1. Medical Genetics 17 出生缺陷 Birth Defects

2. Medical Genetics Birth defects are defined as abnormalities of structure, function, or body metabolism that are present at birth.

3. Medical Genetics 1. General One of the most common worries for expectant parents is that something will be wrong with their baby.

4. Medical Genetics However, most babies are born without problems, while most of those who are can have treatment that will make them much better, or even allow them to lead a normal life.

5. Medical Genetics Understanding the nature and causes of birth defects can help reduce the mystery, fear and guilt often associated with them.

6. Medical Genetics An international monitoring programme shows that, across Europe, just over 2 per cent of babies are discovered at birth to have a defect that will affect their ability to survive or function normally.

7. Medical Genetics Some defects are often not discovered until later (eg deafness and problems in walking).

8. Medical Genetics There is considerable regional variation in the rate of defects seen at birth. Glasgow and Dublin have traditionally been black spots, with rates over 3 per cent, but these figures are falling.

9. Medical Genetics The number of babies actually born with defects is also markedly affected by the availability of prenatal screening, and the availability of voluntary termination of pregnancy in the case of severe abnormalities.

10. Medical Genetics 2. Forms of Birth Defects Defects of limbs, heart and spinal cord represent about half of all abnormalities.

11. Medical Genetics The most common kinds of defect are those affecting the limbs (arms and legs). These include missing or extra fingers or toes, deficiencies in limb length, and abnormalities in positioning, such as club foot.

12. Medical Genetics Heart abnormalities represent the next most common category of defect. Common heart defects include 'holes in the heart' where blood can pass from one side of the heart to the other. Again, these may not all be detected at birth.

13. Medical Genetics The third most common kind of defect affects the spinal cord, such as spina bifida.

14. Medical Genetics Other defects commonly observed include those affecting the face (such as cleft lip and palate), problems with the development of the intestines and stomach, and problems affecting the sexual organs.

15. Medical Genetics Major chromosomal problems such as Down's syndrome (Trisomy 21) are found in about 0.15 per cent of births (about three babies in every 2000).

16. Medical Genetics 3.The cause of birth defects A. Genetics Genetics play a role in some birth defects. One missing or faulty gene can cause a birth defect.

17. Medical Genetics In ancient times, abnormalities were seen as warnings or punishments from the gods. Even quite recently, it was believed that specific events during the pregnancy - such as being frightened by a mouse - would lead to specific defects in the baby, eg a mouse shaped birth mark. Such folk beliefs still persist in places.

18. Medical Genetics However, most defects that can be traced to a single cause have a genetic origin. This does not necessarily mean that the parents suffer from the same defect.

19. Medical Genetics It may be that they are carriers of the condition, or that the genetic problem occurred for the first time in the cells that gave rise to the baby. Known genetic causes account for about 25 per cent of all abnormalities.

20. Medical Genetics B. Environment Environmental causes (including exposure to drugs, radiation and illnesses) can be identified in about 10 per cent of birth defects. The risk of exposure to such environmental factors often causes great concern, although genetic causes are more common.

21. Medical Genetics There are three main kinds of factor that can cause defects: chemical, biological and physical.

22. Medical Genetics Chemical factors, including drugs Thalidomide is perhaps the most notorious example of a drug that caused defects. It was brought on to the market after inadequate testing and specifically prescribed for pregnant women.

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24. Following this, much stricter rules about drug testing were introduced, and international monitoring programmes were put in place. Doctors are also much more cautious about prescribing drugs to women of child-bearing age, so it is unlikely that a disaster on this scale will occur again in the UK.

25. Medical Genetics Several medical treatments pose the risk of birth abnormalities. Tetracycline antibiotics affect hard tissue formation during the foetal period, affecting the long bones and teeth. Some anticonvulsant medicines used for epilepsy may also cause problems. Anyone on long-term medication who is planning to become pregnant, or who has become pregnant, should discuss their situation with their doctor.

