Significance of Serum Inflammatory Markers in Predicting Bacterial Meningitis amongst Neonates with Sepsis

Aparajita Raghav, Ajay Kumar, P. Anand, G. Yadav, R. Gera
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Abstract

Introduction: Neonatal meningitis in developing countries is 0.8- 6.1 per 1000 live births with mortality of 40-85% had morbidity. Since, the clinical signs and symptoms of meningitis are non- specific and like those seen in sepsis, Cerebrospinal Fluid (CSF) examination via Lumbar Puncture (LP) is essential to establish the diagnosis of meningitis. Performing a LP has its own set of complications. The need for lumbar puncture can be averted and early optimal antibiotic can be instituted if serum inflammatory markers are found to be a good predictor of meningitis in suspected neonatal sepsis. Aim: To investigate the role of serum inflammatory markers, to predict bacterial meningitis amongst neonates with sepsis and to determine the cut-off values for these markers to predict bacterial meningitis amongst neonates with sepsis. Materials and Methods:Thiswasacross-sectionalobservational study done over a period of 17 months in the paediatric wards in a tertiary care centre. All neonates presenting with clinical suspicion of sepsis were enrolled. The blood samples were collected for serum inflammatory markers and CSF examination was done as indicated (American Academy of Paediatrics, AAP guidelines). CSF examination findings and serum inflammatory markers were then statistically analysed to determine the significance in predicting bacterial meningitis in neonatal sepsis. A total of 234 neonates were selected as per laboratory investigations for enrollment in the study. Categorical variables were presented in number and percentage (%) and continuous variables were presented as mean±Standard deviation (SD) and median. Diagnostic tests were used to calculate sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV). Results: A total 234 neonates with features suggestive of sepsis and in whom C-Reactive Protein (CRP) >10 mg/L, Erythrocyte Sedimentation Rate (ESR) >15 mm, White Blood Cell (WBC) <4000 cells/mm³, Absolute Neutrophil Count (ANC) <1800/mm3 and in whom LP was recommended as per the AAP guidelines were included in the study. A 222 (94.87%) neonates were in the age group 1-10 days. A total of 134 (57.3%) study subjects were males. No significant association of ANC, WBC, ESR and CRP was seen with meningitis (p-value >0.05). Receiver Operator Curve (ROC) for all the four parameters were constructed, they showed performance was non-significant. Conclusion: Based on the current single site study results, it is implicated that diagnosis and management of neonatal meningitis should be solely based on LP since serum inflammatory markers are poor discriminators for meningitis. Future studies should evaluate the diagnostic parameters from other inflammatory markers like Immature to Total Neutrophil (IT) ratio and micro ESR, which, if proven to be of diagnostic value, can reduce the time to initiate management and avert the need for LP in neonatal meningitis.
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血清炎症标志物在脓毒症新生儿细菌性脑膜炎预测中的意义
在发展中国家,新生儿脑膜炎发病率为每1000例活产0.8- 6.1例,死亡率为40-85%。由于脑膜炎的临床体征和症状不具有特异性,与败血症类似,因此通过腰椎穿刺(LP)检查脑脊液(CSF)对于确定脑膜炎的诊断至关重要。执行LP有其自身的一系列并发症。如果发现血清炎症标记物是疑似新生儿败血症中脑膜炎的良好预测因子,则可以避免腰椎穿刺的需要,并可以制定早期最佳抗生素。目的:探讨血清炎症标志物在预测新生儿脓毒症细菌性脑膜炎中的作用,并确定这些标志物预测新生儿脓毒症细菌性脑膜炎的临界值。材料和方法:这是一项横断面观察性研究,在一家三级护理中心的儿科病房进行了为期17个月的研究。所有临床怀疑为败血症的新生儿均被纳入研究。采集血样检测血清炎症标志物,并按指示进行脑脊液检查(美国儿科学会,AAP指南)。然后统计分析脑脊液检查结果和血清炎症标志物,以确定预测新生儿败血症细菌性脑膜炎的意义。根据实验室调查,共有234名新生儿入选本研究。分类变量以数量和百分比(%)表示,连续变量以均数±标准差(SD)和中位数表示。采用诊断试验计算敏感性、特异性、阳性预测值(PPV)和阴性预测值(NPV)。结果:共有234例新生儿具有脓毒症的特征,其中c反应蛋白(CRP) >10 mg/L,红细胞沉降率(ESR) >15 mm,白细胞(WBC) 0.05。对所有四个参数构建了受试者操作曲线(Receiver Operator Curve, ROC),它们的表现均不显著。结论:基于目前的单点研究结果,提示新生儿脑膜炎的诊断和管理应仅基于LP,因为血清炎症标志物对脑膜炎的鉴别能力较差。未来的研究应评估其他炎症标志物的诊断参数,如未成熟到总中性粒细胞(IT)比率和微ESR,如果被证明具有诊断价值,可以减少开始治疗的时间,避免新生儿脑膜炎需要LP。
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