Second and first trimester estimation of risk for Down syndrome: implementation and performance in the SAFER study.
OBJECTIVE
Document patient choices and screening performance (false positive and detection rates) when three improved Down syndrome screening protocols were introduced coincidentally.


METHODS
Second-trimester 'triple marker' screening was expanded by adding second-trimester dimeric inhibin-A (four-marker), with or without first-trimester pregnancy-associated plasma protein-A (five-marker). Nuchal translucency (NT) measurements were included when available from accredited sonographers (six-marker). For assigning risk, two sets of marker distribution parameters were evaluated.


RESULTS
Over 3.5 years, 8571 women enrolled (median age 30.6 years). Uptake of the four-, five- and six-marker protocols was 18%, 46% and 36%, respectively. Of those selecting an integrated test (five or six markers), 9.7% did not provide the second trimester serum sample. False positive rates decreased with added markers (5.2%, 5.1% and 2.5%, respectively) and varied between the two parameter sets, while detection remained high. Overall, 21 of 23 cases were detected (91%, 95% CI 73-98%) at a 4.2% false positive rate (95% CI 3.3-5.1%).


CONCLUSIONS
Integrated screening protocols were chosen 4.6 times more often than four-marker screening (82% vs. 18% uptake). Overall detection was higher and false positives lower, consistent with recent guidelines. Important performance factors include gestational dating method, risk cut-off, and the parameter set used to assign risk.
MacRae
Andrew R
AR
Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada. macrae@cc.umanitoba.ca
Chodirker
Bernie N
BN
Davies
Gregory A
GA
Palomaki
Glenn E
GE
Knight
George J
GJ
Minett
Jane
J
Kavsak
Peter A
PA
Toi
Ants
A
Chitayat
David
D
Van Caeseele
Paul G
PG
D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000097:blood*; D004314:Down Syndrome / Q000097:blood* / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D048208:Nuchal Translucency Measurement; D057240:Patient Preference; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D018570:Risk Assessment
D015415:Biomarkers