anomalias cromossômicas, principalmente em relação aos casos de trissomia 21, com baixas taxas de falso positivo. Observou-se importante contribuição do teste em reduzir a indicação do exame invasivo comparado ao uso da idade materna como fator de risco.

PURPOSE: to evaluate the performance of the combined first trimester screening for chromosomal abnormalities in a group of the Brazilian population. METHODS: a retrospective study including pregnant women with single fetuses referred to a fetal medicine center to perform the first trimester screening that combines maternal age, nuchal translucency measurement and two maternal serum biochemical markers: free B-hCG and PAPP-A. To evaluate the performance of the test, the detection rate, specificity, negative and positive predicted values and false-positive rates were calculated, considering as high risk the cut-off value above 1 in 300. RESULTS: we studied 456 patients submitted to the test. Advanced maternal age above 35 years was observed in 36.2 percent of cases. The incidence of chromosomal abnormalities in the study population was 2.2 percent. Twenty-one patients (4.6 percent) presented a high risk (above 1:300) by the combined test. Using this cut-off level, the detection rate of the test was 70 percent for all chromosomal abnormalities and 83.3 percent for trisomy 21, for a false-positive rate of 3.1 percent. CONCLUSIONS: the combined first trimester screening was effective to detect chromosomal abnormalities, mainly for trisomy 21, with low false-positive rates. The combined test contributed to decreasing the indication of an invasive test if we compare to maternal age alone as a risk factor.

Ultrassonografia obstétrica entre a 11ª e a 14ª semanas: além do rastreamento de anomalias cromossômicas / Obstetric ultrasound between the 11th and 14th weeks: beyond the screening for chromosomal abnormalities

Esta é uma revisão tradicional (narrativa) que teve como objetivo salientar a contribuição da ultrassonografia (USG) obstétrica entre a 11ª e a 14ª semana de gravidez, comumente denominada ultrassonografia morfológica de primeiro trimestre. Além do rastreamento de anomalias cromossômicas, a USG pode ser empregada neste período para: confirmação ou determinação da idade gestacional; avaliação da anatomia fetal; diagnóstico de malformações; rastreamento de anormalidades estruturais maiores e de síndromes gênicas; definição do prognóstico da gravidez; diagnóstico e caracterização das gestações múltiplas; e rastreamento da pré-eclampsia e da restrição de crescimento intrauterino. Foram incluídos os principais estudos sobre o tema publicados entre 1990 e 2010, pesquisados nas bibliotecas eletrônicas Cochrane e PubMed, e que podem ser incorporados nos níveis de evidência científica I a III.

This is a traditional (narrative) review with the objective of highlighting the contribution of obstetric ultrasonography (US) between the 11th and 14th week of pregnancy, commonly called first trimester anomaly scan. In addition to being used for the screening of chromosomal anomalies, US can be employed during this period to confirm or determine gestational age, evaluate fetal anatomy, diagnose malformations, screen major structural abnormalities and genetic syndromes, define the prognosis of pregnancy, diagnose and characterize multiple pregnancies, and screen preeclampsia and intrauterine growth restriction. The most important studies about this subject published between 1990 and 2010 in the Cochrane and PubMed libraries were included. The selected studies can be classified with scientific levels I to III.

Translucencia nucal aumentada y cariotipo normal / Increased nuchal translucency and normal kariotype

Antecedentes: La exploración ecográfica entre las semanas 11 y 14 tiene un papel fundamental en el cribado de anomalías cromosómicas, siendo la medida de la translucencia nucal un método bien establecido y ampliamente aceptado para este fin. Objetivo: Evaluar retrospectivamente la evolución de los fetos con translucencia nucal aumentada y cariotipo normal. Método: Se recogieron los datos de 104 fetos con TN >percentil 95 (p95) entre las semanas 11 y 14, evaluados en nuestro centro. En los 61 que resultaron eu-ploides, se estudió la incidencia de anomalías estructurales diagnosticadas tanto prenatalmente como tras el nacimiento, así como las pérdidas fetales anteparto. De estos fetos, nacieron sanos el 80 por ciento cuando la TN estaba entre p95 y 3,4 mm, el 50 por ciento con TN entre 3,5 y 4,4 mm, el 30 por ciento con TN entre 4,5 y 5,4 mm, y el 18 por ciento con TN > 5,5 mm. Entre los 4 recién nacidos euploides con patología, hubo 3 con cardiopatía. Conclusión: La presencia de TN aumentada entre las 11 -14 semanas en fetos euploides se asocia a un incremento del riesgo de anomalías estructurales mayores, principalmente cardiacas. La prevalencia de malformaciones aumenta significativamente con TN >3,5 mm, y el pronóstico gestacional adverso empeora conforme aumenta la medida de la TN.

