Wu Yan-Jun, Wu Wei-Chi, Chu Shih-Ming, Lien Reyin, Chiang Ming-Chou, Lee Chien-Chung
Department of Pediatrics, Division of Neonatology, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, Taiwan.
Department of Pediatrics, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan.
Front Pediatr. 2025 Aug 28;13:1667521. doi: 10.3389/fped.2025.1667521. eCollection 2025.
While early-life cytokine profiles have been linked to neurodevelopmental outcomes in preterm infants, their prognostic value is limited by clinical instability and inflammatory comorbidities in the immediate postnatal period. This study explores cytokine levels measured during a more stable developmental window-near term-equivalent age [postmenstrual age (PMA) 34-38 weeks]-and their association with neurodevelopmental outcomes.
We prospectively enrolled 35 preterm infants (birth weight, 500-1,500 g). Serum cytokine levels were measured at PMA 34, 36, and 38 weeks. Neurodevelopment was assessed at 12 months' corrected age using standardized tools (BSID-III). Infants were classified into neurodevelopmental impairment (NDI) and non-NDI groups. Cytokine levels and their changes were compared between groups.
Elevated IFN-γ levels at PMA 34 weeks were associated with a higher risk of NDI. Conversely, higher levels of Eotaxin-2, IL-2, IL-11, IL-16, MIP-1δ, PDGF-BB, TIMP-2, and TNF-β at PMA 36-38 weeks were observed more frequently in the non-NDI group. The trends also differed: increased IL-17 and decreased Eotaxin-1, Eotaxin-2, IL-7, IL-16, MIP-1α, MIP-1β, PDGF-BB, and TIMP-2 between PMA 34-36 weeks, and further declines in ICAM-1, IL-7, MIP-1α, and MIP-1β by PMA 38 weeks were associated with adverse outcomes. All identified biomarkers demonstrated good discriminatory ability, particularly changes in Eotaxin-2 between PMA 34 and 36 weeks and PDGF-BB between PMA 34 and 38 weeks.
Serum cytokine levels and their trajectories during PMA 34-38 weeks may serve as potential biomarkers for identifying preterm infants at risk of neurodevelopmental impairment. Further studies with larger cohorts are needed to clarify their interplay with preterm morbidities.
虽然早期细胞因子谱与早产儿的神经发育结局有关，但其预后价值受到出生后即刻临床不稳定和炎症合并症的限制。本研究探讨了在更稳定的发育窗口（近足月等效年龄，即孕龄34 - 38周）测量的细胞因子水平及其与神经发育结局的关联。
我们前瞻性纳入了35名早产儿（出生体重500 - 1500克）。在孕龄34、36和38周时测量血清细胞因子水平。在矫正年龄12个月时使用标准化工具（BSID-III）评估神经发育情况。将婴儿分为神经发育障碍（NDI）组和非NDI组。比较两组之间的细胞因子水平及其变化。
孕龄34周时干扰素-γ水平升高与NDI风险较高相关。相反，在非NDI组中，孕龄36 - 38周时嗜酸性粒细胞趋化因子-2、白细胞介素-2、白细胞介素-11、白细胞介素-16、巨噬细胞炎症蛋白-1δ、血小板衍生生长因子-BB、基质金属蛋白酶组织抑制因子-2和肿瘤坏死因子-β水平较高更为常见。趋势也有所不同：孕龄34 - 36周期间白细胞介素-17升高，嗜酸性粒细胞趋化因子-1、嗜酸性粒细胞趋化因子-2、白细胞介素-7、白细胞介素-16、巨噬细胞炎症蛋白-1α、巨噬细胞炎症蛋白-1β、血小板衍生生长因子-BB和基质金属蛋白酶组织抑制因子-2降低，以及到孕龄38周时细胞间黏附分子-1、白细胞介素-7、巨噬细胞炎症蛋白-1α和巨噬细胞炎症蛋白-1β进一步下降与不良结局相关。所有确定的生物标志物均显示出良好的辨别能力，特别是孕龄34和36周之间嗜酸性粒细胞趋化因子-2的变化以及孕龄34和38周之间血小板衍生生长因子-BB的变化。
孕龄34 - 38周期间的血清细胞因子水平及其变化轨迹可能作为识别有神经发育障碍风险的早产儿的潜在生物标志物。需要更大样本量的队列进行进一步研究以阐明它们与早产并发症之间的相互作用。
