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

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.