Prenatal Diagnostic Testing

Prenatal diagnostic testing involves testing the fetus before birth (prenatally) to determine whether it has a certain hereditary or spontaneous genetic disorder. The most common tests used to detect abnormalities in a fetus include ultrasonography, chorionic villus sampling, amniocentesis, and percutaneous umbilical blood sampling. Most of these tests are offered primarily to couples with an increased risk of having a baby with a genetic abnormality (particularly neural tube defects) or a chromosomal abnormality (particularly when the woman is aged 35 or older). Ultrasonography is often performed as part of routine prenatal care.

Neural Tube Defects: Prenatal diagnostic testing is commonly used to detect neural tube defects, which are birth defects of the brain or spinal cord. Examples are spina bifida (in which the spine does not completely enclose the spinal cord) and anencephaly (in which a large part of the brain and skull is missing). In the United States, neural tube defects occur in 1 of 500 to 1,000 births. Most of these defects are caused by abnormalities in several genes. A few result from abnormalities in a single gene, chromosomal abnormalities, or exposure to drugs. Prenatal diagnosis by amniocentesis and ultrasonography is recommended for couples who have at least a 1% risk of having a baby with a neural tube defect.

The risk of having a baby with a neural tube defect is increased by having a family history (including the couple's own children) of such defects. For couples who have had a baby with spina bifida or anencephaly, the risk of having another baby with one of these defects is 2 to 3%. For couples who have had two children with these defects, the risk is 5 to 10%. However, about 95% of neural tube defects occur in families without a history of the defects.
Risk also depends on where a person lives. For example, the risk is higher in the United Kingdom than in the United States. Risk may also be increased by a diet that is low in folic acid. Therefore, folic acid supplements are now routinely recommended for all women of childbearing age.
Chromosomal Abnormalities: Chromosomal abnormalities occur in about 1 of 200 live births and account for at least half of all miscarriages that occur during the 1st trimester. Most fetuses that have chromosomal abnormalities die before birth. Tests to diagnose chromosomal abnormalities before birth are considered if a couple has an increased risk of having a baby with a chromosomal abnormality. However,diagnostic tests can have risks, although very small, particularly for the fetus. For some couples, the risks outweigh the benefits of knowing whether their baby has a chromosomal abnormality, so they choose not to be tested.

Several factors increase the risk of having a baby with a chromosomal abnormality. The risk of having a baby with Down syndrome increases with a woman's age—steeply after age 35 (Down syndrome is the most common chromosomal abnormality among live-born babies.) Testing for chromosomal abnormalities in the fetus is usually offered to women who will be 35 or older when they give birth and may be offered to younger women, such as those who have already had a child with Down syndrome. The couple's anxiety, regardless of the woman's age, often justifies prenatal diagnostic testing.
Having a family history (including the couple's own children) of a chromosomal abnormality also increases the risk. If a couple has had one baby with the most common form of Down syndrome (trisomy 21) and the woman is younger than 30, the risk of having another baby with a chromosomal abnormality is increased to about 1%.
Having had a live-born or stillborn baby with a birth defect—even when no one knows whether the baby had a chromosomal abnormality—increases the risk of having a baby with a chromosomal abnormality. About 30% of babies born with a birth defect and 5% of apparently normal stillborn babies have a chromosomal abnormality.

Abnormal levels of certain substances in a pregnant woman's blood indicate that a chromosomal abnormality in the fetus is more likely. Such substances are called markers. An important marker is alpha-fetoprotein (a protein produced by the fetus). Other markers include estriol (an estrogen) and human chorionic gonadotropin (a hormone produced by the placenta). For pregnant women, measuring marker levels is part of routine prenatal care.

PROCEDURES

Several procedures can be used to detect genetic and chromosomal abnormalities.

