DOWN'S SYNDROME SCREENING

by D E Tucker MRCOG

Down's syndrome (DS) is the commonest single cause of mental handicap in children of school age. It is caused by a change in one of the genes in the egg before it is fertilised by the sperm (at the time of conception). This is usually a completely random happening, though it is more common in older mothers. Throughout the world, the frequency of DS is about 3 per 2000 births.

Amniocentesis

Down's syndrome can be diagnosed early in pregnancy (at about 15-16 weeks) by amniocentesis. This involves a very fine needle being passed into the womb, under guidance by ultrasound, and sampling of the (amniotic) fluid around the baby. It is done under local anaesthetic, and most women don't find it too uncomfortable. There is a risk, however, of about 1 in 100 to 200 of a spontaneous miscarriage after the procedure.

Because of this miscarriage rate, amniocentesis is only offered to women deemed to be at high risk of having a baby with Down's syndrome. Similarly, it must be something that you have thought about at length, discussed with your partner and feel that you would opt for a termination of the pregnancy, were you found to be carrying a baby with DS. Clearly, if this is not something you would consider, then you most likely would not wish to risk miscarriage, just to know. It is also important to remember than people with Down's Syndrome can have long, fulfilling lives and are very loving individuals. There are a lot worse things that can happen.

Who is high risk then?

Until recently, the only factor used to identify women at high risk for DS was their age. At age 40, for example, the chance of having a baby with DS is about 1 in 100. This has led to many hospitals offering amniocentesis to women over a certain age, usually 35 or 37. The problem with this is that it only will identify 15-30% of all cases of DS; the majority still occur in women who are younger (because there are more of them having babies, even though, individually their risk is less).

The Down's test

This is known as either the Triple test or Double test depending on which hormones are used as the test. These are AFP & hCG, with or without oestriol. Blood is taken at about 16 weeks gestation, and a risk value is calculated, individualised to yourself. Other factors taken into consideration are maternal age, weight and exact gestation.

The result of the Down's test is expressed either in terms of a risk assessment (eg 1 in 300) or as positive/negative. The latter is the hospital or laboratory's interpretation of the former. A result of 1 in 300 means that about 299 people with this result will not have a Down's baby, and only one will do. As you can see, it is NOT a test for the presence of a DS baby, but a way of comparing your chance of having one to the risk for age alone. So, a 40 year old woman would be very reassured by a result of 1 in 10,000 and a 20 year old woman may opt for amniocentesis if her result was 1 in 50.

Some laboratories don't give a result like this, but have a predetermined cut-off at which the test is considered postitive. A positive test signifies that amniocentesis is recommended. Most use the cut-off of 1 in 250 as being positive (ie a risk assessment of 1 in 251 would be negative and 1 in 249 would be a positive result).

The figure of 1 in 250 is close to the spontaneous miscarriage rate for amniocentesis. A couple might not consider the risk of miscarriage worthwhile if it is significantly greater than the chance of there actually being a DS diagnosed. Also, this rate of 1 in 250 is the most cost-effective level to use for the screening test. In the UK, use of this level gives a cost-per-case-detected of around 50,000 UK pounds.

Clearly if we perform amniocentesis at a lower risk level, we can detect more of the DS fetuses prenatally. Recall that using an age cut-off of 37y will detect about 30% of cases of DS in a population. Below are the detection and false-positive rates of DS screening at different risk cut-offs:

The false positive rate above relates to the total percentage of the population who are advised to have amniocentesis (positive test at the relevant level) but who do not have a DS baby. The detection rate shows how many women in the population will still have a DS baby in spite of their screen being 'negative'. So, for example, at a cut-off rate of 1 in 250, 5.2% of women will have an unneccessary (normal) amniocentesis, and we will still miss 42% of DS cases.

As you can see this is a pretty imperfect test, but it is the best we have at the moment. Many women do not wish to accept the test, as it is presently, and consider the worry & inherent risk of miscarriage in amniocentesis not worthwhile. Others, however, accept its limitations and feel that they could not deal with giving birth to a Down's syndrome child. Many just have the test done as part of the routine bloods without thinking about it - don't be one of those, it may lead to some difficult choices later!