The relationship among the progression of inflammation in umbilical cord, fetal inflammatory response, early-onset neonatal sepsis, and chorioamnionitis

Abstract

Objectives: No information exists about whether fetal inflammatory-response(FIR), early-onset neonatal sepsis(EONS) and chorioamnionitis(an advanced-stage of maternal inflammatory-response in extraplacental membranes) continuously increase according to the progression of inflammation in umbilical-cord(UC). The objective of current-study is to examine this-issue.

Methods: Study-population included 239singleton pregnant-women(gestational-age[GA] at delivery: 21.6~36weeks) who had inflammation in extraplacental membranes or chorionic plate (CP) and either preterm-labor or preterm-PROM. We examined FIR, and the frequency of fetal inflammatory-responses syndrome(FIRS), proven-EONS, suspected-EONS and chorioamnionitis according to the progression of inflammation in UC. The progression of inflammation in UC was divided with a slight-modification from previously reported-criteria as follows: stage0, inflammation-free UC; stage-1: umbilical phlebitis only; stage-2: involvement of at least one UA and either the other UA or UV without extension into WJ; stage-3: the extension of inflammation into WJ. FIR was gauged by umbilical-cord-plasma(UCP) CRP concentration(ng/ml) at birth, and FIRS was defined as an elevated UCP CRP concentration at birth(≥200ng/ml).

Results: Stage-0, stage-1, stage-2 and stage-3 of inflammation in UC were present in 48.1%, 15.5%, 6.7%, and 29.7% of cases. FIR continuously increased according to the progression of inflammation in UC(Kruskal-Wallis test,P<0.001; Spearman-rank-correlation test,P<0.000001,r = 0.546). Moreover, there was a significant and stepwise increase in the frequency of FIRS, proven-EONS, suspected-EONS and chorioamnionitis according to the progression of inflammation in UC(each for P<0.000005 in both chi-square test and linear-by-linear-association). Multiple logistic-regression analysis demonstrated that the more advanced-stage in the progression of inflammation in UC(i.e., stage-1 vs. stage-2 vs. stage-3), the better predictor of suspected-EONS (Odds-ratio[OR]3.358, 95%confidence-interval[CI]:1.020-11.057 vs. OR5.147, 95%CI:1.189-22.275 vs. OR11.040, 95%CI:4.118-29.592) and chorioamnionitis(OR6.593, 95%CI:2.717-15.999 vs. OR16.508, 95%CI:3.916-69.596 vs. OR20.167, 95%CI:8.629-47.137).

Conclusion: FIR, EONS and chorioamnionitis continuously increase according to the progression of inflammation in UC among preterm-gestations with inflammation in extraplacental membranes or CP. This finding may suggest that funisitis(inflammation in UC) is both qualitatively and quantitatively histologic-counterpart of FIRS, and a surrogate-marker for chorioamnionitis.

Fig 1. Relationship between the progression of inflammation in umbilical cord (UC) and umbilical cord plasma (UCP) CRP concentrations at birth (ng/ml).

Kruskal-Wallis test and Spearman rank correlation test were performed, and each P value is shown in graph. The median value and range of UCP CRP concentrations at birth (ng/ml) according to the progression of inflammation in UC are also shown in graph. Of 239 cases which met the entry for this study, 215 patients had UCP CRP concentrations at birth; however, 24 patients did not have an UCP CRP concentration at birth because of the limited amount of the remaining UCP.

Fig 2

The frequency of fetal inflammatory response syndrome (FIRS) [a], proven early-onset neonatal sepsis (EONS) [b], suspected EONS [c] and chorioamnionitis [d] according to the progression of inflammation in UC. Each P value is shown in graph. Of 239 cases which met the entry for this study, 215 patients had UCP CRP concentrations at birth; however, 24 patients did not have an UCP CRP concentration at birth because of the limited amount of the remaining UCP, and therefore, we could not examine the frequency of FIRS. Moreover, twenty-three neonates were excluded from the analysis in the evaluation of proven EONS and suspected EONS because they died shortly after delivery as a result of extremely prematurity (n = 19) or anomaly (n = 4) and thus could not be evaluated with respect to the presence or absence of proven EONS and suspected EONS.