False Negative Pregnancy Tests Still a Real Problem in Home and Hospital Devices

Neg pregnancy testWe have blogged in the past about false negative pregnancy tests due to hCG beta core fragment (hCGbcf).   After about 5 weeks of pregnancy (i.e. 3 weeks after the expected period) concentrations of hCGbcf, in urine, are higher than all other forms of hCG. Our group has shown previously that the concentration of hCGbcf can saturate one of the antibodies used in the point-of-care hospital pregnancy kits. As a result, test shows a negative result. The variant hook effect can be confirmed if testing shows a positive result after diluting the sample. This phenomenon is referred to as the "variant hook effect" and was reported to the FDA in 2009.

Recently, our group took this observation one step further and examined over-the-counter home pregnancy devices to see if they were subject to the same problem.  We examined six over the counter devices and selected two that seemed to be most affected by the variant hook effect. We then compared those two devices to the hospital device that we had made our original observations in four years ago, and to a hospital device that we thought performs best when compared to various other hospital pregnancy devices. Not surprisingly, we found that the over-the-counter home pregnancy devices are also subject to the variant hook effect. However, what was a surprise was that the hospital pregnancy devices were more affected by hCG beta core fragment than the home pregnancy devices!  Furthermore, despite the fact that the variant hook effect was reported to the FDA in 2009, manufacturers have not changed their devices to avoid this problem. To hear more about this paper you can listen to a podcast describing the findings.

Our laboratory is currently working to better define how much hCGbcf is required to cause the variant hook effect. We hope that this will help manufacturers to produce devices that avoid false negative results. In the meantime, several things need to be done:

  1. Physicians, nurses, and other health care professionals need to be educated about this problem-especially in the hospital setting.
  2. The variant hook effect should be made clearly visible in pregnancy test package inserts and they need to state that when a false negative is suspected, a simple dilution can yield a positive result if the patient is truly pregnant. This is very important for centers that have no alternative way of testing for pregnancy.
  3. Finally, in my opinion, quantitative serum hCG testing should be the preferred pregnancy test in centers where it is available. Serum testing is not subject to the variant hook effect because hCGbcf is not present in serum. Furthermore, quantitative serum assays are much more sensitive than the qualitative assays.
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