Stability of intact chorionic gonadotropin (hCG) in serum, liquid whole blood, and dried whole-blood filter-paper spots: impact on screening for Down syndrome by measurement of free beta-hCG subunit

Abstract

The use of multiple maternal serum biochemical markers in screening for Down syndrome is gaining worldwide acceptance. We sought to study the impact of the potential instability of intact human chorionic gonadotropin (hCG) on free beta-hCG subunit, a marker that has recently been used successfully in such screening. We found that, in practice, any changes in free beta-hCG due to the instability of intact hCG do not inhibit the effectiveness of free beta-hCG as a marker for Down syndrome. This was proven by controlled laboratory experiments at various stress temperatures, freeze-thaw studies, and analysis of a large set of screening data with particular reference to time in transit for individual samples. Data from controlled dissociation studies demonstrate that any apparent increase in free beta-hCG due to the instability of intact hCG cannot be attributed simply to the dissociation of intact hCG. Finally, for large-scale mass population screening in areas of the world where transport delays, safety concerns, and high temperatures preclude the shipment of liquid whole blood, dried whole-blood spots in filter paper provide a suitable delivery system with many advantages.