Chorionic Villus Sampling and Amniocentesis

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Chorionic Villus Sampling and Amniocentesis

Recommendations for Prenatal Counseling

Journal article

By: Richard S. Olney

Date: July 21, 1995

Source: Richard S. Olney, et al. "Chorionic Villus Sampling and Amniocentesis: Recommendations for Prenatal Counseling." Morbidity and Mortality Weekly Report 44 (July 21, 1995): 1-12.

About the Author: Richard S. Olney is a physician and scientist at the Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Birth Defects and Developmental Disabilities, Birth Defects and Genetic Diseases Branch, in Atlanta, Georgia.

INTRODUCTION

Prenatal diagnosis uses a tiny sample of cells from the fetus to detect chromosomal abnormalities and some single gene disorders, such as cystic fibrosis, sickle cell anemia, and Tay-Sachs disease. The techniques most often used are chorionic villus sampling (CVS) and amniocentesis, and these are described in some detail in the article below. Prenatal diagnosis must always be accompanied by appropriate counseling so that the prospective parents can make an informed decision.

Counseling for prenatal diagnosis explores two different aspects of risk. First the risk of the fetus actually having the genetic condition or chromosomal abnormality being tested for needs to be discussed. Family history and the state of medical knowledge have a bearing here. As with all health risks, there is a degree of uncertainty involved and the parents need to be made aware of this. They also need to know how likely the test is to give an accurate result. Modern technology and good laboratory practice means that accuracy rates may approach 100 percent—but the possibility of an incorrect result can never be ruled out.

The article below was prompted by reports in 1991 that babies born after CVS were more likely to have birth defects—mainly shortened or missing fingers or toes but also, occasionally, abnormalities of the tongue and jaw. Prenatal diagnosis and counseling aim to provide parents at risk of having a child with a genetic disorder with as much information as possible. With this information they are equipped to make the right decision for them—termination, continuing the pregnancy, or, in some cases, choosing to not undergo the prenatal test.

PRIMARY SOURCE

Chorionic villus sampling (CVS) and amniocentesis are prenatal diagnostic procedures that are performed to detect fetal abnormalities. In 1991, concerns about the relative safety of these procedures arose after reports were published that described a possible association between CVS and birth defects in infants. Subsequent studies support the hypothesis that CVS can cause transverse limb deficiencies. Following CVS, rates of these defects, estimated to be 0.03%-0.10% (1/3,000-1/1,000), generally have been increased over background rates. Rates and severity of limb deficiencies are associated with the timing of CVS; most of the birth defects reported after procedures that were performed at greater than or equal to 70 days' gestation were limited to the fingers or toes.

The risk for either digital or limb deficiency after CVS is only one of several important factors that must be considered in making complex and personal decisions about prenatal testing. For example, CVS is generally done earlier in pregnancy than amniocentesis and is particularly advantageous for detecting certain genetic conditions. Another important factor is the risk for miscarriage, which has been attributed to 0.5%-1.0% of CVS procedures and 0.25%-0.50% of amniocentesis procedures. Prospective parents considering the use of either CVS or amniocentesis should be counseled about the benefits and risks of these procedures. The counselor should also discuss both the mother's and father's risk(s) for transmitting genetic abnormalities to the fetus.

INTRODUCTION

Chorionic villus sampling (CVS) and amniocentesis are prenatal diagnostic procedures used to detect certain fetal genetic abnormalities. Both procedures increase the risk for miscarriage. In addition, concern has been increasing among health-care providers and public health officials about the potential occurrence of birth defects resulting from CVS….

