Screening Tests for Downs Syndrome and Neural Tube Defects

By Julia Young

(Julia is a first year student midwife at Coventry University)

Introduction

This report looks at the widely available screening tests for diagnosing whether a foetus has Downs syndrome or a neural tube defects.  It will explore what the initial tests are and when to have them, what options are available should a problem be detected, the costs and availability of the tests.  The effects on the pregnant women are also discussed.

 Method

Information has been gathered from several sources; books, journals and various Internet sites.

Initial information was gained from The National Childbirth Trust (NCT) book of Pregnancy, Birth & Parenthood with more in depth knowledge from Essential Midwifery and Myles Textbook for Midwives.  No one book about the subject has been found other than Before Birth, which is American based.

 A search of the Internet was made using different search engines and key words.  This revealed direct sites and links.

Findings

The findings in this report are;

a) What Conditions are Screened for?

b) What Methods are used for Screening?

c)      Next Step

d)  Costs and Availability

 e)     Further Developments

a) What Conditions are Screened For?

Neural Tube Defects (NTDs) are when there are problems during the development of the brain and spinal cord.  This form of defect occurs in 1 in 500n pregnancies and can happen in two forms.  Anencephaly is a defect at the top of the head and foetus’ usually miscarry or die within several days of birth, as it is a condition from which sustained life is impossible.   When the defect occurs on the lower back the condition is called Spina Bifida.  When this condition occurs nerves of the spinal cord do not connect properly with those in lower part of the body causing control problems with muscles and organs of the lower body.  Other complications include infections, possible mental retardation or hydrocephalus (increase cerebrospinal fluid with in the skull) (www.aomc.org/, 2001).

 The cause of NTDs is unknown but is predominant in the Britain particularly in Ireland and north-western coast of mainland Britain.  Deprivation of folic acid in the diet is a possible cause suggested by research by The Medical Research Council (1983) (Henderson, C. & Jones, K. 1997).

 Downs syndrome is caused by a chromosomal abnormality where the foetus has an excess number.  Babies are born with a distinct facial appearance and can have other problems including heart abnormalities, digestive problems or mental retardation that can range from mild to acute.  Downs occurs in 1 out of 800 babies born and the chances of having a Downs baby increases with maternal age (www.noah-health.org/. 2001).

b) What Methods are Used for Screening

These conditions can be screened in two ways or more often a combination.  Firstly an ultrasound scan can be performed and this will detect many NTDs in very early pregnancy.  Secondly defects can be found by screening biochemicals in the maternal blood.  This is non invasive unlike the original method of amniocentesis where a needle is inserted through the abdomen using ultrasound to see where the needle is going and then collecting a sample of amniotic fluid for testing.  Blood is taken at 16-18 weeks of pregnancy following an ultrasound dating scan as gestational age can affect results (Tucker, G. et al 1992).  Originally blood was tested for levels of Alpha-feto-protein (AFP) and has been carried out in the United Kingdom since the 1970’s (Bennett,V.R , & Brown, L.K., 1999).  The foetus’ liver produces AFP and some is excreted into the amniotic fluid and then into the maternal blood stream.  If an open tube defect is present then AFP leaks from here into the amniotic fluid and this accounts for high levels present in maternal blood (Nightingale, E. O. & Goodman, M. 1990).   High levels can indicate NTD’s while low levels can indicate the presence of Downs.  In 1 in every 5 cases of spina bifida the spinal opening is covered with skin or thick tissue and unfortunately the blood test cannot detect this form but the condition is usually less severe (www.mds.qmw.ac.uk ,2001).  AFP testing is not 100% accurate but will detect around 85% of fetus’ with open NTD (www.noah-health/org ,2001). 

The 16^th to 18^th week  is optima for testing as the gap between normal and high levels is greatest at this point (Kitzinger, S. 1994).  There are several factors that can affect levels of AFP; gestational age, maternal age, weight and ethnicity (women of Asian origin have a much higher false positive screening of 12.3% versus 3.4% (BMJ 1996)), maternal diabetes, the presence of more than one foetus, family history (www.aomc.org/ .2001) and intrauterine death (Tucker, G. et al  1992).  It is cited by Calvas et al (1990) that levels are higher in boys (Bennett, V.R & Brown L.K., 1999).  Of the tests that are deemed positive 90% of the foetus’ will not have any anomalies (www.pregnancy.minigco.co. 2001).

