Introduction
It is increasingly clear that maternal deaths from infections are more
common than was previously appreciated.1 The burden of
obstetric and non-obstetric infections, which is particularly profound
in low- and middle-income countries,2 has been
addressed in international efforts to prevent maternal
mortality,3 but sepsis remains the third commonest
cause of maternal death worldwide.2 The availability
of accurate and affordable diagnostic tools is an important prerequisite
for diagnosing infection in modern clinical practice, but they can be
prohibitively expensive, and have rarely been validated in pregnant
populations.4, 5 This prompts us to re-evaluate
existing tests, and to consider if we can optimise them for clinical
practice.
C-reactive protein (CRP) is an acute phase reactant that rises in
response to inflammation, and it is most commonly used to investigate
suspected infection. Concentrations of CRP are low in most healthy
individuals6 but the upper reference limits have been
variably reported between 3 and 10 mg/L.7 Pregnancy is
associated with immune cell activation and
proliferation,8 and it has been reported that CRP is
elevated in pregnant women from early in the first
trimester,9 although the extent of this is unclear.
Despite this, current guidelines on suspected sepsis by the Royal
College of Obstetricians and Gynaecologists recommend using an upper
reference limit of 7 mg/L,10 which is similar to most
non-pregnant standards.
The existing reference intervals (RIs) for CRP are usually derived from
non-pregnant populations and often include individuals who are
significantly older than most healthy pregnant women. By making
comparisons to RIs from an unrepresentative population, the diagnostic
accuracy of the test may be compromised. Importantly, pregnancy is a
dynamic physiological state associated with progressive, marked plasma
expansion and altered hepatic and renal function,11 so
it cannot be assumed that concentrations of CRP are stable throughout
pregnancy. Establishing robust, population-specific RIs is essential for
using diagnostic biomarkers safely in clinical practice but, unlike
other tests,12 there is no established RI for CRP in
pregnant women. To address this, we undertook a cross-sectional study of
315 healthy pregnant women to estimate an RI for CRP in uncomplicated
pregnancy and evaluated its diagnostic accuracy for chorioamnionitis, as
an example of an infection.