For many parents, pregnancy is an exciting and happy experience. For others, the experience of friends or family make them apprehensive that their baby may be born with a severe physical or mental disability. In fact, about one in forty babies will suffer from a congenital abnormality (Atkins and Hey, 1991). Abnormalities can range from something now correctable, like a cleft lip, to something severely disabling like congenital heart disease. Recent advances in medicine make it possible to give pregnant women a lot of information about their baby before birth. For the majority of parents- to-be prenatal testing (PNT) provides reassurance; for the minority the test results may indicate a problem with their baby's growth or development.
There are many reasons why a developing baby may have congenital problems (Moore, 1989, p.lO8). Exposure to infections and certain drugs (most commonly, alcohol), chromosomal abnormalities and inherited congenital conditions have all been shown to disrupt normal fetal development. In this article we will concentrate on the diagnosis of chromosomal and genetic disorders during pregnancy.
PNT procedures and their interpretation can be extremely intimidating for parents. It is therefore important that tests are done only after a full explanation of the procedures involved and their possible consequences. The aim of PNT is to inform and prepare parents for the birth of an affected infant, so that they can choose between the possible courses of action (Aksoy, 1996). The possibilities will include: (1) in utero treatment; (2) delivery at a special centre for immediate postnatal treatment; and 3) termination of an affected fetus, i.e. abortion.
Over the years, professional standards and laws have evolved which influence the clinical application of PNT and help to tackle many of the complex ethical issues involved. There is little doubt that relatively non-invasive techniques whose primary purpose is to diagnose treatable disorders and then treat them, before or after birth, would be warmly welcomed by all, especially the parents. The fact is, however, that in practice PNT is generally being used to diagnose abnormality and then terminate the life of the unborn babies. The reality is that prenatal diagnosis rarely leads to fetal therapy
In what follows, we will try to explain the range of prenatal tests available and indications for their appropriate use. We will consider some of the technological advances on the horizon in this field of medicine, as well as some of the ethical dilemmas that arise.
Prenatal diagnostic tests can be divided into two types, invasive and non-invasive. Non-invasive tests simply involve a blood sample taken from the pregnant woman or an ultrasound scan. Invasive tests on the other hand are more complicated and involve obtaining a sample of cells or tissue from the developing foetus, either by amniocentesis or chorionic villus biopsy. The samples obtained by invasive tests can be used, specifically to assess the fetal chromosome pattern, to determine if the fetus has a particular genetic mutation, or for a whole range of biochemical assays.
Maternal Blood Sampling. Between 15 and 19 weeks of pregnancy, the pregnant woman attending ante-natal clinic will be offered a blood test. The blood sample will be analysed to assess the level of three proteins, b human chorionic gonadotropin (b HCG), oestriol and a -fetoprotein (a FR). The three levels in combination with the mother's age can be used to estimate the risk of the baby being affected by a chromosomal problem, especially Down's syndrome (Wald and Cuckle, 1992, pS63). If the test result indicates a high level of risk, the mother will be offered further tests to assess the status of her baby.
Ultrasound Scan. Ultrasound uses high frequency waves to form a picture as the waves are reflected back by tissues of different density. The developing fetus grows in a liquid filled sac (amnion). As fluid shows black on the scan, this provides a good contrast with the fetal parts allowing high resolution images. Early in the first trimester an ultrasound scan can be used assess the viability of a fetus and to estimate its stage of development. Most women will be offered a formal high resolution scan at between 16 and 19 weeks (Sutton, 1990, pp.20- 1). The images from the scan will be the first time the expectant mothers see the baby. For many, this is a happy event; for the others it could be a very sad event if the scan indicates an abnormality.
Amniocentesis. In this test, done between 15 and 20 weeks of pregnancy (Cohen, 1990, pp.19- 20), a very fine needle is passed through the abdomen under ultrasound guidance, avoiding the fetus, and a sample of amniotic fluid containing fetal cells is withdrawn. The sample is cultured to grow more cells so that the chromosome pattern of the cells can be examined or DNA extracted for genetic analysis. This process can take three weeks, a period of considerable anxiety for the parents. There is also a small risk of miscarriage occurring after an amniocentesis.
Chorionic Villus Sampling. In this test, done in the same way as than amniocentesis but five weeks earlier, a sample of tissue is taken from the developing placental tissue. Both chromosomal and genetic analysis can be performed on this tissue, and the results are available quicker and at an earlier stage of the pregnancy than with amniocentesis. However, there is a higher miscarriage rate following chorionic villus sampling than amniocentesis (Boss, 1994).
Fetal Blood Sampling. Occasionally, when there is concern that a pregnant woman has been exposed to an infection early in her pregnancy, a sample of blood will be taken from the umbilical cord with a very fine needle under ultrasound guidance. This sample is used to assess if the fetus has become infected and at high risk of development problems following the maternal exposure.
