Fetal inflammatory response in women with proteomic biomarkers characteristic of intra-amniotic inflammation and preterm birth.
Fetal inflammatory response in women with proteomic biomarkers characteristic of intra-amniotic inflammation and preterm birth.
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DOI：
10.1111/j.1471-0528.2008.01925.x
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发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Buhimschi IA
中科院分区：
文献类型：
--
作者：
Buhimschi CS;Dulay AT;Abdel-Razeq S;Zhao G;Lee S;Hodgson EJ;Bhandari V;Buhimschi IA
确定羊水（AF）炎症特征性生物标志物（防御素2和1，钙颗粒蛋白C和A）的存在与出生时胎儿炎症状态之间的关系。前瞻性观察队列。三级转诊大学医院132名连续母亲（胎龄，中位数[四分位数间距]：29.6 [24.1-33.6]周），他们进行了临床指征穿刺术以排除感染及其新生儿。通过质谱SELDI-TOF诊断羊膜内炎症。AF蛋白质组指纹[质量限制（MR）评分]范围为0-4（无至所有生物标志物存在）。根据蛋白质组学生物标志物的数量对羊膜内炎症的强度进行分级：MR评分0：“无”炎症; MR评分1-2：“轻微”炎症; MR评分3-4：“严重”炎症。在出生时，所有病例均获得脐带血。组织学绒毛膜炎（HCA）和早发性新生儿败血症（EONS）的严重程度是基于既定的组织学和血液学标准。白细胞介素-6（IL-6）水平通过灵敏的免疫测定法测定。脐带血与AF IL-6的比率被用作胎儿与AF隔室中不同炎症反应的指标。将羊膜内感染的蛋白质组生物标志物与脐带血IL-6联系起来，并将后者用作胎儿炎症反应的主要标志物。羊膜腔内炎症的妇女分娩的胎龄较早（ANOVA，P<0.001），且AF IL-6水平较高（P<0.001）。出生时，患有“严重”羊膜内炎症的女性的新生儿具有较高的脐带血IL-6水平（P=0.002）和较高的EONS频率（P=0.002）。EONS患儿脐血IL-6水平显著升高（P<0.001）。在39名由患有“最小”羊膜内炎症的母亲分娩的新生儿中，15名（39%）的脐带血IL-6水平高于该组的平均水平，2名新生儿确诊为败血症。绒毛膜板（P<0.001）、绒毛膜蜕膜（P=0.002）、脐带（P<0.001）中的嗜中性粒细胞浸润的严重程度是脐带血与AF IL-6比值的独立预测因子，但羊膜（P>0.05）不是。在校正胎龄、出生体重、剖宫产至分娩间隔、剖宫产、胎膜状态、种族、MR评分、抗生素和类固醇暴露后，相关性得以维持。我们提供的证据表明，AF中存在炎症特征性蛋白质组学生物标志物与出生时胎儿炎症状态增加相关。新生儿的炎症状态增加，即使在“最小”羊膜内炎症的情况下，血培养也呈阳性。
To determine the relationship between presence of amniotic fluid (AF) biomarkers characteristic of inflammation (defensins 2 and 1, calgranulins C and A) and fetal inflammatory status at birth. Prospective observational cohort. Tertiary referral University hospital 132 consecutive mothers (gestational age, median [interquartile range]: 29.6 [24.1-33.6] weeks), who had a clinically indicated amniocentesis to rule-out infection and their newborns. Intra-amniotic inflammation was diagnosed by mass spectrometry SELDI-TOF. The AF proteomic fingerprint [Mass Restricted (MR) score] ranges from 0-4 (none to all biomarkers present). The intensity of intra-amniotic inflammation was graded based on the number of proteomic biomarkers: MR score 0: “no” inflammation; MR score 1-2: “minimal” inflammation; MR score 3-4: “severe” inflammation. At birth, cord blood was obtained for all cases. Severity of histological chorioamnionitis (HCA) and early onset neonatal sepsis (EONS) was based on established histological and hematological criteria. Interleukin-6 (IL-6) levels were measured by sensitive immunoassays. The cord blood-to-AF IL-6 ratio was used as an indicator of the differential inflammatory response in the fetal versus the AF compartment. to relate proteomic biomarkers of intra-amniotic infection to cord blood IL-6 and to use the latter as the primary marker of fetal inflammatory response. Women with intra-amniotic inflammation delivered at an earlier gestational age (ANOVA, P<0.001) and had higher AF IL-6 levels (P<0.001). At birth, neonates of women with “severe” intra-amniotic inflammation had higher cord blood IL-6 levels (P=0.002) and a higher frequency of EONS (P=0.002). EONS was characterized by significantly elevated cord blood IL-6 levels (P<0.001). Out of the 39 neonates delivered by mothers with “minimal” intra-amniotic inflammation, 15 (39%) had umbilical cord blood IL-6 levels above the mean for the group, and 2 neonates had confirmed sepsis. The severity of the neutrophilic infiltrate in the chorionic plate (P<0.001), choriodecidua (P=0.002), umbilical cord (P<0.001), but not amnion (P>0.05) was an independent predictor of the cord blood-to-AF IL-6 ratio. Relationships were maintained following correction for gestational age, birthweight, amniocentesis-to delivery interval, cesarean delivery, status of the membranes, race, MR score, antibiotics and steroid exposure. We provide evidence that presence in the AF of proteomic biomarkers characteristic of inflammation is associated with an increased inflammatory status of the fetus at birth. Neonates mount an increased inflammatory status and have positive blood cultures even in the context of “minimal” intra-amniotic inflammation.
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影响因子：
7.2
作者：
Buhimschi, Irina A.;Zambrano, Eduardo;Buhimschi, Catalin S.
通讯作者：
Buhimschi, Catalin S.
DOI：
10.1111/j.1471-0528.2004.00340.x
发表时间：
2005-02-01
影响因子：
5.8
作者：
Buhimschi, IA;Christner, R;Buhimschi, CS
通讯作者：
Buhimschi, CS
影响因子：
9.8
作者：
Gonzalez, Juan M.;Xu, Hua;Elovitz, Michal A.
通讯作者：
Elovitz, Michal A.
影响因子：
0.9
作者：
HADLOCK, FP;DETER, RL;PARK, SK
通讯作者：
PARK, SK
影响因子：
3.6
作者：
Dahlgren, Jovanna;Samuelsson, Anne-Maj;Holmang, Agneta
通讯作者：
Holmang, Agneta