Department of Pediatrics, Wayne State University, Detroit, Michigan.
Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina.
Am J Perinatol. 2022 May;39(7):732-749. doi: 10.1055/s-0040-1717072. Epub 2020 Oct 10.
This study aimed to profile the cytokine/chemokine response from day 0 to 7 in infants (≥36 weeks of gestational age) with neonatal encephalopathy (NE) and to explore the association with long-term outcomes.
This was a secondary study of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network randomized controlled trial of whole body hypothermia for NE. Eligible infants with moderate-severe NE were randomized to cooling or normothermia. Blood spots were collected on days 0 to 1, 2 to 4, and 6 to 7. Twenty-four cytokines/chemokines were measured using a multiplex platform. Surviving infants underwent neurodevelopmental assessment at 6 to 7 years. Primary outcome was death or moderate-severe impairment defined by any of the following: intelligence quotient <70, moderate-severe cerebral palsy (CP), blindness, hearing impairment, or epilepsy.
Cytokine blood spots were collected from 109 participants. In total 99 of 109 (91%) were assessed at 6 to 7 years; 54 of 99 (55%) developed death/impairment. Neonates who died or were impaired had lower early regulated upon activation normal T cell expressed and secreted (RANTES) and higher day 7 monocyte chemotactic protein (MCP)-1 levels than neonates who survived without impairment. Though TNF-α levels had no association with death/impairment, higher day 0 to 1 levels were observed among neonates who died/developed CP. On multiple regression analysis adjusted for center, treatment group, sex, race, and level of hypoxic ischemic encephalopathy, higher RANTES was inversely associated with death/impairment (odds ratio (OR): 0.31, 95% confidence interval [CI]: 0.13-0.74), while day seven MCP-1 level was directly associated with death/impairment (OR: 3.70, 95% CI: 1.42-9.61). Targeted cytokine/chemokine levels demonstrated little variation with hypothermia treatment.
RANTES and MCP-1 levels in the first week of life may provide potential targets for future therapies among neonates with encephalopathy.
· Elevation of specific cytokines and chemokines in neonates with encephalopathy has been noted along with increased risk of neurodevelopmental impairment in infancy.. · Cytokine/chemokines at <7 days were assessed among neonates in a trial of hypothermia for HIE.. · Neonates who died or were impaired at 6 to 7 years following hypoxic-ischemic encephalopathy had lower RANTES and higher MCP-1 levels than those who survived without impairment..
本研究旨在描述患有新生儿脑病（NE）的婴儿（胎龄≥36 周）从第 0 天到第 7 天的细胞因子/趋化因子反应，并探讨其与长期结局的关系。
这是美国国立卫生研究院儿童健康与人类发育 Eunice Kennedy Shriver 研究所（NICHD）新生儿研究网络针对 NE 全身低温的随机对照试验的二次研究。符合条件的中重度 NE 婴儿被随机分配到冷却或正常体温组。在第 0 天至 1 天、第 2 天至 4 天和第 6 天至 7 天采集血斑。使用多指标平台测量 24 种细胞因子/趋化因子。存活婴儿在 6 至 7 岁时进行神经发育评估。主要结局为死亡或中重度损伤，定义为以下任何一种情况：智商＜70、中重度脑瘫（CP）、失明、听力障碍或癫痫。
109 名参与者采集了细胞因子血斑。共有 99 名（91%）在 6 至 7 岁时进行了评估；54 名（55%）出现死亡/损伤。死亡/损伤的新生儿早期调节激活正常 T 细胞表达和分泌（RANTES）水平较低，第 7 天单核细胞趋化蛋白（MCP）-1 水平较高，而存活且无损伤的新生儿则较低。虽然 TNF-α水平与死亡/损伤无关联，但在死亡/CP 新生儿中观察到更高的第 0 天至 1 天水平。在多变量回归分析中，调整中心、治疗组、性别、种族和缺氧缺血性脑病的严重程度后，RANTES 水平与死亡/损伤呈负相关（比值比（OR）：0.31，95%置信区间 [CI]：0.13-0.74），而第 7 天 MCP-1 水平与死亡/损伤呈正相关（OR：3.70，95% CI：1.42-9.61）。针对细胞因子/趋化因子的靶向治疗水平与低温治疗的变化不大。
在患有脑病的新生儿中，第一周的 RANTES 和 MCP-1 水平可能为未来的治疗提供潜在的靶点。
· 在患有脑病的新生儿中已观察到特定细胞因子和趋化因子的升高，以及婴儿期神经发育损伤风险的增加。· 在针对缺氧缺血性脑病的低温治疗试验中评估了新生儿出生后 7 天内的细胞因子/趋化因子。· 在缺氧缺血性脑病后 6 至 7 岁时死亡或受损的新生儿 RANTES 水平较低，MCP-1 水平较高，而无损伤存活的新生儿则较低。
