What does the integrated test involve?

The integrated test is performed in two stages. The first stage is ideally performed at 11 weeks of pregnancy, but any time between 10 and 13 weeks of pregnancy is acceptable. The second stage is ideally performed at 15 or 16 weeks of pregnancy, but between 14 and 22 weeks is acceptable.

The first stage involves:
i) An ultrasound scan examination to precisely determine the gestational age of the pregnancy and to measure the nuchal translucency (NT) thickness, a space at the back of the baby's neck.
ii) Taking a sample of your blood to measure the concentration of pregnancy associated plasma protein-A (PAPP-A).
iii) Providing you with a recommended date for taking a second blood sample for the second stage of the test.

The second stage involves:
i) Taking a blood sample to measure the concentration of the following four markers:

• alpha-fetoprotein (AFP)
• free ß-human chorionic gonadotrophin (free ß-hCG)
• unconjugated oestriol (uE3)
• inhibin-A (inhibin)

ii) Integrating the measurements from the first and second stages into a single screening result. The NT measurement and the levels of the five markers in your blood are used, together with your age, to estimate your risk of a Down's syndrome pregnancy.

In pregnancies with Down's syndrome, PAPP-A, AFP and uE3 levels tend to be low and nuchal translucency measurement, inhibin and free ß-hCG levels tend to be raised.

The level of AFP in the second blood sample is also used to determine if there is an increased risk of spina bifida or anencephaly.

Why wait until the second stage to have a risk estimate?
Because by using information from both stages the test is safer and more effective than a test using information form the first stage alone. It will distinguish affected from unaffected pregnancies more effectively, reducing the chance that a Down's syndrome pregnancy is missed as well as reducing the chance that you will need an invasive diagnostic test, such as amniocentesis or chorionic villus sampling (CVS).

Can any other abnormalities be identified?
Yes, the Integrated test also indentifies pregnancies at a high risk of Edwards' syndrome (trisomy 18). The risk of Edwards' syndrome can be identified using NT, PAPP-A, AFP, uE3 and free ß-hCG.

What is defined as a screen-positive result?
Down's syndrome:
If the risk of having a term pregnancy affected with Down's syndrome is 1 in 150 you will be offered an amniocentesis.

Open neural tube defects:
If the AFP level is two and a half times the average level or higher, the result will be screen-positive and a detailed ultrasound scan will be offered.

Edwards' syndrome:
If the risk of having a term pregnancy affected with Edwards' syndrome is 1 in 100 or higher you will be offered another ultrasound examination and amniocentesis.

Performance of the Integrated test using a 1 in 150 at term cut-off

Down's syndrome:
Detection Rate (DR): 90%
90% of women with pregnancies affected with Down's syndrome will receive a screen-positive result. (The remaining 10% of women with pregnancies affected with Down's syndrome will receive a screen-negative result.)
False Positive Rate (FPR) : 1.3%
1.3% of women whose pregnancies are not affected with Down's syndrome will receive a screen positive result. (98.7% of women whose pregnancies are not affected with Down's syndrome will receive a screen-negative result.)
Odds of being affected given a positive result (OAPR): 1:5
Among women in the screen-positive group, 1 woman will have a pregnancy with Down's syndrome for every 5 who do not.

Open neural tube defects
Detection Rate (DR): 85% for open spina bifida; nearly all cases of anencephaly are detected.
False Positive Rate (FPR): 1%

Edwards' syndrome:
Detection Rate (DR): 60%
False Positive Rate: 0.1%

Age specific performance for Down's syndrome

Maternal age group (years)	Probability of a screen-positive result	Proportion of Down’s syndrome pregnancies detected (%)
Under 25	1 in 100	85
25-29	1 in 90	86
30-34	1 in 50	89
35-39	1 in 20	94
40-44	1 in 8	97
45 and over	1 in 5	98
All	1 in 63	90

(mid-trimester estimates of performance, first stage performed at 11 weeks GA)

Arranging an Integrated test
The first stage of the Integrated test is held at the Wolfson Institute of Preventive Medicine, London. To make an appointment, or discuss the test further, please contact the Antenatal Screening Service on 020 7882 6293.

The blood test for the second stage of the Integrated test can be done either at the Wolfson Institute of Preventive Medicine, or by your local midwife or GP (a kit for the second stage will be provided at the first stage appointment).

The results of the test will usually be available the day after the second blood sample is taken. The results can be obtained by telephoning the Antenatal Screening Service on 020 7882 6293 or by post.

Cost

The cost of the Integrated test is £170. This includes the ultrasound scan, blood samples and interpretation of results. For women who receive a screen-positive result and wish to have an amniocentesis and PCR diagnosis, the cost of these is included in the test fee.

Information leaflets

For copies of the Integrated test information leaflets please click on the links below. The leaflets are available in PDF format.

Questions and Answers
Information for Health Professionals