Preventing False-Negative hCG Point-of-Care Results

Avoiding false-negative human chorionic gonadotropin (hCG) results in the emergency department is critical to preventing birth defects or loss of pregnancy, which can result if a pregnant woman is subjected to treatments that are detrimental to a fetus. To reduce these false-negatives, “laboratorians must understand the limitations of point-of-care (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,” write former AACC President Ann M. Gronowski, PhD, DABCC, and Robert D. Nerenz, PhD, in October’s CLN Bench Matters article. Gronowski is a professor of pathology, immunology, and obstetrics and gynecology, and Nerenz is a clinical chemistry fellow at Washington University School of Medicine in St. Louis.

False-negative urine hCG results can happen for a variety of reasons. They are common very early in pregnancy, when hCG concentrations can be as low as 0 IU/L and are likely undetectable. POC pregnancy tests may also encounter interference from hCG variants. One of these variants is hCG β core fragment (hCGβcf), which is present at 10-fold higher concentrations than intact hCG in urine starting around week 6 of pregnancy. “Of particular interest to laboratory personnel, false-negative POC hCG results have been documented in women with high urinary concentrations of hCGβcf,” write Gronowski and Nerenz.

Gronowski and Nerenz recently screened 11 of the most common POC pregnancy tests to evaluate their susceptibility to hCGβcf-related false-negative results. Alarmingly, they discovered that hCGβcf concentrations observed in normal pregnancy cause nine of these devices to perform unreliably.

Given the limitations of currently available POC hCG devices, Gronowski and Nerenz encourage the use of quantitative hCG serum measurement in the central laboratory, which is not susceptible to hCGβcf inhibition, instead of POC urine testing when assessing a patient’s pregnancy status. Laboratorians can also correct for elevated hCGβcf levels in urine samples by diluting the samples, which should prevent a false-negative result. Additionally, the authors recommend that each lab evaluate multiple POC pregnancy tests and use only the one that offers the best combination of sensitivity and resistance to inhibition by hCGβcf.

For more advice on mitigating false-negative hCG point-of-care results, check out the October issue of CLN.