Interpretation
OGTT remains the gold standard test for diagnosing GDM. With the
pressure on health care resources, anxiety associated with the
diagnosis, and the need to start management in timely manner, providing
accurate, precise and rapid results for OGTT is beneficial. The
advancing technology of POC devices can help achieve these goals.
Several studies have investigated the use of a variety of variable POC
glucometers using different diagnosis criteria. Summary of these studies
are included in table 2. The studies used a variety of VPG reference
measurements: from sending samples to the hospital laboratory without
special arrangements as we have done here, which has the advantage being
a comparison to usual clinical practice; through sending to the hospital
laboratory paying strict attention to The National Association of
Clinical Biochemist (NACB) for the diagnosis of GDM guidelines to
minimise impact of pre-analytical factors; through to use of Isotope
Dilution Gas Chromatography Mass Spectrometry. Most studies showed good
agreement between POC testing and VPG with acceptable diagnostic
performance, but no study has advocated for completely replacing
laboratory testing with POC-testing for GDM screening. Other studies
comparing POC with Lab-VPG methods in 50g OGGT also reported
satisfactory performance for POC in GDM
diagnosis.(15-17) However, the case for comparing POC
testing to laboratory testing is far from straightforward due to
multiple factors including clinical and analytical factors.
Clinically, the diagnostic performance is partly depending on the
diagnostic thresholds. The HAPO study showed there is a linear
relationship between increasing glucose concentrations at OGTT and
adverse pregnancy outcomes, such as macrosomia, neonatal hypoglycaemia
and caesarean birth, with no threshold effect.(1)Health care systems impose diagnostic thresholds: those at or above
threshold are managed as GDM and those below are labelled as no GDM.
This is relatively easy to administer and allows healthcare resources to
be directed for those at higher risk of adverse pregnancy outcomes.
However, in this situation, when a linear parameter is converted into a
binary outcome, when different systems are used to measure the linear
parameter there will be diagnostic disagreement, particularly when close
to the diagnostic threshold.
Analytically, POC glucometer performance is subjected to analytical
interferences from variation in haematocrit, pH and oxygen and sample
matrix effect.(9) However, the laboratory methods,
against which POC devices are compared, have inherent analytical and
pre-analytical errors, of which the effect of in-vitro glycolysis is
particularly significant. Uninhibited in-vitro glycolysis can result in
5-10% reduction in VPG(18) and GDM misclassification.
To prevent this, NACB guidelines recommends collecting samples in sodium
fluoride additive tubes, transferring them on slurry ice to be
centrifuged with 30 minutes of collection. Alternatively, citrate tubes
can immediately inhibit the glycolysis.(19) In routine
practice adherence to these guidelines is
suboptimal.(20-22) So the discrepancy in diagnostic
performance might be partly attributed to the negative bias with lab
methods rather than positive bias with POC. Generally, studies that
compared POC without strict measures to control in-vitro glycolysis,
like our study, have reported positive analytical
bias,(23, 24) high sensitivity and
NPV(25-29) for POC with potential for over-diagnosis.
While some studies that religiously applied NACB guidelines have
reported negative analytical bias and potential for
misdiagnosis.(30, 31)