The Clinical Laboratory's Role in Preventing False-Negative hCG Point-of-Care Results

False negative pregnancy tests in the emergency department (ED) can have serious consequences—including birth defects or loss of pregnancy—if pregnant women are subjected to certain treatments potentially harmful to a fetus. While in vitro device manufacturers and ED clinicians must do their part to help minimize the frequency of false-negative test results, laboratory personnel ultimately are responsible for the accuracy of point-of-care (POC) testing. To minimize false-negative­ qualitative human chorionic gonadotropin (hCG) test results, laboratorians must understand the limitations of POC hCG devices, utilize strategies to investigate results that are inconsistent with the clinical presentation, and recommend alternate testing to help establish a definitive diagnosis. Measurement of hCG represents an analytical challenge, as the range of hCG concentrations associated with normal pregnancy spans from 0 IU/L immediately following conception to approximately 200,000 IU/L by weeks 8 to 10. False-negative urine hCG results could be encountered for a number of different reasons. Negative results are common in very early pregnancy, when hCG concentrations in urine likely are below a device's limit of detection. False-negative results may also occur due to the hook effect, a phenomenon characterized by a pathologically high concentration of intact hCG that saturates all available binding sites and prevents an antibody-hCG-antibody sandwich from forming. In normal pregnancy, intact hCG concentrations are not sufficiently elevated to cause a hook effect. However, intact hCG is not the only variant observed in normal pregnancy, and hCG POC devices may either recognize or interfere with these other variants. One such variant, hCG β core fragment (hCGβcf), is present at 10-fold higher concentrations than intact hCG in urine beginning at around week 6 of pregnancy. As a degradation product formed during renal filtration, hCGβcf is exclusively found in urine. Of particular interest to laboratory personnel, false-negative POC hCG results have been documented in women with high urinary concentrations of hCGβcf. Read more here