NICU Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy.
PLoS One. 2019 Feb 8;14(2):e0211484. doi: 10.1371/journal.pone.0211484. eCollection 2019.
To investigate the impact of different stages of intrauterine inflammation (IUI) on neonatal outcomes, before and after adjusting for gestational age (GA) and other perinatal confounders.
This was an observational, prospective, single-center cohort study including all eligible neonates with GA < 35 weeks and/or birth weight ≤ 1500 g born at a 3rd level Neonatal Intensive Care Unit between 2011 and 2014. Pathological patterns of placenta, membranes and cord were classified according to Redline's criteria. Multivariable linear and logistic regression models were applied, either including or not GA among the covariates.
Of the 807 enrolled neonates, 134 (16.6%) had signs of IUI: among these, 54.5% showed just histological chorioamnionitis (HCA), 25.4% had HCA + funisitis (FUN) stage 1, and 20.1% had HCA + FUN stage 2-3. At univariate analysis, HCA increased the risk for retinopathy of prematurity (ROP) and bronchopulmonary dysplasia, while FUN (any stage) had a deleterious impact on all outcomes investigated. After adjustment for covariates not including GA, HCA was a risk factor only for ROP (OR = 2.8, CI: 1-7.8), while FUN (any stage) was still associated with increased ORs for all outcomes (p <0.01). Upon inclusion of GA in the regression model, the results differed remarkably. HCA was associated with lower risk for mechanical ventilation (OR = 0.3, CI: 0.1-0.7) and need for surfactant (OR = 0.5, CI: 0.2-0.9), while FUN (any stage) worsened clinical conditions at birth (p <0.05), increased the risk for early-onset sepsis (p <0.01), and increased the length of mechanical ventilation (FUN stage 2-3 only, RC = 6.5 days, CI: 2-11). No other outcome was affected.
IUI, especially FUN, negatively impact most neonatal morbidities, but its effect is partially reverted adjusting for GA. Considered that GA is an intermediate variable interposed between prenatal causes of prematurity and outcomes, the appropriateness of adjusting for GA may be questionable.
探讨宫内炎症（IUI）不同阶段对小于胎龄儿（GA）和/或出生体重≤1500g 新生儿结局的影响，并对 GA 及其他围生期混杂因素进行校正。
这是一项观察性、前瞻性、单中心队列研究，纳入了 2011 年至 2014 年在三级新生儿重症监护病房出生的所有符合条件的胎龄（GA）<35 周和/或出生体重≤1500g 的新生儿。胎盘、胎膜和脐带的病理性模式根据 Redline 的标准进行分类。应用多变量线性和逻辑回归模型，分别在协变量中包括或不包括 GA。
在 807 名入组新生儿中，134 名（16.6%）有 IUI 迹象：其中，54.5%表现为单纯组织学绒毛膜羊膜炎（HCA），25.4%有 HCA+脐带炎（FUN）1 期，20.1%有 HCA+FUN 2-3 期。单因素分析显示，HCA 增加了早产儿视网膜病变（ROP）和支气管肺发育不良的风险，而 FUN（任何阶段）对所有研究结局均有不良影响。在调整不包括 GA 的协变量后，HCA 仅为 ROP 的危险因素（OR=2.8，95%CI：1-7.8），而 FUN（任何阶段）与所有结局的 OR 增加仍相关（p<0.01）。在将 GA 纳入回归模型后，结果差异显著。HCA 与机械通气（OR=0.3，95%CI：0.1-0.7）和表面活性物质需求（OR=0.5，95%CI：0.2-0.9）的风险降低相关，而 FUN（任何阶段）均使出生时临床状况恶化（p<0.05），增加早发性败血症（p<0.01）的风险，并增加机械通气时间（仅 FUN 2-3 期，RC=6.5 天，95%CI：2-11）。其他结局不受影响。
IUI，尤其是 FUN，对大多数新生儿发病率有负面影响，但通过校正 GA 可部分逆转其影响。考虑到 GA 是早产产前病因和结局之间的中间变量，调整 GA 的适当性可能值得怀疑。
