|
Vol.3 No.2
November, 1999 At conception, a single cell is created by the fertilization of a mother’s egg by a father’s sperm. What then follows is a miraculous series of events in which this single cell divides into countless numbers of daughter cells with specialized functions, forming the developing fetus. Within days of conception, cells have already begun differentiating into distinct structures, and by a few weeks gestation, complex fetal organs. By four weeks after conception, the fetal neural tube has formed, the fetal eye is well developed by five weeks gestation, and the heart is largely formed by the sixth week. The mystery of how cells acquire these specialized functions and develop rapidly into body organs of great complexity has not yet been unraveled. Given the extraordinary complexity of the human body, it is not surprising that normal fetal development sometimes goes awry. In fact, although the majority of babies are normal, some have birth defects or genetic disorders that have occurred due to abnormalities in the egg and/or sperm which conceived the fetus, or to flaws in development which occurred after conception. Each couple, in each pregnancy, has a 2-3 percent chance of having a baby with a significant birth defect or developmental problem. Some of these problems have severe consequences on a baby’s health and may result in a significantly disabling condition or a shortened life span. Other abnormalities may be easily correctable by medical or surgical means and may not interfere with normal growth and development. A generation ago, there were almost no tools available to assess the health of a baby prior to birth. Now, scientific and technological advances offer an ever growing window into the womb, allowing the ability to assess some aspects of fetal health and disease. A number of different testing options are available during pregnancy to women who wish to have information about the health of their fetus. How to determine which testing options are appropriate requires discussions with your obstetrician or obstetric care provider. For couples in which there is a family history of a birth defect or genetic disease, or where the mother’s health, medications, or other environmental factors may place a pregnancy at special risk, consultation with a genetics specialist may be necessary. The most common reason for seeking prenatal diagnosis is to determine whether the fetus has Down syndrome. Down syndrome is due to a chromosomal abnormality and is one of several chromosomal disorders which occurs which increasing frequency as a woman grows older. Most babies with Down syndrome are born to couples who have no family history of the disorder. The standard recommendation for women 35 years and older at the time of delivery is to consider the option of prenatal testing such as chorionic villus sampling (CVS) or amniocentesis which can provide definitive information about the fetal chromosomal status. The accuracy of CVS and amniocentesis for the purpose of diagnosing Down syndrome and similar chromosomal disorders is greater than 99.9%.
Chorionic villus sampling (CVS): CVS is a method of prenatal diagnosis which has the advantage of being a first trimester procedure: early diagnosis, patient privacy, and first trimester termination options. It is performed beginning at 10 weeks gestation. The miscarriage risk associated with CVS is 0.5- 1 percent (1 in 100 to 1 in 200). The risk of serious infection inside the womb appears to be about one in many thousand. The risk of a CVS associated birth defect is remote (estimated at 1 in 2500 or less). CVS involves either inserting a small catheter through the vagina and cervix or passing a thin needle through the abdomen down to the developing placenta. A small sample of villi from the placenta is removed in a procedure which lasts about 20 minutes under simultaneous ultrasound.
Amniocentesis: Amniocentesis in the 15th to 18th weeks of pregnancy will give definitive information about the chromosomal status of the unborn baby. This procedure involves removing a small amount of amniotic fluid from the womb and has a low risk (about 1 in 200) of miscarriage in the hands of an obstetrician experienced with this procedure. Amniocentesis will also give information about the presence or absence of some structural birth defects (such as spina bifida) which are leaking fetal proteins. Amniocentesis can also be performed prior to 15 weeks gestation although there is less information available about the safety of early amniocentesis.
Screening tests for Down syndrome, open neural tube defects and some other rare birth defects The majority of pregnant women are less than 35 years old where the risk of Down syndrome is lower. Paradoxically, the majority of babies with Down syndrome are born to younger women because there are so many more younger women having children. Screening tests described below are the current way to determine whether a younger woman is at increased risk for having a baby with Down syndrome. If a screening test indicates an increased risk, then definitive testing of the fetus is possible by amniocentesis.. There are now screening tests beginning at 15 weeks gestation which can provide woman (younger or older)with a more accurate assessment of Down syndrome risk than that predicted by her age alone. Both younger and older women can use the results of these screening tests to determine whether they should pursue definitive prenatal diagnosis by amniocentesis. It is important to distinguish between a screening test, which can tell a woman whether she is at high or low risk for having a baby with a particular type of birth defect, and a diagnostic test, which can provide definitive information about whether a specific birth defect is present or absent. Most women who have abnormal results of a screening test do not have a baby with a birth defect.