Ultrasonography
Ultrasonography is commonly performed during pregnancy. It has no known risks for the woman or fetus. After the third month, ultrasonography can be used to detect whether the fetus has certain obvious structural birth defects. Ultrasonography is often used to check for abnormalities in the fetus when a pregnant woman has a high or low alpha-fetoprotein level or a family history of birth defects. However, normal results do not guarantee a normal baby, because no test is completely accurate.
Ultrasonography is performed before chorionic villus sampling and amniocentesis to confirm the length of the pregnancy. Chorionic villus sampling and amniocentesis can then be performed at the appropriate time during the pregnancy. Ultrasonography can also locate the placenta and indicate whether the fetus is alive. Ultrasonography is used to monitor the fetus and to guide placement of instruments during chorionic villus sampling or amniocentesis.

Chorionic Villus Sampling
In chorionic villus sampling, a doctor removes a small sample of the chorionic villi, which are tiny projections that make up part of the placenta. This procedure is used to diagnose some disorders in the fetus, usually between 10 and 12 weeks of pregnancy. Chorionic villus sampling may be used instead of amniocentesis unless a sample of amniotic fluid is needed. For example, a sample is needed when the alpha-fetoprotein level in amniotic fluid must be measured.
The main advantage of chorionic villus sampling is that its results are available much earlier in the pregnancy than those of amniocentesis. Thus, if no abnormality is detected, the couple's anxiety can be relieved earlier. If an abnormality is detected earlier, simpler, safer methods can be used to terminate the pregnancy. Also, early detection of an abnormality may be necessary for appropriate treatment of the fetus before birth. For example, a pregnant woman may be given a corticosteroid to prevent male characteristics from developing in a female fetus that has congenital adrenal hyperplasia. In this hereditary disorder, the adrenal glands are enlarged and produce excessive amounts of male hormones (androgens).

Before the procedure, ultrasonography is performed to determine whether the fetus is alive, to confirm the fetus's age, to check for obvious abnormalities, and to locate the placenta.
A sample of the chorionic villi can be removed through the cervix (transcervically) or the abdominal wall (transabdominally). With both methods, ultrasonography is used for guidance and the tissue sample is suctioned into a catheter with a syringe and then analyzed.
To remove tissue through the cervix, a doctor inserts a thin flexible tube (catheter) through the vagina and the cervix into the placenta. The woman lies on her back with her hips and knees bent, usually supported by heel or knee stirrups, as for a pelvic examination. For most women, the procedure feels very similar to a Papanicolaou (Pap) test, but a few women find it more uncomfortable. This method cannot be used in women who have a certain abnormality of the cervix or an active genital infection, such as genital herpes, gonorrhea, or chronic inflammation of the cervix.
To remove tissue through the abdominal wall, a doctor anesthetizes an area of skin over the abdomen and inserts a needle through the abdominal wall into the placenta. Most women do not find this procedure painful. But for some women, the area over the abdomen feels slightly sore for an hour or two afterward.

After chorionic villus sampling, most women who have Rh-negative blood and who do not have antibodies to Rh factor are given an injection of Rh0(D) immune globulin to prevent them from producing antibodies to Rh factor. A woman with Rh-negative blood may produce these antibodies if the fetus has Rh-positive blood that comes into contact with her blood, as it may during chorionic villus sampling. These antibodies can cause problems in the fetus. The injection is not needed if the father also has Rh-negative blood, because the fetus will have Rh-negative blood.
The risks of chorionic villus sampling are comparable to those of amniocentesis, except the risk of injuring the fetus's hands or feet may be slightly higher. Such injury occurs in 1 of 3,000 fetuses. Rarely, the diagnosis is unclear after chorionic villus sampling, and amniocentesis may be necessary. In general, the accuracy of the two procedures is comparable.

Amniocentesis
One of the most common procedures for detecting abnormalities before birth is amniocentesis. In this procedure, a sample of the fluid that surrounds the fetus (amniotic fluid) is removed. Amniocentesis is usually performed at 14 weeks of pregnancy or later. If the reason for performing amniocentesis is a high alpha-fetoprotein level in the woman's blood, the procedure is best performed between 15 and 17 weeks of pregnancy. Amniocentesis enables doctors to measure the alpha-fetoprotein level in the amniotic fluid. This measurement more reliably indicates whether the fetus has a brain or spinal cord defect than measurement of this level in the woman's blood.

