Neonatal sepsis is common, lethal, and hard to diagnose. In combination with clinical findings and blood culture, biomarkers are crucial to make the correct diagnose. A Swedish national inquiry indicated that neonatologists were not quite satisfied with the available biomarkers. We assessed the kinetics of 15 biomarkers simultaneously: ferritin, fibrinogen, granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-γ, interleukin (IL)-1β, −6, −8, −10, macrophage inflammatory protein (MIP)-1β, procalcitonin, resistin, serum amyloid A (SAA), tumor necrosis factor (TNF)-α, tissue plasminogen activator-3 and visfatin. The goal was to observe how quickly they rise in response to infection, and for how long they remain elevated. From a neonatal intensive care unit, newborns ≥28 weeks gestational age were recruited. Sixty-eight newborns were recruited to the study group (SG), and fifty-one to the control group (CG). The study group subjects were divided into three subgroups depending on clinical findings: confirmed sepsis (CSG), suspected sepsis (SSG) and no sepsis. CSG and SSG were also merged into an entire sepsis group (ESG) for sub-analysis. Blood samples were collected at three time-points; 0 h, 12–24 h and 48–72 h, in order to mimic a “clinical setting”. At 0 h, visfatin was elevated in SSG compared to CG; G-CSF, IFN-γ, IL-1β, −8 and − 10 were elevated in SSG and ESG compared to CG, whereas IL-6 and SAA were elevated in all groups compared to CG. At 12–24 h, IL-8 was elevated in ESG compared to CG, visfatin was elevated in ESG and SSG compared to CG, and SAA was elevated in all three groups compared to CG. At 48–72 h, fibrinogen was elevated in ESG compared to CG, IFN-γ and IL-1β were elevated in SSG and ESG compared to CG, whereas IL-8 and SAA were elevated in all three groups compared to CG. A function of time-formula is introduced as a tool for theoretical prediction of biomarker levels at any time-point. We conclude that SAA has the most favorable kinetics regarding diagnosing neonatal sepsis, of the biomarkers studied. It is also readily available methodologically, making it a prime candidate for clinical use.

新生儿败血症是常见的、致命的且难以诊断。结合临床发现和血培养，生物标志物对于做出正确诊断至关重要。瑞典的一项全国调查表明，新生儿学家对现有的生物标志物并不十分满意。我们同时评估了 15 种生物标志物的动力学：铁蛋白、纤维蛋白原、粒细胞集落刺激因子 (G-CSF)、干扰素 (IFN)-γ、白细胞介素 (IL)-1β、-6、-8、-10、巨噬细胞炎症蛋白(MIP)-1β、降钙素原、抵抗素、血清淀粉样蛋白 A (SAA)、肿瘤坏死因子 (TNF)-α、组织纤溶酶原激活剂-3 和内脂素。目标是观察它们对感染的反应有多快，以及它们保持升高的时间。从新生儿重症监护病房招募了 ≥ 28 周胎龄的新生儿。研究组 (SG) 招募了 68 名新生儿，对照组 (CG) 招募了 51 名新生儿。研究组受试者根据临床发现分为三个亚组：确诊脓毒症 (CSG)、疑似脓毒症 (SSG) 和无脓毒症。CSG 和 SSG 也被合并到一个完整的脓毒症组 (ESG) 中进行子分析。在三个时间点采集血样；0 小时、12-24 小时和 48-72 小时，以模拟“临床环境”。在 0 小时时，与 CG 相比，SSG 中的内脂素升高；与CG相比，SSG和ESG中的G-CSF、IFN-γ、IL-1β、-8和-10升高，而与CG相比，所有组的IL-6和SAA均升高。在 12-24 小时，与 CG 相比，ESG 中的 IL-8 升高，与 CG 相比，ESG 和 SSG 中的内脂素升高，并且与 CG 相比，所有三组的 SAA 均升高。在 48-72 小时，与 CG 相比，ESG 中的纤维蛋白原升高，SSG 和 ESG 中的 IFN-γ 和 IL-1β 升高，而与 CG 相比，所有三组的 IL-8 和 SAA 均升高。引入时间公式函数作为在任何时间点对生物标志物水平进行理论预测的工具。我们得出结论，在所研究的生物标志物中，SAA 在诊断新生儿败血症方面具有最有利的动力学。它在方法上也很容易获得，使其成为临床使用的主要候选者。研究的生物标志物。它在方法上也很容易获得，使其成为临床使用的主要候选者。研究的生物标志物。它在方法上也很容易获得，使其成为临床使用的主要候选者。