Introducing alpha

alpha is the leading interpretive software for use in antenatal screening for Down's syndrome and open neural tube defects (NTDs). It was launched in 1988 , and remains the standard against which most others are compared. It is based on published scientific data, and under the supervision of Professor Nicholas Wald is regularly updated in the light of new scientific advances. Over 10 million women in 49 countries have been screened using alpha.

Countries with alpha installations are shown in blue.

alpha uses a woman's age, the levels of screening markers, and other information about the pregnancy, to estimate the woman's risk of having a pregnancy with Down's syndrome or an NTD. The risk of trisomy 18 (Edward's syndrome) and Smith-Lemli-Optiz syndrome (SLOS) can also be printed, if they are high.

alpha is suitable for

• First trimester screening for Down's syndrome using nuchal translucency and biochemical markers
• Second trimester screening for Down's syndrome and NTDs using biochemical markers
• Integrated screening for Down's syndrome, using first and second trimester markers to provide a single estimate of risk

Screen displays and print

Click on the screens below to see examples of the screens and reports provided by alpha

Data entry screen	Screening report	Graph Monthly Medians	Regression

Choice of screening markers

alpha is supplied ready to use with the serum markers alpha-fetoprotein (AFP), unconjugated oestriol (uE3), human chorionic gonadotrophin (hCG) and inhibin from 14 to 22 weeks' gestation and and hCG, pregnancy associated plasma protein A (PAPP-A), and the ultrasound marker nuchal translucency (NT) in first trimester screening (between 10 and 13 weeks of pregnancy).

For example, with alpha version 7.0, you can

Test interpretation and risk estimation

alpha estimates a woman's risk of having a Down's syndrome pregnancy by determining the age-specific risk of Down's syndrome, and modifying it in the light of the screening marker levels, using a multivariate log-Gaussian model derived from published parameters.

The log-Gaussian model is used to generate a likelihood ratio (LR), which is used to modify the age-specific risk, according to the levels of the different screening markers, as follows:-

Test specific risk (as an odds ratio) = LR x Age specific risk (as an odds ratio)

The marker levels are expressed as multiples of the normal median (MoM values), thereby allowing for changes in the normal median with gestational age, and for systematic differences between laboratories and between assay reagents.

The MoM values may be adjusted to allow for other factors which affect the normal median value, such as maternal weight, ethnic group, insulin-dependent diabetes, and multiple pregnancy.

By using MoM values in this way, alpha is independent of the assay reagents used. The software is designed to allow you to monitor the normal medians, and to change them if necessary; for example, to correct for drift in the normal medians, or if you decide to change the assay reagents used.

The methodology has been validated empirically. Studies have found that the risk of Down's syndrome predicted by alpha is in close agreement with the observed risk. Our alphaOutcome page has more information on validating risk estimates produced by alpha.

Monitoring screening performance

alpha provides a range of valuable monitoring features to help you achieve the best screening performance.

For example, with alpha you can :-

• identify and correct any drift in the normal median values of the screening markers
• obtain estimates of the expected screening performance given the age distribution of your population; you can then compare this with the screening performance observed in practice
• obtain an estimate of the expected number of Down's syndrome term births in the screened population, in the absence of screening and therapeutic abortion; this can be compared with the total number of Down's syndrome pregnancies identified

Our Questions & Answers page has more information on monitoring screening performance using alpha.

alphaOutcome

alphaOutcome allows you to specify the outcomes of all pregnancies screened, and to record details of the presence or absence of birth defects. It provides a range of audit facilities which are useful in monitoring screening performance. For example, with alphaOutcome you can:-

• produce summaries of pregnancies with specified abnormalities, according to the screening result
• print a list of screened pregnancies whose outcomes are not yet known, according to the date of screening or the expected date of delivery
• examine the uptake of different prenatal diagnostic procedures, according to the screening result
• compare the observed risk of Down's syndrome (determined after the outcome of pregnancy is known) with the risk predicted by alpha

For more information on alphaOutcome, click here.

Upgrades

It is our policy to keep up-to-date in the light of technical and medical advances in screening. These upgrades are provided as part of the standard license fee, without extra charge, so that users should always have the benefit of being able to use new screening methods.

For more information on the latest version of alpha, click here.

