First-Trimester Screening for Trisomies 21 and 18

doi:10.1056/NEJMoa025273

Volume 349:1405-1413		October 9, 2003		Number 15

First-Trimester Screening for Trisomies 21 and 18

Ronald Wapner, M.D., Elizabeth Thom, Ph.D., Joe Leigh Simpson, M.D., Eugene Pergament, M.D., Ph.D., Richard Silver, M.D., Karen Filkins, M.D., Lawrence Platt, M.D., Maurice Mahoney, M.D., Anthony Johnson, D.O., W. Allen Hogge, M.D., R. Douglas Wilson, M.D., Patrick Mohide, M.D., Douglas Hershey, M.D., David Krantz, B.S., Julia Zachary, Rosalinde Snijders, Ph.D., Naomi Greene, M.P.H., Rudy Sabbagha, M.D., Scott MacGregor, D.O., Lyndon Hill, M.D., Alain Gagnon, M.D., Terrence Hallahan, Ph.D., Laird Jackson, M.D., for the First Trimester Maternal Serum Biochemistry and Fetal Nuchal Translucency Screening (BUN) Study Group

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by Mennuti, M. T.

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ABSTRACT

Background Screening for aneuploid pregnancies is routinelyperformed after 15 weeks of gestation and has a sensitivityof approximately 65 percent, with a false positive rate of 5percent. First-trimester markers of aneuploidy have been developed,but their use in combination has not been adequately evaluatedin clinical practice.

Methods We conducted a multicenter study of screening for trisomies21 and 18 among patients with pregnancies between 74 and 97days of gestation, based on maternal age, maternal levels offree ${beta}$ human chorionic gonadotropin and pregnancy-associatedplasma protein A, and ultrasonographic measurement of fetalnuchal translucency. A screening result was considered to bepositive for trisomy 21 if the calculated risk was at least1 in 270 pregnancies and positive for trisomy 18 if the riskwas at least 1 in 150.

Results Screening was completed in 8514 patients with singletonpregnancies. This approach to screening identified 85.2 percentof the 61 cases of Down's syndrome (95 percent confidence interval,73.8 to 93.0), with a false positive rate of 9.4 percent (95percent confidence interval, 8.8 to 10.1). At a false positiverate of 5 percent, the detection rate was 78.7 percent (95 percentconfidence interval, 66.3 to 88.1). Screening identified 90.9percent of the 11 cases of trisomy 18 (95 percent confidenceinterval, 58.7 to 99.8), with a 2 percent false positive rate.Among women 35 years of age or older, screening identified 89.8percent of fetuses with trisomy 21, with a false positive rateof 15.2 percent, and 100 percent of fetuses with trisomy 18.

Conclusions First-trimester screening for trisomies 21 and 18on the basis of maternal age, maternal levels of free ${beta}$ humanchorionic gonadotropin and pregnancy-associated plasma proteinA, and measurement of fetal nuchal translucency has good sensitivityat an acceptable false positive rate.

Source Information

From Drexel University College of Medicine, Philadelphia (R.W., L.J.); the George Washington University Biostatistics Center, Washington, D.C. (E.T., J.Z.); Baylor College of Medicine, Houston (J.L.S.); the Department of Obstetrics and Gynecology, Northwestern University Medical School, Chicago (E.P., R. Sabbagha); the Fetal Diagnostic Center, Evanston Hospital of Northwestern University Medical School, Evanston, Ill. (R. Silver, S.M.); UCLA Center for the Health Sciences, Los Angeles (K.F.); the Department of Obstetrics and Gynecology, Cedars–Sinai Medical Center, Los Angeles (L.P., R. Snijders, N.G.); Yale University, New Haven, Conn. (M.M.); the Department of Obstetrics and Gynecology, Wayne State University, Detroit (A.J.); Magee Women's Hospital, Pittsburgh (A.H., L.H.); BC Women's Hospital, Vancouver, B.C., Canada (D.W., A.G.); McMaster University Medical Centre, Hamilton, Ont., Canada (P.M.); Prenatal Diagnosis of Northern California Medical Group, Sacramento (D.H.); and NTD Laboratories, Huntington Station, N.Y. (D.K., T.H.).

Address reprint requests to Dr. Wapner at the Department of Obstetrics and Gynecology, Drexel University College of Medicine, 245 N. 15th St., MS 495, Philadelphia, PA 19102.

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N Engl J Med 2004; 350:619-621, Feb 5, 2004. Correspondence

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