Home > Encyclopedia of Nursing & Allied Health > Amniocentesis

Definition

Amniocentesis is an optional but reliable procedure offered to pregnant women in order to obtain more information about a developing fetus in the second trimester of pregnancy. It is primarily offered to pregnant women who are at increased risk, based on their age, family history, or other factor, of having a child with a genetic condition. Amniocentesis provides accurate information about fetal chromosomes or the likelihood of certain physical abnormalities. Additional specialized studies may be performed on an as-needed basis. Women who undergo amniocentesis typically do so either to obtain reassurance about fetal well-being or, if the results are abnormal, to plan for the remainder of their prenatal care. The procedure is associated with a slightly increased chance for pregnancy loss.

Purpose

Amniocentesis has been considered a standard of obstetrical care since the 1970s. It is not, however, offered to all pregnant women. The American College of Obstetricians and Gynecologists (ACOG) recommends that amniocentesis be offered to all expectant mothers age thirty-five and older. This age cut-off has been selected because advancing maternal age is associated with an increasing risk of having a baby with a numerical chromosome abnormality. At age 35, this risk is approximately one in 200 births roughly equivalent to the risk of pregnancy loss associated with amniocentesis.

Amniocentesis is performed for the following reasons:

• Detection of structural chromosome abnormalities or an increased number of chromosomes in the fetus when the mother is in a high risk group. This includes a maternal age of 35 or more; a mother who is known to carry an abnormal chromosome such as a 21/14 translocation; family history of chromosome abnormalities; a genetic disease such as sickle cell anemia for which a DNA test is available; or abnormal triple marker screening test for Down syndrome (i.e., a low serum alpha fetoprotein or estriol or a high chronic gonadotropin level).
• Determination of the sex of the fetus when the mother is a carrier of an X-linked genetic disease such as hemophilia.
• Confirmation of an elevated maternal serum alpha fetoprotein result. Alpha fetoprotein is increased in amniotic fluid in pregnancies associated with open neural tube defects such as spina bifida and several other abnormalities that allow the fluid to leak from the fetus into the amniotic fluid.
• To evaluate the severity of hemolytic disease of the newborn (HDN). In this condition, maternal antibodies, usually anti-Rho (D), cross the placenta and facilitate destruction of Rh positive fetal red blood cells.
• Evaluation of fetal lung maturity (FLM). Respiratory distress syndrome results from collapse of the infant's lungs during expiration if the level of pulmonary surfactants is insufficient. This may occur immediately after birth especially in premature deliveries and when the mother is a diabetic. Measurement of surfactants excreted by the fetus into the amniotic fluid is used to determine the maturity of the fetal lungs.

Evaluation studies of HDN and FLM are performed in the second half of pregnancy, whereas tests for alpha fetoprotein (AFP), chromosome karyotyping, and abnormal genes are performed during the first half of pregnancy, typically between weeks 15 and 18.

Precautions

Amniocentesis is associated with a slightly increased chance of pregnancy loss (approximately 0.5%). Each woman should discuss the potential risks and benefits of amniocentesis with a doctor or genetic counselor and make her own decision about whether or not she desires this testing.

Early amniocentesis, or procedures performed before the thirteenth week of pregnancy, has been associated with an increased risk of clubfoot and of procedure-related pregnancy loss. When collecting amniotic fluid universal precautions should be followed for the prevention of transmission of bloodborne pathogens. Bloody fluid or fluid containing meconium may interfere with the tests for amniotic fluid bilirubin performed to evaluate the severity of HDN. These substances may also interfere with the interpretation of some FLM tests such as the L:S ratio (which is used to determine the level of the fetus's lung development). Some tests such as the amniotic fluid bilirubin test and alpha fetoprotein test must be interpreted with regard to gestational age.

Description

According to the National Center for Health Statistics (NCHS), 112,776 amniocentesis procedures were performed in the United States in 1998, the most recent year for which data is available. The annual birth rate that year was approximately 3.9 million infants. Thus, approximately 3% of pregnant women in the United States had this procedure performed. It is likely that this is an underestimate. The NCHS obtains information from birth certificates registered in each state and the District of Columbia. Although almost all deliveries are registered in the United States, records are still submitted with incomplete information. It is also not possible to know how many amniocentesis procedures were performed for genetic testing, as compared to other indications, as this information is not requested.

