Aneuploidy screening during pregnancy by a three-dimensional Advanced First Trimester Screening model: description of the AFS-3D algorithm.

BACKGROUND: A novel screening method for fetal aneuploidies was developed, in which nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A), and free-ß human chorionic gonadotropin (free-ß hCG) are placed into a three-dimensional scatter plot. Likelihood ratios are directly inferred from the ratio of already observed healthy and diseased fetuses. This method is called 'Three-dimensional Advanced First trimester Screening' (AFS-3D). It was aimed to develop and test a new algorithm based on the results of previous studies. METHODS: A new static-sized sphere model was developed. Several scaling factors of the axes and the optional application of the modifications 'simulation' (SIM) and 'empty sphere positive' were tested on 15,227 data sets. An additional examination was performed on a second collective (n = 458). RESULTS: The application of the new AFS-3D model with static-sized spheres, a re-sampled ∆NT axis by a scaling factor of 0.125, and the application of SIM and Empty Box Positive resulted in a marked improvement of the test performance (area under curve, AUC = 0.9668). Analogous results (AUC = 0.9807) were found for the second test collective. CONCLUSIONS: This novel approach is promising and should be tested on a larger, independent collective.

Comparison of measured concentration values of biochemical serum markers with two immunoassay systems in first trimester screening for fetal aneuploidy.

Non-invasive first trimester screening for fetal aneuploidy is based on the consideration of fetal nuchal translucency, biochemical serum markers 'pregnancy associated plasma protein A' (PAPP-A), and 'free beta-humane chorionic gonadotropin' (fß-hCG). The blood sera of 168 pregnant women in 11 + 0 to 13 + 6 weeks of gestation were examined by both the COBAS (Roche Holding GmbH, Germany) and KRYPTOR (Brahms GmbH, Germany) immunoassay systems in two quality controlled laboratories. The concentration values were converted into multiple of median (MoM) values and compared through a two-tailed t test. The concentration values of PAPP-A differed significantly from each other (p < 0.0001). COBAS produced on average 0.09 MoM higher values in comparison to KRYPTOR (CI 95% = 0.06-0.11 MoM). In contrast, the concentration values of fß-hCG did not differ significantly (p value = 0.20). The values produced by COBAS were on average only 0.02 MoM higher in comparison to KRYPTOR (CI 95% = -0.01 to 0.05 MoM). Which of the two systems generates the more precise results should be evaluated in a large-scale prospective study with the pregnancy outcomes.

Is the yolk sac a new marker for chromosomal abnormalities in early pregnancy?

INTRODUCTION: Abnormal yolk sac size is associated with fetal miscarriage. This is a case report of two pregnancies with abnormal yolk sacs. MATERIALS AND METHODS: In one case, a twofold sac was found; in the other case, the yolk sac was not of spherical form. CONCLUSION: Currently available publications demonstrate a correlation between abnormal yolk sac size and miscarriage. However, in both cases a trisomy was confirmed. It should therefore be discussed whether form and size of the yolk sac could be a marker for chromosomal abnormalities of the fetus.

[Comparison of current methods of prenatal screening for down syndrome]. / Comparación de los métodos actuales de cribado prenatal del síndrome de down.

BACKGROUND: In Spain all pregnant women aged 35 years and older are offered genetic examination through invasive testing in order to detect fetal trisomy 21 cases (maternal age indication (MAI)). In the last decade five distinct software programs utilizing the "first trimester screening (FTS)" were developed. The objective of this study is to compare the test performance of the different screening methods in order to detect the best current approach. METHODS: 7.736 complete first trimester screenings, including the fetal outcome, were realized between 31.08.1999 and 24.05.2007 in three prenatal health centres in Hannover, Peine, and Wolfenbüttel in Germany. Out of these 6.508 cases were analyzed retrospectively in this study. Maternal age was determined and risk calculation with the software programs PIA, PRC, JOY, AFS and AFS-3D was executed. RESULTS: The MAI reached a sensitivity of 57.50%, detecting only 23 out of 40 trisomy 21 cases, and a false positive rate of 21.60%. In comparison, all risk calculation programs obtained superior results, attaining a sensitivity between 90.00% (AFS) and 92.50% (PIA, PRC, JOY, AFS-3D) and a false positive rate between 2.64% (AFS-3D) and 7.87% (PIA). The difference was highly significant (p<0.0001) CONCLUSIONS: The MAI is obsolete and inadequate in comparison with the risk calculation software, out of which all obtained test performances within the range of comparable international publications. Among these programs, JOY, AFS, and AFS-3D obtained the best results.

