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)
- total human chorionic gonadotrophin (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 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 or higher 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): 1.0%
Edwards' syndrome:
Detection Rate (DR): about 85%
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)
Performance of the Integrated Test using fetal Nasal Bone at a 1 in 150 term cut-off:
In some centres (including the London Ultrasound Centre) the NB is measured along with the nuchal translucency (NT) at the first trimester ultrasound scan. In pregnancies affected by Down’s syndrome the nasal bone tends to be absent.
Down’s syndrome
Detection Rate (DR): 94%
94% of women with pregnancies affected with Down’s syndrome will receive a screen-positive result. (The remaining 6% of women with pregnancies affected by Down’s syndrome will receive a screen-negative result.)
False Positive Rate (FPR): 1.0%
1.0% of women whose pregnancies are not affected with Down’s syndrome will receive a screen-positive result. (99% 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): 1:4
Among women in the screen-positive group, 1 woman will have a pregnancy with Down’s syndrome for every 4 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): 1.0%
Edward’s syndrome
Detection Rate (DR): about 85%
False Positive Rate (FPR): < 0.1%
Arranging an Integrated test
The ultrasound scan and blood sample for the Integrated test are performed at the London Ultrasound Centre. The analysis and interpretation are performed by the Antenatal Screening Service at the Wolfson Institute. For further information please contact the London Ultrasound Centre on 020 7935 4450.
Cost
The cost of the Integrated test at the London Ultrasound Centre is from £225. This includes the first trimester scan to measure the NT and NB and the two blood samples.
Information leaflets
For copies of the information leaflets please click on the links below. The leaflets are available in pdf format.
The Integrated Test
Questions
and Answers
Information
for Health Professionals
The Integrated Test using fetal Nasal Bone (performed at the London Ultrasound Centre)
Question and Answers
Information for Health Professionals
The Serum Integrated Test
The serum integrated test is an option for women who are unable to have a nuchal translucency measurement performed.
What does the serum integrated test involve?
The serum 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, but between 14 and 22 weeks is acceptable.
The first stage involves:
- Taking a sample of your blood to measure the concentration of pregnancy associated plasma protein-A (PAPP-A).
- Providing you with a recommended date for taking a second blood sample for the second stage of the test.
The second stage involves:
- Taking a blood sample to measure the concentration of the following four markers:
- alpha-fetoprotein (AFP)
- total human chorionic gonadotrophin (hCG)
- unconjugated oestriol (uE3)
- inhibin-A (inhibin)
ii)Integrating the measurements from the first and second stages into a single screening result. 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 inhibin and 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.
Can any other abnormalities be identified?
Yes, the Serum Integrated test also identifies pregnancies at a high risk of Edward’s syndrome (trisomy 18).
The risk of Edward’s syndrome can be identified using PAPP-A, AFP, uE3 and 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 or higher 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.
Edward’s syndrome:
If the risk of having a term pregnancy affected with Edward’s syndrome is 1 in 100 or higher you will be offered an ultrasound scan and amniocentesis.
Performance of the Serum Integrated test using a 1 in 150 term cut-off
Down’s syndrome
Detection Rate (DR): 82%
82% of women with pregnancies affected with Down’s syndrome will receive a screen-positive result. (The remaining 18% of women with pregnancies affected by Down’s syndrome will receive a screen-negative result.)
False Positive Rate (FPR): 2.7%
2.7% of women whose pregnancies are not affected with Down’s syndrome will receive a screen-positive result. (97.3% 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): 1:12
Among women in the screen-positive group, 1 woman will have a pregnancy with Down’s syndrome for every 12 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): 1.0%
Edward’s syndrome
Detection Rate (DR): about 75%
False Positive Rate (FPR): < 0.1%
Arranging a Serum Integrated test
The blood samples for the Serum Integrated test can be taken either at the Wolfson Institute of Preventive Medicine, London or by your local midwife or GP. The Antenatal Screening Service provide a sample kit which contains the necessary equipment for taking and transporting the sample. The sample should be returned in the envelope provided using the Royal Mail Special Delivery service. To request a sample kit, make an appointment at the Wolfson Institute, or discuss the test further please contact the Antenatal Screening Service on 020 7882 6293.
Cost
The cost of the Serum Integrated test is £120.
Information leaflets
For copies of the information leaflets please click on the links below. The leaflets are available in pdf format.
The Integrated Test
Question and Answers
Information for Health Professionals
