Integrated screening for Down's syndrome based on tests performed during the first and second trimesters

Background Both first-trimester screening and second-trimester screening fo r Down's syndrome are effective means of selecting women for chorionic-vill us sampling or amniocentesis, but there is uncertainty about which screenin g method should be used in practice. We propose a new screening method in w hich measurements obtained during both trimesters are integrated to provide a single estimate of a woman's risk of having a pregnancy affected by Down 's syndrome. Methods We used data from published studies of various screening methods em ployed during the first and second trimesters. The first-trimester screenin g consisted of measurement of serum pregnancy-associated plasma protein A i n 77 pregnancies affected by Down's syndrome and 383 unaffected pregnancies and measurements of nuchal translucency obtained by ultrasonography in 326 affected and 95,476 unaffected pregnancies. The second-trimester tests wer e various combinations of measurements of serum alpha-fetoprotein, unconjug ated estriol, human chorionic gonadotropin, and inhibin A in 77 affected an d 385 unaffected pregnancies. Results When we used a risk of 1 in 120 or greater as the cutoff to define a positive result on the integrated screening test, the rate of detection o f Down's syndrome was 85 percent, with a false positive rate of 0.9 percent . To achieve the same rate of detection, current screening tests would have higher false positive rates (5 to 22 percent). If the integrated test were to replace the triple test (measurements of serum alpha-fetoprotein, uncon jugated estriol, and human chorionic gonadotropin), currently used with a 5 percent false positive rate, for screening during the second trimester, th e detection rate would be higher (85 percent vs. 69 percent), with a reduct ion of four fifths in the number of invasive diagnostic procedures and cons equent losses of normal fetuses. Conclusions The integrated test detects more cases of Down's syndrome with a much lower false positive rate than the best currently available test. (N Engl J Med 1999;341:461-7.) (C) 1999, Massachusetts Medical Society.