A high-sensitivity alternative to "routine" genetic amniocentesis: Multiple urinary analytes, nuchal thickness, and age

OBJECTIVE: Our purpose was to evaluate the Down syndrome screening efficien cy of a new algorithm consisting of multiple urinary biochemical and ultras ound markers for use in high-risk groups such as women of advanced maternal age. STUDY DESIGN: The urinary beta-core fragment of human chorionic gonadotropi n (beta-core fragment) and total urinary estriol, along with fetal nuchal t hickness, were measured prospectively in pregnant women who were undergoing genetic amniocentesis at midtrimester (15 to 24 weeks). The most common in dication for amniocentesis was advanced maternal age (90.2%). An analyte ra tio (beta-core fragment/total estriol ratio) was developed. The values were expressed as multiples of the normal median. An increase in the observed n uchal thickness (delta nuchal thickness) above that expected on the basis o f the biparietal diameter was calculated. On the basis of the mean and stan dard deviations of the urinary analyte ratio in normal fetuses and also Dow n syndrome, we calculated individual Down syndrome likelihood ratios for ea ch of the two parameters, using gaussian analysis. The product of the likel ihood ratios, based on delta nuchal thickness and urinary beta-core fragmen t-total estriol Values times the maternal age-related risk, gave the overal l Down syndrome risk. The screening efficiency of our algorithm at various risk thresholds was determined. RESULTS: There were 13 (2.8%) cases of Down syndrome in a total study popul ation of 457. At a risk threshold of >1 in 70, the sensitivity was 92.3% fo r a false-positive rate of 4.5%. Corresponding values at a risk threshold o f >1 in 78 were a sensitivity of 100% with a false-positive rate of 5.2%. CONCLUSION: By combining urinary analyte, nuchal thickness, and maternal ag e data, we achieved a high Down syndrome detection rate with a low false-po sitive rate. This algorithm would be attractive as an alternative to "routi ne" amniocentesis based solely on advanced maternal age. The potential bene fits of this protocol could include a significant reduction in the rate of amniocentesis, along with substantial savings in medical expenditures.