Measurement of hCG (human chorionic gonadotropin) in blood or urine is used mainly in the determination of pregnancy.
In a healthcare setting, urine samples are the preferred choice and they are tested for hCG using a qualitative point-of-care (POC) device. Urine hCG POC tests generally have low false-negative rates. However, sometimes qualitative hCG tests may not be sensitive enough to detect very early pregnancy. A study published in medical journal JAMA in 2001 reported that although POC tests routinely claim a “99% detection rate”, their sensitivity in detecting pregnancy at 1 week actually ranges only up to 97%.
False-negative hCG POC results can prove disastrous if the pregnant woman is in emergency care and is subjected to treatments that may harm the fetus. Experts point out that clinical labs have an important role in preventing errors in hCG POC reporting.
Challenges in Measurement of hCG
There are many reasons why POC testing can fail to detect early pregnancy:
- Some POC assays may not detect certain hCG variants as well as others
- Some POC test kits may not detect certain hCG variants at all
- Studies have found that most urine pregnancy tests have poor sensitivity for H-hCG, the hyperglycosylated form of human chorionic gonadotropin (hCG) present in early pregnancy
- Urine hCG POC tests can fail in pregnancy detection when hCG is excessively present and dilution is not performed to wash the excess hCG variant away. When in excess, the variant can bind one antibody quite well and the other not at all, resulting in a false-negative result
- High concentrations of hCGβcf saturate, the predominant form of hCG found in urine after six weeks of pregnancy, can also give rise to false negatives. This hCG variant effect prevents the development of a positive signal and generates a negative result even if intact hCG is present in the urine sample
Manufacturers of laboratory equipment, clinicians and laboratory personnel – all have a role in preventing false-negative hCG POC results. Here’s what experts recommend:
In view of the fact that uhCG testing routinely takes place at many stages of pregnancy, manufacturers should improve their equipment to minimize hCGβcf interference. Tests must be optimized to detect early and mid-stage pregnancy, and QA measures established to eliminate lot-to-lot variability.
Clinicians need to be knowledgeable about and familiar with the limitations of the specific type of uhCG POC tests that they use. They should be alert to the possibility of false-negative hCG POC results under certain circumstances so that patient care does not suffer. Getting a quantitative hCG serum measurement done in a central laboratory is a viable alternative to POC qualitative (yes/no) urine testing. In addition to being more sensitive, serum quantitative assays are not prone to inhibition by hCGβcf.
Clinical labs should know that dilution is key to an accurate test when there are high concentrations of hCG or hCGβcf. Diluting the sample would generate a positive result. Laboratorians should also evaluate and compare medical lab devices and choose the one provides sensitive analysis and is not affected by hCGβcf.