26. Medical Genetics Moderate alcohol use in pregnancy is a particularly tricky problem.

27. Medical Genetics Smoking is bad for the development of the baby in a number of ways. Pregnant women should not smoke under any circumstances.

28. Medical Genetics Lack of something may be as damaging as the presence of something. Extensive trials have confirmed that taking folic acid before pregnancy can reduce the number of spinal cord defects such as spina bifida.

29. Medical Genetics Biological factors, including illnesses The rubella virus, which causes German measles, poses a serious hazard to the developing baby. It can cross the placenta and attack the baby to cause a range of defects. The proportion of mothers infected with the rubella virus during the first 12 weeks of pregnancy who have an abnormal child can reach 20 per cent.

30. Medical Genetics Other viruses, such as cytomegalovirus and herpes simplex, can also cause problems. Bacteria such as salmonella, present in undercooked meat (especially chicken), and listeria (found in some cheeses), can cause problems for the continuation of the pregnancy (rather than birth defects).

31. Medical Genetics Physical factors (including radiation) X-rays and radiation given as cancer therapy can affect the baby. Your medical carers will be very cautious about giving you an abdominal X-ray if you are pregnant or potentially pregnant (this means almost every woman of child- bearing age!).

32. Medical Genetics C. Other factors The exact causes of the remaining 65 per cent of defects are currently unclear. Many of these defects arise from an interplay of genetic and environmental factors.

33. Medical Genetics For instance, some babies may have a genetic susceptibility to certain environmental factors. If exposed to such factors during development, they may develop an abnormality. If they are not exposed to the factor, they will be perfectly normal. Another baby exposed to the same environmental factor, but who doesn't have the genetic susceptibility, may be entirely normal. This can make it difficult to pin down the exact cause of a defect.

34. Medical Genetics The Human Genome Project has worked out the normal sequence of all genes found in people. In the future, this will be invaluable in teasing out the relative roles of genetics and the environment in causing birth defects.

35. Medical Genetics 4. When a baby most vulnerable The time at which the developing baby is exposed to a possibly damaging environmental factor is more important in determining the nature of the likely abnormality than the nature of the factor itself.

36. Medical Genetics In fact, if babies are exposed to the same damaging factor at different times in their development, the nature of the damage is likely to be different.

37. Medical Genetics Conversely, if babies are exposed to different damaging factors at the same stage in development, the damage caused may well be similar.

38. Medical Genetics For instance, exposure to the rubella virus at three weeks after fertilisation may cause heart defects, and at six weeks after fertilisation, it may cause deafness. Exposure to, say, radiation at three weeks may cause similar damage to rubella.

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40. The developing baby is particularly vulnerable to environmental factors during a five- week period starting about three weeks after fertilisation, and lasting till about the end of the eighth week after fertilisation.

41. Medical Genetics Pregnancy is usually timed from the last menstrual period, which is generally about a fortnight before fertilisation. 'Three weeks after fertilisation' therefore corresponds to the 'fifth week of pregnancy' and 'eight weeks after fertilisation' to the '10th week of pregnancy'.

42. Medical Genetics This five-week interval is often called the 'sensitive period' as it is crucial to normal development. Even within this period, the body organs form at different times. Sometimes it is possible to estimate retrospectively from the nature of the defect when the baby might have been exposed to a possible environmental factor. The mother's medical history can then be examined to see what she was exposed to over this period.

43. Medical Genetics 5. How detected in advance Diagnosis of birth defects has been revolutionised by the widespread use of ultrasound. Ultrasound scanning seems to be very safe in normal use.

44. Medical Genetics Blood tests for expectant mothers are also valuable. The 'triple test' is widely used. In this, levels of alpha- fetoprotein, human chorionic gonadotrophin and oestriol in the mother's blood are measured. Various abnormalities are associated with alterations in their levels.

45. Medical Genetics A common further test is amniocentesis, when a sample of the fluid surrounding the baby is removed, and the cells in the fluid are checked. This procedure poses a small risk of inducing a termination of pregnancy.

