A survey of current clinical practice of chorionic villus sampling.

OBJECTIVE: The number of invasive procedures (chorionic villus sampling (CVS) or amniocentesis) for fetal testing is decreasing because of the availability of non-invasive prenatal test (NIPT) leading to a centralisation of prenatal diagnostic services to accredited fetal medicine centres. A new survey was conducted 10 years after the previous one to update the current clinical practice among clinicians who regularly perform CVS. METHOD: Consultants from 32 centres in the United Kingdom were invited to take part in an online survey evaluating: The total number of CVS procedures carried out in the unit in a typical week, the preferred route (transabdominal [TA] vs transcervical [TC]), technique (use of local anaesthetic [LA] and needle technique). RESULTS: Response rate was 96.9%; TA was the preferred route (96.8%) in all centres except one. Single-needle technique is used exclusively in half the centres (51.6%). LA is used by most operators (90.3%) before the procedure. Three centres did not routinely use LA for CVS. CONCLUSIONS: Operators across the United Kingdom almost exclusively use the TA route for CVS with single-needle technique in 51.6% of cases. The use of LA prior to CVS is a very common practice in the United Kingdom.

Trends in invasive prenatal diagnostic testing at a single institution.

OBJECTIVE: As diagnostic methodologies evolve, we sought to determine whether invasive testing rates would decline, whether there would be a shift in indications for invasive testing, and whether the diagnostic yield would increase. METHODS: We conducted a retrospective, observational study from 2006 through 2015. We quantified the number of invasive procedures per year and examined what percentage of these procedures yielded abnormal results. We also examined the indications for testing and determined the trend of these indications during the study period. RESULTS: The number of amniocenteses showed a steady decline (P < .05). The number of CVS procedures has increased and was recently equivalent to amniocentesis. The percentage of abnormal results steadily increased from 11.4% to 27.0% (P < .001). The abnormal aneuploidy screening indication remained constant over time. Advanced maternal age (AMA) as the sole indication substantially declined from 42.3% to 15.52% (P < .001). Testing for a known single gene disorder steadily increased from 3.0% to 9.20% (P = .018). CONCLUSION: Our study showed a significant decline in the number of amniocenteses, a steady increase in the percentage of abnormal results from invasive testing, and a decline in AMA as the sole indication for invasive testing.

Diagnóstico prenatal y diagnóstico preconcepcional. Perspectivas del análisis genético / Prenatal diagnosis and preconception diagnosis. Prospects for genetic analysis

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Rotura prematura de membranas en gestación previable con feto con Síndrome de Down / Previable premature rupture of membranes with a Down syndrome fetus

La literatura sobre roturas prematuras de membranas en embarazos con Síndrome de Down (SD) es escasa. El presente caso relata la dificultad de asesoramiento prenatal en el caso de una rotura prematura de membranas en una gestación previable con SD. El resultado en nuestro caso resultó ser mejor al esperado. Exponemos el caso de un embarazo de SD con oligoamnios severo desde la semana 17 de edad gestacional, debido a una rotura prematura de membranas. La paciente tuvo el parto en la semana 33 más 3 días. Nació una niña sana, con SD, sin signos o síntomas de hipoplasia pulmonar, anormalidades esqueléticas o morbilidad infecciosa. En el caso de una rotura prematura de membranas en una gestación previable, la muerte fetal es común. Cuando se alcanza una edad gestacional viable, las complicaciones respiratorias y otras morbilidades como la sepsis son frecuentes. Los recién nacidos con SD tienen un mayor riesgo de infecciones de las vías respiratorias, lo que en conjunto, con el mayor riesgo de presentar anomalías congénitas, nos hizo creer en un mal pronóstico. Se necesitan más artículos acerca de este tema con el fin de ofrecer un mejor asesoramiento prenatal a los padres (AU)

There is a scarcitiy of literature about Previable Premature Rupture of Membranes in Down Syndrome (DS) Pregnancies. The present report concerns the difficulty in prenatal counseling in a Previable Premature Rupture of Membranes in a DS Pregnancy. The outcome appears improved in our case. We report the case of a DS Pregnancy with severe oligohydramnios since the 17th week of gestational age due to Previable Premature Rupture of Membranes. She delivered at the gestational age of 33 weeks and 3 days a healthy DS baby without signs or symptoms of neonatal pulmonary hypoplasia, skeletal abnormalities or infectious morbidity. In Previable Premature Rupture of Membranes, fetal death is common. When a viable gestational age is reached, respiratory complications and other morbidities such as sepsis are frequent. Newborns with DS have an increased risk of respiratory tract infections, what added to the risk of congenital diseases, made us believe in a poor prognosis. More reports are needed in order to provide a better prenatal counselling (AU)

Declining invasive prenatal diagnostic procedures: A comparison of tertiary hospital and national data from 2012 to 2015.