Normal persons have a total of 46 chromosomes in each body cell, with the exception of sperm or egg cells that should have only 23. As women get older, there is an increased risk of producing an egg cell with an extra chromosome. This leads to an egg cell with 24 chromosomes rather than the normal 23. Pregnancies with an abnormal number of chromosomes are referred to as aneuploid. Aneuploidy results in a conceptus with either too much or too little genetic material. This, in turn, leads to abnormal development. Aneuploidy results from failure of the chromatids to separate either during meiosis or in the germ line cells of the embryo. Common effects of aneuploidy include an increased risk for pregnancy loss or, in living fetuses, for mental retardation and physical abnormalities.

Down syndrome is the most common form of aneuploidy in live born infants, occurring in approximately one in 800 births, regardless of maternal age. The most common form of Down syndrome is 21 trisomy. One of the gametes contains an extra chromosome number 21 resulting in three number 21 chromosomes following fertilization. In women who are 35 years old, the risk of having a child with Down syndrome is higher, roughly one in 385 at delivery. It is important to realize that Down syndrome is not the only chromosome abnormality that may occur. Other numerical abnormalities are possible, yielding genetic conditions that may be either more or less severe than Down syndrome. Thus, a woman is often at risk, based solely on her age, of having a child with any type of chromosome abnormality. At age 35, this total risk is approximately one in 200. By age 40, this risk has increased to one in 65, and, at age 45, this risk is one in 20. These numbers reflect the risk at the time of delivery.

Women younger than 35 years may also have children with chromosomal or other genetic disorders. Therefore, other indications for amniocentesis or other forms of prenatal diagnosis include a family history of or a previous child with a known genetic condition, abnormal prenatal screening results, such as ultrasound or a blood test, or one parent with a previously identified structural chromosome rearrangement. All of the above may make it more likely for a couple to have a child with a genetic condition.

Amniocentesis is the most common invasive prenatal diagnosis technique offered to pregnant women. Its safety and accuracy are well-established, and it is generally considered the standard by which other prenatal diagnosis techniques are measured. To perform the procedure, a doctor inserts a thin needle into the mother's uterus and the amniotic sac. A continuous ultrasound evaluation is typically used so that the doctor can avoid touching either the baby or the umbilical cord with the needle. The amniotic sac is made up of two membranes: the inner amnion and the outer chorion. The amnion and chorion both develop from the fertilized egg. They are initially separate but begin to fuse early in pregnancy. This fusion is usually completed by approximately the fourteenth to fifteenth week of pregnancy.

Amniocentesis is usually performed in the second trimester, usually during weeks fifteen to eighteen (mid-trimester). The amniotic sac holds the fetus suspended within the amniotic fluid, an almost colorless fluid that protects the fetus from harm, helps maintain a consistent temperature, and prevents the fetus, or parts of it, from becoming attached to the amnion. The amniotic fluid is produced and absorbed by the fetus and the mother throughout pregnancy. Fetal cells, primarily derived from the skin, digestive system, and urinary tract, are suspended within the fluid. A smaller number of cells from the amnion and placenta are also present. Finally, the fetus produces a number of different chemical substances that also pass into the amniotic fluid. One of these substances is bilirubin, a breakdown product of hemoglobin.

Bilirubin in amniotic fluid is measured to determine the extent of fetal red cell destruction in HDN. Pulmonary surfactants are used in some higher-risk pregnancies to assess fetal lung maturity, and alpha-fetoprotein is used to screen for certain structural birth defects.

It is possible to perform amniocentesis in a twin pregnancy. Amniocentesis in some higher-order pregnancies, such as triplets, has also been reported. In a multiple pregnancy, it is important to ensure that a separate sample of amniotic fluid is obtained from each fetus. To accomplish this, a doctor injects a small amount of harmless blue dye into the amniotic sac of the first baby after a sample has been withdrawn. The dye will temporarily tinge the fluid blue-green. A second needle is inserted into the next amniotic sac with ultrasound guidance. If the fluid withdrawn is pale yellow, a sample from the next fetus has been successfully obtained. Since monoamniotic twins share the same amniotic sac, the second sample will be blue.

