Chorionic Villus Sampling And Amniocentesis - CDC

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Chorionic Villus Sampling and Amniocentesis: Recommendations for Prenatal Counseling

The following CDC staff members prepared this report:

Richard S. Olney, M.D., M.P.H.

Cynthia A. Moore, M.D. Muin J. Khoury, M.D., Ph.D. J. David Erickson, D.D.S., Ph.D.

Larry D. Edmonds, M.S.P.H.

Lorenzo D. Botto, M.D.

Division of Birth Defects and Developmental Disabilities

National Center for Environmental Health

Hani K. Atrash, M.D., M.P.H. Division of Reproductive Health National Center for Chronic Disease Prevention and Health Promotion

Summary

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 (1). In addition, concern has been increasing among health-care providers and public health officials about the potential occurrence of birth defects resulting from CVS (2).

This report describes CVS and amniocentesis, provides information on indications for their use, reviews studies about the safety of the procedures, compares the benefits and risks of the two procedures (focusing particularly on the risk for limb deficiency after CVS), and provides recommendations for counseling about these issues. A public meeting was convened on March 11, 1994, to discuss the results of studies of CVS-associated limb deficiencies and preliminary counseling recommendations that had been drafted at CDC (3). Participants included geneticists, obstetricians, pediatricians, epidemiologists, teratologists, dysmorphologists, and genetic counselors who had a particular interest in CVS studies or who represented professional organizations and government agencies. Participants provided diverse opinions about recommendations for counseling both at the meeting and in subsequent written correspondence; input from participants has been incorporated into this document.

USE OF CVS AND AMNIOCENTESIS

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%) (1). 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 (4).

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 (5). 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 (6). More than 80,000 procedures were reported to the International Registry from 1983-1992 (6); approximately 200,000 procedures were registered from 1983-1995 (L. Jackson, personal communication). 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 (7). Another group of obstetricians did not see an increase in overall utilization when CVS was introduced (8). 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 (9).

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