Neural Tube Defects: Prenatal diagnostic testing is commonly used to detect neural tube defects, which are birth defects of the brain or spinal cord. Examples are spina bifida (in which the spine does not completely enclose the spinal cord) and anencephaly (in which a large part of the brain and skull is missing). In the United States, neural tube defects occur in 1 of 500 to 1,000 births. Most of these defects are caused by abnormalities in several genes. A few result from abnormalities in a single gene, chromosomal abnormalities, or exposure to drugs. Prenatal diagnosis by amniocentesis and ultrasonography is recommended for couples who have at least a 1% risk of having a baby with a neural tube defect.
The risk of having a baby with a neural tube defect is increased by having a family history (including the couple's own children) of such defects. For couples who have had a baby with spina bifida or anencephaly, the risk of having another baby with one of these defects is 2 to 3%. For couples who have had two children with these defects, the risk is 5 to 10%. However, about 95% of neural tube defects occur in families without a history of the defects.
Risk also depends on where a person lives. For example, the risk is higher in the United Kingdom than in the United States. Risk may also be increased by a diet that is low in folic acid. Therefore, folic acid supplements are now routinely recommended for all women of childbearing age.

Chromosomal Abnormalities: Chromosomal abnormalities occur in about 1 of 200 live births and account for at least half of all miscarriages that occur during the 1st trimester. Most fetuses that have chromosomal abnormalities die before birth. Tests to diagnose chromosomal abnormalities before birth are considered if a couple has an increased risk of having a baby with a chromosomal abnormality. However,diagnostic tests can have risks, although very small, particularly for the fetus. For some couples, the risks outweigh the benefits of knowing whether their baby has a chromosomal abnormality, so they choose not to be tested.
Several factors increase the risk of having a baby with a chromosomal abnormality. The risk of having a baby with Down syndrome increases with a woman's age—steeply after age 35 (Down syndrome is the most common chromosomal abnormality among live-born babies.) Testing for chromosomal abnormalities in the fetus is usually offered to women who will be 35 or older when they give birth and may be offered to younger women, such as those who have already had a child with Down syndrome. The couple's anxiety, regardless of the woman's age, often justifies prenatal diagnostic testing.
Having a family history (including the couple's own children) of a chromosomal abnormality also increases the risk. If a couple has had one baby with the most common form of Down syndrome (trisomy 21) and the woman is younger than 30, the risk of having another baby with a chromosomal abnormality is increased to about 1%.
Having had a live-born or stillborn baby with a birth defect—even when no one knows whether the baby had a chromosomal abnormality—increases the risk of having a baby with a chromosomal abnormality. About 30% of babies born with a birth defect and 5% of apparently normal stillborn babies have a chromosomal abnormality.

A chromosomal abnormality in one or both parents increases the risk, even if the parent is only a carrier, is healthy, and has no physical sign of the abnormality.
Having had several miscarriages may increase the risk of having a baby with a chromosomal abnormality. If the fetus in a first miscarriage has a chromosomal abnormality, a fetus in subsequent miscarriages is also likely to have one, although not necessarily the same one. If a woman has had several miscarriages, the couple's chromosomes should be analyzed before they try to have another baby. If abnormalities are identified, the couple may choose to have prenatal diagnostic testing early in the next pregnancy.
Abnormal levels of certain substances in a pregnant woman's blood indicate that a chromosomal abnormality in the fetus is more likely. Such substances are called markers. An important marker is alpha-fetoprotein (a protein produced by the fetus). Other markers include estriol (an estrogen) and human chorionic gonadotropin (a hormone produced by the placenta). For pregnant women, measuring marker levels is part of routine prenatal care.

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