Screening Tests: Biochemical serum screening: This is a simple blood test performed at 15-18 weeks gestation which provides a more precise estimate of risk for Down syndrome, spina bifida, some other rare birth defects and certain pregnancy complications than the risk based on a woman’s age and background alone. Common names for these test are triple screen test, quad screen test, and AFP plus. The blood test measures certain chemicals in a pregnant woman’s blood. About 1 in 10 women who have biochemical serum screening will have a result which places them at increased risk for having a baby with Down syndrome or a neural tube defect. If biochemical serum screening indicates an increased risk, then further testing, including detailed ultrasound examination and amniocentesis, will be offered. The majority of women who have an increased risk for Down syndrome, spina bifida or other rare birth defects based on the results of biochemical serum screening will not have a baby with that birth defect. Biochemical serum screening will provide information about some, but not all, of the other chromosomal abnormalities for which older women are at increased risk.
Detailed ultrasound examination: Detailed ultrasound examination performed by a specialist physician can also provide information which may help in a decision about amniocentesis. Some fetuses with Down syndrome have detectable physical changes which can be seen on ultrasound examination. However, an abnormal finding would not mean that the fetus has Down syndrome or another fetal chromosomal abnormality; rather the risk of a fetal chromosomal abnormality would be increased over that predicted by a woman’s age or biochemical screening results. Conversely, a normal ultrasound examination reduces the probability of a fetal chromosomal abnormality but does not exclude that possibility. Current data suggest that one-third to one-half of fetuses with Down syndrome will have some demonstrable signs on ultrasound examination performed by a specialist physician under optimal imaging circumstances. Detailed ultrasound examination performed by physician specialists beginning at 17 weeks gestation will detect about 95% of fetuses with an open spina bifida under optimal imaging circumstances. Detailed ultrasound examination will provide information about some, but not all, of the other chromosomal abnormalities for which older women are at increased risk. Detailed ultrasound examination will also provide information about the presence or absence of some major structural birth defects but cannot find all serious birth defects.
Testing for recessive genes Normal results of CVS or amniocentesis and ultrasound examination or biochemical serum screening and ultrasound examination will eliminate or significantly reduce the risk of some major birth defects. Many genetic disorders cannot be detected by these testing methods because they are not caused by chromosomal abnormalities which are visible under the microscope and do not have associated structural defects. In the absence of a family history, these disorders are relatively uncommon. Everyone carries a few abnormal "hidden" or recessive genes. These abnormal recessive genes are passed from generation to generation, usually without causing any problems. However, if BOTH the mother and the father happen to have the SAME abnormal recessive gene, they could have a child with a recessive disease. When BOTH parents carry ONE copy of the SAME recessive gene, the parents are said to be at high risk of having children with the disease. With such a high risk couple, there is a one in four chance in EACH pregnancy that a child will inherit TWO copies of the gene and be affected by the disease. Even in such a high risk couple, there is a three in four chance in EACH pregnancy of having a child WITHOUT the disease. Carrier testing can find most couples of north European ancestry or European Jewish ancestry who are at high risk (one in four chance) for having children with cystic fibrosis. In addition, carrier testing can find most couples of Ashkenazi (east European) Jewish ancestry who are at high risk of having children with Tay-Sachs disease, Canavan disease, Niemann Pick disease type A, Fanconi anemia Group C, Bloom syndrome and Gaucher disease. Carrier testing can also find almost all couples of African, Mediterranean, Hispanic, Asian, and Middle Eastern ancestry who are at high risk for having children with a serious inherited anemia. Fragile X syndrome is the second most common genetic cause of mental retardation, after Down syndrome, and occurs among people of all ethnic backgrounds. A gene which is sex-linked is responsible for causing fragile X syndrome and almost all women who carry that gene can be found. Only women who carry an abnormal fragile X gene are at risk for having children with the disorder. Boys with fragile X syndrome have moderate to severe mental retardation. In girls who have the fragile X gene, about half show borderline to mild retardation and the other half have normal intelligence. If BOTH members of a couple are found to carry the SAME recessive gene for one of the above diseases, or if a woman is found to carry an abnormal fragile X gene, then highly accurate prenatal diagnosis of the disease is possible. This is done by chorionic villus sampling (CVS) beginning at 10 weeks of pregnancy or by amniocentesis beginning at 15 weeks. Whether to have carrier testing is a personal decision. The information received from the testing may be of help in deciding whether to become pregnant, planning the course of a pregnancy, or in preparing for the birth of a child who might have special needs. It may also be useful for future family planning. Results of carrier testing are usually available within two to three weeks.
. |