Cord blood levels of interleukin-6 and interleukin-8 for the immediate diagnosis of early-onset infection in premature infants

BACKGROUND: Cytokine plasma levels are suggested to be sensitive indicators of neonatal sepsis, but conventional assays are time consuming. This study aimed at evaluating the significance of cord blood levels of interleukin (IL)-6 and IL-8 determined by a fully automated random access assay within 90 min of admission to predict systemic bacterial infection. PATIENTS AND METHODS: Cord blood levels of IL-6 and IL-8 were determined in 71 mature and 100 premature infants by a chemiluminescence assay (Immulite). Patients were divided into four groups according to a clinical and laboratory scoring system. Group A: documented early-onset infection; group B: infection possible; group C: infection unlikely, and group D: healthy newborns. RESULTS: Median IL-6 levels in the subgroup of premature newborns were as follows: group A, 1,920 pg/ml (5-95% confidence interval 308-4,660 pg/ml); group B, 50 (15-102) pg/ml; group C, 21 (12-71) pg/ml, and group D, 8 (6-11) pg/ml. For IL-8, median levels for groups A-D were 289 (226-514) pg/ml, 87 (40-107) pg/ml, 44 (33-98) pg/ml and 21 (16-25) pg/ml, respectively. The difference between group A and the other groups was highly significant (IL-6 p < 0.0001, IL-8 p < 0.001). At a cut-off of 80 pg/ml, the sensitivity of IL-6 for the diagnosis of sepsis was 96% (specificity 95%). For IL-8 (cut-off 90 pg/ml), the sensitivity was 87% (specificity 94%). CONCLUSION: In premature infants, the diagnosis of an early-onset infection can be established or ruled out with a high level of confidence by measuring IL-6 or IL-8 levels from cord blood using a random access chemiluminescence assay.     

C-REACTIVE PROTEIN (CRP) IN EARLY DIAGNOSIS OF NEONATAL SEPTICEMIA

Abstract. The usefulness of CRP in early detection of neonatal septicemia/meningitis and urinary tract infection was studied in a neonatal unit using a semiquantitative latex-agglutination as a rapid screening method, and electroimmuno assay as reference method for CRP determination. In 94% of non-infected infants CRP was 15 mg/l and 82 % had CRP <10 mg/l up to 3 days of age. After 3 days of age 96% had CRP < 10 mg/l. The initial CRP level was increased in 16 out of 18 patients (89%) with bacterial septicemia. Low CRP was seen in one patient with total agranulocytosis and septicemia from Streptococcus type B and in one patient with Staphylococcus albus sepsis. A rise in CRP was also seen in very pre-term infants with septicemia. Increased initial CRP was uncommon in neonatal urinary tract infection (2 of 9), but a rise was seen in 3 additional patients. A comparison between CRP, total neutrophil blood cell count and band neutrophil count as diagnostic parameters was in favour of CRP at this early stage of infection. CRP is of definite value as an aid in early diagnosis of neonatal septicemia and bacterial meningitis.     

C-reactive protein (CRP) in early diagnosis of neonatal septicemia.

The usefulness of CRP in early detection of neonatal septicemia/meningitis and urinary tract infection was studied in a neonatal unit using a semiquantitative latex-agglutination as a rapid screening method, and electroimmuno assay as reference method for CRP determination. In 94% of non-infected infants CRP was less than or equal to 15 mg/l and 82% had CRP less than 10 mg/l up to 3 days of age. After 3 days of age 96% had CRP less than 10 mg/l. The initial CRP level was increased in 16 out of 18 patients (89%) with bacterial septicemia. Low CRP was seen in one patient with total agranulocytosis and septicemia from Streptococcus type B and in one patient with Staphylococcus albus sepsis. A rise in CRP was also seen in very pre-term infants with septicemia. Increased initial CRP was uncommon in neonatal urinary tract infection (2 of 9), but a rise was seen in 3 additional patients. A comparison between CRP, total neutrophil blood cell count and band neutrophil count as diagnostic parameters was in favour of CRP at this early stage of infection. CRP is of definite value as an aid in early diagnosis of neonatal septicemia and bacterial meningitis.     

Serum Interleukin 8 Level as a Diagnostic Marker in Late Neonatal Sepsis

Objective

Late-onset sepsis is responsible for high morbidity and mortality in newborn infants in the world and in particular in developing countries. In this study, we evaluated whether clinical characteristics, laboratory parameters and measurements of serum interleukin-8 (IL-8) are able to discriminate between late neonatal sepsis and normal baby.