BACKGROUND: In recent years, the superior accuracy of maternal plasma cell-free DNA-based prenatal screening has resulted in >50% national decline in amniocenteses and chorionic villus sampling (CVS), creating new implications for specialist training. OBJECTIVE: To compare the annual figures on amniocenteses and CVS in a tertiary hospital with national population-based trends between 2012 and 2015. METHODS: Retrospective study examining the amniocentesis and CVS procedures performed in a tertiary hospital between 2012 and 2015. Numbers of procedures, indications for testing, type of test and diagnostic results were analysed. Trends in the annual numbers of procedures were compared to national population-based data from Medicare Benefits Schedule database. RESULTS: The annual numbers of diagnostic procedures in our tertiary centre fell from 267 to 215 over the study period, representing a 19.5% decline. This was significantly smaller than the corresponding national decline of 53.7% for the same period (P < 0.0001). In 2015, ultrasound abnormality (including nuchal translucency ≥ 3.5 mm) surpassed high-risk screening results as the most common indication for invasive testing. Thirty percent of procedures performed for an ultrasound abnormality occurred prior to 18 weeks gestation. CONCLUSION: Our tertiary centre experienced a relatively smaller decline in prenatal diagnostic procedures compared with national figures, largely due to an increase in testing for ultrasound abnormalities. Our results demonstrate the increasing contribution of first trimester ultrasound in the detection of fetal abnormalities in the cell-free DNA era and the continued viability of specialist training in invasive procedures.

Teoría de la decisión y cribado del Síndrome de Down: cálculo individualizado del dintel de normalidad / Decision making and Down Syndrome screening: individualized cutoff

Objetivos: demostrar mediante la teoría de la decisión que el cribado bioquímico-ecográfico del síndrome de Down no debe aplicarse de forma universal sino teniendo en cuenta los umbrales de decisión. Desarrollar el cálculo matemático individualizado para cada gestante de los umbrales de decisión siguiendo el modelo de Pauker-Kassirer. Implementar un método simple para la obtención individualizada de las utilidades que intervienen. Material y métodos: definimos un diagrama de influencia con: variables aleatorias: tener Síndrome de Down, resultado del cribado, pérdida gestacional tras amniocentesis. Decisiones: aplicar el cribado, realizar amniocentesis. Utilidades relativas a los diferentes resultados posibles calculadas en un grupo de 10 gestantes consecutivas mediante diagramas de equivalencia temporal para el cálculo del tiempo de vida ajustado en calidad. Realizamos un análisis de sensibilidad comparando la utilidad de cada estrategia en función de la probabilidad a priori. Los cálculos fueron realizados con OpenMarkov (http://www.openmarkov.org). Resultados: con las utilidades obtenidas (tener un hijo sano 1; tener un hijo con síndrome de Down 0,57; interrumpir el embarazo por diagnóstico de síndrome de Down 0,90; pérdida gestacional secundaria a amniocentesis 0,80) en gestantes con una probabilidad a priori mayor de 0,014 (Odds de 1/70, corresponde al riesgo de una gestante de 41 años) se obtiene la máxima utilidad realizando directamente una amniocentesis. Al resto deberemos aplicar el cribado porque el umbral diagnóstico (0,0002) es menor que el riesgo en las gestantes más jóvenes. Discusión: la gran variabilidad interindividual de las utilidades aconseja que el cálculo de los umbrales de decisión se individualicen para cada gestante; para ello proponemos un método matemático basado en Pauker-Kassirer (AU)

