What is amniocentesis?

Indications and Procedures

Human pregnancy begins after an egg cell and a sperm cell unite to become a fertilized egg. This process, called conception, occurs in one of the Fallopian tubes, and about a week later the fertilized egg enters the uterus. Cell division during the time period between fertilization and its entry into the uterus converts the fertilized egg into an organized cell cluster that attaches to the lining of the uterus. Following this attachment, the cluster penetrates the lining and becomes closely entwined with uterine tissues, developing three parts: the placenta, the embryo, and an amniotic sac (filled with the fluid within which the embryo is suspended). Two months after conception, the embryo—then an inch-long fetus—possesses all the anatomic features that will be present when it is born. During the remainder of the pregnancy, the fetus will grow much larger, and all its internal and external anatomic details will be elaborated.

Amniocentesis is used to provide diagnostic information before a fetus is born. It can be carried out anytime after fourteen weeks gestational age. At this point, the amniotic fluid pockets are large enough to sample safely with minimal risk to the fetus, and an adequate volume of amniotic fluid may be obtained for genetic and biochemical analysis. In general, amniocentesis or other forms of prenatal diagnosis in early pregnancy (that is, before twenty-four weeks gestational age) are indicated when the risk that the fetus is abnormal is as least as great as the risk of miscarriage from the procedure.

Amniocentesis is indicated in cases where a fetal anomaly is suspected or found on ultrasound, and additional information can be gained through the amniotic fluid regarding the nature of the defect. It is also indicated in women over the age of thirty-five, as the risk for chromosomal defects increases with maternal age. At the age of thirty-five, the risk of Down syndrome
outweighs the risk of performing amniocentesis, thereby making the procedure a reasonable one to perform routinely. Other indications for an amniocentesis include women with a previous pregnancy complicated by chromosomal abnormalities and in cases where either parent is a carrier for a chromosomal abnormality.

Another indication for amniocentesis is a known family history of a genetic defect. The types of disorders that can be ruled out via amniocentesis tend to be single-gene defects, and either parents have usually been diagnosed as having the disease or are known carriers of the disease. Examples of these diseases include cystic fibrosis, Duchenne or Becker muscular dystrophy, fragile X syndrome, hemophilia, Huntington’s disease, neurofibromatosis type 1, sickle cell disease, Tay-Sachs disease, Phenylketonuria (PKU), and thalassemias.

In the third trimester, amniocentesis is indicated if fetal developmental maturity and well-being need to be assessed. These factors help guide decision-making in treating a patient and her fetus. Commonly, amniocentesis is used to determine fetal lung maturity. This piece of information will help the obstetrician better weigh the risks of early delivery versus prolonging a pregnancy in cases where complications put the infant and/or mother at risk. Another indication for amniocentesis in the third trimester is to assess the level of fetal anemia, such as in cases of Rh isoimmunization. Amniocentesis can provide samples of amniotic fluid that can be analyzed to determine the degree of fetal red blood cell destruction and anemia. Futhermore, these samples also can be analyzed for fetal lung maturity. If the fetal lungs are mature and the fetal anemia is profound, then the obstetrician may opt for early delivery of the infant in order to minimize the risks posed to the fetus by remaining in utero.

Another indication for performing amniocentesis in the third trimester is to rule out an infection. When an intra-amniotic infection is suspected, an analysis of amniotic fluid via amniocentesis can determine the presence or absence of an infection and help the obstetrician determine a treatment plan, such as antibiotics or delivery of the infant.

Amniocentesis in the third trimester may also be indicated for therapeutic purposes. For instance, it may be performed in cases in which the amount of amniotic fluid is excessive, which is termed polyhydramnios. In this situation, the removal of amniotic fluid may relieve maternal symptoms of extreme discomfort and pressure. Another example of a therapeutic use for amniocentesis is in cases of twin gestation in which unequal sharing of the placenta is present. This can lead to a condition in which the amniotic sac of one twin contains dramatically more fluid than that of the other twin. In such cases, amniotic fluid may be aspirated from the twin with the excess amniotic fluid in order to relieve the uneven distribution of fluid between the two fetuses.

