Effect on Down syndrome screening performance of adjusting for marker levels in a previous pregnancy.
OBJECTIVE
In prenatal screening for Down syndrome, serum marker values can be adjusted using values from a previous pregnancy to avoid the problem of women having a high chance of recurrent false-positive results. We investigate the effect of such adjustment on overall screening performance.


METHODS
Monte Carlo simulation was used to investigate the effect of this adjustment on five widely used screening tests for Down syndrome (Triple, Quadruple, Combined, serum Integrated, Integrated tests).


RESULTS
Adjustment for screening marker values (expressed in multiples of the median, (MoM)) in a previous pregnancy improved screening performance. The detection rate for a 1% false-positive rate (FPR) increased from 54 to 59% with the Triple test, from 63 to 68% with the Quadruple test, from 70 [corrected] to 75% for the Combined test, from 70 [corrected] to 76% for the serum Integrated test, and from 85 to 88% for the Integrated test. The FPR for an 85% detection rate decreased from 10 to 7.9%, 7.1 to 4.9%, 4.9 to 3.7%, 4.7 to 2.9% and 1.1 to 0.7% respectively for the five tests. Among women who have had a false-positive result in a previous pregnancy, adjustment substantially lowers the false-positive rate, for example, from 18 [corrected] to 7.3% with the Combined test using a 1 in 250 risk cut-off.


CONCLUSIONS
MoM adjustment for values in a previous pregnancy improves overall screening performance and substantially reduces the high recurrent false-positive rate. This adjustment can be routinely applied in screening programmes through the screening software used to interpret a woman's screening results.
Wald
Nicholas J
NJ
Wolfson Institute of Preventive Medicine, Barts and The London Queen Mary's School of Medicine and Dentistry, UK. n.j.wald@qmul.ac.uk
Barnes
Isobel M
IM
Birger
Ruthie
R
Huttly
Wayne
W
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D004314:Down Syndrome / Q000175:diagnosis* / Q000196:embryology; D005189:False Positive Reactions; D005260:Female; D005865:Gestational Age; D020073:Gravidity; D006801:Humans; D008423:Maternal Age; D008875:Middle Aged; D008962:Models, Theoretical; D048208:Nuchal Translucency Measurement / Q000379:methods / Q000706:statistics & numerical data; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011262:Pregnancy Trimester, Second / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis; D011296:Prenatal Diagnosis / Q000379:methods*; D020379:Risk Adjustment / Q000379:methods*
D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A