First trimester Down syndrome screening with dried blood spots using a dual analyte free beta hCG and PAPP-A immunofluorometric assay.

OBJECTIVE: To determine the effectiveness of first trimester Down syndrome screening with dried blood spots using a dual analyte free beta human chorionic gonadotrophin (hCG)/pregnancy-associated plasma protein A (PAPP-A) immunofluorometric assay. METHOD: An initial retrospective study of 54 Down syndrome cases and 1064 control specimens was performed followed by a series of 146,513 specimens from routine screening. Detection rates at a fixed 5% false-positive rate were determined separately based on reference data from the retrospective study set and then adjusted based on the routine screening study set. RESULTS: On the basis of the retrospective analysis, the estimated detection rate using free beta hCG, PAPP-A and maternal age varied from 78% at 9 weeks of pregnancy to 70% at 13 weeks of pregnancy. Using a combined protocol, including NT, the detection rate varied from 92 to 90% between 9 and 13 weeks of gestation. Adjusting distribution parameters based on the routine screening dataset reduced the detection rate by at most 1%. CONCLUSION: Analysis of free beta hCG and PAPP-A using a dual analyte dried blood spot assay is an effective tool in Down syndrome screening, adding an important option for those considering implementation or modification of existing prenatal screening programs.

Are second-trimester minor sonographic markers for Down syndrome useful in patients who have undergone first-trimester combined screening?

OBJECTIVE: We sought to determine efficacy of minor markers for detection of Down syndrome (DS) in a population prescreened with first-trimester combined screening (FTS). STUDY DESIGN: FTS was modified using established likelihood ratios to generate a new composite risk (NCR). RESULTS: Of 3845 women, 390 had ≥1 marker. There were 10/3845 cases of DS; 3 were among patients with low-risk FTS (n = 3727). In 55 patients, NCR adjusted the risk from low to high without increasing detection rate. NCR did not modify risk to allow for detection of the 3 DS among patients with low-risk FTS even though 2 of these fetuses had 1 minor marker each. There were 7 DS among patients with high-risk FTS (n = 118). Use of NCR increased positive predictive value from 7/118 (5.1%) to 7/53 (13.2%). CONCLUSION: Screening for minor markers is useful in patients with high-risk FTS. It is of questionable benefit in patients with low-risk FTS.