Background: Ultrasound scan has a main role at the 11-14 weeks screening for chromosomal abnormalities. The measurement of nuchal translucency (NT) thickness is a widespread stablished method to achieve this target. Objective: To assess retrospectively the outcome of fetuses with increased nuchal translucency and normal karyotype. Method: Data were collected from 104 fetuses with NT > 95th percentile at 11 to 14 weeks of gestation, followed in our institution. The sixty one euploid fetuses were studied in order to determine the incidence of structural abnormalities, diagnosed either before or after delivery, as well as antenatal fetal loss. Among these fetuses, there were no malformations at birth in 80 percent for NT between the 95th percentile and 3.4 mm; 50 percent for NT between 3.5 and 4.4 mm; 30 percent for NT of 4.5-5.4 mm; and 18 percent for NT > 5.5 mm. There were 4 euploid newborns with some kind of structural defect at birth, 3 of them presented a cardiac malformation. Conclusion: The presence of increased NT at 11-14 weeks scan in euploid fetuses it's associated with a higher risk of major structural abnormalities, mainly cardiac ones. The prevalence of malformations is significantly increased for NT > 3.5 mm, and the adverse perinatal outcome is directly associated with the thickness of NT.

Valor de los marcadores epidemiológicos y sonográficos del primer trimestre como indicadores de riesgo de cromosomopatías / Value of first trimester epidemiologic and sonographic markers as chromosome-diseases risk indicators

La pesquisa prenatal de anomalías cromosómicas mediante el uso de marcadores epidemiológicos y sonográficos del primer trimestre, permite identificar gestantes con riesgo incrementado de cromosomopatías, se ofrece la opción del diagnóstico prenatal citogenético. OBJETIVOS: realizar una evaluación preliminar de la utilidad de los marcadores ecográficos del primer trimestre, como predictores de anomalías cromosómicas en las gestantes que se realizaron diagnóstico prenatal citogenético. MÉTODOS: se realizó un estudio descriptivo retrospectivo de corte transversal con el objetivo de realizar una evaluación preliminar de la utilidad de los marcadores ultrasonográficos, como predictores de anomalías cromosómicas durante el primer trimestre. Para la realización de esta investigación fue analizada una muestra de 2 507 gestantes que se realizaron el estudio citogenético indicado en la consulta citogenética del Departamento Provincial de Genética de Ciudad de la Habana, perteneciente al Hospital Ginecoobstétrico Ramón González Coro, en el período comprendido entre enero del año 2006 y diciembre de 2007. RESULTADOS: la translucencia nucal elevada incrementó de forma significativa el riesgo de anomalías cromosómicas. El hueso nasal, no mostró asociación con los cariotipos positivos. Dada la no realización sistemática del ductus venoso, no se pudo establecer una asociación estadística. CONCLUSIONES la translucencia nucal aumentada, incrementó significativamente el riesgo de defectos cromosómicos, no obstante, su sensibilidad estuvo por debajo de lo previamente descrito en otras investigaciones

Prenatal screening of chromosomal anomalies using epidemiological and sonographic markers during the first trimester, allow identifying pregnant with high risk of chromosome disease; we offer the cytogenetics prenatal diagnosis as option. OBJECTIVES: to made a preliminary assessment on usefulness of echographic marker during the first trimester like predictors of chromosomal anomalies in pregnant with a cytogenetics prenatal diagnosis. METHODS: a descriptive, retrospective and cross-sectional study was conducted for a preliminary assessment on usefulness of ultrasonograpic markers like predictors of chromosomal anomalies during the first trimester. In research a sample including 2 507 pregnants with cytogenetics study prescribed in cytogenetics consultation of Genetics Provincial department of Havana City from the Ramón González Cor Gynecology-Obstetrics Hospital during January, 2006 and December, 2007. RESULTS: the high transillumination nuchal increased in a significant way the risk of chromosomal anomalies. Nasal bone has not association with other positive karyotypes. Given the no systemic performing of ductus venous, it was impossible to establish a statistical association. CONCLUSIONS: the increase nuchal transillumination increases significantly the risk of chromosomal defects; however, its sensitivity was below the previously described in other researches

