Aug 15, 2014

Negative results of pregnancy tests. Why they fail?

Prof. Richard T. Griffey et col. have discussed uhCG POC tests, reviewed  false-negative rate, and described mechanisms for false negatives and potential remedies.

These results may include missed ectopic pregnancy (the leading cause of first-trimester pregnancy-related maternal death), administration of medications contraindicated in pregnancy, fetal radiation exposure, patient complaints, and lawsuits. This has led to the emergency medicine dictum to check for pregnancy in all women of child-bearing age.

General pregnancy test usage includes qualitative urine point-of-care (POC) tests in laboratories, clinics, and EDs; over-the-counter (OTC) urine tests for consumer/layperson use; and qualitative and quantitative serum tests. With their high level of reliability, POC tests have become a widely accepted, fast, and accurate method for determining pregnancy.

Like all tests, POC uhCG tests have limitations like false-negative results that have been reported in urine-based POC qualitative hCG tests due to what is known as the "hook effect phenomenon".

"We described these phenomena, present data from a review of false-negative uhCG tests in our ED, and discuss urine hCG POC testing and potential remedies for these false-negative results". In the majority of the cases identified, no reporting was initiated for laboratory follow-up to ascertain the etiology.

POC tests usually employ monoclonal antibodies or a combination of mono- and polyclonal antibodies to detect the intact hCG (human chorionic gonadotropin) hormone in urine, a glycoprotein produced in the placenta after implantation. These so-called "sandwich assays" consist of a fixed solid-phase antibody attached to some matrix and a separate free or soluble antibody to which a "reporter" label is attached. These antibodies bind different epitopes of an antigen (here, hCG), forming a "sandwich," which then results in a visible signal that the user can read to indicate the test is positive (Figure 2).

The β-subunit of hCG is what is measured in pregnancy tests and exists in several forms, including hyperglycosylated hCG (H-hCG), nicked hCG, free β subunit, the core fragment of β-hCG (hCG-βcf), and others, some of which could be the cause of false negative results due to "hook-like" effect phenomenon (Figure) at different stages of pregnancy.

In general, urine hCG POC tests generally perform very well, with low false-negative rates. Manufacturers should just characterize the hCG variants recognized by their tests, optimize their tests to detect both early and mid-stage pregnancy, and institute quality assurance measures eliminating lot-to-lot variability. Clinicians must familiarize themselves with the mechanisms and limitations of the specific type of urine point-of-care used in their practice while recognizing that under certain circumstances, false-negative tests can occur.


Written by Dra. Belén Suárez Jiménez for The All Results Journals.

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