TRC  Trisomy Risk Calculator

  Purpose of  TRC

Trisomy Risk Calculator (TRC) for trisomy 21 and 18-13 is an online computer tool developed by SBP Soft 2007 S.L. It demonstrates and confirms the huge potential of prenatal screening for Down's, Edwards and Patau's syndromes (the most common trisomies), and it can be used to contrast with risk estimates currently provided by specialized centers. Under no circumstances is this computer application intended to substitute or contribute to clinical diagnosis, and on no account do SBP Soft 2007 S.L., its proprietors or developers take responsibility for results or decisions derived of its use in a given patient or group of patients, even if the user has correctly entered the requested parameters. Trisomy 21 and 18-13 prenatal detection estimates a pregnant woman’s probability or Risk of carrying a trisomy-affected fetus, according to her age and a combination of biochemical markers (analyzed in maternal blood) and/or an ultrasound (assessed using a fetal sonogram). When this risk is high the presence or absence of the suspected trisomy should be confirmed by an invasive test (chorionic villus sampling, amniocentesis, etc.), as the risk is only a statistical estimate, not a definite diagnosis, which accounts for variability in risk estimates provided by different computer systems.

  Important information

MoM (Multiples of the Median) calculation of the biochemical markers values (AFP, uE3, Inhibin A, hCG and PAPP-A) can only be obtained by a specialized Clinical Analysis Laboratory. MoM values are usually printed in the screening report.

  How to use  TRC

The mother’s age at the expected delivery date (EDD) must be entered in the first text box. It should be indicated with a decimal number representing the decimal fraction of a month. As in all the other text boxes, either the comma or the point can be used as the decimal separator symbol.

Next, the results of the different assessed markers from the Calculation Profile should be entered, in MoMs (Multiples of the Median as per the printed report from the laboratory or the sonographer, which allow the values of these markers to be separated from the gestation length from which they were determined and from other variables like the mother's weight, race, etc.).

TRC can only manage 4 calculations or screening profiles, those outlined at the bottom of the screen (1 for first trimester and 3 for second trimester). Each calculation can be carried out if all the required markers have been selected, such that you will only be able to carry out risk calculations if the markers for a given profile have been chosen correctly. The profile type is automatically selected based on the markers entered before the checkbox is verified.

The checkboxes located directly above the "Compute" button, labeled "NT Value" and "CRL", unlike the other markers that require values to be typed in MoMs, allow NT MoMs to be calculated directly from the NT and the corresponding fetus length, all in millimeters. The last checkbox should be selected and the penultimate one unselected (the NT MoMs checkbox, which, once calculated, will appear to the right of the ultrasound icon indicating the NT MoMs measurement).

Once all the markers and the maternal age at the EDD have been entered for a given profile, you can click the "Calculate" button to send the data to the SBP Soft 2007 server. The server will carry out the calculations, return the results and present them at the bottom of the screen, in graphic and numeric format. 3 parallel bars will appear: the top bar presents the a priori trisomy 21 risk for maternal age at EDD (the bar will be in yellow, its length proportional to the risk); the middle bar presents the trisomy 21 risk calculated from the combination of the maternal age at EDD and the markers from the given profile (this bar will be in green when the risk is below the cut-off level of 1:250, and in red when it exceeds this level, and its length will be proportional to the risk); and finally the bottom bar presents the trisomy 18-13 risk, calculated from the combination of the maternal age at EDD and the markers from the given profile (variations in color and length are the same as for the middle bar). It is important to highlight that all the risks are expressed at term (delivery date), not at screening date as in some computer programs. In the latter case, the trisomy 21 risk estimates are between 29 and 50% higher for the second and first trimester, and the trisomy 18-13 risk estimates are between 75 and 85% higher in the same trimesters.

Negative Risk Example:

Positive Risk Example:

Clicking the "Reset" button clears all values entered by the user and prepares TRC for a new risk calculation.

  Scientific basis of TRC

These days, prenatal screening to evaluate a pregnant woman’s risk of carrying a trisomy-affected fetus is a very important aspect of both the prenatal diagnosis of congenital anomalies and of pregnancy monitoring.

The risk evaluation procedure, or simply risk estimation in a given pregnancy, consists of a sequence of mathematical-statistical methods that are successively applied to obtain a risk index or probability.

