Abstract
ObjectivesNo 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.MethodsStudy-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).ResultsStage-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).ConclusionFIR, 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.
Highlights
Ascending intrauterine infection/inflammation (AIUI) is a central pathophysiology of spontaneous preterm birth due to either preterm labor and intact membranes (PTL) or preterm premature rupture of membranes [1,2,3]
fetal inflammatory response (FIR), early-onset neonatal sepsis (EONS) and chorioamnionitis continuously increase according to the progression of inflammation in umbilical cord (UC) among preterm-gestations with inflammation in extraplacental membranes or chorionic plate (CP)
This finding may suggest that funisitis(inflammation in UC) is both qualitatively and quantitatively histologic-counterpart of fetal inflammatory response syndrome (FIRS), and a surrogate-marker for chorioamnionitis
Summary
Ascending intrauterine infection/inflammation (AIUI) is a central pathophysiology of spontaneous preterm birth due to either preterm labor and intact membranes (PTL) or preterm premature rupture of membranes (preterm-PROM) [1,2,3]. Inflammation of the umbilical vessels begins in umbilical vein (UV) (umbilical phlebitis) and is followed by involvement of either umbilical artery (UA) or umbilical arteries (UAs) (umbilical arteritis) [9], and the extension of inflammation into WJ is considered to be a more advanced stage than inflammation restricted to umbilical vessels based on the finding that the presence of extension of neutrophils into WJ was associated with a more increased FIR than the absence of that lesion in the context of inflammation in UV and/or UA [10] Both inflammation in UC [6, 11] and FIRS [7, 8] are closely associated with fetal infectious morbidity such as early-onset neonatal sepsis (EONS) and chorioamnionitis as an advanced stage of maternal inflammatory response (MIR) in extraplacental membranes [5]. There is a good chance for the more frequent development of chorioamnionitis according to the progression of inflammation in UC, considering that both chorioamnionitis and inflammation in UC are an advanced stage of AIUI [1,2,3]
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