The Combined Test

Antenatal Screening

Antenatal Screening for Down's syndrome, Edwards syndrome and Patau syndrome

The Combined Test

Questions and Answers for women considering the test

The Wolfson Institute of Preventive Medicine Barts and The London School of Medicine and Dentistry Antenatal Screening

This leaflet answers some of the common questions women ask about their screening test – we hope you find it helpful. You are welcome to discuss the test with your midwife or consultant before you decide whether you would like to be screened. If you have any further questions screening staff at the Wolfson Institute are available to talk to you on 020 7882 6293.

What is Down's syndrome? What are Edwards and Patau syndrome? Down's syndrome (trisomy 21) is Edwards syndrome (trisomy 18) is defined by the presence of an extra defined by the presence of an extra chromosome number 21 in the cells chromosome number 18 in the cells of the fetus or affected individual. In of the fetus or affected individual an unscreened population about 1 in while Patau syndrome (trisomy 13) every 500 babies is born with Down's is defined by an extra chromosome syndrome. Usually it is not inherited number 13 in the cells of the fetus or and so a baby can be affected affected individual. Both syndromes even if there is no history of Down's affect multiple organs with a high risk syndrome in the family. of fetal death. Down's syndrome is the most At 12 weeks of pregnancy Edwards common cause of severe learning syndrome has a prevalence of about disability and is often associated 1 in 1,500 and Patau syndrome has a with physical problems such as heart prevalence of about 1 in 3,500 in an defects and difficulties with sight and unscreened population. hearing. It is not possible to assess the degree of disability before the Babies born with either condition, on baby is born. About 9 out of 10 babies average, live for around two weeks with Down's syndrome will survive with only 1 in 12 surviving for one their first year and nearly half of these year or more. Babies born with will reach 60 years of age. Edwards or Patau syndrome typically have severe structural defects (including defects of the heart, kidney, brain, skeleton and face) as well as severe learning disability.

2 What is the screening test procedure? When will the screening result be available? If you have the test one blood sample will be taken in the 11th, 12th or 13th For most women the result of the test week of pregnancy. is usually ready within 3 days of the sample being taken. Results are sent The Combined test involves: to your antenatal clinic and a letter is i) performing an ultrasound sent to you to let you know that the scan examination to precisely result is ready. determine the gestational age of Your screening result is either screen- the pregnancy and to measure positive or screen-negative. the nuchal translucency (NT) thickness (a space at the back of the baby’s neck). What does a screen-positive result ii) taking a sample of your blood mean? to measure the concentration of A screen-positive result means that pregnancy associated plasma you are in a high risk group (equal to protein-A (PAPP-A) and free ß or greater than 1 in 150) for having human chorionic gonadotrophin a baby with Down's, Edwards or (free ß-hCG). Patau syndrome. If you are in this In pregnancies with Down's group, you will be offered a diagnostic syndrome, the PAPP-A level tends to chorionic villus sampling (CVS) or be low and NT measurement and the possibly an amniocentesis (see page free ß-hCG level tend to be raised. 5). Most women with screen-positive results will not have a pregnancy with In pregnancies with Edwards or Patau Down's, Edwards or Patau syndrome. syndrome the NT measurement tends to be raised while the PAPP-A and free ß-hCG levels tend to be low. What does a screen-negative result mean? What is a ‘risk’? If the risk of Down's, Edwards and A risk is the chance of an event Patau syndrome is lower than 1 in occurring. For example, a risk of 150 then the result is called screen- Down's syndrome of 1 in 100 means negative. that if 100 women have this risk, we expect that 1 of these women will Although a screen-negative result have a baby with Down's syndrome indicates that your risk of having a and that 99 will not. This is the same baby with Down's, Edwards or Patau as a 1% chance that the baby has syndrome is low it cannot rule out the Down's syndrome and a 99% chance possibility of a pregnancy with these that the baby does not. disorders (false-negative result). 3 Antenatal Screening

Does the Combined test detect all What happens if the ultrasound pregnancies with Down's, Edwards scan shows that I am too late for or Patau syndrome? the Combined test? About 4 out of 5 cases of Down's The Combined test would not syndrome are detected (screen- be carried out but you could still positive). This means that 1 out of 5 be offered screening using the pregnancies with Down's syndrome is Quadruple test. This involves missed (screen-negative). collecting a blood sample at around 15 weeks of pregnancy and About 4 out of 5 cases of Edwards measuring the concentrations of four and Patau syndrome are detected. screening markers and using this About 1 out of 5 cases is missed. information to estimate your risk of having an affected pregnancy. Is my age taken into account?

