Effectiveness of combining maternal serum alpha-fetoprotein and hCG in a second-trimester screening program for Down syndrome

Abstract

Objective: To evaluate the efficacy of combining hCG and alpha-fetoprotein (AFP) with maternal age in a two-analyte maternal serum screening program for Down syndrome.

Methods: A prospective study involved the screening of 12,170 maternal sera from patients at 14-25 weeks of gestation. The risk for Down syndrome at term was calculated from maternal serum hCG and AFP, and maternal age. For women 36 years of age and younger, a risk of 1:307 or greater was considered screen-positive. For women over 36, a risk greater than that a priori was considered screen-positive. False-positive rates and detection rates were compared with those resulting from a screening protocol using only AFP and age.

Results: Seven hundred eighty-two sera were initially screen-positive (6.4%). Subsequent sonography decreased this total to 687 (5.6%), and 467 (3.8%) of these patients accepted amniocentesis. Ten cases of Down syndrome and seven other chromosomal abnormalities were detected. Follow-up investigations revealed eight additional Down syndrome cases that were missed by screening. The identification of 18 Down syndrome cases in 12,170 pregnancies corresponds closely with the prediction of 14.1 Down syndrome births (18.2 second-trimester fetuses) in this population calculated from age-dependent risks. The detection rate for Down syndrome was 56% (ten of 18 expected cases). Only five of 18 (28%) would have been detected by AFP and age alone.

Conclusion: These results support the mathematical model that hCG is the major contributor to the increased sensitivity of multi-analyte screening and demonstrate that screening programs can attain substantial improvement in detection of second-trimester Down syndrome by adding hCG to AFP and age.