FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 338:955-962 April 2, 1998 Number 14 Next

	Full Text PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Screening of maternal serum to identify fetuses with Down's syndrome is now routinely offered during the second trimester of pregnancy. Prenatal screening by means of serum assays or ultrasonographic measurements, either alone or in combination, may also be possible in the first trimester.

Methods We measured serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin (hCG), the free beta subunit of hCG, and pregnancy-associated protein A in 4412 women (82 percent of whom were 35 years of age or older) who came to 16 prenatal diagnostic centers for chorionic-villus sampling or early amniocentesis at 9 to 15 weeks of gestation. Ultrasound measurements of fetal nuchal translucency were also reported. Fetal chromosomal analysis was performed in all pregnancies. Altogether, there were 61 fetuses with Down's syndrome.

Results A total of 48 pregnancies affected by Down's syndrome and 3169 unaffected pregnancies were identified before 14 weeks of gestation; the rates of detection of Down's syndrome for the five serum markers were as follows: 17 percent for alpha-fetoprotein, 4 percent for unconjugated estriol, 29 percent for hCG, 25 percent for the free beta subunit of hCG, and 42 percent for pregnancy-associated protein A, at false positive rates of 5 percent. The results of the measurements of serum hCG and its free beta subunit were highly correlated. When used in combination with the serum concentration of pregnancy-associated protein A and maternal age, the detection rate was 63 percent for hCG (95 percent confidence interval, 47 to 76 percent) and 60 percent for its free beta subunit (95 percent confidence interval, 45 to 74 percent). Measurements of nuchal translucency varied considerably between centers and could not be reliably incorporated into our calculations.

Conclusions Screening for Down's syndrome in the first trimester is feasible, with use of measurements of pregnancy-associated protein A and either hCG or its free beta subunit in maternal serum.

Source Information

From the Foundation for Blood Research, Scarborough, Me. (J.E.H., G.E.P., G.J.K., J.W.); and the Prenatal Diagnostic Center, Lexington, Mass. (W.A.M., A.J.).

Address reprint requests to Dr. Haddow at P.O. Box 190, Scarborough, ME 04070-0190.

Full Text of this Article

This article has been cited by other articles:

