Study Downgrades Amniocentesis RiskStudy Downgrades Amniocentesis Risk

The risk of miscarriage as a result of amniocentesis to detect chromosomal abnormalities in a fetus has long caused concern for women considering the invasive procedure and likely has deterred some from having it. Now, results from a large multicenter trial suggest that these risks may be much smaller than previously believed.

Guidelines from the US Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists (ACOG) have cited the risk of miscarriage after amniocentesis at 0.5% or 1 in 200 pregnancies. But results from a recent study suggest the risk of miscarriage is 0.06% or 1 in 1600 pregnancies (Eddleman KA et al. Obstet Gynecol. 2006;108:1067-1072). In fact, the study found no significant difference in rates of pregnancy loss between women who had an amniocentesis and those who did not.

Improvements in amniocentesis techniques and greater experience among clinicians performing the procedure may explain its improved safety. Keith A. Eddleman, MD, lead author of the study and division director of maternal-fetal medicine at the Mount Sinai School of Medicine in New York City, explained that the 0.5% miscarriage risk was based on research conducted in the 1970s, when ultrasound guidance was not routinely used for the procedure and ultrasound technologies were far inferior to those currently available.

The findings are the latest data reported from the First And Second Trimester Evaluation of Risk for Aneuploidy trial (FASTER). The trial's primary goal was to compare traditional second-trimester prenatal screening for chromosomal abnormalities with more recently available first-trimester screening methods, said Eddleman. Between 1999 and 2002 more than 35 000 unselected women with viable singleton pregnancies from 12 medical centers around the country were enrolled in the trial with follow-up through the end of their pregnancy. Of those women, 3096 had amniocentesis and 31 907 did not.

Although the study has limitations, such as not being a randomized trial, factors such as the inclusion of large numbers of women at multiple centers make the trial outcomes as close to definitive as possible, Eddleman said. He explained that because previous studies had concluded that amniocentesis was associated with an elevated risk of miscarriage, it would be unethical to randomly assign women to undergo the procedure and women would be unlikely to volunteer for such a trial, so a randomized study would be impossible.

Because the study included women treated at academic medical centers, it is difficult to determine whether the results are generalizable to the wider community or whether higher skill levels among clinicians at the medical centers contributed to the findings, noted Benjamin Sachs, MD, professor at Harvard Medical School in Boston. Thus, the findings raise questions about who should be doing the procedure and whether it is less safe in the general community.

Eddleman said that although the FASTER trial did not collect data on the level of skill and experience of the clinicians who conducted the amniocentesis, these would be important questions for future studies to address.

Regardless of the study's limitations, its findings are likely to affect the way physicians counsel their patients and may foster broader prenatal screening.

ACOG’s 2001 guidelines on prenatal diagnosis of fetal chromosomal abnormalities recommend that women aged 35 years or older and those at greater risk because of their medical history be offered prenatal diagnosis for fetal chromosomal defects (http://www.guideline.gov/summary/summary.aspx?doc_id=3976). But Eddleman thinks the age-based recommendation should be reconsidered. He explained that that age was selected because the traditionally cited 0.5% pregnancy loss rate after amniocentesis was roughly equal to the risk of a woman aged 35 years or older having a child with a chromosomal abnormality.

“Women should be counseled about amniocentesis based on their individual pregnancy-specific risk, rather than just their age,” he said.

Sachs agreed that the age-based recommendation is somewhat arbitrary, noting that the factors that increase a woman's risk of having a child with a chromosomal abnormality probably begin at age 25 years and gradually increase thereafter. Still, he said, rather than offering invasive prenatal screening tests such as amniocentesis to all women instead of just those older than 35 years or with other risk factors, he would suggest that women at low risk first consider noninvasive screening tests, such as blood screening or an ultrasound scan of the nuchal fold (tissue on the fetus' neck), which may suggest the presence of a chromosomal abnormality. Other results from the FASTER trial, for example, have shown first trimester blood screening combined with nuchal fold screening performed as well or better than second trimester blood screening, and that the combined test has a 5% false-positive rate (Malone FD et al. N Engl J Med. 2005;353:2001-2011).