Methods

This was a prospective (case-control) study conducted between March 2007 and April 2008, at the neonatal intensive care unit, Ghaem Hospital, Mashhad, Iran. The study comprised 93 neonates ≥72 hours of life. The infants were categorized in two groups based on the clinical presentation, and biochemical markers including complete blood count, C-reactive protein (CRP) and blood culture: 1) Control group including 42 infants with routine screening and 2) Case group consisting of 38 infants with definitive infection (positive blood and/or cerebrospinal fluid culture) or clinical sepsis (clinical and laboratory signs of infection without positive blood or CSF culture). Receiver-operating characteristic curves were used for the determination of thresholds for the infection group versus healthy neonate group.

Findings

Eighty infants were enrolled in this study. IL-8 and CRP decreased in order of definitive infection, clinical sepsis and healthy subjects respectively (P<0.001). Sensitivity, specificity, positive predictive value, negative predictive value for serum levels were 0.95, 0.1, 0.97, 0.1 for IL-8 and 0.83, 0.86, 0.83, 0.69 for CRP respectively (cut-off point for IL-8 >60pg/ml and for CRP>6mg/dl).

Conclusion

IL-8 may be a valid and early predictive marker of neonatal infection. Also, IL-8 is associated with severity of infection.     

线粒体偶联因子6、细胞色素C在新生儿败血症中的变化及临床意义

目的 检测新生儿败血症时血浆线粒体偶联因子6(coupling factor 6,CF6)、细胞色素C水平的变化,探讨其在新生儿败血症中的临床意义.方法 以2015年1月至2015年4月湖南省儿童医院新生儿科收治的日龄3~28d内的足月新生儿88例为研究对象,根据感染情况将患儿分为非败血症组(42例)和败血症组(46例);根据感染严重程度,进一步将非败血症组分为无感染组(20例)、感染致炎症反应组(22例),败血症组分为普通败血症组(31例,无器官功能衰竭)和重症败血症组(15例,有多器官功能衰竭).所有患儿均在入院后未用抗生素前采集股静脉血,用ELISA法检测入院后血浆CF6、细胞色素C的活性水平,同时检测C-反应蛋白(C-reactive protein,CRP)、降钙素原(procalcitonin,PCT),比较血浆CF6、细胞色素C的变化情况;与传统临床诊断新生儿败血症的非特异性指标(CRP、PCT)进行比较,探讨其敏感度及特异度;对CF6、细胞色素C的活性水平与新生儿危重症评分进行相关性分析.结果 (1)入院时败血症组CF6、细胞色素C水平分别为(109.7±8.9)pg/ml和(44.5±4.9)ng/ml,显著高于非败血症组[(46.3±6.0)pg/ml、(31.8±6.7)ng/ml,P均<0.01];(2)无感染组、感染致炎症反应组、普通败血症组、重症败血症组CF6水平分别为(32.1±8.9)pg/ml、(59.3±7.2)pg/ml、(79.3±5.9)pg/ml、(172.6±6.1)pg/ml;细胞色素C水平分别为(29.3±8.6)ng/ml、(35.4±4.1)ng/ml、(43.1±5.9)ng/ml、(44.5±5.9)ng/ml;各组间比较差异有统计学意义(P<0.01);(3)受试者工作特征曲线分析显示,CF6、细胞色素C的敏感度和特异度分别为0.761、0.732,0.739、0.714;(4)血浆CF6、细胞色素C与新生儿危重症评分呈负相关(r=-0.599,P<0.001;r=-0.337,P<0.01).CF6、细胞色素C随着病情严重程度的加重而升高.结论 新生儿败血症时血浆CF6、细胞色素C水平有升高趋势,其可能与线粒体受损有关.血浆CF6、细胞色素C水平与新生儿败血症病情严重程度具有相关性,对临床有一定指导意义.     

Diagnostic value of plasma levels of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) in newborns with sepsis

The aim of this study was to examine if TNFα and IL-6 plasma levels could be of value in diagnosing neonatal sepsis. Tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) plasma levels were determined in 15 newborn infants with confirmed sepsis (group I), 18 with suspected sepsis (group II) and 22 control infants (group III). In 33 newborns, initially suspected of having sepsis (groups I and 11), a positive test result for plasma concentration of TNFα (> 70 pg/ml) had a sensitivity of 73 % and a specificity of 94%. A positive test result for IL-6 (>500 pg/ml) had a sensitivity of 80% and a specificity of 78%. When plasma levels of TNFα and IL-6 were combined for the diagnosis of neonatal sepsis, a positive test result for both tests had a sensitivity of 60% and a specificity of 100%. When both tests are positive the diagnosis of neonatal sepsis is almost certain (likelihood ratio =α. The combination of TNFα and IL-6 determinations appears to be a good predictor of neonatal sepsis.     

