Circulating trophoblast cell clusters for early detection of placenta accreta spectrum disorders.

Placenta accreta spectrum (PAS) is a high-risk obstetrical condition associated with significant morbidity and mortality. Current clinical screening modalities for PAS are not always conclusive. Here, we report a nanostructure-embedded microchip that efficiently enriches both single and clustered circulating trophoblasts (cTBs) from maternal blood for detecting PAS. We discover a uniquely high prevalence of cTB-clusters in PAS and subsequently optimize the device to preserve the intactness of these clusters. Our feasibility study on the enumeration of cTBs and cTB-clusters from 168 pregnant women demonstrates excellent diagnostic performance for distinguishing PAS from non-PAS. A logistic regression model is constructed using a training cohort and then cross-validated and tested using an independent cohort. The combined cTB assay achieves an Area Under ROC Curve of 0.942 (throughout gestation) and 0.924 (early gestation) for distinguishing PAS from non-PAS. Our assay holds the potential to improve current diagnostic modalities for the early detection of PAS.

Análisis de los resultados del programa de cribado prenatal de cromosomopatías en el Área Hospitalaria de Valme (Sevilla). Identificación de áreas para la mejora de la calidad / Analysis of the results of the programme of prenatal screening for chromosomal abnormalities in the Hospital Area of Valme (Sevilla). Identification of measures for the improvement of the quality

Introducción. En los programas de cribado prenatal de aneuploidías el análisis crítico de los resultados del control de calidad, entendido de forma amplia, podría ser una herramienta útil para mejorar la eficacia, sin necesidad de aumentar la complejidad o los costes en dichos programas. En el presente trabajo analizamos nuestros resultados en el periodo 2005-2011 para trisomía 21. Material y método. Se valoraron retrospectivamente los siguientes parámetros: cobertura, solicitudes no conformes, imprecisión y sesgo en la medición de BHCG libre y PAPP-A, evolución de las medianas de múltiplos de mediana de BHCG libre, PAPP-A y translucencia nucal, tasa de detección, tasa de falsos positivos y análisis de falsos negativos para trisomía 21. Los parámetros bioquímicos se determinaron mediante quimioluminiscencia. La estimación del riesgo se realizó mediante el software PRISCA V4.0. Resultados. Se realizaron 26.363 cribados. Cobertura 95,11%. No conformidades entre 12,2% (2005) y 5,8% (2010). Imprecisión inferior al 5% y sesgo inferior al 20% tanto para PAPP-A como para BHCG libre. Mediana de múltiplos de mediana corregidos de 1,066 (PAPP-A), 1,027 (BHCG libre) y 0,829 (translucencia nucal). Sensibilidad del 80% para cribado combinado de primer trimestre (4,6% falsos positivos) con 13 falsos negativos sobre 66 diagnósticos genéticos de trisomía 21. Para trisomía 18, sensibilidad del 77% (4,3% falsos positivos). Conclusión. Áreas de mejoras detectadas: universalización del programa, gestión de solicitudes no conformes, control de calidad ecográfico, diseño del software de cálculo y valoración conjunta de los resultados finales en colaboración entre Unidades de Laboratorio y Obstetricia(AU)

Introduction. Critical analysis of the results of quality control could be a useful tool to improve efficacy without increasing complexity or costs in such programs. We analyzed the results of the prenatal screening program in Valme Hospital in order to, detect and introduce improvement areas. Material and methods. We have studied the non-conformities of the application received, the precision and bias in the measurement of B-HCG and PAPP-A, the medians of PAPP-A, BHCG and nuchal translucency multiples of the medians, the sensibility and false positives rate. We have studied the false negatives results. The biochemical parameters were determined by a chemiluminiscence inmunoassay. Risks estimation was performed using PRISCA V4.0 software. Results. A total of 26,363 prenatal screening were performed. The program reached a coverage of 95,11%. Non-conformities fell from the 12.2 to 5.8%. Imprecision was less than 5% and bias less than 20% for biochemical markers. The corrected medians for PAPP-A, BHCG and nuchal translucency multiples of the medians were 1.066, 1.027 and 0,829, respectively. The sensibility for the first trimester combined screening was 80% (4,6% false positive) for Down's syndrome for a total 66 chromosomal abnormalities diagnosed. We recorded a total of 13 false negatives for trisomy 21. For trysomy 18 detection rate was 77% (4.3% false positive). Conclusion. Areas for improvement identified were: universalization of the program, non-conformities of the received application management, ultrasound quality control, design of risk calculation software and joint evaluation of the final results in collaboration between laboratory and obstetrics units(AU)

