Comparing three screening strategies for combining first- and second-trimester Down syndrome markers.
OBJECTIVE
To describe the choices and tradeoffs inherent in 3 published strategies that combine first- and second-trimester markers for Down syndrome screening.


METHODS
Published marker distributions for Down syndrome and unaffected pregnancies in the first and second trimesters were combined with a maternal age distribution and age-associated Down syndrome risk in a statistical model to compare sequential, contingent, and integrated screening.


RESULTS
Sequential and contingent screening strategies are always less efficient (higher false-positive rate for a given detection rate) than integrated screening, but the reduction in efficiency is dependent on the combination of risk cutoffs chosen. At a fixed false-positive rate, sequential and contingent strategies perform better when a higher proportion of the false positives occur in the second trimester. For all 3 strategies, increasing the overall false-positive rate from 2% to 5% increases detection (from approximately 85% to 91%). Although associated with reduced screening efficiency compared with integrated screening, both sequential and contingent screening identify the majority of detected Down syndrome cases early. With contingent screening, the process is also completed in the first trimester for most women.


CONCLUSIONS
Integrated screening is the most efficient of the 3 strategies, but it is possible to select risk cutoffs for both sequential and contingent strategies that minimize losses in efficiency while maintaining early detection and early completion. For all of these strategies, well-designed intervention trials are needed to determine acceptability to women and providers in primary care settings and to assess real-world performance.


METHODS
III.
Palomaki
Glenn E
GE
Division of Medical Screening, Department of Pathology and Laboratory Medicine, Women & Infants Hospital, Providence, RI 02903, USA. gpalomaki@ipmms.org
Steinort
Klaus
K
Knight
George J
GJ
Haddow
James E
JE
D000328:Adult; D015415:Biomarkers / Q000097:blood; D003663:Decision Trees; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000379:methods*
D015415:Biomarkers