Multi-user version

alpha is available in a basic single-user configuration, or with multi-user access. Benefits of multi-user access include:-

• increased throughput - several users can enter data simultaneously at different workstations
• greater convenience - reports can be viewed or printed from any location on the network
• Multi-user access is available for a small increase in the license fee. Please contact us if you are interested in multi-user access for alpha.

Main features of αlpha

Reporting

• Provides estimates of risk for Down’s syndrome between 10 and 22 weeks and neural tube defects (NTD) between 15 and 22 weeks

• αlpha version 7.0 uses statistical parameters (means, standard deviations and correlation coefficients of the screening markers) in estimating a woman’s risk of having a pregnancy affected with Down’s syndrome from the Serum, Urine and Ultrasound Screening Study (SURUSS)

• Allows user to specify separate screening cut-off levels for different screening tests

• Allows for maternal age, gestational age, ultrasound measurements, ethnic group, maternal weight, past history of NTD and Down’s syndrome.  Normal medians for the screening markers are derived from local data

• Allows for differences in marker levels and maternal weight in up to five ethnic groups, either using separate medians and weight adjustment curves or correction factors

• Includes information on the presence or absence of fetal nasal bone in the interpretation for Down’s syndrome.

• Provides appropriate interpretations in twin pregnancies and diabetic pregnancies.  The  interpretation of screening tests for  twin pregnancies can use ultrasound markers (nuchal translucency or nasal bone).

• Interprets integrated test results - the safest and most effective screening test for Down’s syndrome

• A woman who has a false-positive screening result in one pregnancy is much more likely to have one in a subsequent pregnancy than women in general.  αlpha version 7.0 by adjusting serum markers in women who have been screened in a previous pregnancy and who have not had a previous pregnancy with Down’s syndrome

• Repeat testing is best avoided, but if done, it requires an interpretation which takes into account the previous result; only αlpha  does this

• Stores patient information in a database which can be accessed to retrieve previous test results

• Calculates gestational age from head circumference measurements

• Laboratory's name and address can be printed on the report preserving their own style and format avoiding the need to use special stationery.

Monitoring

• αlpha provides what is probably the widest range of monitoring features including a facility to examine drift in the normal median values of the screening markers and set them to ensure that the expected screening performance is achieved

• One of αlpha’s unique features is the facility to estimate expected screening performance in terms of detection rate and false positive rate, based on the age distribution of the user’s own screened population. This can be compared with the observed performance to monitor the screening programme

• αlpha can be used to determine the expected screening performance for any combination of screening markers. This is customized for the exact age distribution of women in the screening programme concerned. It can also be used to examine screening performance in different age groups.

• αlpha users can benefit from our free αlphaCheck™ service. We will, at regular intervals, guide you through the steps involved in monitoring screening performance, and provide expert advice in correcting any problems identified. αlphaCheck will help to ensure that the women you screen receive a service of the highest quality

• αlpha Outcome™ is available as a separate programme, which allows users to record details of the presence or absence of birth defects for monitoring performance. αlpha  Outcome provides a range of audit facilities

• For centres offering more than one type of screening test, separate statistical summaries can be produced for first trimester, second trimester and integrated screening results

• αlpha Outcome provides an empirical validation of the screening method, by tabulating the observed prevalence of Down’s syndrome according to the risk predicted by αlpha

• αlpha automatically creates audit trails of patient reports, changes to statistical information controlling the interpretation of screening and diagnostic results (e.g. median equations), and changes in screening policy (e.g. cut-off levels)

• Separate median equations for gestational age estimated by dates and by scan, if desired

• Calculates gestational age from various fetal measurements

• Facility for identifying pregnancies with a high risk of trisomy 18 and printing the risk, either at term or mid-trimester, using the same methodology used in Down’s syndrome risk interpretation

• Custom-designed report layouts are available on request

• αlpha  adjusts serum marker levels in IVF pregnancies to correct the otherwise high false positive rate

• Allows screening for Down’s syndrome in the first trimester using serum markers and nuchal translucency, either alone or in combination

• Nuchal translucency measurements adjusted for crown rump length (CRL)

• αlpha  offers the option of sonographer specific nuchal translucency medians to allow for systematic differences between measurements made by different sonographers. This simple measure provides a useful improvement in screening performance

• Option to identify pregnancies at high risk of Smith-Lemli-Opitz Syndrome (SLOS)