Objectives: To evaluate by decision making if biochemical and ultrasonographic universal screening of Down syndrome is accurate, or they must be used in a selective way related to decision thresholds. To develope a probabilistic model to calcule the decision thresholds following Pauker-Kassirer model. To design a method of utility assessment to quantify women´s individual preferences. Material and methods: An influence diagram with uncertainty nodes (affected or unaffected birth, positive or negative screening, amniocentesis related miscarriage or no complicated technique), decision nodes (to perform screening, to perform amniocentesis) and utilities was developed. Utilities were the average of 10 consecutive pregnant women preference measures using the time trade-off model to obtain quality-adjusted life years. A sensitivity analysis comparing utility for every strategy related to prior probability was done. To perform mathematical results the free software programme OpenMarkov (http://www.openmarkov.org) was used. Results: Utilities were: unaffected birth 1, Down syndrome-affected birth 0.57, elective abortion after Down syndrome diagnosis 0.9 and amniocentesis procedure related miscarriage 0.8. Over 41 year-old risk (Odds 1/70) invasive diagnostic testing has the maximum expected utility. The testing threshold is lower than the lowest-risk women. Therefore, screening is the best option under that prior probability. Discussion: We agree with prior published data: current cutoff is not appropriate because it assumes that women value equally burdensome procedure-related miscarriage of a normal fetus and Down syndrome-affected birth. There was a substantial subject-to-subject variation; individual preferences should be used to stablish a personalised cutoff following Pauker-Kassirer model (AU)

Cytogenetic highlights and transitions.

Medical cytogenetics, genetic diagnostics, and medical genetics had their origins in the late 1950's, as evaluation of human chromosomes became possible, and it was recognized that chromosomal abnormalities could cause a variety of clinical phenotypes. Dr. Laird Jackson began his medical and scientific career just as this field was emerging and he was an early adopter and driver of several key trends in the development of these fields, notably in the area of prenatal diagnostics. Laird's greatest impact was in his work to demonstrate the clinical utility of amniocentesis, chorionic villous sampling, and chromosomal microarray analysis for prenatal diagnosis. © 2016 Wiley Periodicals, Inc.

Changing indications for invasive testing in an era of improved screening.

Prenatal diagnostic testing is available for a growing number of disorders. The goal of prenatal diagnosis was initially focused on the identification of Down syndrome in women aged 35 years and older, but invasive prenatal genetic techniques can now detect a far broader array of conditions. The risks of invasive procedures have also decreased over time. Advances in genomic medicine allow testing for smaller but significant chromosomal abnormalities known as copy number variants, in addition to major aneuploidies and structural rearrangements. Molecular DNA techniques can detect many single-gene conditions. In the future, it is likely that whole-exome and whole-genome sequencing will be applied to prenatal genetic testing to allow identification of yet more genetic disorders. With advances in technology, the indications for testing have likewise evolved far beyond recommendations based solely on maternal age to include a more patient-centered view of the goals of prenatal testing.

Genetics: update on prenatal screening and diagnosis.

There have been tremendous advances in the ability to screen for the "odds" of having a genetic disorder (both mendelian and chromosomal). With microarray analyses on fetal tissue now showing a minimum risk for any pregnancy being at least 1 in 150 and ultimately greater than 1%, it is thought that all patients, regardless of age, should be offered chorionic villus sampling/amniocentesis and microarray analysis. As sequencing techniques replace other laboratory methods, the only question will be whether these tests are performed on villi, amniotic fluid cells, or maternal blood.

Uptake of Noninvasive Prenatal Testing in Chinese Women following Positive Down Syndrome Screening.

OBJECTIVES: To investigate how the introduction of noninvasive prenatal testing (NIPT) influenced women's testing choices following a positive Down syndrome screening. METHODS: A retrospective study was conducted to compare differences in the uptake rates of invasive prenatal diagnosis (IPD) or no testing in one public hospital 1 year before (pre-NIPT) and 1 and 2 years after the introduction of NIPT in private in August 2011 using descriptive analysis and a χ² test. Conventional screening was funded publicly, but NIPT was not. Multivariable binary logistic regression was used to determine factors affecting choices. RESULTS: In pre-NIPT and in years 1 and 2 after the introduction of NIPT, 306, 362 and 401 women who screened positive were seen, respectively. In year 1 and year 2, 12.6 and 26.7% of them underwent NIPT while IPD was decreased by 16.3 and 25.6%, respectively (p < 0.001). Both chorionic villus sampling and amniocentesis decreased in year 1, but only the former in year 2. However, the rate of declining further testing was similar before and after NIPT (p = 0.213). In multivariable analysis, first trimester screening, nulliparity and working women were significant predictors of accepting NIPT, while only nulliparity was a predictor of declining IPD (OR = 0.61). CONCLUSIONS: Introduction of NIPT resulted in a significant decrease in IPD for 2 consecutive years..

The impact of utilization of early aneuploidy screening on amniocenteses available for training in obstetrics and fetal medicine.

