Combining first and second trimester markers for Down syndrome screening: think twice.
OBJECTIVE
This study compares different screening strategies for the detection of Down syndrome and considers practical implications of using multiple screening protocols.


METHODS
The performance characteristics of each screening strategy were assessed based on datasets of Down syndrome (n=11) and unaffected pregnancies (n=1006) tested in both first and second trimester, as well as data from first trimester (n=18,901) and second trimester (n=40,748) pregnancies.


RESULTS
For a detection rate of 91%, the false positive rates for integrated and serum integrated screening were 2.5% and 6.3%, respectively, compared with combined first trimester (4.6%) and second trimester (12.6%) screening. Contingent and sequential screening protocols achieved detection rates of 82 to 91% with false positive rates between 2.6 and 2.9%. Contingent protocols require retesting of 15 to 20% of cases in the second trimester. Sequential and integrated protocols require retesting of 98 to 100% of cases in the second trimester. The various screening strategies did not always detect the same Down syndrome pregnancies.


CONCLUSIONS
Combining first and second trimester markers for Down syndrome screening better defines the at-risk population. However, integrated protocols complicate management of screening programs and may not be suitable as primary screening strategies. It may be a better use of resources to refine current first and second trimester programs through improved access and new markers. We therefore suggest thinking twice before embracing integrated population screening programs.
Cocciolone
Robert
R
Department of Genetic Medicine, University of Adelaide, Adelaide, South Australia, Australia. robert.cocciolone@cywhs.sa.gov.au
Brameld
Kate
K
O'Leary
Peter
P
Haan
Eric
E
Muller
Peter
P
Shand
Karen
K
D000328:Adult; D015415:Biomarkers / Q000097:blood; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods / Q000592:standards; D016017:Odds Ratio; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011262:Pregnancy Trimester, Second / Q000097:blood*; D011296:Prenatal Diagnosis / Q000379:methods* / Q000592:standards*; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity
D015415:Biomarkers