Amniocentesis can be an office procedure. The woman is usually supine or lying on her side. Ultrasound is performed to determine the location of the fetus, the location of the placenta, and the location of the largest and most accessible pockets of amniotic fluid. The optimal location for needle insertion is then determined, and the site of needle puncture on the abdomen is cleaned to prevent infection. Local anesthetic may be injected at the puncture site to minimize discomfort. Under ultrasound guidance, a needle attached to a syringe is inserted through the skin, subcutaneous fat, and uterine wall and finally into a pocket of amniotic fluid. Correct placement of the needle is confirmed by the aspiration of amniotic fluid. A sample of the fluid is then aspirated into the syringe. The syringe is disconnected from the needle, and the needle is removed. Obstetricians will almost always monitor the well-being of the fetus through fetal heart tones before and after the procedure in order to ensure that the fetus tolerated the procedure well.

Uses and Complications

In the second trimester, amniocentesis can be very helpful in identifying chromosomal abnormalities, particularly in women over the age of thirty-five. The amniotic fluid obtained from amniocentesis contains fetal cells that can be grown in tissue culture and examined for abnormalities in the chromosomes. Chromosomal problems can lead to a fetus with syndromes such as Down syndrome or trisomy 18. After a woman tests positive for a chromosomal abnormality, she should receive genetic counseling
regarding the nature of the abnormality and known consequences of fetuses carrying it. Knowledge of the chromosomal abnormality can help the pregnant woman plan for the future and can help the obstetrician and pediatrician plan for the safest delivery possible for the baby. Some women who discover that they are carrying a fetus with a chromosomal abnormality may opt for termination of the pregnancy; others may wish to continue it. In cases in which the amniocentesis results are normal, the woman’s anxiety and fears regarding having a baby with serious genetic defects may be greatly reduced.

Other uses of amniocentesis include analysis of the fetal cells to determine the presence of hereditary diseases such as cystic fibrosis. Amniocentesis can also identify the sex of the fetus. The amniotic fluid from amniocentesis may also be used to identify levels of biochemical markers such as acetyl cholinesterase, which may be indicative of structural abnormalities in the fetus.

In the third trimester, the most common use of amniocentesis is to determine fetal lung maturity in cases where the obstetrician anticipates an early delivery of the baby. The amniotic fluid can be analyzed for levels of substances secreted by the developing fetal lung (such as the ratio of lecithin and sphingomyelin). Because the respiratory system is one of the last organs to mature in the fetus, the level of these chemical markers that indicate fetal lung maturity enables physicians to assess whether the lungs are mature. Immature fetal lungs can lead to a serious condition called respiratory distress syndrome
after the baby is born. In cases in which amniocentesis indicates that the fetal lungs are not yet mature, steroid injections may be given to the mother to induce fetal lung maturity prior to the delivery of the infant.

Another use of amniocentesis in the third trimester is to follow the severity of fetal anemia in Rh isoimmunization. In these cases, the mother produces an antibody, a type of protein, which attacks the fetus’s red blood cells, leading to anemia. As the pregnancy progresses, fetal anemia can become very severe and can even lead to fetal death. Therefore, the ability to track the progression of fetal anemia is extremely important. This is possible through serial amniocenteses. The amniotic fluid obtained from amniocentesis is analyzed for its optical density. The result helps guide the physician in determining whether it is safer for the fetus to continue in the uterus or whether it should be delivered. In cases in which the fetus is very premature and early delivery is undesirable, drastic measures such as an intrauterine transfusion of blood to the fetus via the umbilical cord may be performed.

For most patients, amniocentesis is relatively painless and involves only an initial pinprick and/or a sensation of pressure. Amniocentesis is very safe for both mother and fetus, and it may be repeated more than once during a pregnancy if necessary. The chances of a complication from an amniocentesis are on average less than 0.5 percent. The risk is even lower in the hands of experienced practitioners. Potential complications include fetal loss when the amniocentesis is performed in early pregnancy. When performed in the third trimester of pregnancy, complications include precipitation of labor, placental trauma leading to bleeding, and injury to the fetus, for example, if the needle punctures delicate parts of the fetus. As with any invasive procedure, there is always a risk of bleeding or infection (in this case, to both the mother and the fetus). However, these risks are small when the proper procedures are followed.

