What is prenatal diagnosis? |

Prenatal Testing

Prenatal testing is administered to a large number of women, and the tests are becoming more informative. Some of the tests are only mildly invasive to the mother, but others involve obtaining fetal cells. Some are becoming routine for all pregnant women; others are offered only when an expectant mother meets a certain set of criteria. Some physicians will not offer the testing (especially the more invasive procedures) unless the parents have agreed that they will abort the fetus if the testing reveals a major developmental problem, such as Down syndrome or Tay-Sachs disease. Others will order testing without any such agreements, believing that test results will give the parents time to prepare themselves for a special-needs baby. The test results are also used to determine whether additional medical teams should be present at the delivery to deal with a newborn who is not normal and healthy. Most often, prenatal testing is offered if the mother is age thirty-five or older, if a particular disorder is present in relatives on one or both sides of the family, or if the parents have already produced one child with a genetic disorder.

Maternal Blood Tests and Ultrasound

Screening maternal blood for the presence of alpha fetoprotein (AFP) is offered to pregnant women who are about eighteen weeks into a pregnancy. Although AFP is produced by the fetal liver, some will cross the placenta into the mother’s blood. Elevated levels of AFP can indicate an open neural tube defect
(such as spina bifida), although it can also indicate twins. Unusual AFP findings are usually followed up by ultrasound examination of the fetus.

Other tests of maternal blood measure the amounts of two substances that are produced by the fetal part of the placenta: hCG and UE3. Lower-than-average levels of AFP and UE3, combined with a higher-than-average amount of hCG, increases the risk that the woman is carrying a Down syndrome (trisomy 21) fetus. For example, a nineteen-year-old woman has a baseline risk of conceiving a fetus with Down syndrome of 1 in 1,193. When blood-test results show low AFP and UE3 along with high hCG, the probability of Down syndrome rises to 1 in 145.

During an ultrasound examination, harmless sound waves are bounced off the fetus from an emitter placed on the surface of the mother’s abdomen or in her vagina. They are used to make a picture of the fetus on a television monitor. Measurements on the monitor can often be used to determine the overall size, the head size, and the sex of the fetus, and whether all the arms and legs are formed and of the proper length. Successive ultrasound tests will indicate if the fetus is growing normally. Certain ultrasound findings, such as shortened long bones, may indicate an increased probability for a Down syndrome baby. Because Down syndrome is a highly variable condition, normal ultrasound findings do not guarantee that the child will be born without Down syndrome. Only a chromosome analysis can determine this for certain.

Amniocentesis, Karyotyping, and FISH

Amniocentesis is the process of collecting fetal cells from the amniotic fluid. Fetal cells collected by amniocentesis can be grown in culture; then the fluid around the cells is collected and analyzed for enzymes produced by the cells. If an enzyme is missing (as in the case of Tay-Sachs disease), the fetus may be diagnosed with the disorder before it is born. Because disorders such as Tay-Sachs disease are untreatable and fatal, a woman who has had one Tay-Sachs child may not wish to give birth to another. Early diagnosis of a second Tay-Sachs fetus would permit her to have a therapeutic abortion.

Chromosomes in the cells obtained by amniocentesis may be stained to produce a karyotype. In a normal karyotype, the chromosomes will be present in pairs. If the fetus has Down syndrome (trisomy 21), there will be three copies of chromosome 21. Other types of chromosome abnormalities that also appear in karyotypes are changes within a single chromosome. If a chromosome has lost a piece, it is said to contain a deletion. Large deletions will be obvious when a karyotype is analyzed because the chromosome will appear smaller than normal. Sometimes the deletion is so small that it is not visible on a karyotype.

If chromosome analysis is needed early in pregnancy before the volume of amniotic fluid is large enough to permit amniocentesis, the mother and doctor may opt for chorionic villus sampling (CVS). The embryo produces finger-like projections (villi) into the uterine lining. Because these projections are produced by the embryo, their cells will have the same chromosome number as the rest of the embryonic cells. After growing in culture, the cells may be karyotyped in the same way as those obtained by amniocentesis. Both amniocentesis and CVS carry risks of infection and miscarriage. Normally these procedures are not offered unless the risk of having an affected child is found to be greater than the risk of complications from the procedures.

If the doctor is convinced that the fetus has a tiny chromosomal defect that is not visible on a karyotype, it will then be necessary to probe the fetal chromosomes using fluorescence in situ hybridization (FISH). A chromosome probe is a piece of DNA that is complementary to DNA within a gene. Complementary pieces of DNA will stick together (hybridize) when they come in contact. The probe also has an attached molecule that will glow when viewed under fluorescent light. A probe for a particular gene will stick to the part of the chromosome where the gene is located and make a glowing spot. If the gene is not present because it has been lost, no spot will appear. Probes have been developed for many individual genes that cause developmental abnormalities when they are deleted from the chromosomes.

Cells obtained by amniocentesis can be probed in less time than it takes to grow and prepare them for karyotyping. Probes have been developed for the centromeres of the chromosomes that are frequently present in extra copies, such as 13, 18, 21, X, and Y. Y chromosomes that have been probed appear as red spots, X chromosomes as green spots, and number 18 chromosomes as aqua spots. A second set of probes attached to other cells from the same fetus will cause number 13 chromosomes to appear as green spots and number 21 chromosomes to appear as red spots. Cells from a girl with trisomy 21 would have two green spots and two aqua spots, but no red spot when the first set of probes is used. Some other cells from the same girl will show two red spots, but three green ones, when the second set of probes is used.

Tests for many more genetic defects using advanced molecular genetics tests have been developed. DNA can be isolated from fetal cells, obtained by one of the methods already described, which is then probed for single gene defects. Hundreds of potential genetic defects can be detected in this way, although only a few such tests are generally available. Another barrier to their use is their high cost. Costs will likely drop in the future as the tests are perfected and are used more widely. These same tests may be performed on the parents to determine whether they are carriers of certain genetic diseases.

Impact and Applications

Until the development of prenatal techniques, pregnant women had to wait until delivery day to find out the sex of their child and whether or not the baby was normal. Now much more information is available to both the woman and her doctor weeks before the baby is due. Even though tests are not available for all possible birth defects, normal blood tests, karyotypes, or FISH can be very comforting. On the other hand, abnormal test results give the parents definite information about birth defects, as opposed to the possibilities inherent in a statement of risk. The parents must decide whether to continue the pregnancy. If they opt to continue the pregnancy, they must then cope with the fact that they are not going to have a normal child. When properly administered, the test results are explained by a genetic counselor who is also equipped to help the parents deal with the strong emotions that bad news can produce. Genetic testing also has far-reaching implications. If insurance companies pay for the prenatal testing, they receive copies of the results. Insurance companies could potentially use the information about genetic abnormalities to deny claims arising from treatment of the newborn or to deny insurance to the individual later in life.

Key Terms



amniotic fluid

:

the liquid that surrounds the developing fetus





neural tube

:

the embryonic structure that becomes the brain and spinal cord





placenta


:

an organ composed of both fetal and maternal tissue through which the fetus is nourished




trisomy

:

the presence of three copies (instead of two) of a particular chromosome in a cell





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