Inflammatory mediators for the diagnosis and treatment of sepsis in early infancy

Interleukin-6 (IL-6), interleukin-8 (IL-8), and procalcitonin (PCT) are important parameters in the diagnosis of sepsis and for differentiating between viral and bacterial infection in children. We compared the value of IL-6, IL-8, and PCT with C-reactive protein (CRP) in the diagnosis and treatment of late-onset sepsis among infants admitted to the neonatal intensive care unit (group I) and febrile infants admitted to general hospitals from home (group II). Group I was divided into subgroups Ia, positive blood culture (all Gram-positive cocci); Ib, negative blood culture; and Ic, controls. Group II was divided into subgroups IIa, systemic enterovirus infection, and IIb, no enterovirus infection. Enterovirus was identified by real-time (RT) polymerase chain reaction (PCR) and/or by culture in blood and cerebrospinal fluid (CSF). The positive predictive values of IL-6, IL-8, and PCT (78%, 72%, and 83%, respectively) were better than that of CRP (63%) in the diagnosis of neonatal sepsis. After 48 h of antibiotic treatment, IL-6 and IL-8 levels significantly decreased and PCT stabilized in clinically recovered patients, suggesting that these markers may be useful in distinguishing patients in which antibiotic treatment may be discontinued. Among infants of subgroup IIa, 80%-90% had normal values of IL-6, IL-8, and PCT, whereas CRP was increased in 40%. In conclusion, IL-6, IL-8, and PCT are better parameters than CRP in the diagnosis and follow-up of neonatal sepsis due to coagulase-negative staphylococci (CoNS) and in the exclusion of bacterial infection among those with enteroviral infection among febrile infants presenting from home.     

Procalcitonin: a marker of neonatal sepsis

This study was designed to assess the value of procalcitonin in establishing the diagnosis and evaluating the prognosis of neonatal sepsis. Thirty-four infants with neonatal sepsis were included in the study. Procalcitonin values of the cases with sepsis were (2.21 +/- 2.48 ng/ml) significantly higher than the values in the control group (0.71 +/- 0.5 ng/ml; p = 0.01). On the 7th day of therapy neonates who had achieved clinical recovery had a significant decrease of procalcitonin levels (0.55 +/- 0.27 ng/ml) compared to the initial values (p = 0.001). Initial mean procalcitonin levels of the cases resulting in death were 4.31 +/- 3.66 g/ml. This was significantly higher than the initial values of the patients who had clinical recovery (1.18 +/- 1.24 ng/ml;p = 0.02). Procalcitonin is a valuable marker for diagnosis, for evaluating prognosis and response to therapy in neonatal sepsis.     

降钙素原及C-反应蛋白联合检测在新生儿院内感染早期诊断中的意义

目的：新生儿败血症的早期缺乏特异的临床表现,极易误诊和漏诊,本文通过对新生儿血清降钙素原(procaicltonin,PCT)和C-反应蛋白(C-reactive protein,CRP)水平进行动态监测,阐明联合应用PCT及CRP检测在新生儿院内感染早期诊断中的临床价值。方法采用回顾性分析方法,选取2013年6月至2014年8月中国医科大学附属盛京医院第一新生儿科收治的患儿111例,其中确诊败血症组37例,临床败血症组42例,对照组32例(同期住院的非感染患儿)。败血症组在感染发生时(抗生素治疗前),感染发生(抗生素治疗后)12h、24h,感染控制后3d、7d,对照组在入院后应用抗生素前分别采集血清,采用酶联荧光分析法定量测定PCT、免疫比浊法测定CRP水平。结果与对照组比较, PCT、CRP含量在确诊败血症组和临床败血症组于抗生素治疗前均明显增高(P﹤0.01)。在确诊败血症组和临床败血症组,PCT 于感染发生后12h 达峰值[分别为(15.00±15.51)ng/ml 和(17.93±13.44)ng/ml],感染控制后3d降至正常[分别为(0.49±0.47)ng/ml和(0.42±0.34)ng/ml],CRP于感染发生24h后达峰值[分别为(37.53±30.29)mg/L和(32.41±29.33)mg/L],7d后降至正常[分别为(5.72±2.98)mg/L和(5.06±3.07)mg/L]。当PCT﹥2ng/ml、CRP﹥10mg/L时准确性最好(约登指数分别为76.11%,59.45%),其敏感性分别为88.61%,75.70%;特异性分别为87.5%,83.75%;阳性预测值分别为94.59%,95.65%;阴性预测值分别为75.68%,46.15%。联合检测PCT与CRP时,各诊断效率指标均明显改善。二者受试者工作特征曲线下面积分别为0.964,0.887。结论在感染早期时,CRP和PCT均升高,当CRP﹥10mg/L,PCT﹥2ng/ml时诊断准确性好。但前者在感染后24h达峰值,7d降至正常,而后者在感染后12h达峰值,感染控制后3d恢复正常,联合检测PCT及CRP可提高检测的敏感度、特异度,准确性最佳。     

