Is there a role for C-reactive protein during and after labour?

Dear Editor,

We read with interest the article by Joyce et al. ¹ This study reported that C-reactive protein (CRP) was raised in late pregnancy, with a marked further elevation on the first day after delivery. Where serial measurements were made, concentrations were persistently raised on day 3.

Our group recently defined the pregnancy-specific reference interval for CRP in uncomplicated pregnancy, and we subsequently demonstrated that using this significantly increases the diagnostic accuracy for chorioamnionitis before the onset of labour. ² Both groups have reported that CRP is elevated in pregnancy, although the upper limit reported by Joyce et al. (34.8 mg/L) was higher than ours (19 mg/L). We propose two main reasons for this. Firstly, we recruited 322 women without evidence of pre-existing inflammatory diseases that are known to elevate CRP. In contrast, Joyce et al. do not appear to have selected participants except to exclude infection, so it does not meet the conventional definition of a healthy reference population. Secondly, we reported the central 95% of data after having excluded outliers, in line with IFCC guidance, ³ which narrows the interval. As in another of our studies, the authors reported similar concentrations of procalcitonin (PCT) in pregnant and non-pregnant women before labour (≤0.05 ng/mL). ⁴

To further investigate and confirm how both markers subsequently change during and after labour, we prospectively identified a sample of 95 consecutive women on the labour ward at John Radcliffe Hospital, Oxford, all of whom had no evidence of infection (negative blood, urine and genital cultures), and we measured CRP and PCT on samples that had already been collected as part of routine care (unpublished data). The median CRP was elevated at 27 mg/L (interquartile range 11–47), which is in keeping with the day 1 postpartum results reported by Joyce et al. Importantly, CRP was elevated above 19 mg/L in 60% of these women; thus, the antenatal upper reference limit cannot be extrapolated for peripartum use. The median peripartum PCT was 0.1 ng/mL (IQR 0.05–0.1), which is also consistent with their findings that PCT increased only slightly after labour, and it is consistently below 0.25 ng/mL, a recommended decision point for antibiotic stewardship. ⁵

We agree that this is a promising finding in support of using PCT as a marker of maternal sepsis. However, by demonstrating that CRP is elevated after delivery, we are uncertain whether Joyce et al. are proposing that CRP should be interpreted using a peripartum-specific reference interval, or that its huge variation after delivery preclude its use? We propose that the growing body of evidence suggests that CRP has limited clinical utility after the onset of labour (an inflammatory process), but PCT is a stable and specific diagnostic test with great potential. The added benefit of using PCT for diagnosing and managing infection has been extensively demonstrated in other fields but, despite the global burden of maternal infection, there is an unmet need for a suitably powered diagnostic accuracy study for its application in obstetrics.