OBJECTIVE: First-trimester aneuploidy screening has high detection rates and low false-positive rates. Their use as well as the implementation of non-invasive prenatal testing may affect specialty training in prenatal diagnosis procedures. STUDY DESIGN: Descriptive study of first-trimester aneuploidy screening and amniocentesis in an obstetric training program. Screening methods were tracked from their introduction in 2004 through 2011. The volume of amniocentesis procedures from 2000 to 2011 was evaluated. RESULTS: First-trimester screening tests increased from 283 to 1225 between 2005 and 2011, whereas genetic amniocenteses declined from 460 to 168 during the same period. The percent of older women who chose a first-trimester screen test rose from 12.7% to 44.2% CONCLUSION: First-trimester screening options reduce genetic amniocenteses available for training. Fetal medicine and general obstetrics training programs need to evaluate their clinical experience and determine whether simulation training methods are needed for education.

Diagnóstico de aneuplodias en células en interfase de líquido amniótico mediante hibridación in situ fluorescente. Concordancia con el cariotipo / Diagnosis of aneuploidy in interphase cells of amniotic fluid by fluorescence in situ hybridization. Concordance with the karyotype

Introducción. En los últimos años la aplicación de la hibridación in situ fluorescente (FISH) permite el diagnóstico precoz de aneuploidias. El objetivo de este estudio es el análisis descriptivo mediante FISH de los líquidos amnióticos procesados en el laboratorio y la concordancia con el cariotipo. Material y métodos. Análisis de 821 muestras de líquidos amnióticos (enero 2009 a diciembre 2010) remitidas por Medicina Fetal desde la semana 13 a 36 de gestación para estudio prenatal de aneuploidias, (kit Aneuvysion) con sondas centroméricas para los cromosomas X, Y y 18, y locus específicas para los cromosomas 13 y 21. El estudio se completa con el cariotipo mediante método de bandeo G. Resultados. De las 821 muestras, 776 (94,52%) fueron normales y 45 (5,48%) presentaron aneuploidias: en 22 casos (48,88%) el sexo cromosómico del feto fue masculino, en las 23 restantes (51,12%) femenino. La cromosopatía más frecuente fue la trisomía 21 (19 casos en fetos masculinos y 11 femeninos), la de menor presentación fue la trisomía 13 (2 casos) que representa el 0,24% del total de los líquidos amnióticos procesados. En todos los casos, la concordancia con el cariotipo fue del 100%. Conclusiones. El estudio de aneuploidias mediante FISH en núcleos en interfase en líquido amniótico permite un diagnóstico prenatal rápido de las principales cromosomopatías, siendo la trisomía 21 la más frecuentemente detectada. Los resultados del FISH coincidieron en el 100% con el cariotipo, gold estándar en el diagnóstico prenatal de cromosomopatías (AU)

Background. The application of fluorescence in situ hybridization (FISH) techniques in the last few years has led to the prenatal diagnosis of aneuploidies. The objective of this investigation was a descriptive analysis of amniotic fluids processed in the laboratory using FISH and the agreement with the karyotype. Material and methods. A total of 821 amniotic fluid samples (January 2009 to December 2010) at gestational ages 13 to 36 weeks, from Fetal Medicine Unit for prenatal testing for aneuploidies (Aneuvysion kit) with centromeric probes for chromosomes X,Y and 18, and locus specific for chromosomes 13 and 21. The study was complemented by the karyotype by G-banding method. Results. Of the 821 samples, 776 (94.52%) were normal and 45 (5.48%) had aneuploidy: in 22 cases (48.88%) the chromosomal sex of the foetus was male, in the remaining 23 (51.12%) female. The most common chromosomal abnormality detected was trisomy 21 (19 cases in males and 11 cases in female foetuses), the lowest performance was the trisomy 13 (2 cases) representing 0.24% of total processed amniotic fluids. In all cases, the concordance with the karyotype was 100%. Conclusions. The study of aneuploidy by FISH of interphase nuclei present in the amniotic fluid enables rapid prenatal diagnosis of major chromosomal abnormalities, trisomy 21 was more frequently detected. FISH results in 100% agreed with the karyotype, the gold standard in prenatal diagnosis of chromosomal abnormalities (AU)

Cribado combinado de síndrome de Down en primer trimestre: comparación de resultados de 4 años de aplicación con los 4 años precedentes / First-trimester combined screening for Down syndrome: comparison of the 4-year results with the previous 4 years