Control de la infección por Trypanosoma cruzi / Enfermedad de Chagas en gestantes Latinoamericanas y sus hijos / Control of Chagas disease in pregnant Latin-American women and her children

La Enfermedad de Chagas es una infección crónica y sistémica causada por Trypanosoma cruzi y según estimaciones de la OMS afecta a 10 millones de personas en el mundo. En los últimos años, en la Comunidad Autónoma de Madrid (CAM), la tasa de natalidad en mujeres inmigrantes de origen latinoamericano ha aumentado, y como T. cruzi puede transmitirse de madre a niño, al menos 11 casos de transmisión vertical se han confirmado en la CAM. Por ello, este documento tiene por objeto promover la máxima cobertura en la detección de anticuerpos anti-T. cruzi en gestantes procedentes de zona endémica. Así mediante esta estrategia realizar una búsqueda activa de embarazadas y recién nacidos infectados para la instauración precoz de un tratamiento específico. De esta forma, contribuir en el control de la enfermedad de Chagas en área no endémica (AU)

Chagas disease is a chronic and systemic infection caused by Trypanosoma cruzi. According to estimates from WHO, 10 million people are affected by this parasite. In the last years, birthrate among the immigrant women from Latin America settled in the Comunidad Autónoma de Madrid has been increasing, and as T. cruzi can be transmitted from mother to child, in fact 11 cases of congenital Chagas disease have been confirmed. Therefore, the aim of this paper is encouraging improvements in the coverage of the anti-T. cruzi antibodies detection in pregnant women from endemic areas. By this strategy, an active search for infected pregnant women and early detection of her infected newborns could be conducted, and then an early specific treatment could be administrated. Thus, there could be an important contribution to the control of Chagas disease in non-endemic area (AU)

Feasibility study of semiconductor sequencing for noninvasive prenatal detection of fetal aneuploidy.

BACKGROUND: Noninvasive prenatal detection of common fetal aneuploidies with cell-free DNA from maternal plasma has been achieved with high-throughput next-generation sequencing platforms. Turnaround times for previously tested platforms are still unsatisfactory for clinical applications, however, because of the time spent on sequencing. The development of semiconductor sequencing technology has provided a way to shorten overall run times. We studied the feasibility of using semiconductor sequencing technology for the noninvasive detection of fetal aneuploidy. METHODS: Maternal plasma DNA from 13 pregnant women, corresponding to 4 euploid, 6 trisomy 21 (T21), 2 trisomy 18 (T18), and 1 trisomy 13 (T13) pregnancies, were sequenced on the Ion Torrent Personal Genome Machine sequencer platform with 318 chips. The data were analyzed with the T statistic method after correcting for GC bias, and the T value was calculated as an indicator of fetal aneuploidy. RESULTS: We obtained a mean of 3 524 401 high-quality reads per sample, with an efficiency rate of 77.9%. All of the T21, T13, and T18 fetuses could be clearly distinguished from euploid fetuses, and the time spent on library preparation and sequencing was 24 h. CONCLUSIONS: Semiconductor sequencing represents a suitable technology for the noninvasive prenatal detection of fetal aneuploidy. With this platform, sequencing times can be substantially reduced; however, a further larger-scale study is needed to determine the imprecision of noninvasive fetal aneuploidy detection with this system.