与系统性炎症早产儿神经发育相关的因素。
Factors associated with neurodevelopment in preterm infants with systematic inflammation.
机构信息
Department of Pediatrics, Seoul National University Children's Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
Department of Radiology, Seoul National University Children's Hospital, Seoul, South Korea.
出版信息
BMC Pediatr. 2021 Mar 8;21(1):114. doi: 10.1186/s12887-021-02583-6.
BACKGROUND
Several studies have suggested that adverse neurodevelopment could be induced by systemic inflammation in preterm infants. We aimed to investigate whether preterm infants with systemic inflammation would have impaired neurodevelopment and which biomarkers and neurophysiologic studies during inflammation are associated with poor neurodevelopment.
METHODS
This prospective cohort study enrolled infants born before 30 weeks of gestation or with birth weight < 1250 g. Infants were grouped according to the presence of systemic inflammation: Control (no inflammation, n = 49), I (systemic inflammation, n = 45). Blood and cerebrospinal fluid samples for markers of brain injury and inflammation were collected and amplitude-integrated electroencephalography (aEEG) was performed within 4 h of septic workup. We evaluated aEEG at 35 weeks postmenstrual age (PMA), head circumference at 36 weeks PMA, and brain MRI at discharge. The Bayley Scales of Infant and Toddler Development III (Bayley-III) was performed at a corrected age (CA) of 18 months.
RESULTS
The I group had more white matter injuries (2 vs. 26.7%, Control vs. I, respectively) at the time of discharge, lower brain functional maturation (9.5 vs. 8), and smaller head size (z-score - 1.45 vs. -2.12) at near-term age and poorer neurodevelopment at a CA of 18 months than the control (p < 0.05). Among the I group, the proportion of immature neutrophils (I/T ratios) and IL-1 beta levels in the CSF were associated with aEEG measures at the day of symptom onset (D0). Seizure spike on aEEG at D0 was significantly correlated with motor and social-emotional domains of Bayley-III (p < 0.05). The I/T ratio and CRP and TNF-α levels of blood at D0, white matter injury on MRI at discharge, head circumference and seizure spikes on aEEG at near-term age were associated with Bayley-III scores at a CA of 18 months.
CONCLUSIONS
Systemic inflammation induced by clinical infection and NEC are associated with neurodevelopmental impairment in preterm infants. The seizure spike on aEEG, elevated I/T ratio, CRP, and plasma TNF-alpha during inflammatory episodes are associated with poor neurodevelopment.
背景
多项研究表明，全身炎症可能导致早产儿神经发育不良。本研究旨在探讨全身炎症是否会导致早产儿神经发育受损，以及炎症期间的哪些生物标志物和神经生理研究与不良神经发育相关。
方法
本前瞻性队列研究纳入了胎龄<30 周或出生体重<1250g 的早产儿。根据是否存在全身炎症将婴儿分为两组：对照组（无炎症，n=49）和 I 组（全身炎症，n=45）。在感染性检查后 4 小时内采集血液和脑脊液样本，以检测脑损伤和炎症标志物，并进行振幅整合脑电图（aEEG）检查。我们在 35 周校正胎龄（PMA）时评估 aEEG，在 36 周 PMA 时评估头围，在出院时评估脑 MRI。在矫正年龄（CA）为 18 个月时，采用贝利婴幼儿发育量表第三版（Bayley-III）进行评估。
结果
I 组在出院时的脑白质损伤更多（2%对 26.7%，对照组对 I 组），在接近足月时的脑功能成熟度更低（9.5 对 8），头围更小（z 评分-1.45 对-2.12），且在 CA 为 18 个月时的神经发育更差（p<0.05）。在 I 组中，CSF 中不成熟中性粒细胞（I/T 比值）和白细胞介素-1β（IL-1β）水平与症状发作日（D0）的 aEEG 测量值相关。D0 时的脑电图棘波与 Bayley-III 的运动和社会情感领域显著相关（p<0.05）。D0 时的 I/T 比值、CRP 和 TNF-α 水平、出院时的脑 MRI 白质损伤、近足月时的头围和 aEEG 棘波与 CA 为 18 个月时的 Bayley-III 评分相关。
结论
临床感染和 NEC 引起的全身炎症与早产儿的神经发育障碍有关。炎症发作期间的脑电图棘波、升高的 I/T 比值、CRP 和血浆 TNF-α 与不良神经发育有关。
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