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ORIGINAL RESEARCH |
From the Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ–Robert Wood Johnson Medical School/Saint Peter’s University Hospital, New Brunswick, New Jersey.
Address reprint requests to: Anthony M. Vintzileos, MD, UMDNJ—Robert Wood Johnson Medical School, Saint Peter’s University Hospital, Division of Maternal-Fetal Medicine, 254 Easton Avenue, MOB 4th Floor, New Brunswick, NJ 08903-0591; E-mail: vintziam{at}umdnj.edu.
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ABSTRACT |
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METHODS: Since July 1999, a prospective collection and recording of all individual triple screen risks for fetal Down syndrome was initiated for all patients with advanced maternal age presenting in our ultrasound unit for second-trimester genetic sonography. Genetic sonography evaluated the presence or absence of multiple aneuploidy markers. Outcome information included the results of genetic amniocentesis, if performed, and the results of pediatric assessment and follow-up after birth.
RESULTS: By June 2001, 959 patients with advanced maternal age and normal triple screen were identified. Outcome information was obtained in 768 patients. The median risk for fetal Down syndrome based on maternal age was 1:213 (range 1:37–1:274). The median risk for fetal Down syndrome based on triple screen results was 1:1069 (range 1:275–1:40,000). A total of 673 patients had normal genetic sonography, and none (0%) had Down syndrome; 95 had one or more aneuploidy markers present, and four (4.2%) had fetuses with Down syndrome. The triple screen risks for these four fetuses ranged from 1:319 to 1:833.
CONCLUSION: This study suggests that patients with advanced maternal age and normal genetic sonography carried very little risk for Down syndrome. The use of genetic sonography may increase the detection rate of fetal Down syndrome in this group of pregnant women.
One of the greatest challenges in prenatal diagnosis is to reduce the loss of fetuses from invasive procedures without compromising the detection rate of abnormal fetuses. Second-trimester maternal serum biochemistry and genetic sonography have been proposed by various investigators as means of adjusting the risk for Down syndrome, and therefore the need for amniocentesis.1–6 In our institution, there is an ever-increasing proportion of women with advanced maternal age who prefer to have a genetic sonogram and triple screen as risk modifiers to potentially avoid amniocentesis.4 Most of these pregnant women with advanced age decide against amniocentesis if both triple screen and genetic sonography are normal. However, there are only few data regarding the usefulness of genetic sonography in the presence of advanced maternal age and normal triple screen. Therefore, we undertook this study to determine the value of second-trimester genetic sonography in detecting fetal Down syndrome in patients with advanced maternal age and normal triple screen.
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MATERIALS AND METHODS |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The study was approved by the Institutional Review Board. The financial support for this study was provided by our Department of Obstetrics, Gynecology, and Reproductive Sciences.
The method used to perform genetic sonography has been previously described.3,4 The genetic sonograms are performed by an experienced sonographer or a maternal-fetal medicine fellow and also a maternal-fetal medicine attending physician. In addition to the basic ultrasound fetal biometry, the following fetal aneuploidy markers were assessed: facial (clefts, nose, orbital) anomalies, hand anomalies, cardiac anomalies (four-chamber view as well as both outflow tracts), short long bones (femur, humerus, tibia, fibula), pyelectasis, nuchal fold thickening at least 6 mm, echogenic bowel, choroid plexus cysts at least 10 mm, echogenic intracardiac focus, clinodactyly, sandal gap, and two-vessel umbilical cord. In approximately 7% of the patients, the fetal face or heart was not adequately visualized. For the purpose of this study, such sonograms were considered "normal" in the absence of any other sonographic findings. The patients were counseled immediately after the sonogram. Those who desired to proceed with a genetic amniocentesis had the procedure done immediately or within a few days. Outcome information was obtained by reviewing the results of genetic amniocentesis, if performed, or by contacting the patient or the pediatrician after birth.
Statistical analysis included descriptive statistics, and analysis was based on the Fisher exact test. A P value < .05 was considered significant, and all tests were two-tailed.
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RESULTS |
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Of the 768 patients, 673 had normal genetic sonography, and none (0%) had Down syndrome; 95 patients had abnormal genetic sonography (one or more aneuploidy markers present), and four (4.2%) had fetuses with Down syndrome (P < .001). As shown in Table 1
, the triple screen risks for these four fetuses ranged from 1:319 to 1:833, and three of these four fetuses had at least two aneuploidy markers present. Of the 91 fetuses with abnormal sonogram and no aneuploidy, eight were found to have the following anomalies: atrial septal defect (two), atrioventricular septal defect (one), hydrocephalus (one), left renal agenesis (one), bilateral club feet (one), absence of fourth toe (one), and persistent right umbilical vein (one).