Translucência nucal aumentada e cariótipo normal: evolução pré e pós-natal / Increased fetal nuchal translucency thickness and normal karyotype: prenatal and postnatal follow-up

OBJETIVO: O objetivo do presente estudo foi avaliar a evolução pré e pós-natal dos fetos com translucência nucal (TN) aumentada e cariótipo normal. MÉTODOS: Duzentos e setenta e cinco fetos com TN aumentada foram avaliados no setor de Medicina Fetal da Clínica Obstétrica do HC-FMUSP. Esses casos foram submetidos à avaliação do cariótipo, ultrassonografia seriada, ecocardiografias fetal e pós-natal e avaliação clínica genética pós-natal. RESULTADOS: Em 14,2 por cento dos casos, o cariótipo esteve alterado e em 85,8 por cento o cariótipo ou fenótipo foi normal. Nos casos com cariótipo normal, a ultrassonografia morfológica de segundo trimestre esteve alterada em 24,7 por cento, destes, um terço apresentou malformações estruturais maiores, sendo 35,7 por cento cardíacas. Resultados gestacionais adversos, como abortamento, óbitos intraútero e neonatal ocorreram em 10,2 por cento dos casos. A avaliação pós-natal foi realizada em 72,7 por cento das crianças, mostrando-se alterada em 14,8 por cento. A frequência de criança viva e saudável diminuiu com o aumento da medida da TN, sendo de 37,5 por cento quando a TN foi igual ou maior que 4,5 mm. CONCLUSÃO: Nos fetos com TN aumentada e cariótipo normal, quanto maior a medida da TN maior a frequência de malformações estruturais, em especial defeitos cardíacos, resultados gestacionais adversos e alterações na avaliação pós-natal.

OBJECTIVE: The aim of this study was to evaluate pregnancy and postnatal outcomes of fetuses with increased nuchal translucency thickness (NT) and normal karyotype. METHODS: Two hundred seventy five fetuses with increased NT were examined with karyotyping analysis, serial ultrasound scans, echocardiography and postnatal clinical and genetic evaluation at the Fetal Medicine Unit - Department of Obstetrics - São Paulo University. RESULTS: The karyotype was abnormal in 14.2 percent of the cases and normal in 85.8 percent. In cases with normal karyotype 24.7 percent presented structural abnormalities at the anomaly scan, one third of these were major malformations with 35.7 percent of heart defects. Adverse pregnancy outcome such as miscarriages, intrauterine and neonatal deaths occurred in 10.2 percent of cases. Of the infants 72.7 percent had postnatal examination, with 14.8 percent presenting abnormalities. Chances of having a live and healthy child decreased with increased NT thickness, and were of 37.5 percent for NT above 4.5mm. CONCLUSION: In cases with increased NT thickness and normal karyotype, the frequency of fetal malformations, especially heart defects, adverse pregnancy outcome and postnatal abnormalities is related to the NT thickness.

Anomalias e prognóstico fetal associados à translucência nucal aumentada e cariótipo anormal / Fetal abnormalities and prognosis associated with increased nuchal translucency and abnormal karyotype