Comparación de los métodos actuales de cribado prenatal del Síndrome de Down / Comparison of current methods of prenatal screening for down syndrome

Fundamento: En España se ofrece a todas las mujeres gestantesa partir de los 35 años un examen genético a través de un diagnósticoinvasivo (indicación por edad materna (IPEM)) para detectarcasos fetales de trisomía 21. En la última década se elaboraron cincodistintos programas de cálculo de riesgo utilizando el «cribado delprimer trimestre». El objetivo de este estudio es comparar los resultadosde los diferentes métodos de screening para detectar el mejorprocedimiento en la actualidad.Métodos: Desde el 31.08.1999 hasta el 24.05.2007 se realizaron7.736 screenings del primer trimestre completos, incluyendo el estadode salud del feto, en tres centros de medicina prenatal en las ciudadesde Hannover, Peine y Wolfenbüttel en Alemania, de los cualesse analizaron en este estudio retrospectivamente 6.508 casos dedatos. Se determinó la edad materna y se efectuaron cálculos de riesgocon los programas PIA, PRC, JOY, AFS y AFS-3D.Resultados: La IPEM alcanzó una sensibilidad de 57,50%,detectando 23 de 40 casos de trisomía, y una tasa de falsos positivosde 21,60%. En comparación, todos los programas obtuvieron mejoresresultados alcanzando una sensibilidad entre 90,00% (AFS) y92,50% (PIA, PRC, JOY, AFS-3D) y una tasa de falsos positivosentre 2,64% (AFS-3D) y 7,87% (PIA). La diferencia fue de alta significancia(p<0,0001).Conclusiones: La IPEM es obsoleta e inadecuada en comparacióna los programas de cálculo de riesgo, de los cuales todos demostraronrendimientos que se encuentran dentro del rango de publicacionesinternacionales comparables. Entre estos programas JOY,AFS y AFS-3D obtuvieron los mejores resultados(AU)

Background: In Spain all pregnant women aged 35 years andolder are offered genetic examination through invasive testing inorder to detect fetal trisomy 21 cases (maternal age indication(MAI)). In the last decade five distinct software programs utilizingthe «first trimester screening (FTS)» were developed. The objectiveof this study is to compare the test performance of the different screeningmethods in order to detect the best current approach.Methods: 7.736 complete first trimester screenings, includingthe fetal outcome, were realized between 31.08.1999 and 24.05.2007in three prenatal health centres in Hannover, Peine, and Wolfenbüttelin Germany. Out of these 6.508 cases were analyzed retrospectivelyin this study. Maternal age was determined and risk calculation withthe software programs PIA, PRC, JOY, AFS and AFS-3D was executed.Results: The MAI reached a sensitivity of 57.50%, detectingonly 23 out of 40 trisomy 21 cases, and a false positive rate of21.60%. In comparison, all risk calculation programs obtained superiorresults, attaining a sensitivity between 90.00% (AFS) and92.50% (PIA, PRC, JOY, AFS-3D) and a false positive rate between2.64% (AFS-3D) and 7.87% (PIA). The difference was highly significant(p<0.0001)Conclusions: The MAI is obsolete and inadequate in comparisonwith the risk calculation software, out of which all obtained testperformances within the range of comparable international publications.Among these programs, JOY, AFS, and AFS-3D obtained thebest results(AU)

Preliminary analysis of the new 'Prenatal Risk Calculation (PRC)' software.

OBJECTIVES: In February 2007, the "Fetal Medicine Foundation Germany (FMF-D)" introduced its new calculation software for First Trimester Screening (FTS), called "Prenatal risk calculation (PRC)". The aim of this study was to retrospectively investigate the test performance of PRC in comparison to the "NT module of the JOY software (JOY)". METHODS: A total of 3,516 combined first trimester screenings from 11 + 0 to 13 + 6 weeks of gestation were accomplished according to the FMF-standard. Adjusted risk calculation for aneuploidy was performed with PRC and JOY. RESULTS: A total of 2,202 complete data sets of singleton pregnancies were analyzed, including 10 trisomy 21 cases, 4 trisomy 18 cases, and 1 trisomy 13 case. Risk calculation with PRC and JOY showed highly significant results (P value<0.0001). JOY attained, at a cut-off of 1:300 (sensitivity 82.4%, false-positive rate 3.6%, positive predictive value 15.2%) and at a cut-off of 1:230 (82.4, 2.4, 21.2%), a better test performance in comparison to PRC (76.5, 7.1, 7.7% and 76.5, 5.3, 10.2%, respectively). The differences were highly significant (P value<0.0001). CONCLUSION: In this preliminary study, PRC demonstrated highly significant results in detecting aneuploidies in FTS. However, in comparison to JOY, its test performance was significantly inferior. A twice higher false positive rate would have doubled unnecessary invasive testing in a prospective setting. We therefore recommend a methodical revision of PRC.

Improved prenatal aneuploidy screening using the novel advanced first-trimester screening algorithm: a multicenter study of 10,017 pregnancies.

PURPOSE: : It has been postulated that the maternal age component should be completely excluded from first-trimester screening (FTS) for fetal aneuploidies. In this study, we tested a new algorithm known as advanced first-trimester screening (AFS), which disregards maternal age. METHOD: : In a multicenter study, FTS findings were retrieved from 10,017 pregnancies. FTS risk assessment was performed using the Nicolaides method, and the AFS score was calculated. The results of both methods were compared. RESULTS: : Within this population, 81 fetuses had an abnormal karyotype. The sensitivity of the 2 algorithms was 86.4%. When the AFS method was used, the positive predictive value rose from 9.6% (FTS) to 12.4% (AFS). Using AFS, the test positive rate could be decreased by 161 cases (-22.2%) (p < 0.0001), due to a reduction of false positive cases. As a result, the false positive rate of AFS was 24.5% lower than that of FTS, while the same number of aneuploidies was detected. CONCLUSION: : AFS can markedly reduce the rate of false positive test results. If these results are confirmed by larger multicenter studies, the new AFS will represent a great improvement in fetal aneuploidy screening. (c) 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008.