First-Trimester or Second-Trimester Screening, or Both, for Down???s Syndrome (2006)

Debate continues over whether to screen pregnant women for fetal Down syndrome in the first or the second trimester of pregnancy or in both trimesters. The First- and Second-Trimester Evaluation of Risk Factors (FASTER) Trial obtained direct comparative data on current screening methods from 38,167 women with singleton pregnancies who were cared for at 15 U.S. centers over approximately 3 years in 1999–2002. Down syndrome was found in 117 instances. Inclusion criteria included a maternal age of 16 or older and a fetal crown-rump length of 36 to 79 mm—consistent with a gestational age of 10 weeks 3 days through 13 weeks 6 days. First-trimester screening combined measurement of the nuchal translucency with maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fβhCG) levels. Quadruple screening in the second trimester, from 15 to 18 weeks gestation, included alpha-fetoprotein, total hCG, unconjugated estriol, and inhibin. Stepwise sequential screening, in which the Down syndrome risk estimate was provided after each test, was compared with “fully integrated” screening, which yielded only a single risk result after both the first- and second-trimester screening tests had been done. Although first-trimester serum screening and measurement of nuchal translucency gave similar results, the combination proved to be superior for detecting Down syndrome at 11 to 13 weeks gestation. When the false-positive rate was 5%, first-trimester combined screening at 11, 12, and 13 weeks identified 87%, 85%, and 82% of Down syndrome cases, respectively. The detection rate for second-trimester quadruple screening was 81%. Quadruple screening outperformed triple screening, resulting in a higher detection rate at a lower false-positive rate. With fully integrated screening, in which the first-trimester studies were performed at 11 weeks gestation, 96% of cases were detected. For women younger than 35 years of age, first-trimester combined screening detected 75% of cases at a 5% false-positive rate, compared with 77% and 2.3%, respectively, for second-trimester quadruple screening and 77% and 0.4% for fully integrated screening. In women aged 35 and older, first-trimester combined screening detected 95% of cases with a false-positive rate of 22%. The respective figures for second-trimester quadruple screening were 92% and 13%, and for integrated screening with first-trimester markers measured at 11 weeks, 91% and 2%. In stepwise sequential screening, women have combined screening in the first trimester and results are provided immediately. Women with positive results are offered chorionic villus sampling. Women with negative results return at 15 weeks for quadruple testing, and a combined risk estimate is provided at that time. Using this approach and setting the false-positive rate for each component at 2.5%, 95% of cases were detected with a false-positive rate of 4.9%. For fully integrated screening, in which both first- and second-trimester tests are done but the woman gets only one risk estimate after the second-trimester tests are completed, setting the Down syndrome detection rate at 95% resulted in a false-positive rate of 4%. First-trimester combined screening is an effective means of detecting Down syndrome, assuming that there is adequate quality control for measuring nuchal translucency. Both stepwise sequential screening and fully integrated screening have high detection rates at acceptably low false-positive results. The lower false-positive rate must be weighed against the advantages of earlier diagnosis using sequential screening.