What does the Quadruple test involve?

A sample of your blood is taken at around 15 or 16 weeks of pregnancy (between 14 and 22 weeks is acceptable). The stage of pregnancy is best estimated by an ultrasound dating scan. The concentration of four substances in your blood will be measured.

The four markers are:

alpha-fetoprotein (AFP)

total human chorionic gonadotrophin (hCG)

unconjugated oestriol (uE3 )

inhibin-A (inhibin)

In pregnancies with Down's syndrome, AFP and uE3 levels tend to be low and hCG and inhibin levels tend to be raised.

The level of AFP is also used to determine if there is an increased risk of spina bifida or anencephaly.

Can any other abnormalities be identified?
Yes, the Quadruple test also identifies pregnancies at a high risk of Edward's syndrome (trisomy 18). The risk of Edward's syndrome can be identified using 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 the result will be screen-positive and you will be offered an amniocentesis. If the risk is lower than 1 in 150 the result will be screen-negative and an amniocentesis will not be recommended.

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 an ultrasound examination and amniocentesis.

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

Down's syndrome:
Detection Rate (DR): 80%
80% of women with pregnancies affected with Down's syndrome will receive a screen-positive result. (The remaining 20% of women with pregnancies affected with Down's syndrome will receive a screen-negative result.)
False Positive Rate (FPR): 3.5%
3.5% of women whose pregnancies are not affected with Down's syndrome will receive a screen-positive result. (96.5% 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): 1:15
Among women in the screen-positive group, 1 woman will have a pregnancy with Down's syndrome for every 15 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 73%
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 80	60
25-29	1 in 60	62
30-34	1 in 35	70
35-39	1 in 10	85
40-44	1 in 5	93
45 and over	1 in 3	96
All	1 in 27	80

(mid-trimester estimates of performance)

The Quadruple plus NT Test

The Quadruple plus NT test is an option for women who have had a nuchal translucency (NT) performed but wish to utilise the second trimester serum markers to improve screening performance. The NT measurement is incorporated into the Quadruple test interpretation.

What does the Quadruple plus NT test involve?

A sample of your blood is taken at around 15 or 16 weeks of pregnancy (between 14 and 22 weeks is acceptable). The stage of pregnancy is best estimated by an ultrasound dating scan. The concentration of four substances in your blood will be measured.

The four markers are:

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

The NT from a first trimester ultrasound scan is used with the levels of the four markers to calculate the risk of the pregnancy being affected with Down’s syndrome.

In pregnancies with Down’s syndrome, AFP and uE3 levels tend to be low and hCG, inhibin and NT levels tend to be raised.

The level of AFP is also used to determine if there is an increased risk of spina bifida or anencephaly.

Can any other abnormalities be identified?
Yes, the Quadruple plus NT test also identifies pregnancies at high risk of Edward’s syndrome (trisomy 18).
The risk of Edward’s syndrome can be identified using NT, 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 the result will be screen-positive and you will be offered an amniocentesis. If the risk is lower than 1 in 150 the result will be screen-negative and an amniocentesis will not be recommended.

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 1in 100 or higher you will be offered an ultrasound scan and amniocentesis.

Performance of the Quadruple plus NT test using a 1in 150 at term cut-off

Down’s syndrome:
Detection Rate (DR): 89%
89% of women with pregnancies affected with Down’s syndrome will receive a screen-positive result. (The remaining 11% of women with pregnancies affected with Down’s syndrome will receive a screen-negative result.)
False Positive Rate (FPR): 1.6%
1.6% of women whose pregnancies are not affected with Down’s syndrome will receive a screen-positive result. (98.4% 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): 1:6
Among women in the screen-positive group, 1 woman will have a pregnancy with Down’s syndrome for every 6 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): 0.2%

Arranging a test

The blood sample for the Quadruple 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.

The results of the test will usually be available the day after the 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 Quadruple test is £90. There is no additional cost for incorporating a nuchal translucency measurement in the interpretation for the Quadruple plus NT test.

Information leaflets

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

Questions and Answers
Information for Health Professionals