Chorionic villus sampling

Mid-trimester amniocentesis has been available for nearly thirty years. Chorionic villus sampling (CVS) has been available in the United States since the 1980s. CVS is usually performed between ten and twelve weeks of pregnancy. It involves the removal of a small sample of the developing placenta, or chorionic villi. It has been an attractive alternative to amniocentesis, particularly for those women who desire both testing and results earlier in their pregnancies. Some of the benefits of earlier testing include reassurance sooner in pregnancy and fewer physical complications following first trimester pregnancy termination, for those couples with abnormal babies who choose this option. CVS is, however, associated with a higher risk of miscarriage than mid-trimester amniocentesis and because it is performed earlier than amniocentesis more fatal chromosome abnormalities are detected that would not come to term. At experienced centers, this risk is approximately 1% (or one in 100).

Early amniocentesis

Early amniocentesis is performed before the thirteenth completed week of pregnancy. It has been considered investigational for many years. The results of the largest early amniocentesis trial, published in 1998, have, however, caused physicians worldwide to reconsider the benefit and risks of this earlier procedure. The Canadian Early and Mid-trimester Amniocentesis Trial (CEMAT) is the largest, multi-center, randomized clinical trial of early amniocentesis conducted to date. The purpose of the trial was to examine and compare the safety and accuracy of early amniocentesis (EA) versus mid-trimester amniocentesis (MTA). In order to accomplish this, 4,374 pregnant women were identified and enrolled in the study. Ultrasound was performed in the first trimester to confirm the gestational age of all pregnancies. Computer randomization was used to evenly divide the women into either the EA or MTA groups. Ultimately, 1,916 women underwent EA and 1,775 women had MTA. Follow-up was obtained on nearly all pregnancies. Two striking conclusions were reached: EA is associated with an increased incidence of clubfoot and an increased risk of procedure-related pregnancy loss. EA was also linked to an increased number of laboratory culture failures (no growth of cells and no results) compared to MTA. The total waiting time for results was slightly longer in the EA group. This is not entirely a surprise. A smaller amount of fluid is obtained when EA is performed. Hence, there are fewer cells, and culture times take longer.

Chromosome tests

Genetic testing is available on amniotic fluid obtained by amniocentesis. The most common test is a complete analysis of the fetal chromosomes called karyotyping. This procedure detects only those chromosome abnormalities that produce either a structurally abnormal chromosome (e.g., a long or short arm deletion) or aneuploidy. It does not detect mutations within genes that are responsible for specific diseases or inborn errors of metabolism (e.g., cystic fibrosis). However, many DNA based tests are available that will detect disease genes that are caused by point mutations (single base substitutions) within the genes.

After a sample of amniotic fluid is obtained, the cytogenetic laboratory isolates the cells, referred to as amniocytes, out of the fluid. The cells are placed into two or more containers filled with liquid nutrients, establishing different cultures in which the cells will continue to grow. The cells are cultured anywhere between seven to 10 days before the actual analysis begins. Culture time can be reduced to five to six days by growing a monolayer of fetal cells directly onto a coverglass. Culture is performed in order to obtain sufficient metaphase cells and to synchronize the growth of the cells. Cells in metaphase are selected for analysis because at this stage the chromatids have duplicated but not separated and the individual chromosomes are most visible under the microscope.

Once there appears to be an adequate number of cells to study, the cultures are harvested. Harvesting prevents additional cell growth and stops the cells at whatever point they were in the cell cycle. Cells are washed, exposed to hypotonic saline, and fixed with methanol and acetic acid. The cells are spread on a glass slide, heat fixed and treated with trypsin and stained with Giemsa or other chromosome stain. Smears are examined under 400x magnification and the modal chromosome count is recorded. Large clear metaphase cells are selected for photography or image analysis using chromosome-sorting software. Chromosomes are classified by size, centromere position, banding pattern, secondary constriction, and satellite appendages. The karyotype or chromosome map that results identifies translocations, aneuploidy, deletions, and other abnormalities in the appearance of the chromosomes. Typically, chromosome results are available within seven to 14 days after amniocentesis. Results may be delayed by slow-growing cultures. This rarely reflects an abnormal result but does extend the time until final results are available.

Many laboratories now perform a technique called fluorescence in situ hybridization (FISH) into their chromosome studies. This adjunct testing provides limited information about certain chromosomes within one to two days after amniocentesis. It does not replace a complete chromosome study using amniocyte cultures. In fact, FISH results are often reported as preliminary, pending confirmation by cultured results. They can, however, be very useful, particularly when there is already a high level of suspicion of a fetal chromosome abnormality.

