Dubiel Mariusz, Seremak-Mrozikiewicz Agnieszka, Breborowicz Grzegorz H, Drews Krzysztof, Pietryga Marek, Gudmundsson Saemundur
University School of Medical Sciences, Department of Perinatology and Gynecology, University Hospital, Poznan, Poland.
J Perinat Med. 2005;33(1):17-21. doi: 10.1515/JPM.2005.002.
Fetal hypoxia and preterm delivery are reported to be strongly associated with brain damage and neurodevelopmental delay. Doppler signs of fetal brain sparing have been described during chronic hypoxia, but whether they are related to brain damage is unknown. The aim of this study was to evaluate if markers of tissue injury, i.e., tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are related to signs of increased perinatal vascular impedance and/or fetal brain sparing in high-risk pregnancies.
TNF-alpha and IL-6 levels were evaluated in maternal blood serum of 67 high-risk pregnancies. Serum samples were taken at the time of umbilical, middle cerebral artery and uterine artery Doppler velocimetry examination. The values for TNF-a and IL-6 were correlated with reference median values obtained with gestational age in the form of a Z-score.
TNF-alpha levels showed values within the normal range in only four cases. IL-6 values were found normal in 14 cases. The Z-score for mean middle cerebral artery pulsatility index (PI) showed a significant correlation to TNF-alpha and IL-6 levels, P < 0.0001 and P < 0.003, respectively. This might suggest a strong correlation between signs of fetal brain sparing and increased maternal serum TNF-alpha and IL-6 levels. Abnormal uterine artery PI and the presence of a "notch" were also highly significantly related to TNF-alpha and IL-6 levels, which were nearly two-fold higher compared to normal uterine artery blood flow and the absence of a "notch". Abnormal cerebro/placental ratios showed significant correlations to TNF-alpha and IL-6 levels.
The present results suggest a strong correlation between levels of TNF-alpha and IL-6 not only for signs of fetal brain sparing, but also for uteroplacental blood flow. This finding supports the role of tissue injury in cases of fetal brain sparing, but whether this is a reflection of brain damage or secondary to placental pathology needs further evaluation.
据报道，胎儿缺氧和早产与脑损伤及神经发育迟缓密切相关。慢性缺氧期间已描述了胎儿脑保护的多普勒征象，但它们是否与脑损伤相关尚不清楚。本研究的目的是评估组织损伤标志物，即肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）是否与高危妊娠中围产期血管阻抗增加和/或胎儿脑保护征象相关。
对67例高危妊娠孕妇的血清进行TNF-α和IL-6水平评估。在脐动脉、大脑中动脉和子宫动脉多普勒测速检查时采集血清样本。TNF-α和IL-6的值与以Z分数形式表示的胎龄参考中位数进行相关性分析。
仅4例患者的TNF-α水平在正常范围内。14例患者的IL-6值正常。大脑中动脉平均搏动指数（PI）的Z分数与TNF-α和IL-6水平显著相关，分别为P < 0.0001和P < 0.003。这可能表明胎儿脑保护征象与孕妇血清TNF-α和IL-6水平升高之间存在密切相关性。子宫动脉PI异常和出现“切迹”也与TNF-α和IL-6水平高度显著相关，与正常子宫动脉血流和无“切迹”相比，其水平几乎高出两倍。脑/胎盘比率异常与TNF-α和IL-6水平显著相关。
目前的结果表明，TNF-α和IL-6水平不仅与胎儿脑保护征象密切相关，而且与子宫胎盘血流密切相关。这一发现支持了组织损伤在胎儿脑保护情况下的作用，但这是脑损伤的反映还是继发于胎盘病理情况，还需要进一步评估。
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