Perspective and Prospects

The ability for physicians to diagnose fetal abnormalities essentially began with the development of amniocentesis in the 1950s. Its first application was in the diagnosis of Rh isoimmunization. In 1966, M. W. Steele and W. R. Breg Jr. demonstrated that the fetal cells from the amniotic fluid could be cultured and the chromosomal makeup of the fetus could be analyzed. This led to the development of the field of prenatal diagnosis.

Besides amniocentesis, a common technique used for prenatal diagnosis is chorionic villus sampling. In this procedure, placental tissue and amniotic fluid are sampled and sent for analysis. A catheter is inserted into the uterus through the vaginal opening and then guided by ultrasonography until its tip reaches the many chorionic villi that edge the placenta at its connection to the uterus. Gentle suction is applied, and a few of the villi are sucked out, first into the catheter and then into a sampling device. The cells that are obtained are tested in the same manner as with cells obtained through amniocentesis.

Chorionic villus sampling arose from the demonstration of the clear value of the information derived from fetal cells obtained from amniotic fluid. This useful procedure was devised to shorten the time period after amniocentesis, often several weeks long, that is needed to grow enough fetal cells in tissue culture to provide the amount of tissue required for successful karyotyping or DNA sequencing work. Another advantage of the chorionic villus sampling procedure is that it can be carried out with younger fetuses, as young as twelve weeks old, although the risk to such a fetus (fetal loss) is somewhat higher than that which is seen after amniocentesis. However, earlier diagnosis of a fetal abnormality allows for more time to obtain counseling and for decision-making. If termination of the pregnancy is desired, then the earlier it is performed, the safer it is for the mother.

Prenatal diagnosis has multiple purposes beyond the diagnosis of fetal abnormalities in utero. Traditionally, many couples have been discouraged from obtaining prenatal diagnosis if termination of the pregnancy is not an option for them. Nevertheless, prenatal diagnosis can be invaluable in helping parents make informed choices when their fetus is at risk for an abnormality. Often, couples find it difficult to make decisions regarding the pregnancy, and the more information available to them, the more likely the best decisions will be made in keeping with the couple’s values. Another purpose of prenatal diagnosis is that normal results from prenatal testing can go a long way in reassuring women and their partners who are at high risk for an abnormal fetus. Finally, a third purpose of prenatal diagnosis is to allow couples who are afraid to have children because of a known familial or personal history of abnormalities to proceed with pregnancy, with the knowledge that abnormalities can be detected early in utero.

Unfortunately, most fetal abnormalities that are found are not easily repairable, reversible, or curable prior to birth. In recent years, a small number of research-oriented medical centers in the United States have started pioneering programs for fetal surgery.
Fetal surgery involves surgical correction of anomalies while the fetus is in utero, with the hope that early correction will result in better results and fewer morbidities than waiting until after the baby is born. In fetal surgery, both the mother and the fetus must undergo surgery. The uterus is accessed through incisions on the mother’s abdomen. The fetus may be temporarily removed from the uterus while the defect is being repaired. The fetus is then replaced in the uterus, and the woman’s uterus and the abdominal incision are closed. Neural tube defects and congenital diaphragmatic hernias (in which a defect in the fetal diaphragm enables the fetal bowel to enter the thoracic cavity and prevent the fetal lungs from developing) are examples of fetal defects that can be repaired through fetal surgery. Fetal surgery carries considerable risks to the mother and fetus. There are the usual risks of major surgery to the mother, such as bleeding, infection, and risk of internal injury. The fetus is at increased risk of premature delivery and of persistent loss of amniotic fluid from leaks in the amniotic sac. Hence, fetal surgery is still considered experimental, and results from these procedures have been mixed at best.

Finally, amniocentesis has enabled physicians to minimize morbidity and mortality of infants in many situations in which an effective intervention exists, once the diagnosis of a disease state is established. This is especially true for maternal or fetal problems in the third trimester. Hence, the utility of amniocentesis not only involves potentially decreased stays in neonatal intensive care units but in many cases may be cost effective in the long run as well. However, the complexity of determining which specific parameters should be used to determine cost effectiveness (for example, relevant clinical options, variables, outcomes, and placement of values on the outcomes) makes this analysis extremely difficult.

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