First-Trimester or Second-Trimester Screening, or Both, for Down's Syndrome

doi:10.1056/NEJMoa043693

Volume 353:2001-2011		November 10, 2005		Number 19

First-Trimester or Second-Trimester Screening, or Both, for Down's Syndrome

Fergal D. Malone, M.D., Jacob A. Canick, Ph.D., Robert H. Ball, M.D., David A. Nyberg, M.D., Christine H. Comstock, M.D., Radek Bukowski, M.D., Richard L. Berkowitz, M.D., Susan J. Gross, M.D., Lorraine Dugoff, M.D., Sabrina D. Craigo, M.D., Ilan E. Timor-Tritsch, M.D., Stephen R. Carr, M.D., Honor M. Wolfe, M.D., Kimberly Dukes, Ph.D., Diana W. Bianchi, M.D., Alicja R. Rudnicka, Ph.D., Allan K. Hackshaw, M.Sc., Geralyn Lambert-Messerlian, Ph.D., Nicholas J. Wald, F.R.C.P., Mary E. D'Alton, M.D., for the First- and Second-Trimester Evaluation of Risk (FASTER) Research Consortium

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by Simpson, J. L.

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ABSTRACT

Background It is uncertain how best to screen pregnant womenfor the presence of fetal Down's syndrome: to perform first-trimesterscreening, to perform second-trimester screening, or to usestrategies incorporating measurements in both trimesters.

Methods Women with singleton pregnancies underwent first-trimestercombined screening (measurement of nuchal translucency, pregnancy-associatedplasma protein A [PAPP-A], and the free beta subunit of humanchorionic gonadotropin at 10 weeks 3 days through 13 weeks 6days of gestation) and second-trimester quadruple screening(measurement of alpha-fetoprotein, total human chorionic gonadotropin,unconjugated estriol, and inhibin A at 15 through 18 weeks ofgestation). We compared the results of stepwise sequential screening(risk results provided after each test), fully integrated screening(single risk result provided), and serum integrated screening(identical to fully integrated screening, but without nuchaltranslucency).

Results First-trimester screening was performed in 38,167 patients;117 had a fetus with Down's syndrome. At a 5 percent false positiverate, the rates of detection of Down's syndrome were as follows:with first-trimester combined screening, 87 percent, 85 percent,and 82 percent for measurements performed at 11, 12, and 13weeks, respectively; with second-trimester quadruple screening,81 percent; with stepwise sequential screening, 95 percent;with serum integrated screening, 88 percent; and with fullyintegrated screening with first-trimester measurements performedat 11 weeks, 96 percent. Paired comparisons found significantdifferences between the tests, except for the comparison betweenserum integrated screening and combined screening.

Conclusions First-trimester combined screening at 11 weeks ofgestation is better than second-trimester quadruple screeningbut at 13 weeks has results similar to second-trimester quadruplescreening. Both stepwise sequential screening and fully integratedscreening have high rates of detection of Down's syndrome, withlow false positive rates.

Source Information

From the Columbia University College of Physicians and Surgeons, New York (F.D.M., M.E.D.); the Royal College of Surgeons in Ireland, Dublin (F.D.M.); Brown University School of Medicine, Providence, R.I. (J.A.C., S.R.C., G.L.-M.); the University of Utah and Intermountain HealthCare, Salt Lake City (R.H.B.); the Swedish Medical Center, Seattle (D.A.N.); William Beaumont Hospital, Royal Oak, Mich. (C.H.C.); the University of Texas Medical Branch, Galveston (R.B.); Mount Sinai School of Medicine, New York (R.L.B.); Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, N.Y. (S.J.G.); the University of Colorado Health Sciences Center, Denver (L.D.); Tufts University School of Medicine, Boston (S.D.C., D.W.B.); New York University School of Medicine, New York (I.E.T.-T.); the University of North Carolina Medical Center, Chapel Hill (H.M.W.); DM-STAT, Boston (K.D.); the Wolfson Institute of Preventive Medicine, London (A.R.R., A.K.H., N.J.W.); and University College London, London (A.K.H.).

Address reprint requests to Dr. Malone at the Department of Obstetrics and Gynaecology, Royal College of Surgeons in Ireland, Rotunda Hospital, Parnell Square, Dublin 1, Ireland, or at fmalone{at}rcsi.ie.

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