Advances in prenatal diagnosis have followed rapidly from technological improvements in ultrasound equipment, refinement and experience of current techniques, and the development of new tests. The aim of research in this area is to provide the earliest possible accurate information about the health of the developing baby, and to do so in the way safest for the expectant mothers and their babies. If the information is reassuring, the couple can enjoy the remainder of the pregnancy in the knowledge that everything will progress normally. However, if the result are unfavourable and an abnormality is diagnosed, earlier decisions about potential treatment or termination are possible and so may be less traumatic for those involved.
Fluorescent in situ Hybridisation (FISH). FISH is a technique which uses a specific DNA sequence as a probe to recognise its complementary sequence on a chromosome. The probe has a fluorescent tag attached which lights up when it is attached to the recognised chromosome segment. Recently FISH has been applied to analysis of amniocentesis samples to assess if an extra chromosome 21 is present or not in the cells. Because the amniocentesis cells do not require culturing for this technique the test results can potentially be available sooner than following standard amniocentesis.
Fetal Blood Cells in the Maternal Circulation. At about 6 weeks fetal blood cells can be found in a blood sample taken from a pregnant woman. These cells exists in very small numbers. Recent work has extracted and purified these cells to allow assessment of the fetal chromosome pattern and to determine if the fetus has a specific genetic mutation. Although this technique is very new it has the potential to make the currently used invasive techniques obsolete and will allow very early diagnosis.
Preimplantation Diagnosis. This procedure involves the use of technology developed with in vitro fertilisation (IVF). An oocyte is removed from the woman and brought into contact with spermatozoa from her partner under controlled conditions. One of the spermatozoa effects fertilisation to form a zygote. Following three stages of cell division (this eight-cell stage is termed, the blastocyst), one cell can be removed and used for analysis (Aksoy, 1997a). The DNA sequence of this cell can be determined to identify the presence or absence of a gene mutation that has caused illness in one of the parents. If the cell does not contain the mutation, the blastocyst can be implanted in the womans uterus (womb) to develop into a fetus which is unaffected by the condition that has affected other family members.
Human Genome Project. The aim of the Human Genome Project is to have identified the entire human DNA sequence (genome) by 2005. The extra information generated about specific genes and their association with specific disorders has the potential to expand dramatically the number of genetic tests available to couples with a family history of a genetic condition.
It is important to understand the purpose of prenatal diagnosis. It is done to provide parents with information about the health and development of their baby, not to provide them with a reason to have a termination of pregnancy. There are 180,000 terminations performed each year in the United Kingdom, of these 5000 are because of fetal abnormalities diagnosed by prenatal tests. Abortion is a serious problem itself in all regions of the world, developed and developing, and we discussed it in an earlier issue of this magazine (Aksoy 1997b). When prenatal tests reveal that a baby has health problems, parents face a number of difficult questions. Is any treatment available? What are the baby's chances of survival? What would be the baby's quality of life if he or she did survive? Some illnesses can be treated during pregnancy and after delivery. One of the main aims of fetal medicine is to develop therapies to treat fetuses and improve the survival. However, some conditions are fatal despite all treatment. In these circumstances couples sometimes take the extremely difficult decision to have a termination of pregnancy
For religious, moral or other reasons many couples opt not to have any tests performed during pregnancy. They feel that even if the results of any test indicated that their baby was affected by a serious condition they should and would continue with the pregnancy. It is important in each situation that the parents' decisions are respected and supported. The parents need to be given appropriate guidance and counselling rather than be met with disapproval.
In some countries prenatal testing has been extensively used to determine the sex of the baby at an early stage, with the intention of ensuring that only male babies are born (Kusum, 1993). In the United Kingdom, as in many other places, prenatal diagnosis to determine fetal sex is deemed morally unacceptable. It is important that new advances in medicine are paralleled by an informed ethical debate. Prenatal tests should reflect what is appropriate within a society rather than just allowing what is technically feasible. A number of regulatory groups have been formed, including the Human Fertilisation and Embryology Authority (HFEA), to monitor and regulate new advances in this area.
In sum: prenatal diagnosis is a rapidly expanding area of medicine. New techniques are constantly being developed which are aimed at allowing earlier diagnosis, less invasive methods and, ultimately, treatment. It is important that developments are monitored and regulated to ensure that the techniques available are applied within an ethical framework.
Aksoy, S. (1996) 'Prenatal Testing: An Ethical Perspective', The New Journal of Medicine, 13:2, pp.12-14.
Aksoy, S. (1997) 'Moral Controversies on Preimplantation Genetic Testing', paper presented at UNESCO Asian Bioetlncs Conference, Kobc-Japan, November 1997.
Aksoy, S. (1997), 'Abortion: Mercy or Murder?', The Fountain, 2:17 pp.32-5.
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