Journal of Genetic Counseling

, Volume 14, Issue 6, pp 409–413 | Cite as

Sequential Down Syndrome Screening: The Importance of First and Second Trimester Test Correlations when Calculating Risk

Research Article


Down syndrome screening can be particularly effective when both first and second trimester tests are performed. However, the counseling of women who have received sequential first and second trimester screening can be problematic. We evaluated an approximation where the post-test risk from the first trimester screening is used as the new a priori risk for the second trimester screening. The approximation disregards between-trimester test correlations. The Down syndrome detection rate based on the approximation (90.2%) would be close to that obtained when all correlations were considered (90.8%) but the false positive rate would be 26% higher (3.9% versus 3.1%, respectively). For any particular woman, the use of the approximation could result in highly inaccurate risks. We conclude that the correlations that exist between first and second trimester screening tests preclude the use of second trimester risks derived from the direct product of separate first and second trimester screening. Counseling issues in the delivery of sequential screening are discussed.

Key Words

first trimester screening second trimester screening Down syndrome sequential screening 


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  1. Benn, P. A., Fang, M., Egan, J. F. X., Horne, D., & Collins, R. (2003). Incorporation of Inhibin-A in second-trimester screening for Down syndrome. Obstet Gynecol, 10, 451–454.Google Scholar
  2. Benn, P., Wright, D., & Cuckle, D. (2005). Practical strategies for contingent sequential screening for Down's syndrome. Prenat Diagn, 25, 645–652.CrossRefPubMedGoogle Scholar
  3. Bindra, A., Heath, V., Liao, A., Spencer, K., & Nicolaides, K. H. (2002). One-stop clinic for assessment for risk for trisomy 21 at 11–14 weeks: A prospective study of 15,030 pregnancies. Ultrasound Obstet Gynecol, 20, 219–225.CrossRefPubMedGoogle Scholar
  4. Bray, I., Wright, D. E., Davies, C., & Hook, E. B. (1998). Joint estimation of Down syndrome risk and ascertainment rates: a meta-analysis of nine published data sets. Prenat Diagn, 18, 9–20.PubMedGoogle Scholar
  5. Chen, J., Heffley, D., Beazoglou, T., & Benn, P. A. (2000). Utilization of amniocentesis by women screen-positive for Down syndrome by the second trimester triple test. Community Genet, 3, 24–30.CrossRefGoogle Scholar
  6. Copel, J. A., & Bahado-Singh, R. O. (1990). Prenatal screening for Down's syndrome—a search for family's values. N Engl J Med, 341, 521–522.Google Scholar
  7. Malone, F. (2005). Letter to the Editor: Sequential pathways of testing after first-trimester screening for trisomy 21. Obstet Gynecol, 105, 438.Google Scholar
  8. National Center for Health Statistics. (2002). Vital statistics of the United States, 2000. Natality Data Set. Hyattsville, MD. CD ROM, Series 21:14, Hyattsville, MD.Google Scholar
  9. Platt, L. D., Greene, N., Johnson, A., Zachary, J., Thom, E., Krantz, D., et al. (2004). Sequential pathways of testing after first-trimester screening for trisomy 21. Obstet Gynecol, 104, 661–666.PubMedGoogle Scholar
  10. Wald, N. J., Cuckle, H. S., Densem, J. W., Nanchahal, K., Royston, P., Chard, T., et al. (1988). Maternal serum screening for Down's syndrome in early pregnancy. BMJ, 297, 883–887.PubMedGoogle Scholar
  11. Wald, N., Watt, H. C., & Hackshaw, A. K. (1999). Integrated screening for Down's syndrome based on tests performed during the first and second trimesters. N Engl J Med, 341, 461–467.CrossRefPubMedGoogle Scholar
  12. Wald, N. (2000). Down's syndrome. In N. Wald & I. Leck (Eds.), Antenatal and neonatal screening, 2nd ed. (pp. 83–115). Oxford, UK: Oxford University Press.Google Scholar
  13. Wald, N. J., Huttley, W. J., & Hackshaw, A. K. (2003a). Antenatal screening for Down's syndrome with the quadruple test. Lancet, 361, 835–836.CrossRefGoogle Scholar
  14. Wald, N. J., Rodeck, C., Hackshaw, A. K., Walters, J., Chitty, L., & Mackinson, A. M. (2003b). First and second trimester antenatal screening for Down's syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). J Med Screen, 10, 56–104.Google Scholar
  15. Wald, N., Rodeck, C., Rudnicka, A., & Hackshaw, A. (2004). Letter to the editor. Nuchal translucency and gestational age. Prenat Diagn, 24, 150–151.PubMedGoogle Scholar
  16. Wapner, R., Thom, E., Simpson, J. L., Pergament, E., Silver, R., Filkins, K., et al. (2003). First trimester screening for trisomies 21 and 18. N Engl J Med, 349, 1405–1413.CrossRefPubMedGoogle Scholar
  17. Wright, D., Bradbury, I., Benn, P., Cuckle, H., & Ritchie, K. (2004). Contingent screening for Down syndrome is an efficient alternative to non-disclosure sequential screening. Prenat Diagn, 24, 762–766.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Division of Human Genetics, Department of Genetics and Developmental BiologyUniversity of ConnecticutFarmington
  2. 2.Genzyme GeneticsPhiladelphia
  3. 3.Genzyme GeneticsPhiladelphia

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