Institute for Women's Health, University College London, London, UK.
Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Pediatr Res. 2022 Jul;92(1):180-189. doi: 10.1038/s41390-021-01438-1. Epub 2021 Mar 5.
Neonatal encephalopathy (NE) contributes substantially to child mortality and disability globally. We compared cytokine profiles in term Ugandan neonates with and without NE, with and without perinatal infection or inflammation and identified biomarkers predicting neonatal and early childhood outcomes.
In this exploratory biomarker study, serum IL-1α, IL-6, IL-8, IL-10, TNFα, and VEGF (<12 h) were compared between NE and non-NE infants with and without perinatal infection/inflammation. Neonatal (severity of NE, mortality) and early childhood (death or neurodevelopmental impairment to 2.5 years) outcomes were assessed. Predictors of outcomes were explored with multivariable linear and logistic regression and receiver-operating characteristic analyses.
Cytokine assays on 159 NE and 157 non-NE infants were performed; data on early childhood outcomes were available for 150 and 129, respectively. NE infants had higher IL-10 (p < 0.001), higher IL-6 (p < 0.017), and lower VEGF (p < 0.001) levels. Moderate and severe NE was associated with higher IL-10 levels compared to non-NE infants (p < 0.001). Elevated IL-1α was associated with perinatal infection/inflammation (p = 0.013). Among NE infants, IL-10 predicted neonatal mortality (p = 0.01) and adverse early childhood outcome (adjusted OR 2.28, 95% CI 1.35-3.86, p = 0.002).
Our findings support a potential role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy.
Neonatal encephalopathy is a common cause of child death and disability globally. Inflammatory cytokines are potential biomarkers of encephalopathy severity and outcome. In this Ugandan health facility-based cohort, neonatal encephalopathy was associated with elevated serum IL-10 and IL-6, and reduced VEGF at birth. Elevated serum IL-10 within 12 h after birth predicted severity of neonatal encephalopathy, neonatal mortality, and adverse early childhood developmental outcomes, independent of perinatal infection or inflammation, and provides evidence to the contribution of the inflammatory processes. Our findings support a role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy in a sub-Saharan African cohort.
新生儿脑病（NE）在全球范围内是导致儿童死亡和残疾的主要原因。我们比较了有和没有围产期感染或炎症的足月乌干达新生儿中细胞因子谱，并确定了预测新生儿和幼儿结局的生物标志物。
在这项探索性生物标志物研究中，比较了有和没有围产期感染/炎症的 NE 和非 NE 婴儿出生后 12 小时内的血清 IL-1α、IL-6、IL-8、IL-10、TNFα 和 VEGF。评估了新生儿（NE 严重程度、死亡率）和幼儿（2.5 岁时死亡或神经发育障碍）结局。使用多变量线性和逻辑回归以及受试者工作特征分析探讨了结局的预测因素。
对 159 名 NE 和 157 名非 NE 婴儿进行了细胞因子检测；分别有 150 名和 129 名婴儿可获得幼儿期结局数据。NE 婴儿的 IL-10（p<0.001）更高，IL-6（p<0.017）更高，VEGF（p<0.001）更低。与非 NE 婴儿相比，中度和重度 NE 与更高的 IL-10 水平相关（p<0.001）。IL-1α 升高与围产期感染/炎症相关（p=0.013）。在 NE 婴儿中，IL-10 预测新生儿死亡率（p=0.01）和不良幼儿期结局（调整后的 OR 2.28，95%CI 1.35-3.86，p=0.002）。
我们的研究结果支持 IL-10 作为新生儿脑病不良结局的潜在生物标志物。
新生儿脑病是全球儿童死亡和残疾的常见原因。炎性细胞因子是脑病严重程度和结局的潜在生物标志物。在这项乌干达医疗机构为基础的队列研究中，新生儿脑病与出生时血清 IL-10 和 IL-6 升高以及 VEGF 降低有关。出生后 12 小时内血清 IL-10 升高预测新生儿脑病的严重程度、新生儿死亡率和不良幼儿期发育结局，独立于围产期感染或炎症，为炎症过程的贡献提供了证据。我们的研究结果支持在撒哈拉以南非洲队列中，IL-10 作为新生儿脑病不良结局的生物标志物的作用。
