Mind the "CRP gender gap"! sex differences in CRP evolution over time in neonatal sepsis: a monocentric retrospective...

C-reactive protein (CRP) is a readily available test widely used to assess neonatal sepsis (NS). In children with sepsis or other infectious conditions, CRP is more likely to be higher in females than males, however, evidence is lacking on sex differences in CRP in the neonatal population. This study aims to describe sex differences of CRP evolution in the ascending and decreasing phase after its peak in neonates with likely NS.

This is a monocentric retrospective cohort study conducted at Etterbeek-Ixelles Hospital in Brussels. We included all neonates born in the facility between January 2017 and December 2022 who received antibiotics in the first 72 hours of life. Patients whose CRP concentrations remained under 10 mg/L were excluded. To describe the ascending kinetics of CRP and its logarithm for male and female neonates, we fitted a piecewise linear mixed-effects regression model with birth considered as time zero and one knot at 12 hours of life. We used a linear mixed-effects regression model with CRP peak considered as time zero to describe CRP's descending kinetics and its logarithm for male and female neonates.

We included 506 neonates (60.1% male and 39.9% female). CRP concentration in the first 12 hours of life doubled every 3.2 and 2.8 hours, respectively, in males and females, with female neonates having a statistically significant faster rise of base 2 logarithm of CRP (+0.04 log2 mg/L/hour 95% CI= +0.01 +0.07). After 12 hours of life, CRP doubled every 6.5 and 8.6 hours, respectively, in males and females, with female neonates having a statistically significant slower rise of base 2 logarithm of CRP (-0.039 log2 mg/L/hour 95% CI= -0.02 -0.06). After its peak, CRP decreased by half every 31.1 and 30.9 hours, respectively, for males and females. No statistically significant sex differences were found in CRP peak or decline.

In neonates of both sexes with likely but unconfirmed NS, CRP seems to increase, reach a peak, and then decrease, following a logarithmic pattern. Before antibiotic treatment, female neonates in our population showed an earlier increase in CRP levels, with no difference in peak CRP levels.