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DISCUSSION |
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Because there is an ever-increasing proportion of pregnant patients with advanced maternal age who seek reassurance from a normal triple screen combined with a normal genetic sonogram, we sought to determine the value of genetic sonography in this setting. We found no cases of fetal Down syndrome among women with advanced maternal age and normal genetic sonography. This finding was not surprising given the high (over 80%) sensitivity of genetic sonography to detect fetal Down syndrome in our institution. However, we identified some striking findings. First, the observed prevalence of fetal Down syndrome in our population sample corresponded to the expected based on maternal age rather than the triple screen results. Therefore, it appears that the prevalence of Down syndrome was underestimated by the triple screen in our pregnant women with advanced maternal age. Secondly, the triple screen risks in patients with fetal Down syndrome were from 1:319 to 1:833, a range which has been recently categorized by DeVore and Romero as "moderate" risk (1:190–1:1000).11 Thirdly, all four fetuses with Down syndrome were detected by genetic sonography and, as shown in Table 1
, three of these four fetuses had at least two aneuploidy markers present.
At this point, it should be emphasized that one of the shortcomings of our study is the small number of cases with fetal Down syndrome. However, a post hoc power analysis indicated that our study had a power of 91% (
error 0.05). Thus, this preliminary study suggests that patients with advanced maternal age and normal second-trimester genetic sonography carry very little risk for fetal Down syndrome, and that the use of genetic sonography may increase the detection rate of fetal Down syndrome especially in those with moderate triple screen risks. Future studies including a larger number of patients are needed to confirm the utility of second-trimester sonography in patients with advanced maternal age and normal triple screen. In addition, larger studies are needed to address the observation that triple screen risks may underestimate the actual risks for Down syndrome in the presence of advanced maternal age.
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Footnotes |
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Received October 23, 2001. Received in revised form February 1, 2002. Accepted February 21, 2002.
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REFERENCES |
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2. Haddow JE, Palomaki GE, Knight GJ, Cunningham GC, Lustig LS, Boyd PA. Reducing the need for amniocentesis in women 35 years of age or older with serum markers for screening. N Engl J Med 1994;330:1114–8.
3. Vintzileos AM, Campbell WA, Rodis JF, Guzman ER, Smulian JC, Knuppel RA. The use of second-trimester genetic sonogram in guiding clinical management of patients at increased risk for fetal trisomy 21. Obstet Gynecol 1996;97:948–52.
4. Vintzileos AM, Guzman ER, Smulian JC, McLean DA, Ananth CV. Choice of second-trimester genetic sonogram for detection of fetal trisomy 21. Obstet Gynecol 1997;90: 187–90.[Abstract]
5. DeVore GR, Alfi O. The use of color Doppler ultrasound to identify fetuses at increased risk for trisomy 21: An alternative for high-risk patients who decline genetic amniocentesis. Obstet Gynecol 1995;85:378–86.[Abstract]
6. Bahado-Singh R, Deren O, Oz U, Tan A, Hunter D, Copel J, et al. An alternative for women initially declining genetic amniocentesis: Individual Down syndrome odds on the basis of maternal age and multiple ultrasonographic markers. Am J Obstet Gynecol 1998;179:514–9.[Medline]
7. Vintzileos AM, Guzman ER, Smulian JC, Day-Salvatore DL, Knuppel RA. Indication-specific accuracy of second-trimester genetic ultrasonography for the detection of trisomy 21. Am J Obstet Gynecol 1999;181:1045–8.[Medline]
8. Benacerraf BR, Neuberg D, Bromley B, Frigoletto FD. Sonographic scoring index for prenatal detection of chromosomal abnormalities. J Ultrasound Med 1992;11: 449–58.[Abstract]
9. Nadel AS, Bromley B, Frigoletto FD, Beracerraf BR. Can the presumed risk of autosomal trisomy be decreased in fetuses of older women following a normal sonogram? J Ultrasound Med 1995;14:297–302.[Abstract]
10. Bahado-Sing RO, Oz AU, Gomez K, Hunter D, Copel J, Baumgarten A, et al. Combined ultrasound biometry, serum markers and age for Down syndrome risk estimation. Ultrasound Obstet Gynecol 2000;15:199–204.[Medline]
11. DeVore GR, Romero R. Combined use of genetic sonography and maternal serum triple-marker screening: An effective method for increasing the detection of trisomy 21 in women younger than 35 years. J Ultrasound Med 2001;20:645–54.
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