OBJETIVO: Descrever a frequência de anomalias cromossômicas em fetos com translucência nucal (TN) aumentada, e a frequência de malformações estruturais, a evolução e o resultado da gestação nos fetos com TN aumentada e cariótipo anormal. MÉTODOS: Estudo retrospectivo envolvendo 246 casos com medida da TN acima do percentil 95º para a idade gestacional, com cariótipo fetal conhecido ou avaliação clínica das crianças no período pós-natal. Os casos foram acompanhados no setor de Medicina Fetal do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. RESULTADOS: O resultado do cariótipo fetal esteve alterado em 14,2 por cento dos casos. O acompanhamento dessas gestações revelou anormalidade estruturais em 80,8 por cento dos fetos, sendo as anormalidades cardíacas as mais comuns (61,5 por cento). Resultados gestacionais adversos, como abortamento, óbitos intraútero e neonatal ocorreram em 76,5 por cento dos fetos. CONCLUSÃO: Translucência nucal aumentada, entre 11 - 13 semanas e 6 dias, é importante marcador de anomalias cromossômicas fetais e malformações estruturais fetais, principalmente cardíacas. Diante deste achado, há aumento do risco de abortamento, óbito intrauterino e neonatal para estas gestações.

OBJECTIVES: This study aimed to evaluate the incidence of chromosomal abnormalities in fetuses with increased nuchal translucency (NT) measurement. Incidence of structural abnormalities and pregnancy outcome was also described in fetuses with increased NT and abnormal karyotype. METHODS: This was a retrospective study involving 246 fetuses with increased NT and known karyotype followed at the Fetal Medicine Unit, Hospital das Clínicas, São Paulo University Medical School. RESULTS: Fetal karyotype was abnormal in 14.2 percent of the cases. Ultrasound anomaly scan and specialized echocardiographic studies in these cases showed fetal structural abnormalities in 80.8 percent and cardiac defects were found in 61.5 percent of the fetuses. Pregnancy outcome was abnormal in 76.5 percent of these women. CONCLUSION: Increased NT measurement at 11 to 13 weeks and 6 days is an important marker for fetal chromosomal and structural abnormalities, mainly fetal cardiac defects. This finding also indicates increased risk of spontaneous fetal and neonatal death.

Indicaciones de estudio genético invasivo en una población seleccionada: Agosto de 2005 a diciembre de 2007 / Indications for invasive genetic studies in a population-based sample: August 2005 to december 2007

Antecedentes: la mayor utilización de ecografía prenatal y procedimientos diagnósticos invasivos ha permitido mejorar la identificación de malformaciones fetales al nacimiento. El dilema conlleva un riesgo relacionado con el procedimiento, por lo que los médicos siguen lidiando con la manera de identificar las pacientes con riesgo elevado para no someter a las de bajo riesgo a procedimientos diagnósticos innecesarios. En el presente estudio nos hemos planteado describir las diferentes indicaciones para el diagnóstico genético invasivo de alteraciones cromosómicas en una población seleccionada de Bogotá D.C. Pacientes y métodos: se realizó un estudio descriptivo de corte transversal entre el 1 de agosto de 2005 y el 31 de diciembre de 2007. Se revisaron las historias clínicas de embarazadas remitidas con indicación de estudio genético invasivo por anomalías cromosómicas. Resultados: se analizaron 374 embarazos, de los cuales el 98,9% (n=370) eran simples y el 1,1% (n=4) correspondían a gemelares, para un total de 378 análisis del cariotipo fetal. La edad materna promedio fue de 35 años y la gestacional promedio de 17,4 semanas. Se realizaron 366 amniocentesis (96,8%) y 12 biopsias de vellosidades coriónicas (3,2%). El estudio citogenético más solicitado fue el cariotipo 64,8% (n=245) y en 33,6% (n=127) de los casos se hizo análisis por FISH y cariotipo. Entre las indicaciones para solicitar estudio genético invasivo se destacan la edad materna con 35,7% (n=135), seguida de malformaciones menores ecográficas 14,8% (n=56), tamizaje segundo trimestre 9,3% (n=35), sonolucencia nucal aumentada 6,9% (n=26) y malformaciones mayores ecográficas 6,3% (n=24). Se reportaron 54 estudios citogenéticos alterados (14,3%); de ellos, 36 correspondieron a aneuploidías (66,67%) y dieciocho a variaciones estructurales (33,33%). Cuando la edad materna fue la única indicación de un procedimiento invasivo, sólo se detectó el 6,66% de cariotipos alterados, mientras que en el grupo...

