Integrated Screening For Down's Syndrome
by Frederick M. Chen
Wald NJ, Watt HC, Hackshaw AK. Integrated screening for Down's syndrome based on tests performed during the first and second trimesters. N Engl J Med 1999; 341:461-7.
Clinical question What is the optimal prenatal screening strategy for Down's syndrome?
Background Prenatal screening for Down's syndrome is currently performed with either first trimester testing (ultrasound for nuchal translucency, free [Beta] human chorionic gonadotropin [HCG], plasma protein A) or second trimester serum marker testing (the widely used triple test). Although current tests are quite sensitive and detect most cases of Down's syndrome, false-positive results cause anxiety, and subsequent invasive diagnostic testing can result in fetal loss. The authors propose an integrated screening test, combining both first and second trimester tests as a way to reduce the number of false-positive screening results.
Population studied The authors estimated the sensitivity and false-positive rates of first and second trimester screening tests using results from published studies. Although only 3 published studies were used, the test characteristics in these studies were consistent with other estimates of their performance.[1]
Study design and validity The proposed integrated test uses measurements of plasma protein A and nuchal translucency in the first trimester, and serum [Alpha]-fetoprotein, unconjugated estriol, HCG, and inhibin A in the second trimester. The authors fitted a multivariate model to the performance characteristics of each of these screening tests and calculated the performance of the integrated test. The model included coefficients of correlation between markers, in an attempt to account for the relative contribution of each marker to a positive result.
Outcomes measured The authors reported the sensitivity and false-positive rate of the integrated test and compared them with characteristics of the existing screening strategies.
Results The integrated test reduced the false-positive rate of prenatal screening for Down's syndrome from 5% to 0.9% and had a higher sensitivity than the screening tests currently used. Depending on the false-positive rate set in the model, the positive likelihood ratio for the integrated test varied from 19 to 85, which is better than any of the current screening strategies. For example, the triple test has an 88% sensitivity and a false-positive rate of 19% (positive likelihood ratio = 4.6) for women older than 35 years. Using the integrated test for these women, the false-positive rate would in theory decrease from 19% to 3%.
Recommendations for clinical practice Although the integrated test, which combines first and second trimester screening tests for Down's syndrome, appears to be a better screening test with fewer false-positive results, there are several reservations about its utility. These conclusions are based on a multivariate model, and no clinical trial of the integrated test has been performed. The increased cost of the additional screening tests, as well as the limited availability of certain serum markers, must be considered before widespread adoption of this strategy is recommended. Finally, because the integrated test depends on a combination of first and second trimester test results, mothers would learn the results of their first trimester test and then be asked to postpone any decision making until their second trimester results are available. This could cause significant anxiety and confusion, and the combination of these factors may make the integrated test impractical.
Frederick M. Chen, MD, MPH University of Washington Seattle Email: fchen@u.washington.edu
REFERENCE
[1.] US Preventive Services Task Force. Guide to clinical preventive services. 2nd ed. Baltimore, Md: Williams & Wilkins; 1996.
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