Does the delivery mode affect post-birth neonatal serum C-reactive protein levels? A causal effect analysis

Aim To determine if the delivery mode has a causal effect on neonatal serum C-reactive protein (CRP) levels. If such a causal effect exists, we aim to quantify its magnitude. Methods We investigated the causal effect of the delivery mode on serum CRP levels 6-8 h after delivery, with appropriate statistical tools for retrospective studies, combining classical and machine-learning methods. The statistical inference is followed by sensitivity analysis to quantify the magnitude of unobserved bias required in order to alter the study's conclusion. Results This retrospective study reviewed laboratory records of neonates after birth who underwent blood tests due to suspected sepsis. A total of 440 newborns were included, 324 of which underwent a vaginal delivery, 59 an urgent caesarean delivery, and 57 an elective caesarean delivery. Our results revealed that serum CRP values following elective caesarean deliveries were 50% less than those following a vaginal delivery (P = 0.030; -0.907; 95% CI [-1.545, -0.268] in log-CRP units). No significant effect was found for urgent caesarean deliveries compared to vaginal deliveries (P = 0.887). Those results were strengthened by (1) a sensitivity magnitude of 1.6 to unobserved bias and (2) non-significant effects when analysis is repeated on blood collected 12-24 h after birth. Conclusion CRP concentrations in neonatal blood during the first 6-8 h of life are higher following vaginal deliveries compared to elective caesarean deliveries. Further studies with the intent of improving EONS detection should include information on the delivery mode.