FISH is performed using a small sample of uncultured amniotic fluid cells. Special molecular tags consisting of single-stranded DNA that are attached (covalently conjugated) to fluorescent dyes are used. Each tag is bound to a different combination of dyes. When excited by ultraviolet light, the fluorochromes emit visible light of characteristic colors. Tags are available that recognize a specific segment of DNA from chromosomes 13, 18, 21, X, and Y. Abnormalities of these five chromosomes account for nearly 95% of all chromosomal abnormalities. The cells are prepared onto slides as described for karyotyping, denatured to separate the DNA strands, and the probe mixture is added. Each probe hybridizes with the complementary DNA sequence of the target chromosome. When the fetal cells are examined under a fluorescent microscope, a small spot of a specific color will appear on each of these chromosomes. If an extra autosomal chromosome is present, three colored spots appear within the nucleus of the cell instead of two. In addition to determining sex, FISH detects extra sex chromosomes such as 47,XXY which is responsible for Klinefelter syndrome or the absence of one sex chromosome, and 45,X0 which is responsible for Turner syndrome. Other chromosomal abnormalities will not be detected unless a full chromosome evaluation on cultured cells is performed.

A new fluorescent mapping technique called spectral karyotyping (SKY) is available to aid in identifying chromosomes. A DNA probe specific for each chromosome is tagged with between one to five fluorescent dyes. Hybridization between the tag and DNA of the specific chromosome produces a unique color for each one. Using fluorescent microscopy, and a color camera, the karyotype showing each of the 24 different colored chromosomes is constructed. Chromosomes in which translocations occur are bi-colored. The color coding facilitates the identification of the regions of each of the chromosomes involved.

DNA tests are offered to those couples who, based on their family history or other information, are at increased risk of having a child with a single gene, or Mendelian, disorder. Testing for disease genes is prima-rily accomplished using the polymerase chain reaction (PCR). This technique permits a small segment of DNA within a gene to be amplified exponentially. Within two hours, the target DNA sequence can be copied over one million times, yielding sufficient DNA to identify with a radiolabeled or enzyme-conjugated probe. An example of this technique has been applied extensively to the prenatal diagnosis of cystic fibrosis. There are over 200 different point mutations identified in the CF gene, a segment of 27 coding regions called exons. Various probes may be used to identify most of these. For example, approximately 85% of all CF genes can be identified in the North American white population. DNA tests are available for sickle cell disease, muscular dystrophy, retinoblastoma, hyperlipoproteinemia, Huntington's chorea, Tay-Sachs disease, congenital adrenal hyperplasia, hemophilia, and many other conditions.

Biochemical testing of amniotic fluid is performed using the same methods as are applied to other body fluids. For example, fluorescence polarization and thin layer chromatography are techniques used to measure pulmonary surfactants. Bilirubin in amniotic fluid is analyzed by direct absorbance measurement using a scanning or diode array spectrophotometer. Bilirubin absorbs light maximally at 450 nm, and if present in the amniotic fluid, it will produce an absorbance peak at this wavelength. Hemoglobin contributes to the absorbance peak by also absorbing light at this wavelength. The interference from hemoglobin can be corrected by measuring its absorbance peak at 410 nm. The contribution of hemoglobin to the 450 nm peak is equal to 5% of its absorbance at 410 nm. Therefore, the 5% of the absorbance at 410 nm is subtracted from the absorbance at 450 nm to determine the corrected absorbance which is proportional to bilirubin concentration.

Alpha fetoprotein in amniotic fluid is measured by a sandwich type enzyme immunoassay, the same method used for maternal blood. AFP is a protein made by the fetal liver. It passes out of the fetus and enters both the amniotic fluid and the mother's blood. Screening for open neural tube defects, abnormal openings in the fetal head or spinal cord, or ventral wall defects, openings along the abdominal wall, can be performed by measuring AFP during the fifteenth to twentieth weeks of preg-nancy. An unusually high level of serum AFP does not necessarily indicate a problem with fetal development, but is cause for some concern. A high AFP level in amniotic fluid will detect up to 98% of all openings on the fetal body that are not covered by skin. Further studies may be suggested if the AFP is high. Most initial AFP results are available within two to three days after amniocentesis.

Preparation

The usual precautions concerning sterility of the injection site and sterility of equipment and the hands of those who will come into contact with a woman must be taken during amniocentesis.

Counseling must be offered to a woman or couple to ensure that they fully understand the results of an amniocentesis test. Counseling should be offered prior to the procedure so that a woman or couple can understand the procedure and slight risk of miscarriage that is associated with amniocentesis.