Antecedents: increased use of prenatal ultrasound and invasive diagnostic procedures has improved the detection of congenital fetal defects. The dilemma entails a procedure-related risk for which physicians continue to put up with a way to identify highrisk patients to avoid unnecessary diagnostic procedures in low-risk patients. This population-based study, conducted in Bogotá D.C., describes the various indications for an invasive genetic study to identify chromosomal abnormalities. Patients and methods: this is a descriptive cross-sectional study performed between August 1st 2005 and December 31st 2007. The clinicalrecords of pregnant women referred with an indication for invasive prenatal testing due to chromosomal abnormalities were reviewed. Results: 374 pregnancies were assessed, where 98.9% (n=370) were single pregnancies and 1.1% (n=4) twin pregnancies, thus, 378 fetal karyotype analyses were conducted. The mean age was 35 years and the mean gestational age was 17.4 weeks. We performed 366 amniocentesis (96.8%) and 12 choryonic villus sampling (3.2%). Karyotype analysis was the most frequently requested cytogenetic study accounting for 64.8% (n=245) of cases and FISH and karyotype analyses wereperformed in 33.6% (n=127). Advanced maternal age in 35.7% (n=135) was the main indication for invasive genetic studies request, followed by minor malformations detected by ultrasound 14.8% (n=56), second-trimester screening 9.3% (n=35), enhanced nuchal translucency 6.9% (n=26) and major defects detected by ultrasound 6.3% (n=24). Fifty-four (54) cytogenetic studies were reported as abnormal (14.3%); 36 corresponding to aneuploidy (66.67%) and 18 to structural variations (33.33%). Only 6.66% abnormal karyotypes were determined when maternal age was the only indication for an invasive procedure, while aneuploidy was diagnosed in the minor or major defect or nuchal translucency groups in 25%, 29% and 26% respectively...

Comparación de cribado combinado (ecográfico y bioquímico) de cromosomopatías en el primer y segundo trimestre de gestación en el hospital Teodoro Maldonado Carbo, Guayaquil – Ecuador / Combined cribation (echographic and biochemical) comparison of chromosomal pathologies in pregnancy first and second quarters in Teodoro Maldonado Carbo hospital, Guayaquil – Ecuador

Tipo de estudio: prospectivo, observacional, longitudinal. Objetivo general: comparar los hallazgos ecográficos con los del triple test como métodos de tamizaje para diagnóstico prenatal en mujeres de alto riesgo. Metodología: pacientes gestantes escogidas al azar ≥ 35 años atendidas en el área materno infantil del hospital “Teodoro Maldonado Carbo” del IESS, durante el período comprendido entre diciembre 2006 a mayo de 2007. Se les realizó a las 11-14 semanas de gestación (SG) el tamizaje ecográfico para cromosomopatías. Durante las 15 - 20 semanas el estudio bioquímico (triple test) en el laboratorio Medilabsa. A las 18 – 22 SG se les repitió el tamizaje ecográfico para cromosomopatías para confirmar resultados. Resultados: de las 31 pacientes valorados los productos obtenidos fueron: un aborto espontáneo a las 16.4 SG, (3.22); dos pacientes presentaron productos con Síndrome de Down, (6.25), primer producto reportó durante la valoración de la ecografía del primer trimestre TN > 3mm, Triple test positivo riesgo 1:50, ecografía 3D presentó inserción baja de la oreja, sexo masculino; segundo producto reportó en la ecografía del primer trimestre TN 3.2mm, ductus venoso invertido, triple test positivo, riesgo 1:30. Eco 3D presentó inserción baja de las orejas, atresia duodenal, comunicación interauricular. Conclusiones: combinado ambos tamizajes (primer y segundo trimestre) para el diagnóstico de cromosomopatías, se presenta un mejor perfil de eficacia, seguridad y costo-eficiencia. Mediante ambos métodos no invasivos, inocuos, sin riesgos para el binomio madre – feto y poseen una amplia aplicación clínica.

