Accuracy of expected risk of Down syndrome using the second-trimester triple test.

Second-trimester maternal serum screening (MSS) for Down syndrome has been widely used in routine prenatal care in developed countries. The screening combines maternal age-specific risk of Down syndrome with risk estimation obtained by measuring maternal serum markers to assign women an expected risk of having a term Down syndrome pregnancy. Diagnostic tests were offered to women whose risk exceeded the risk cutoff determined by the screening program. The commonly used triple test, which involves the use of maternal age, serum -fetoprotein, unconjugated estriol, and human chorionic gonadotropin, was expected to have a Down syndrome detection rate of 60–65% and false-positive rate of 5% (1 ). Although the expected screening performance has been achieved in many screening programs, the accuracy of individual risk calculated by a relatively complex computation based on a statistical model was not immediately obvious. Good agreement between the expected risk of Down syndrome and observed prevalence has been reported previously in several screening programs (2–5). We evaluated the accuracy of expected risk of Down syndrome in a large provincial, multiple test center, MSS program in Ontario, Canada. MSS has been coordinated at the provincial level in Ontario since 1993. Triple maker screening ( -fetoprotein, unconjugated estriol, and -human chorionic gonadotropin) was carried out in seven regional laboratory centers. Information including screen utilization, results, follow-up data, and the pregnancy outcomes of all women screened in the seven centers was collected in the Ontario MSS database. Data on outcomes for all pregnancies screened were obtained through the Canadian Institute of Health Information, which records every hospital admission in Canada. Where necessary, information was verified through provincial genetic-counseling centers and cytogenetic laboratories. Using this protocol, we obtained 94.4% of outcomes. The study was based on 311 256 women screened in the Ontario MSS program between October 1993 and September 1998. Of the 311 256 women screened, a Down syndrome risk level was recorded for 301 700, and 284 804 (94.4%) of them had outcome data from Canadian Institute of Health Information, including 506 pregnancies associated with Down syndrome. The expected risks of a term Down syndrome pregnancy were calculated with AFP Expert (Benetech). The risk cutoff used in the Ontario MSS program was 1 in 385. Using a technique described by Wald et al. (2 ), we ranked the women screened according to their individual expected risk of Down syndrome. They were divided into 10 groups, each group containing 44–59 cases of Down syndrome pregnancies. Two factors were considered when grouping the cases: (a) that each risk group covered an appropriate risk range; and (b) that there was a similar number of cases in each group. The mean expected term risks of an affected pregnancy were calculated for each