Estimates for the sensitivity and false-positive rates for second trimester serum screening for Down syndrome and trisomy 18 with adjustment for cross-identification and double-positive results

Second trimester screening fur fetal Down syndrome and trisomy 18 is availa ble through separate protocols that combine the maternal age-specific risk and the analysis of maternal serum markers. We have determined the extent t o which additional Down syndrome affected pregnancies may be identified thr ough trisomy 18 screening, and the extent to which additional cases of tris omy 18 may be screen-positive for Down syndrome. The combined false-positiv e rate, taking into consideration those pregnancies that are screen-positiv e by both protocols. has also been determined. Sensitivity and false-positi ve rates were determined by computer simulation of results that incorporate d previously published statistical variables into the model. Using second t rimester risk cut-errs of 1 : 270 for Down syndrome and 1 : 100 for trisomy 18. it was found that few additional cases of Down syndrome are identified through trisomy 18 screening. However, approximately 6-10% of trisomy 18 a ffected pregnancies will be screen-positive for Down syndrome but screen-ne gative for trisomy 18. For women aged 40 or more, the false-positive rate f or trisomy 18 exceeds 1% and approximately half of these cases will also be screen-positive for Down syndrome. For ii population with maternal ages eq uivalent to that in the United States in 1998, after adjusting for the cros s-identification. the sensitivity for three-analyte trisomy 18 screening is 78%. If this testing is performed in conjunction with Down syndrome 'tripl e' screening, the Down syndrome sensitivity is 75%, and the combined false- positive rate is 8.5%. If the three-analyte trisomy 18 screening is perform ed with the Down syndrome 'quad' screen, the trisomy 18 sensitivity remains at 78%, the Down syndrome sensitivity is 79%. and combined false-positive rate is 7.5%. Sensitivity and false-positive rates are also provided for ot her widely used Down syndrome and trisomy 18 risk cut-offs. Sensitivity and false-positive rates that take into consideration cross-identification and double-positives should be helpful for pre-test counseling and the evaluat ion of serum screening programs. Copyright (C) 2001 John Wiley & Sons, Ltd.