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OB/GYN Genetic Sonograms May Reduce Need for AmniocentesisIt may be surprising to learn that age 35 is an arbitrary threshold for a pregnant woman to undergo amniocentesis to test for Down syndrome, the most common clinically significant genetic abnormality for newborns. Since the 1970s, when this age was set, up to four new blood tests have been added for women of all ages, improving the Down detection rate from 30 percent to 65 percent. Now, a growing body of controversial literature suggests an additional test may help pregnant women avoid unnecessary amniocentesis.
The first to identify many genetic sonogram markers of Down syndrome, Beryl Benacerraf has published the most clinical studies advocating further ultrasound screening to refine risk assessment based on age alone or calculated from serum testing. (Photo by Graham Ramsay) "You're not off the hook if you're under age 35, but if you do amniocentesis based on age alone, you will lose one normal fetus for every Down syndrome you pick up," said radiologist Beryl Benacerraf, HMS clinical professor of obstetrics, gynecology and reproductive biology at Brigham and Women's Hospital. "There has to be a better way." Assessing RiskTo Benacerraf, a handful of like-minded maternal-fetal ultrasound specialists, and a growing number of older pregnant women, the better way means clarifying the risk of a genetic abnormality by adding a detailed ultrasound known as a genetic sonogram. In skilled hands, the method may pick up about 80 percent of Down syndrome fetuses while reducing the risk for most high-risk women."Amniocentesis for advanced maternal age alone is no longer appropriate," concluded a study in the October Journal of Ultrasound Medicine by senior author Benacerraf and her medical associates in the private, independent practice she founded 20 years ago on Longwood Avenue. "We envision a practice paradigm in which risk assessment for Down syndrome is based on first- and second-trimester screening with biochemical markers and sonography to provide each patient with an individual risk assessment before deciding on whether to pursue invasive testing."
The chart shows how the study's likelihood ratios may affect the risk assessments based on age and serum screening. A high-risk group for which amniocentesis is typically recommended is defined as 1:270. The study offers "likelihood ratios" to refine a woman's risk of a Down syndrome fetus based on 820 women evaluated by Benacerraf and her associates from 1990 to 2000. The prospective study reviewed sonograms and karyotypes of 164 Down fetuses and 656 unaffected fetuses of women referred for advanced maternal age (over 35) or for results of serum triple screening tests. The scans were conducted between 15 and 20 weeks of pregnancy on women who had amniocentesis at the clinic at the time of the ultrasound. An unusually thick nuchal fold--skin at the back of the neck--remained the single strongest predictor of Down fetuses. Only about 25 percent of Down fetuses show the associated major health-threatening abnormalities, such as a hole between heart chambers. The nuchal fold was the first nonpathological ultrasound marker identified for Down syndrome, first reported by Benacerraf in 1985 and seen by her and others in about 40 to 50 percent of Down cases with a 1 percent false positive rate. Benacerraf subsequently identified most of the minor features of Down and confirmed others, including a bright spot in the heart. Not included is a new major Down marker that may be as sensitive and specific as a thick nuchal fold: a short or missing nose bone. The new marker is reported in another study by Bryann Bromley, HMS associate clinical professor of obstetrics, gynecology and reproductive biology at Massachusetts General Hospital; Benacerraf; and their HMS colleagues that is in press in the December Journal of Ultrasound Medicine, where Benacerraf is the top editor. Maternal-fetal medicine specialist Anthony Vintzileos, professor of obstetrics and gynecology and reproductive sciences at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, anticipates publishing similar results next year. Individually, the minor, or "soft," sonogram features are common enough in normal fetuses to make little or no difference in risk. Some of them are ethnically variable, and detection accuracy may depend upon experienced sonographers. But having two or more minor markers can ramp up the risk for the small number of fetuses presenting such clusters. For most women in the study, genetic sonograms reduced the risk. A normal scan yielded a likelihood ratio of 0.2, which translates clinically into an 80 percent reduction of the a priori risk. "This may be the single most clinically useful ramification of the genetic sonogram, because many women are declining traditional recommendations for amniocentesis based on age alone," wrote first author Bromley. "It's not perfect," said Benacerraf. "The decision-making is still there." Even with a revised risk from a genetic sonogram, women need to figure out how to use the information. Benacerraf credits genetic sonograms for reduced amniocentesis rates at her practice, down from 2,600 in 1990, when 118 amniocenteses were performed for every one Down syndrome fetus identified by karyotyping, to 1,512 in 2001, when 75 of the tests were performed for every one Down fetus identified. Using or Ignoring the InformationGenetic sonography has a staunch opponent in Rebecca Smith-Bindman, an assistant professor of radiology, epidemiology and biostatistics at the University of California, San Francisco, who argues it cannot be used reliably to determine reduced or increased risk of Down. In a meta-analysis of genetic sonogram studies published in The Journal of the American Medical Association last year, she noted large variations in the results and the higher reliability of serum testing. Smith-Bindman also objects to efforts to extrapolate data from high-risk women to all women. In an editorial in Ultrasound in Obstetrics and Gynecology, Benacerraf also cautions about misuse of the sonogram markers. "The thought is to use the risk assessment from the blood test on everybody and alter it based on the genetic sonogram," she said. "In most cases, the risk will remain low."Proponents believe pregnant women benefit from the extra information from genetic sonograms, especially if caveats are clearly communicated. "It all needs to be tested prospectively in several thousand people to determine correct assignments of risk," said maternal-fetal medicine specialist Joshua Copel, professor of obstetrics and gynecology and pediatrics at Yale Medical School, who specializes in genetic sonograms. "It's a work in progress. We all want to give people accurate numbers. Unfortunately, we can't give them what they really want, a risk-free way of finding out about Down syndrome." Genetic sonograms are a service mostly driven by patients of advanced maternal age who may be pregnant after infertility treatment and who want better odds before deciding upon amniocentesis and its attendant risk of pregnancy loss. "The bottom line is that genetic sonograms save lives," said Vintzileos, also director of maternal-fetal medicine and obstetrics at St. Peter's University Hospital. "We found three quarters of women in our unit at high risk will choose a genetic sonogram as the first option before deciding about amniocentesis. That's how most women use the genetic sonogram today, and that's how it should be used." --Carol Cruzan Morton |