Aftercare

Physical care after an amniocentesis procedure involves the site of needle insertion. It should be kept clean and dry. Covering the puncture site with a sterile bandage is usually sufficient.

Mental care after an amniocentesis may be more important than physical care. Many women or couples require emotional support and reassurance while they are waiting for test results. Those receiving abnormal results often require ongoing support while they weigh options and make decisions that are appropriate for them. Some may require long-term support as they adjust to the outcomes of their decisions.

Complications

Women who have had an amniocentesis often describe it as uncomfortable, involving some mild pressure or pain as the needle is inserted. Fewer women

describe it as extremely painful. A local anesthetic may be used to numb the upper layer of the mother's skin prior to testing. This medicine has no effect on the fetus, but may help the mother feel more comfortable during the procedure. An experienced physician can, on average, perform amniocentesis in approximately one to two minutes.

Common complaints after amniocentesis include mild abdominal tenderness at the site of needle insertion or mild cramping. These usually go away within one to two days. More serious complications are significantly less common but include leakage of amniotic fluid, vaginal bleeding, or uterine infection. These complications are estimated to occur in less than 1% of pregnancies. In some women, complications after amniocentesis may lead to a miscarriage, or loss of the pregnancy. A woman's background risk of having a miscarriage, without amniocentesis, is approximately 2-3% in her second trimester. In experienced hands, the risk for an amniocentesis-related pregnancy loss is estimated to be an additional 0.25-0.50%, or roughly one in every 200-400 pregnancies.

Much attention is often paid to the physical side effects of amniocentesis. However, it is important to also emphasize some of the emotional side effects of amniocentesis. Many of these are also applicable to other forms of prenatal diagnosis.

The offer of prenatal testing is associated with increased anxiety. This appears to be true whether a woman knew prenatal testing would be offered to her during the pregnancy or if it comes about unexpectedly, as is usually the case following abnormal screening results. Women to whom genetic amniocentesis is presented must consider the perceived benefits of testing, such as the reassurance that comes when results are normal, and compare them to the possible risks. Examples of potential risks include not only the risk of a complication after testing but also the potential burden of knowing that she will have a child with a serious disability or chronic medical condition. The nature of the child's possible diagnosis is also important. For example, could it lead to an early death, be more subtle and cause few outward signs of a problem, or be somewhere in between? There are few treatments available to correct the hundreds of known genetic disorders. Couples may wish to consider whether or not they would consider a termination of the pregnancy if a serious abnormality were detected. The definition of serious is often a matter of personal opinion. A couple's value system and family history, including that of other pregnancies and their outcomes, all influence their decision regarding amniocentesis. Ideally, a woman and her partner will have discussed at least some of these issues with each other and with either the woman's doctor or a genetic counselor prior to testing. The choice to have amniocentesis depends on many factors and should remain a personal decision.

Results

It is important to emphasize that normal results from tests performed on amniotic fluid do not necessarily guarantee the birth of a normal infant. Each couple in the general population faces a risk of roughly 3-4% of having a child with any type of congenital birth defect. Many of these will not be detected with tests performed on amniotic fluid samples obtained by amniocentesis. Babies with birth defects are often born into families with no history of genetic disorders.

Chromosome karyotyping is interpreted according to standardized nomenclature, International System of Cytogenetic Nomenclature (ISCN). The system describes the number of chromosomes, the sex chromosomes, and then any abnormalities seen in specific chromosomes using a numerical system to identify banding characteristics. Bands are numbered starting at the centromere. Standardized symbols and abbreviations describe the type of abnormality. For example, a + sign designates an extra chromosome and 47,XY,+21 designates a male with an extra chromosome 21. The designation 46,XX, t(3:5)(q21;p15.2) means that the subject is a female with a normal number of chromosomes. There is a translocation (exchange) between chromosomes three and five involving band 21 of the long arm of number three and band 15.2 of the short arm of chromosome five.

Amniotic fluid is normally clear or slightly turbid. The concentration of AFP is reported as multiples of the median (MOM). Normal values are dependent upon the sampling time. For example, the median AFP at 15 weeks is 16.3 micrograms per mL and at 20 weeks is 8.1 micrograms per mL. Bilirubin is also time-dependent normally decreasing during gestation. The concentration should be below 0.075 mg/dL at 20 weeks and below 0.025 mg/dL at 40 weeks (full term).