Study type: prospective, observational, and longitudinal. General objective: to compare echographic findings with those of the triple test as cribation methods for prenatal diagnosis in high risk women. Methodology: pregnant patients randomly chosen≥35 years old seen in the maternal-infantile area of the “Teodoro Maldonado Carbo” IESS hospital from december/2006 to may/2007. At 11th-14th pregnancy weeks (PW) echographic cribation for chromosomal pathologies . At 15-20 weeks biochemical study (triple test) in Medilabsa laboratory. At 18-22 PW the echographic cribation for chromosomal pathologies was made once again to confirm results. Results: out of 31 assessed patients: one spontaneous abortion at PW 16.4 (3.22); two Down’s Syndrome (6.25), the first one in the 1st. quarter echography showed NT > 3mm, positive risk 1:50 triple test; 3D echography showed low insertion of the ear, male. The second one showed in 1st quarter echography NT > 3.2mm, inverted venous ductus, positive,risk 1:30 triple test; 3D echography showed low insertion of the ears, duodenal atresia, atrial septum defect. Conclusions: making a combination of both cribations (1st and 2nd quarters) for diagnosing chromosome pathologies, we have more efficiency, safety and better cost-benefit. Both methods are non invasive, innocuous, risk free for mother as well as for fetus and are extensively applied as a clinical procedure.

Estudo da translucência nucal, ducto venoso, osso nasal e idade materna na detecção de cromossomopatia fetal em uma população de alto risco / Study of nuchal translucency, ductus venosus, nasal bone and maternal age for detection of fetal chromosomal disorders in a high-risk population", "_i": "en

OBJETIVO: Avaliar a translucência nucal, o ducto venoso, o osso nasal e a idade materna > 35 anos como testes de rastreamento para aneuploidias entre 12 e 14 semanas de gestação em pacientes de alto risco. MATERIAIS E MÉTODOS: Estudo prospectivo observacional envolvendo 92 gestantes entre 12 e 14 semanas submetidas a biópsia de vilo corial por alto risco de trissomia, baseado na medida da translucência nucal (17,4 por cento) e idade materna >35 anos (78,3 por cento). Antes da biópsia de vilo corial, realizaram-se medida da translucência nucal, avaliação de fluxo no ducto venoso e identificação do osso nasal. Calcularam-se a sensibilidade, a especificidade, o valor preditivo positivo e o valor preditivo negativo para testes realizados em paralelo e em seqüência. RESULTADOS: Encontrou-se alteração cromossômica em 12 (13,5 por cento) fetos; 7 (58,3 por cento) apresentavam trissomia 21. Osso nasal foi identificado em todos os fetos com trissomia. Translucência nucal, ducto venoso e idade materna isolados mostraram baixa sensibilidade (41,67-58,33 por cento) e baixo valor preditivo positivo (10-45,45 por cento). A associação translucência nucal + ducto venoso + idade materna apresentou o melhor resultado (sensibilidade: 100 por cento; especificidade: 6,49 por cento; valor preditivo positivo: 14,29 por cento; valor preditivo negayivo: 100 por cento). CONCLUSÃO: Em gestantes com idade > 35 anos, a associação translucência nucal + ducto venoso mostra-se como a mais sensível para a indicação de procedimento invasivo.

OBJECTIVE: To evaluate fetal nuchal translucency, ductus venosus, nasal bone and maternal age > 35 years by means of aneuploidy screening between the 12th and 14th gestational weeks in a high-risk population. MATERIALS AND METHODS: Prospective, observational study involving 92 pregnant women at 12-14 gestational weeks, who were submitted to chorionic villus sampling because of high risk for trisomy 21 based on the measurement of nuchal translucency thickness (17.4 percent) or on maternal age > 35 years (78.3 percent). Before the chorionic villus sampling, fetal nuchal translucency thickness was measured, ductus venosus flow was evaluated and the nasal bone was identified. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for tests in parallel and in sequence. RESULTS: Chromosomal abnormalities were found in 12 fetuses (13.5 percent); 7 (58.3 percent) were positive for trisomy 21. The nasal bone was present in all cases with chromosomal abnormalities. Isolated nuchal translucency, ductus venosus or maternal age showed low sensitivity (41.67-58.33 percent) and low positive predictive value (10-45.45 percent). Combined nuchal translucency + ductus venosus + maternal age showed the best results (100 percent sensitivity; 6.49 percent specificity; 14.29 percent positive predictive value; 100 percent negative predictive value). CONCLUSION: In pregnant women with >35 years of age, combined nuchal translucency + ductus venosus have showed the highest sensitivity as an indication for invasive procedure.