46. Medical Genetics 6. Spina Bifida Spina bifida is a birth defect that involves the incomplete development of the spinal cord or its coverings. The term spina bifida comes from Latin and literally means "split" or "open" spine.

47. Medical Genetics Spina bifida occurs at the end of the first month of pregnancy when the two sides of the embryo's spine fail to join together, leaving an open area. In some cases, the spinal cord or other membranes may push through this opening in the embryo's back. The condition can typically be detected before a baby is born and treated right away.

48. Medical Genetics A. Types of Spina Bifida The causes of spina bifida are largely unknown. Some evidence suggests that genes may be involved. A high fever during pregnancy may increase a woman's chances of having a baby with spina bifida. Women with epilepsy who have taken the drug valproic acid to control seizures may have an increased risk of having a baby with spina bifida.

49. Medical Genetics There are two forms of spina bifida — spina bifida occulta and spina bifida manifesta.

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54. 7. Congenital heart defects A congenital heart defect is a structural problem (or defect) in the heart that is present at birth. A baby's heart begins to develop shortly after conception. During development, structural defects can occur.

55. Medical Genetics These defects can involve the walls of the heart, the valves of the heart, and the arteries and veins near the heart. Congenital heart defects can disrupt the normal flow of blood through the heart.

56. Medical Genetics Multiple genetic and environmental factors interact to alter the development of the heart during the early stages of a fetus' development (the first 8 to 9 weeks during pregnancy).

57. Medical Genetics Types of Congenital Heart Defects There are many types of congenital heart defects. They include: 1.Abnormal passages in the heart or between blood vessels 2.Problems with the heart valves 3.Problems with the placement or development of blood vessels near the heart 4.Problems with development of the heart itself

58. Medical Genetics A.Abnormal passages in the heart or between blood vessels Atrial septal defect (ASD) Ventricular septal defect (VSD) Atrioventricular septal defect (AVSD) Patent ductus arteriosus (PDA)

59. Medical Genetics Atrial septal defect (ASD) is a hole in the wall that separates the upper chambers (atria (AY-tree-uh)) of the heart. This causes blood to leak from one atrium to the other.

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61. Ventricular septal defect (VSD) is a hole in the wall that separates the lower chambers (ventricles (VEN-trih-kuls)) of the heart. This causes blood to leak from one ventricle to the other.

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63. Patent ductus arteriosus (PDA) is a persistent connection between the aorta and the pulmonary (PULL-mun-ary) artery. This connection is called the ductus arteriosus and is normally present before birth. In most babies, the vessel closes within a few hours or days after birth. In some children, the vessel fails to close, resulting in PDA.

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65. B. Problems with the heart valves Congenital heart defects can involve any of the valves and include the following types of problems: Stenosis. Atresia. Regurgitation.

66. Medical Genetics C. Problems with placement or development of blood vessels near the heart Transposition of the great vessels Tetralogy of Fallot Truncus arteriosus Coarctation of the aorta Anomalous pulmonary venous return

67. Medical Genetics Tetralogy of Fallot is a combination of four defects: Pulmonary valve stenosis is the narrowing of the pulmonary valve. The narrowing slows the flow of blood from the right ventricle to the lungs. VSD is a hole in the wall that separates the left and right ventricles. Overriding aorta is a defect in which the aorta is positioned between the left and right ventricles, over the VSD. Right ventricular hypertrophy is the thickening of the right ventricle. The thickening is caused by the heart having to work harder because of the other defects.

68. Medical Genetics D. Problems with development of the heart Hypoplastic left heart syndrome is a combination of defects in which the left side of the heart does not develop properly. Defects usually include mitral atresia, aortic atresia, and a tiny left ventricle. Single ventricle describes a group of heart defects in which only one ventricle is present instead of two. It can be a single right or a single left ventricle. The other ventricle is usually absent or very tiny. Hypoplastic left heart syndrome is an example of a single ventricle defect.