An L:S ratio of 2.0 or higher correlates with fetal lung maturity. Lecithin greater than 0.10 mg/dL also correlates with fetal lung maturity.

Health care team roles

Actual samples of amniotic fluid or placenta are obtained by persons with specialized training. These are usually obstetricians or gynecologists with additional training. Sonographers assist in amniocentesis. Specially trained nurses prepare women for amniocentesis. Cytogenetic technologists, CLSp(CG) perform cell culture, karyotyping, and DNA analysis of fetal cells. Clinical laboratory scientists/medical technologists perform biochemical testing, and may also perform DNA and some molecular tests on fetal cells from the fluid. Pathologists with special training in genetics interpret results. Obstetricians or geneticists provide results to a woman or couple and discuss treatment options that may be available. Genetic counselors and other mental health professionals may provide additional support and counseling to a woman or couple after the results of amniocentesis have been returned.

---

KEY TERMS

---

Alpha fetoprotein—A protein found in amniotic fluid that is commonly used to screen for certain structural birth defects.

Amnion—A thin, transparent membrane that holds the fetus in the amniotic fluid. The amniotic sac is sometimes called the bag of waters.

Anesthetic—Drug used to temporarily cause loss of sensation in an area of the body. An anesthetic may either be general, associated with a loss of consciousness, or local, affecting one area only without loss of consciousness. Anesthetics are administered via inhalation, topical application or needle injection.

Aneuploid—A fetus with an abnormal number of chromosomes.

Chorion—The outer membrane of the amniotic sac. Chorionic villi develop from its outer surface early in pregnancy. The villi establish a physical connection with the wall of the uterus. The chorionic villi eventually develop into the placenta.

Chromosome—A linear thread of genetic material contained within every cell. Humans have 46 chromosomes arranged into 23 distinct pairs. Each parent contributes one set of chromosomes, or 23, to a child. Changes in the total number of chromosomes, the shape and size (structure) of a chromosome or the contents of a chromosome may lead to abnormalities in the amount of genetic material. These abnormalities often lead to abnormal physical and mental development.

Conceptus—The product of conception, or the union of a sperm and egg cell at fertilization.

Cystic fibrosis—An inherited disease characterized by repeated lung infections, functional abnormalities of the pancreas, and an elevated level of salt in sweat. Individuals with cystic fibrosis require long- term aggressive medical care. Survival into adulthood is common, in part due to advances in treatment. Death, however, is frequently caused by respiratory failure. Although cystic fibrosis is more common among Caucasians, it has been reported in individuals of other races.

Down syndrome—A genetic condition characterized by moderate to severe mental retardation, a characteristic facial appearance, and, in some individuals, abnormalities of some internal organs. Down syndrome is always caused by an extra copy of chromosome 21, thus there are three rather than the normal two. For this reason, Down syndrome is also known as trisomy 21.

Fetus—The term used to describe a developing human infant from approximately the third month of pregnancy until delivery. The term embryo is used prior to the third month.

Fibroid—A non-cancerous tumor of connective tissue. It is made up of elongated, threadlike structures, or fibers, which usually grow slowly and are contained within an irregular shape. Fibroids are firm in consistency but may become painful if they start to break down or apply pressure to areas within the body. They frequently occur in the uterus and are generally left alone unless growing rapidly or causing other problems. Surgery is needed to remove fibroids.

Sickle cell anemia—An hereditary form of anemia due to abnormal sickle-shaped red blood cells. As a result, the cells cannot efficiently carry oxygen to body tissues. Common clinical features of sickle cell anemia include severe pain in the joints and abdomen, swelling of the tops of hands and feet, and fever. Sickle cell anemia is frequently found among individuals with ancestors who lived in central Africa.

Tay-Sachs disease—An inherited biochemical disease caused by lack of a specific enzyme in the body. In classical Tay-Sachs disease, previously normal children become blind and mentally handicapped, develop seizures, and rapidly decline. Death often occurs between the ages of three to five years. Tay-Sachs disease is common among individuals of eastern European Jewish background but has been reported in other ethnic groups.

Trimester—A three-month period. Human pregnancies are normally divided into three trimesters: first (conception to week 12), second (week 13 to week 24), and third (week 25 until delivery).

Uterus—A muscular, hollow organ of the female reproductive tract. The uterus contains and nourishes an embryo or fetus from the time the fertilized egg is implanted until birth.

---

L. Fleming Fallon, Jr., MD, DrPH