Procalcitonin versus CRP as an early indicator of fetal infection in preterm premature rupture of membranes

The aim of this study was to examine the diagnostic sensitivity and specificity of C-reactive protein (CRP) and procalcitonin (PCT) in neonates who were born after preterm premature rupture of membranes (PPROM) and compare these with interleukin-6 (IL-6). The study involved 74 preterm neonates who were born after PPROM. IL-6, CRP, complete blood count and leukocyte ratios, and PCT levels were measured in the 1st day of life, and CRP, PCT, and blood counts were repeated on the 3rd day of life. Seventy-four infants with PPROM were divided into two groups according to the development of sepsis and infection (Group 1: sepsis, n = 32; Group 2: no sepsis, n = 42). There were no significant differences between these groups with respect to gestational age, birthweight and duration of membrane rupture. There were significant differences between the two groups in the 1st day CRP (Group 1: 0.85 -/+ 1.36 mg/dl, Group 2: 0.23 +/- 0.25 mg/dl; p = 0.016), 1st day PCT (Group 1: 7.2 +/- 7.6 ng/ml, Group 2, 1.6 +/- 4.0 ng/ml; p < 0.001), and 3rd day PCT (Group 1: 9.01 +/-11.5 ng/ml, Group 2: 1.34 +/- 1.35 ng/ml; p = 0.001) and IL-6 (Group 1: 80.7 +/- 67.2 pg/ml, Group 2: 3.4 +/- 3.5 ng/ml; p < 0.001) levels. CRP levels were not significantly different between Group 1 (1.2 +/- 1.7 mg/dl) and Group 2 (0.58 +/- 1.1 mg/dl) on the 3rd day of life (p=0.059). CRP levels on the 1st day of life had a cut-off value of 0.72 mg/dl with a sensitivity and specificity of 56% and 58%, respectively. CRP levels on the 3rd day had a cut-off level of 0.78 mg/dl with 60% sensitivity and 63% specificity. PCT levels had a cut-off level of 1.74 ng/ml with 76% sensitivity and 85% specificity on the 1st day of life, and of 1.8 with 89% sensitivity and 86% specificity on the 3rd day of life. Statistical analysis revealed that the cut-off value of 7.6 pg/ml for IL-6 had a 93% sensitivity and 96.7% specificity. Interleukin (IL)-6 is the most reliable marker for the detection of early-onset sepsis in preterm neonates with PPROM. Early PCT levels seemed to be more sensitive than early CRP in this population.     

Cord blood interleukin-6 as a predictor of early-onset neonatal sepsis

Aim: To compare diagnostic accuracy in cord blood of interleukin‐6 (IL‐6) with C‐reactive protein (CRP) as predictors of early‐onset neonatal sepsis (EOS) in newborns with prenatal risk factors for infection. Methods: During 12 months, cord blood IL‐6 and CRP were measured immediately after birth in neonates with prenatal risk factors of infection. The odds of developing sepsis based on IL‐6 and CRP values were calculated using likelihood ratios (LR), and their accuracy as predictors was compared by binary logistic regression. Multivariable logistic regression analyses were performed to identify independent risk factors for sepsis. Results: Ten of 128 neonates (7.8%) were diagnosed with EOS confirmed with positive blood culture in five cases (3.9%). Cord blood IL‐6 was a greater predictor of sepsis than CRP [ROC for IL‐6 (0.88) vs. CRP (0.70)]. IL‐6‐positive and IL‐6‐negative LR [7.14 vs. ?0.11] were superior to those calculated for CRP [2.86 vs. ?0.51]. Chorioamnionitis and Apgar at 1 min were identified as independent risk factors for EOS. Conclusions: Cord blood IL‐6 showed superior LR than CRP; therefore, it is a better predictor to initiate treatment in neonates with prenatal infectious risk factors immediately after birth.     