 As AFP levels are not significant on their own and are compromised by many factors so the triple test was developed.  This is also known as the maternal serum screening tests or Bart’s test due to its development at St Bartholomew’s hospital in London (Tucker, G. et al 1992).  This test looks at AFP levels along with oestriol levels and human chorionic gonadotrophin  (HCG) levels.  Low oestriol and low HCG levels indicate Downs, both have normal levels with regard to indicating NTD’s (www.pregnancy.about.com 2001).

A woman would be assessed as ‘screen negative’ if AFP levels are not too high and risk of Downs is at less than 1 in 250.  If AFP levels are 2 times that of normal and the risk factor is increased then a ‘screen positive’ would be given, 9 out of 10 women will be ‘screen negative’.  Although this test is also not 100% accurate it does detect;

·        2 out 3 cases of Downs

·        nearly all cases of anencephaly

·        4 out 5 cases spina bifida

As with the AFP test timing is important.  The woman should be at least 15 weeks gestation but not more than 22 weeks for accuracy in testing levels of all three substances (Tucker, G. et al 1992).  Confirming gestation age using ultrasound increases the tests efficiency by about 5% and thereby reduces the number of ‘false negative’ or ‘false positive’ results (Bennett, V.B & Brown, L.K. 1999).

c) Next Step

The options open to women with a ‘screen positive’ test result are a detailed scan which is non invasive, an amniocentesis or chrionic villus sampling (CVS), both of which are invasive.  A scan can be done to rule out testing conflicts such as incorrect gestational age,  multiple pregnancy, intrauterine death or look for formation defects.  For Downs the heart, digestive tract, leg length and neck thickness are carefully checked  and for NTD’s the spine and head are checked.  This can also give information with regard to delivery of the baby as it generally considered that a caesarean section if better in cases of spina bifida.  Amniocentesis can check the actual amount of AFP and is 99% accurate at detecting spina bifida.  With ultrasound, although there has been vast improvements in the technology and equipment since it was first used in the late 1950’s (www.ob-ultrasound.net/ 2001), it is only as good as the operator and small defects can be missed.  For a ‘screen positive’ of Downs only an amniocentesis or CVS can give a definite diagnosis or exclusion (www.stanf.edu. 2001).

 Following an affirmed case of an abnormality a woman then has to choose whether to continue the pregnancy or go for a termination.

d) Costs and Availability

According to the BMJ (2000) the costs for tests are as follows:

·        Double test @ £10

·        Triple test @ £11

·        Aminocentesis @ £208

·        CVS @ £249

·        Termination @ £495

(Unfortunately the cost of the single test for AFP has not been listed but this used on its own is now outdated).

The triple test was originally offered routinely to women in the London borough of Hackney and a few centres around the country (Kitzinger, S. 1992).  It is now more widely either solely ( eg. (Ipswich Hospital, Furness General, Perth Royale Infirmary) or as well as the AFP test (eg. Newham General, Colchester General, Dunoon District General).  (www.home.drfoster.co.uk 2001)  For women who wish to have the test but is not available in their area they can have it done privately at a cost of £50 (www.ridgeway-surgery.demon.co.uk 2001).

e)     Further Developments

Following on from the development of the triple test there is the quadruple test.  In this the same three biochemicals are looked at as in the triple but with an added one, inhibin A (BMJ 2001).  There has also been the introduction of Ultrasound Nuchal Thickness Screening which is an alternative to biochemical screening for Downs.  This test is done at 11 to 14 weeks gestation and measures the amount of fluid behind the foetus’ neck.  This information is put into a computer along with maternal age, foetal size and heart rate.  The computer then calculates the risk of there being an abnormality.  The test sensitivity is 85% with a 5% false positive rate, this compares to a biochemical screening result of 55-60% and 5% (www.prenataldiagnosis.co.uk 2001).

