Pregnancy Tests Evaluated During Early Gravidity

The predominant hormone human chorionic gonadotropin (hCG) variant in urine, hCG β core fragment (hCGβcf), has been demonstrated to cause false-negative results in qualitative point-of-care (POC) hCG devices.

In a hospital setting, failure to detect pregnancy can lead to major consequences such as administration of medications that cause birth defects, fetal radiation exposure, or failure to diagnose ectopic pregnancy, which is the leading cause of first-trimester pregnancy-related maternal death.


Scientists at Washington University School of Medicine (St. Louis, MO, USA) tested a wide range of purified hCG and hCGβcf concentrations, which were mixed and tested on two POC devices. By use of those results, a screening method was defined and nine additional POC devices were evaluated. Two solutions containing 500 pmol/L (171 IU/L) intact hCG without hCGβcf and 500 pmol/L intact hCG with 500,000 pmol/L hCGβcf were used to screen all POC devices.

Varying concentrations of intact hCG and hCGβcf were combined in an hCG-negative urine matrix. Each solution was tested in duplicate by use of the SP hCG Combo Rapid Test (Cardinal Health; Dublin, OH, USA) and the OSOM hCG Combo Test (OSOM; Lexington, MA, USA). This screening method was then used to evaluate the performance of nine additional qualitative hCG POC devices. Visible differences in device performance were evident, resulting in the classification of the devices into three distinct groups: best performance, moderate performance, and poor performance.

The two best-performing devices were the Beckman Coulter Icon 20 (Brea, CA, USA) and the Alere hCG Combo (Waltham, MA, USA). The Icon 20 was the only device to exhibit an increased signal when hCGβcf was added to intact hCG. The Alere device was very modestly affected by the addition of hCGβcf. Two other tests present an unacceptable risk of false-negative results to patients after 5–7 weeks of pregnancy and the accuracy of the remaining seven tests was moderately affected by hCG beta core fragment.

Ann M. Gronowski, PhD, the senior author of the study said, “There are three important take home messages here. One, physicians, nurses, and other healthcare professionals need to be educated that this is a problem. Two, manufacturers need to make the possibility of false negatives clearly visible in their package inserts and work to develop better tests. And three, in centers where quantitative blood hCG testing is available, this should be the preferred pregnancy test. Blood testing is not subject to this effect because hCG beta core fragment is not present in serum.” The study was published in the April 2014 issue of the journal Clinical Chemistry.

Related Links:
Washington University School of Medicine 
Cardinal Health
Beckman Coulter