Principles of screening
Patients and doctors alike are used to associating an investigation with the confirmation or exclusion of a diagnosis. It is not surprising, therefore, to find that an enormous amount of anxiety can be created by the use of screening tests, particularly in pregnancy, where so much is at stake. Screening tests simply select populations into low and high risk groups, for the purpose of planning the next level of care for a particular issue or diagnosis. They can be useful in a variety of situations in pregnancy. It is essential that the patient understands the nature of a screening test before agreeing to the investigation, so that true informed consent is obtained, to minimise the anxiety of a false positive result, and appreciate the possibility of a false negative result. The situation is made more confusing by the fact that many diagnostic tests applied to the whole population are described as ‘screening’, using the lay, rather than scientific meaning of the word.
Screening for Down’s syndrome
Our genes determine who we are, and our genes are stored in chromosomes (46 in 23 pairs). Occasionally during reproduction an extra chromosome is added, making one pair of chromosomes into a triple (trisomy). Down’s syndrome is where there are three of the 21st pair of chromosomes (Trisomy 21). There are lots of errors made in the reproduction process, but trisomy 21 remains the most common chromosome anomaly found after the first trimester, when the majority of these problems are dealt with by miscarriage (see Early pregnancy and Threatened miscarriage). A chromosomal abnormality can only be diagnosed with an invasive procedure (amniocentesis, chorion villus sampling, cordocentesis), which carry a 1% risk of miscarriage. Naturally, many women do not wish to take this risk unless they believe the risk of finding a chromosomal abnormality is high.
Screening tests, such as nuchal translucency measurement or placental hormone assay, or both, refine the calculation of risk. With this information the woman, usually in discussion with her partner, can decide if they are happy to live with risk of trisomy 21, or take the risk of an invasive procedure. There is no right and wrong answer to this dilemma. Every woman/couple have to weigh up the risks and decide for themselves.
The woman who has had four miscarriages and is 41 years of age will be much more reluctant to consider an invasive procedure, when compared to the mother who already has an affected child.
Diagnosis of abnormalities
ith the introduction of real time ultrasound it is possible to diagnose many physical abnormalities that occasionally affect a fetus. Some of these problems are not serious, some will require surgery or medical treatment, which can be planned, and a small number will be more serious, leading to major handicap or death. We traditionally rely on ultrasound at around twenty weeks to check for abnormalities, but improved technology means that we can now diagnose many problems as early as the 12 week scan.
Diagnosis of genetic disorders
It is difficult to check for gene defects unless you know precisely where the gene is. Although we have mapped the human genome, we still do not know the location of many of the more rare genetic disorders, which often happen as one off problems in a pregnancy.
More common geneteic disorders, where there is a family history and precise knowledge of the gene site, can be tested for.
The common gene defects looked for in Europe include:
- Tay-Sachs disease (Ashkenazi Jews)
- Sickle Cell Disease (African- Caribbean)
- Thallassaemia (Mediterranean and middle east)
There are other common gene defects throughout the world, reflecting the local population.
Fetal hydrops and anaemia
Since the introduction of ultrasound into clinical practice by Ian Donald in Glasgow in 1960, it has rapidly acquired an important place in maternity care, but this has not been without certain drawbacks and limitations due to its operator dependent nature. It has however, an established place in antenatal care in a number of areas. It is important in accurate pregnancy dating required for the purposes of monitoring fetal growth through pregnancy.
In the first trimester, ultrasound can be used to confirm the presence of an intra-uterine pregnancy, and determine its viability.
The crown rump length measurement is used in dating until about 14 weeks, after which the biparietal diameter, head and abdominal circumferences, and femur length are used. Many of the major structural abnormalities can now be diagnosed at this stage in pregnancy. If the pregnancy is multiple, the number and chorionicity can be noted. Between 10 and 14 weeks, the fluid at the back of the neck of the fetus can measured (nuchal translucency). This is a useful screening test for predicting the likely risk of the fetus being affected by a chromosomal anomaly. If this test is unavailable, reliable dating by ultrasound is essential for biochemical screening for chromosomal abnormality, as the hormone levels vary with gestational age.
The second trimester ultrasound scan is usually done between 18 and 22 weeks gestation. This involves a search for morphological abnormalities, including anomalies associated with chromosomal disorders (markers), and an assessment of fetal growth. Doppler ultrasound of the uterine arteries is performed between 20 and 24 weeks gestation. Abnormal uterine artery Doppler waveform patterns are predictive of uteroplacental complications that may occur later in the pregnancy.
In the third trimester, or when the fetus becomes potentially viable, ultrasound can be use to monitor growth, or help in the diagnosis of fetal growth restriction. In addition to the growth of the fetus, ultrasound allows us to investigate its environment in utero, and determine the ability of the fetus to cope with adverse situations. Biophysical assessment, including liquor estimation and assessment of body and breathing movement, fetal heart rate analysis, and umbilical artery Doppler are accepted tests of wellbeing, performed throughout the world. Doppler assessment of the fetal circulation provides more specific information regarding the fetal condition in-utero, but is not routinely available.
The safety of ultrasound examinations during pregnancy has naturally been questioned. The consensus of opinion is that no detrimental effects of ultrasound use have been reported during pregnancy. At the levels of power and intensity currently used, there are numerous benefits derived but no known complications.
Diagnostic invasive procedures
A small needle is inserted, under ultrasound guidance, into the amniotic fluid that surrounds the fetus. Some cells from the fetus are in the fluid. These are then either amplified (with a technique known as PCR) and/or cultured, so that the chromosomes in the cells can be looked at. As with all invasive procedures there is approximately 1% risk of miscarriage.
Chorionic villi sampling (CVS)
A small needle is inserted, under ultrasound guidance, into the placenta. The cells in the placenta have the same genes and chromosomes as the fetus. These are then either amplified (with a technique known as PCR) and/or cultured, so that the chromosomes in the cells can be looked at. There are more cells obtained with CVS, compared to amniocentesis, so this technique is usually preferred when looking for genetic anomalies. As with all invasive procedures there is approximately 1% risk of miscarriage.
Cordocentesis (Fetal blood sampling)
A small needle is inserted, under ultrasound guidance, into the umbilical cord of the fetus. The fetal blood cells can then be either amplified (with a technique known as PCR) and/or cultured, so that the chromosomes in the cells can be looked at. There is approximately 1% – 5% risk of miscarriage, depending on the indication for the fetal blood sampling.