There is also an integrated test and the procedure is carried out in two stages.  The first stage should be ideally actioned at 12 weeks gestation but between 10-13 weeks is acceptable.  An ultrasound scan is performed for dating and measuring nuchal translucency, and a blood sample taken and the concentration of pregnancy associated plasma protein A (PAPP-A) is measured.  The second stage is done at 15 to 16 weeks and no later than 22 weeks and consists of the quadruple test.  Results from the two stages are combined to ascertain the risk factors (www.mds.qmw.ac.uk 2002).

Discussion

Pregnancy causes many strains on a woman and her family but the added stress of screening can have long reaching psychological effects.  Screening was introduced but the effect of the procedure was not fully evaluated as cited by Chard & Macintosh (1992) (Robinson, J. 2001).  Reports undertaken by the Royal College of Obstetricians & Gynaecologists and Enkin, M. et al in 1995 pointed out that women and their partners should be given unbiased information with regard to screening and diagnostic tests.  They should have explained what is being looked for, the accuracy and the options available should a positive test  be returned.  Information should be given both orally and visually, with any abnormalities found given in person (www.rcog.org.uk/ 2001).  This enables parties to ask questions of which there will be many including the availability of termination.

 As screening has become a routine event of pregnancy do they cause hidden costs?  The Advisory Committee on Genetic Testing states that women should not have to undergo tests unless they wish to do so (www.nhsatoz.org 2001).  There is need for improving the quality and co-ordination of antenatal screening programme to enable women to make informed choices that they consider are the best for themselves and unborn child (www.nsc.nhs.uk 2001).  The availability of tests can have an impact.  Testing for AFP alone has a detection rate of 20-25% as cited by Cuckle (1984) and when combined with more than one biochemical, detection rate increases to 48-91% for Downs syndrome.  Even the triple test is not 100% guaranteed that having a negative screen test will mean a baby being born free of Downs syndrome.  Recommendations by the UK National Screening Committee are that all pregnant women, regardless of age, should be offered 2^nd trimester serum screening.  The test should be at least the double but for laboratories to undertake performing the triple or quadruple test would be preferable.  The tests should have a cut off risk of 1:250 (www.nsc.nhs.uk/ 2001).  There is a need to for the most effective test to be used.

 For those that ‘screen positive’ they have the anxiety of waiting for the original results then waiting for further tests and then the results of these.  Following an amniocentesis, AFP level results are available within a few days but chromosomal analysis in the case of Downs, the results can take four weeks (Tucker, G. et al 1992).

 The tests that are widely available have not kept up with developments.  In 1998 very few NHS providers (7%) were offering the more effective nuchal translucency measurement and only 3% the quadruple test.  The most effective method is the integrated test (nuchal translucency and PAPP-A in the 1^st trimester and quadruple test in the 2^nd trimester) which is only available privately (BJM, 2001).  When taking into account that a woman with a 1:200 result for AFP is considered high risk and the risk of procedure related miscarriage is 1:100 there is the potential for the loss of a large number of healthy babies (Bennett, V. 2001).  The amount of emotional pain is incalculable therefore the test that is most effective should be the one that is in common use.

Conclusion

Prenatal screening should be standardised and modernised.  The fact that the most effective method –the integrated test- is only available privately is sociably and ethically unacceptable.  As with other areas of healthcare it is a postcode lottery as to what is available.  All women and their foetus’ have a right to a standard of care that is the same for all.  The initial cost of the integrated test is more but as it is the most efficient method what is this against the emotional cost to a woman and her family especially if a child is lost by what may be an unnecessary amniocentesis which in itself is far more expensive in money terms (£208 against £22 for the integrated test (BMJ 2000)).

Along with standardisation all women should be fully informed that the screening tests are for risk assessment and are not diagnostic.  In line with section 1.6 of Changing Childbirth (1994), tests should be clearly defined and have relevance to a woman’s particular circumstances and not forced to take part because they are deemed routine.  Screening is obviously beneficial and can save lives but the hidden costs are beyond calculation.

 © Julia Young 2002 - No part of this text may be reproduced without permission from [email protected]

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