Yes, any woman may have a baby with Down's, Edwards or Patau syndrome but the chance of this happening increases as a woman gets older and so we use age as one of the factors when working out your risk of having a pregnancy with any of these disorders.

4 What are the diagnostic tests? Amniocentesis An amniocentesis is a widely If your Combined test result is used procedure. It is performed at screen-positive, you will be offered a about 16 weeks of pregnancy and diagnostic test, usually a chorionic involves collecting a small sample of villus sampling (CVS) or possibly an amniotic ﬂuid from around the baby amniocentesis. by inserting a needle through the The diagnostic test will determine abdominal wall. This ﬂuid contains whether or not the pregnancy cells from the baby. As with CVS, is actually affected with Down's QF-PCR is used to provide a rapid syndrome, Edwards syndrome or diagnosis for Down's, Edwards and Patau syndrome. Patau syndrome usually within 48 hours of the amniocentesis being performed.

Chorionic Villus Sampling (CVS) Will these diagnostic tests CVS involves taking a sample guarantee that my baby is free of of placental tissue, by inserting all birth defects? a needle through the abdominal wall or a fine instrument through No test can guarantee that your the cervix. Down's, Edwards and baby will be free of all birth defects Patau syndrome are diagnosed but if the result of the CVS or using a technique called quantitative amniocentesis is negative it will ﬂuorescence polymerase chain almost certainly rule out Down's, reaction (QF-PCR) which provides Edwards and Patau syndrome. a rapid diagnosis usually within 48 hours. There is a small chance (about 1 in 100) that the CVS will Is it safe to have a CVS or an not provide a conclusive diagnosis. amniocentesis? If this happens you will be offered an CVS and amniocentesis have been amniocentesis in order to provide a offered for many years but the definitive diagnosis. procedure is not without risk. It is estimated that about 1 in 100 women will have a miscarriage as a result of the procedure.

5 Antenatal Screening

If the diagnostic test is negative What happens if my baby and I do not have an affected does have Down's, Edwards or pregnancy how could I have had a Patau syndrome? screen-positive result? If your baby does have one of Most women with Combined test these abnormalities you will be screen-positive results will not have offered counselling to discuss the an affected pregnancy. Although implications and your options. If the screening test offered here you decide to continue with the discriminates well between women pregnancy you could discuss the with affected and unaffected support that is available with your pregnancies it cannot do so perfectly. consultant or midwife. If you decide Your screening result is based on to have a termination of pregnancy your age, the NT measurement and your consultant or midwife can make the free ß-hCG and PAPP-A values. arrangements for this. The three markers naturally vary between women and therefore there is usually no apparent reason for women having either high or low levels and so most women with screen-positive results will not have an affected pregnancy. A screen- positive result only indicates who is in a higher risk group so that we know who should be offered a diagnostic test.

OTHER USEFUL ORGANISATIONS Down's Syndrome Association www.Downs-syndrome.org.uk ...... 0333 1212 300 [email protected]

Antenatal Results and Choices (ARC) www.arc-uk.org ...... 0845 077 2290 [email protected]

Support Organisation For Trisomy 18/13(SOFT) UK www.soft.org.uk ...... 0121 351 3122 [email protected]

7 Antenatal Screening

For further information, please contact: Antenatal Screening Wolfson Institute of Preventive Medicine Barts and The London School of Medicine and Dentistry Queen Mary, University of London Charterhouse Square London EC1M 6BQ Telephone: 020 7882 6293/4 e-mail: [email protected] or find us at: www.wolfson.qmul.ac.uk/service-1/antenatal-screening

The Wolfson Institute of Preventive Medicine has played a leading role in the discovery, development and implementation of antenatal screening methods. It is committed to improving the efficacy and safety of screening. We use information collected as part of our screening programme, including measurements on stored blood samples, to audit our screening programme and ensure that it is meeting our expected quality standards. Such information may also be used to help discover and validate new tests that improve the quality of screening services.