Objetivo. Analizar los resultados de 4 años de aplicación del programa de cribado combinado del primer trimestre y su impacto sobre las tasas de detección de síndrome de Down, cobertura poblacional y procedimientos invasivos. Sujetos y métodos. Estudio retrospectivo poblacional de 8 años consecutivos (17.564 gestaciones que contienen 51 síndromes de Down), en 2 periodos: 31 de enero de 2002 a 30 de enero de 2006, sin cribado (8.182 gestaciones y 24 síndromes de Down) y 31 de enero de 2006 a 30 de enero de 2010, con cribado (8.382 gestaciones y 27 síndromes de Down). El cribado se aplicó en 2 fases: bioquímica a la 10 semana y ecografía a la 12 semana. Se comparan los resultados del cribado con los del periodo precedente basado en la edad materna y la medida de la translucencia nucal. Resultados. La cobertura poblacional fue de 93%. La tasa de detección de síndrome de Down por aplicación del cribado combinado ha sido del 89% (91% para feto único) para un 3,5% de falsos positivos y se realizaron 824 procedimientos invasivos (34,3 para 1 diagnóstico). En los 4 años previos a la aplicación del cribado, la tasa de detección era del 71% y se realizaron 1.406 procedimientos invasivos (87,8 para un diagnóstico). Conclusión. El cribado combinado ha mejorado las tasas de detección para síndrome de Down en un 18%, al tiempo que ha permitido reducir en un 41% los procedimientos invasivos (AU)

Objective. To analyze the 4-year results of first-trimester combined screening and its impact on rates of Down syndrome detection, population coverage and invasive procedures. Subjects and methods. We performed a retrospective population-based study over 8 consecutive years (17,564 gestations with 51 cases of Down syndrome) divided in two periods: from January 31, 2002 to January 30, 2006 without combined screening (8,182 gestations and 24 cases of Down syndrome) and from January 31, 2006 to January 30, 2010 with combined screening (8,382 gestations and 27 cases of Down syndrome). Combined screening was applied in two phases: biochemical analysis was performed in the 10th week of pregnancy and ultrasound examination in the 12th week. We compared the results of screening with the previous period based on maternal age and fetal nuchal translucency measurement. Results. Population coverage was 93%. The rate of Down syndrome detection due to the application of combined screening was 89% (91% for a single fetus) with a false-positive rate of 3.5%. There were 824 invasive procedures (34.1 to diagnose one episode). During the 4 years prior to the application of combined screening, the detection rate was 71% with 1,406 invasive procedures (87.8 to diagnose one episode). Conclusion. Combined screening has improved the Down syndrome detection rate by 18% and has reduced the use of invasive procedures by 41% (AU)

Utilidad de la inhibina A en el cribado de síndrome de Down en el segundo trimestre / Inhibin A in second trimester screening of Down's syndrome

Objetivo. Comprobar la eficacia de la incorporación de la inhibina A en el cribado de segundo trimestre del síndrome de Down en términos de tasa de detección y porcentaje de cribados positivos. Métodos. Estudio retrospectivo de 3.380 embarazadas, que se sometieron al cribado de segundo trimestre, clasificadas en 2 grupos en función de la incorporación de la inhibina A (1.921 mujeres) o no (1.459 mujeres).Resultados. La tasa de detección con un punto de corte de 1:250 fue del 90% en el grupo de inhibina A y 84,6% sin inhibina A, pero con un porcentaje de cribados positivos significativamente menor en el primero (11 vs. 15,9%; p < 0,001). Este concepto también se refleja al comparar el likelihood ratio positivo entre ambos grupos (8,47 vs. 5,54; p <0,001). Conclusión. Es aconsejable la incorporación de la inhibina A en el cribado de segundo trimestre, ya que se observa un menor porcentaje de casos positivos, con la consiguiente reducción en el número de amniocentesis a realizar(AU)

Objective. To evaluate the efficacy of inhibin A in second trimester screening of Down's syndrome in terms of detection rate and percentage of positive results. Methods. A retrospective study of 3380 pregnant women who underwent second trimester screening, classified into 2 groups, one which included inhibin A (1921 pregnant women) and one that did not (1459 pregnant women). Results. The detection rate (cut-off: 1:250) was 90% in the group with inhibin A and 84.6% in the other group, but the percentage of positive results was significantly lower in the first group (11% vs. 15.9%, P<.001). The results were similar if we compared the positive likelihood ratio between groups (8.47 vs. 5.54, P<.001). Conclusion. Inhibin A is a useful marker in second trimester screening due to the low percentage of positive cases observed, thereby reducing the number of amniocentesis(AU)