CVS utilizes either a catheter or needle to biopsy placental cells that are derived from the same fertilized egg as the fetus. During amniocentesis, a small sample of the fluid that surrounds the fetus is removed. This fluid contains cells that are shed primarily from the fetal skin, bladder, gastrointestinal tract, and amnion. Typically, CVS is done at 10-12 weeks' gestation, and amniocentesis is done at 15-18 weeks' gestation. In the United States, the current standard of care in obstetrical practice is to offer either CVS or amniocentesis to women who will be greater than or equal to 35 years of age when they give birth, because these women are at increased risk for giving birth to infants with Down syndrome and certain other types of aneuploidy. Karyotyping of cells obtained by either amniocentesis or CVS is the standard and definitive means of diagnosing aneuploidy in fetuses. The risk that a woman will give birth to an infant with Down syndrome increases with age. For example, for women 35 years of age, the risk is 1 per 385 births (0.3%), whereas for women 45 years of age, the risk is 1 per 30 births (3%). The background risk for major birth defects (with or without chromosomal abnormalities) for women of all ages is approximately 3%.

Before widespread use of amniocentesis, several controlled studies were conducted to evaluate the safety of the procedure. The major finding from these studies was that amniocentesis increases the rate for miscarriage (i.e., spontaneous abortions) by approximately 0.5%. Subsequent to these studies, amniocentesis became an accepted standard of care in the 1970s. In 1990, more than 200,000 amniocentesis procedures were performed in the United States.

In the 1960s and 1970s, exploratory studies were conducted revealing that the placenta (i.e., chorionic villi) could be biopsied through a catheter and that sufficient placental cells could be obtained to permit certain genetic analyses earlier in pregnancy than through amniocentesis. In the United States, this procedure was initially evaluated in a controlled trial designed to determine the miscarriage rate. The difference in fetal-loss rate was estimated to be 0.8% higher after CVS compared with amniocentesis, although this difference was not statistically significant. Because that study was designed to determine miscarriage rates, it had limited statistical power to detect small increases in risks for individual birth defects.

CVS had become widely used worldwide by the early 1980s. The World Health Organization (WHO) sponsors an International Registry of CVS procedures; data in the International Registry probably represent less than half of all procedures performed worldwide. More than 80,000 procedures were reported to the International Registry from 1983–1992; approximately 200,000 procedures were registered from 1983–1995. CVS is performed in hospitals, outpatient clinics, selected obstetricians' offices, and university settings; these facilities are often collectively referred to as prenatal diagnostic centers. Some investigators have reported that the availability of CVS increased the overall utilization of prenatal diagnostic procedures among women greater than or equal to 35 years of age, suggesting that access to first-trimester testing may make prenatal chromosome analysis appealing to a larger number of women. Another group of obstetricians did not see an increase in overall utilization when CVS was introduced. The increase in CVS procedures was offset by a decrease in amniocentesis, suggesting that the effect of CVS availability on the utilization of prenatal diagnostic testing depends on local factors. In the United States, an estimated 40% of pregnant women greater than or equal to 35 years of age underwent either amniocentesis or CVS in 1990.

Although maternal age-related risk for fetal aneuploidy is the usual indication for CVS or amniocentesis, prospective mothers or fathers of any age might desire fetal testing when they are at risk for passing on certain mendelian (single-gene) conditions. In a randomized trial conducted in the United States, 19% of women who underwent CVS were 35 years of age. (DNA-based diagnoses of mendelian conditions, such as cystic fibrosis, hemophilia, muscular dystrophy, and hemoglobinopathies, can be made by direct analysis of uncultured chorionic villus cells (a more efficient method than culturing amniocytes). However, amniocentesis is particularly useful to prospective parents who have a family history of neural tube defects, because alphafetoprotein (AFP) testing can be done on amniotic fluid but cannot be done on CVS specimens.

When testing for chromosomal abnormalities resulting from advanced maternal age, CVS may be more acceptable than amniocentesis to some women because of the psychological and medical advantages provided by CVS through earlier diagnosis of abnormalities. Fetal movement is usually felt and uterine growth is visible at 17-19 weeks' gestation, the time when abnormalities are detected by amniocentesis; thus, deciding what action to take if an abnormality is detected at this time may be more difficult psychologically. Using CVS to diagnose chromosomal abnormalities during the first trimester allows a prospective parent to make this decision earlier than will amniocentesis….

