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.