• Canick, J. A., Palomaki, G. E., Lambert-Messerlian, G. M., Malone, F. D., D'Alton, M. E. (2007). Comparison of Serum Markers in First-Trimester Down Syndrome Screening. Obstet Gynecol 109: 783-783 [Full Text]  
• Canick, J. A., Lambert-Messerlian, G. M., Palomaki, G. E., Neveux, L. M., Malone, F. D., Ball, R. H., Nyberg, D. A., Comstock, C. H., Bukowski, R., Saade, G. R., Berkowitz, R. L., Dar, P., Dugoff, L., Craigo, S. D., Timor-Tritsch, I. E., Carr, S. R., Wolfe, H. M., D'Alton, M. E., for the First and Second Trimester Evaluation of R, (2006). Comparison of Serum Markers in First-Trimester Down Syndrome Screening.. Obstet Gynecol 108: 1192-1199 [Abstract] [Full Text]  
• Palomaki, G. E., Knight, G. J., Neveux, L. M., Haddow, J. E., Pandian, R. (2006). First-Trimester Down Syndrome Screening: Reply. Clin. Chem. 52: 161-161 [Full Text]  
• Palomaki, G. E., Knight, G. J., Neveux, L. M., Pandian, R., Haddow, J. E. (2005). Maternal Serum Invasive Trophoblast Antigen and First-Trimester Down Syndrome Screening. Clin. Chem. 51: 1499-1504 [Abstract] [Full Text]  
• Platt, L. D., Greene, N., Johnson, A., Zachary, J., Thom, E., Krantz, D., Simpson, J. L., Silver, R. K., Snijders, R. J. M., Goetzl, L., Pergament, E., Filkins, K., Mahoney, M. J., Hogge, W A., Wilson, R D., Mohide, P., Hershey, D., MacGregor, S., Bahado-Singh, R., Jackson, L. G., Wapner, R. (2004). Sequential Pathways of Testing After First-Trimester Screening for Trisomy 21. Obstet Gynecol 104: 661-666 [Abstract] [Full Text]  
• Goetzl, L., Krantz, D., Simpson, J. L., Silver, R. K., Zachary, J. M., Pergament, E., Platt, L. D., Mahoney, M. J., Wapner, R. J. (2004). Pregnancy-Associated Plasma Protein A, Free {beta}-hCG, Nuchal Translucency, and Risk of Pregnancy Loss. Obstet Gynecol 104: 30-36 [Abstract] [Full Text]  
• Malone, F. D., D'Alton, M. E. (2003). First-Trimester Sonographic Screening for Down Syndrome. Obstet Gynecol 102: 1066-1079 [Abstract] [Full Text]  
• Wapner, R., Thom, E., Simpson, J. L., Pergament, E., Silver, R., Filkins, K., Platt, L., Mahoney, M., Johnson, A., Hogge, W. A., Wilson, R. D., Mohide, P., Hershey, D., Krantz, D., Zachary, J., Snijders, R., Greene, N., Sabbagha, R., MacGregor, S., Hill, L., Gagnon, A., Hallahan, T., Jackson, L., the First Trimester Maternal Serum Biochemistry an, (2003). First-Trimester Screening for Trisomies 21 and 18. NEJM 349: 1405-1413 [Abstract] [Full Text]  
• Welch, K. K., Malone, F. D. (2002). Advances in Prenatal Screening: Nuchal Translucency Ultrasonography in the First Trimester. NeoReviews 3: e202-208 [Full Text]  
• Welch, K. K., Malone, F. D. (2002). Advances in Prenatal Screening: Maternal Serum Screening for Down Syndrome. NeoReviews 3: e209-213 [Full Text]  
• Reis, F. M., D'Antona, D., Petraglia, F. (2002). Predictive Value of Hormone Measurements in Maternal and Fetal Complications of Pregnancy. Endocr. Rev. 23: 230-257 [Abstract] [Full Text]  
• Maymon, R., Shulman, A. (2002). Serial first- and second-trimester Down's syndrome screening tests among IVF-versus naturally-conceived singletons. Hum Reprod 17: 1081-1085 [Abstract] [Full Text]  
• Rozenberg, P., Malagrida, L., Cuckle, H., Durand-Zaleski, I., Nisand, I., Audibert, F., Benattar, C., Tribalat, S., Cartron, M., Lemarie, P., Stoessel, J., Capolagui, P., Janse-Marec, J., Barbier, D., Allouch, C., Perdu, M., Roberto, A., Lahna, Z., Giudicelli, Y., Ville, Y. (2002). Down's syndrome screening with nuchal translucency at 12+0-14+0 weeks and maternal serum markers at 14+1-17+0 weeks: a prospective study. Hum Reprod 17: 1093-1098 [Abstract] [Full Text]  
• Liu, S., Joseph, K. S., Kramer, M. S., Allen, A. C., Sauve, R., Rusen, I. D., Wen, S. W., for the Fetal and Infant Health Study Group of the, (2002). Relationship of Prenatal Diagnosis and Pregnancy Termination to Overall Infant Mortality in Canada. JAMA 287: 1561-1567 [Abstract] [Full Text]  
• Qin, Q.-P., Christiansen, M., Pettersson, K. (2002). Point-of-Care Time-resolved Immunofluorometric Assay for Human Pregnancy-associated Plasma Protein A: Use in First-Trimester Screening for Down Syndrome. Clin. Chem. 48: 473-483 [Abstract] [Full Text]  
• Gilbert, R E, Augood, C, Gupta, R, Ades, A E, Logan, S, Sculpher, M, van der Meulen, J H P, Wallace, E. M, Mulvey, S. (2001). Screening for Down's syndrome: effects, safety, and cost effectiveness of first and second trimester strategies Commentary: Results may not be widely applicable Authors' response. BMJ 323: 423-423 [Abstract] [Full Text]  
• Reynolds, T M (2000). Down's syndrome screening: a controversial test, with more controversy to come!. J. Clin. Pathol. 53: 893-898 [Abstract] [Full Text]  
• KRANTZ, D. A., HALLAHAN, T. W., ORLANDI, F., BUCHANAN, P., LARSEN, J. W. Jr, MACRI, J. N. (2000). First-Trimester Down Syndrome Screening Using Dried Blood Biochemistry and Nuchal Translucency. Obstet Gynecol 96: 207-213 [Abstract] [Full Text]  
• PHIPPS, M. G., HOGAN, J. W., PEIPERT, J. F., LAMBERT-MESSERLIAN, G. M., CANICK, J. A., SEIFER, D. B. (2000). Progesterone, Inhibin, and hCG Multiple Marker Strategy to Differentiate Viable From Nonviable Pregnancies. Obstet Gynecol 95: 227-231 [Abstract] [Full Text]  
• Goshen, R. (1999). What factors regulate HCG production in Down's syndrome pregnancies?: Screening for Down's syndrome using HCG concentrations - a common practice but still and enigma. Mol Hum Reprod 5: 893-895 [Full Text]  
• Knofler, M. (1999). What factors regulate HCG production in Down's syndrome pregnancies?: Regulation of HCG during normal gestation and in pregnancies affected by Down's syndrome. Mol Hum Reprod 5: 895-897 [Full Text]  
• Overgaard, M. T., Oxvig, C., Christiansen, M., Lawrence, J. B., Conover, C. A., Gleich, G. J., Sottrup-Jensen, L., Haaning, J. (1999). Messenger Ribonucleic Acid Levels of Pregnancy-Associated Plasma Protein-A and the Proform of Eosinophil Major Basic Protein: Expression in Human Reproductive and Nonreproductive Tissues. Biol. Reprod. 61: 1083-1089 [Abstract] [Full Text]  
• Wald, N.J., Watt, H.C., Hackshaw, A.K. (1999). Integrated Screening for Down's Syndrome Based on Tests Performed during the First and Second Trimesters. NEJM 341: 461-467 [Abstract] [Full Text]  
• Copel, J. A., Bahado-Singh, R. O. (1999). Prenatal Screening for Down's Syndrome -- A Search for the Family's Values. NEJM 341: 521-522 [Full Text]  
• Maymon, R., Dreazen, E., Tovbin, Y., Bukovsky, I., Weinraub, Z., Herman, A. (1999). The feasibility of nuchal translucency measurement in higher order multiple gestations achieved by assisted reproduction. Hum Reprod 14: 2102-2105 [Abstract] [Full Text]  
• Bersinger, N.A., Meisser, A., Bessou, T., Seguin, P., Birkhauser, M.H., Bischof, P. (1999). Production and characterization of monoclonal antibodies against pregnancy-associated plasma protein A. Mol Hum Reprod 5: 675-681 [Abstract] [Full Text]  
• (1998). First-Trimester Serum Screening for Down Syndrome. JWatch Women's Health 1998: 2-2 [Full Text]