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

Abstract

Objective: Our purpose was to evaluate the Down syndrome screening efficiency of a new algorithm consisting of multiple urinary biochemical and ultrasound markers for use in high-risk groups such as women of advanced maternal age.

Study design: The urinary beta-core fragment of human chorionic gonadotropin (beta-core fragment) and total urinary estriol, along with fetal nuchal thickness, were measured prospectively in pregnant women who were undergoing genetic amniocentesis at midtrimester (15 to 24 weeks). The most common indication for amniocentesis was advanced maternal age (90.2%). An analyte ratio (beta-core fragment/total estriol ratio) was developed. The values were expressed as multiples of the normal median. An increase in the observed nuchal thickness (delta nuchal thickness) above that expected on the basis of the biparietal diameter was calculated. On the basis of the mean and standard deviations of the urinary analyte ratio in normal fetuses and also Down syndrome, we calculated individual Down syndrome likelihood ratios for each of the two parameters, using gaussian analysis. The product of the likelihood ratios, based on delta nuchal thickness and urinary beta-core fragment-total estriol values times the maternal age-related risk, gave the overall 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 population of 457. At a risk threshold of >1 in 70, the sensitivity was 92.3% for a false-positive rate of 4.5%. Corresponding values at a risk threshold of >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 age data, we achieved a high Down syndrome detection rate with a low false-positive rate. This algorithm would be attractive as an alternative to "routine" amniocentesis based solely on advanced maternal age. The potential benefits of this protocol could include a significant reduction in the rate of amniocentesis, along with substantial savings in medical expenditures.