TRC calculates the risk using the "likelihood method" published by Palomaki GE and Haddow JE in ‘Maternal serum alpha-fetoprotein, age, and Down syndrome risk’ (Am J Obstet Gynecol 1987;156:460-3). This combines the a priori maternal age risk, obtained from the meta-analysis by Cuckle HS, Wald NJ and Thompson SG published in ‘Estimating a woman's risk of having a pregnancy associated with Down's syndrome using her age and serum alpha-fetoprotein level’ (Br J Obstet Gynaecol 1987;94:387-2), with the likelihood ratio obtained from the combined MoMs from the various markers used in each profile, calculated using the multivariate normal distribution published by Reynolds TM and Penney MD in ‘The mathematical basis of multivariate risk screening: with special reference to screening for Down’s syndrome associated pregnancy’ (Ann Clin Biochem 1990; 27:452-8).

To calculate multivariate normal distribution we use "population parameters", which describe the shape of the Gaussian curve for fetuses affected and not affected by trisomy 21 or 18-13 (mean log 10 and standard deviation), and the correlation coefficient between each pair of markers included in the combination or profile. More specifically, for all second trimester profiles (double, triple and quadruple tests) that calculate trisomy 21 risk, TRC uses the population parameters published in the SURUSS trial (Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L, Mackinson AM in ‘First and second trimester antenatal screening for Down’s syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS)’, in Health Technol Assess 2003;7(II)); and for the first trimester, the profile population parameters outlined in DSQA Tools software (Decision Support Tools for screening QA Version 2.0 from Media Innovations Ltd, a University of Leeds and UK National Screening Committee partnership), belonging to Ellipse 2002 (derived from meta-analyses published by Cuckle 1995, Wald et al 1995, Barkai et al 1993, Nicolaides et al 1998 and Cuckle 2001). For all profiles, in the trisomy 18-13 risk calculations, we have also taken population parameters from Ellipse 2002 for consistency with the trisomy 21 calculations. These population parameters have been chosen as DSQA Tools is a reputable software validation program for trisomy 21 screening in the United Kingdom, and therefore all of the risks calculated by TRC and DSQA Tools coincide exactly.

To calculate CRL (fetus length) and NT (Nuchal Translucency) MoMs, respectively, we have used Robinson HP and Fleming JE charts published in ‘A critical evaluation of sonar crown-rump length measurements (BJOG 1975;82:702-10) and the equation published by K.H. Nicolaides, R.J.M. Snijders and H.S. Cuckle in ‘Correct estimation of parameters for ultrasound nuchal translucency screening’ (Prenat Diagn 1998;18:519-21).

  Intellectual property

All the intellectual property rights for TRC are reserved to SBP Soft 2007 S.L. and to the authors of the software. It is completely prohibited to decompile copies of TRC software or its documentation for any system that has not been authorized by the proprietors of the program or their legally authorized representatives.

  TRC VS SsdwLab 5

TRC (Trisomy Risk Calculator) uses the same calculation engine as SsdwLab 5, which has thoroughly demonstrated reliability and robustness in over 3 years of clinical use in many centers across all five continents.

TRC also incorporates an access interface, which is web compatible with any navigator or current operating system with Adobe Flash installed. Calculations are carried out on an online server when the customer’s navigator requests a calculation and sends the necessary data. Once the calculations have been carried out, the server sends the customer the results if it has been possible to calculate them or, if not, it sends an information message.

This is the modern technology used in the new version, SsdwLab5 Net, which is in the advanced development stages and will operate on the Internet and on local networks. An almost unlimited number of users and centers will be able to work concurrently on a single installation, and tasks from other corporate computer systems will be automated, with total connectivity to external devices like laboratory auto-analyzers, ultrasound machines, etc.

TRC can be considered a reduced demonstration version of the wide range possibilities of SsdwLab5 Net. The vast configuration potential has been limited, as have the new Gaussian and dichotomic markers, the personalization of medians, statistical and quality monitoring, the storing of screening data and perinatal results, and the generation and personalization of printed reports. Most of these features are already available in previous versions of our authorized software for prenatal detection of trisomies and neural tube defects.