RECOMMENDATIONS

An analysis of all aspects of CVS and amniocentesis indicates that the occasional occurrence of CVS-related limb defects is only one of several factors that must be considered in counseling prospective parents about prenatal testing. Factors that can influence prospective parents' choices about prenatal testing include their risk for transmitting genetic abnormalities to the fetus and their perception of potential complications and benefits of both CVS and amniocentesis. Prospective parents who are considering the use of either procedure should be provided with current data for informed decision making. Individualized counseling should address the following:

Indications for procedures and limitations of prenatal testing:

Counselors should discuss the prospective parents' degree of risk for transmitting genetic abnormalities based on factors such as maternal age, race, and family history.
Prospective parents should be made aware of both the limitations and usefulness of either CVS or amniocentesis in detecting abnormalities.

Potential serious complications from CVS and amniocentesis:

Counselors should discuss the risk for miscarriage attributable to both procedures: the risk from amniocentesis at 15-18 weeks' gestation is approximately 0.25%-0.50% (1/400-1/200), and the miscarriage risk from CVS is approximately 0.5%-1.0% (1/200-1/100).
Current data indicate that the overall risk for trans-verse limb deficiency from CVS is 0.03%-0.10% (1/3,000-1/1,000). Current data indicate no increase in risk for limb deficiency after amniocentesis at 15-18 weeks' gestation.
The risk and severity of limb deficiency appear to be associated with the timing of CVS: the risk at 10 weeks' gestation (0.20%) is higher than the risk from CVS done at greater than or equal to 10 weeks' gestation (0.07%). Most defects associated with CVS at greater than or equal to 10 weeks' gestation have been limited to the digits.

Timing of procedures:

The timing of obtaining results from either CVS or amniocentesis is relevant because of the increased risks for maternal morbidity and mortality associated with terminating pregnancy during the second trimester compared with the first trimester.
Many amniocentesis procedures are now done at 11-14 weeks' gestation; however, further controlled studies are necessary to fully assess the safety of early amniocentesis.

SIGNIFICANCE

Medical counseling has to be continually updated in the light of new research and advances in science. Concern over birth defects among babies whose mothers underwent CVS prompted the recommendations outlined above. This concern also led to further studies, which produced conflicting results. Some found that CVS was not linked to birth defects, while others found that it was, both before and after ten weeksof pregnancy. A 1999 study from the World Health Organization's ongoing CVS Registry found no increased risk of birth defects in the babies of more than 200,000 women who had undergone the procedure.

Since the report excerpted above was issued, the science of prenatal diagnosis has provided new options to future parents. In-vitro fertilization (IVF) was once seen only as a treatment for infertility. It involves mixing the man's sperm and the woman's egg in a glass dish and implanting the resulting embryo in the woman's womb. It is now possible to create embryos in this way and then screen them for genetic disorders, such as cystic fibrosis, by analyzing the DNA of a single cell taken from the embryo. This is made possible thanks to a technique, now well-established, called polymerase chain reaction (PCR), which allows the amplification of DNA from a sample as tiny as a single cell. With enough DNA, a genetic analysis can be ready within days.

With pre-implantation diagnosis, only healthy embryos are placed in the mother's womb. She can continue with the pregnancy knowing that her child does not carry the genetic defect that was screened for. Pre-implantation diagnosis has been welcomed by those whose religious beliefs do not permit them to terminate a pregnancy. However, it is still a specialized technique that is available only at selected facilities.

Moreover, IVF does not always lead to pregnancy, even in a fertile woman. There is still a place for prenatal diagnosis following natural conception. Researchers have evidence that some fetal cells circulate in the mother's blood supply. In the future, they hope that this can be the basis of non-invasive prenatal diagnosis, which involves testing the mother's blood. This would eliminate the slight risk of harm to the fetus that is posed by both CVS and amniocentesis.