The role of procalcitonin as a predictor of nosocomial sepsis in preterm infants

AIM: To assess the role of procalcitonin in detecting nosocomial sepsis in preterm infants, after the onset of clinical symptoms. SUBJECTS: 100 preterm infants, 24-36 wk of gestation, were followed from the age of 3 d until discharge. Procalcitonin and C-reactive protein (CRP) levels were measured within 3 d of sepsis workup events. RESULTS: 141 blood samples were drawn from 36 infants during 85 episodes of sepsis workup performed between 4 and 66 d of life. Of these episodes, 51 (60%) were not a result of documented sepsis and thereby served as the negative comparison group. Median procalcitonin levels were higher in the septic group compared with the non-septic group at the time of the sepsis workup (2.7 vs 0.5 ng/ml, p=0.003), at 1-24 h after the sepsis workup (4.6 vs 0.6 ng/ml, p=0.003), and at 25-48 h (6.9 vs 2.0 ng/ml, p=0.016). Using high cutoff levels, both procalcitonin (2.3 ng/ml) and CRP (30 mg/l) had high specificity and positive predictive value (97%, 91% and 96%, 87%, respectively) but low sensitivity (48% and 41%, respectively) to detect sepsis. Areas under the ROC curve for procalcitonin and CRP were 0.74 and 0.73, respectively. CONCLUSION: Procalcitonin >2.3 ng/ml or CRP >30 mg/l indicates a high likelihood for neonatal sepsis, and antibiotic therapy should be continued even in the presence of sterile cultures.     

Role of procalcitonin, C-reactive protein, interleukin-6, interleukin-8 and tumor necrosis factor-alpha in the diagnosis of neonatal sepsis

Diagnosis of neonatal sepsis may be difficult because clinical presentations are often nonspecific, bacterial cultures are time-consuming and other laboratory tests lack sensitivity and specificity. In this study, we aimed to investigate the role of procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) in establishing the diagnosis and evaluating the prognosis of neonatal sepsis. Twenty-six neonates with blood-culture positivity and clinical sepsis, hospitalized for clinical suspicion of neonatal sepsis in neonatal intensive care units of Balcali Hospital, Cukurova University and Adana State Hospital between May 2000 and January 2001 (Group I) and 29 healthy neonates followed at the neonatal units and outpatient clinics of these hospitals (Group II) in the same period were studied. Among the septic neonates, 13 had early-onset (Group Ia) and 13 had late-onset (Group Ib) neonatal sepsis, while 14 of the healthy neonates had perinatal risk factors (Group IIa) and 15 of them had no risk factors (Group IIb). The demographic and clinical characteristics of the septic and healthy neonates were recorded, blood samples for determining serum PCT, CRP, IL-6, IL-8 and TNF-alpha were collected from the healthy and the septic neonates before starting treatment, and these investigations were repeated on the 3rd and 7th days of treatment. In this study, it was found that: (a) pre-treatment mean serum PCT, CRP, IL-6, IL-8 and TNF-alpha levels were significantly higher in the septic neonates than in the healthy ones, (b) compared with the pre-treatment values, serum PCT, IL-6 and TNF-alpha had progressively decreased on the 3rd and 7th days of the treatment in the 17 recovered patients, though they progressively increased in nine patients who died during treatment, (c) the area under the receiver operating characteristic (ROC) curve (AUC) for PCT, TNF-alpha, IL-6, CRP, and IL-8 were 1.00, 1.00, 0.97, 0.90 and 0.68, respectively. For the cut-off value of PCT > or = 0.34 ng/ml, the test was found to have a sensitivity of 100%, specificity of 96.5%, positive predictive value of 96.2%, negative predictive value of 100% and diagnostic efficacy of 98.3% for bacterial sepsis in neonates. For the cut-off value of TNF-alpha > or = 7.5 pg/ml, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic efficacy were found to be 100%, 96.6%, 96.2%, 96.5% and 98.3%, respectively. It was detected that sensitivity, specificity and diagnostic efficacy values were lower for IL-6, CRP and IL-8. We conclude that PCT and TNF-alpha are the best markers in the diagnosis of neonatal sepsis, and these markers are also valuable in following the effectiveness of treatment and determining the prognosis of the disease.     

新生儿HIE、感染性疾病及早产儿IL-2、IL-6检测

目的　 探讨新生儿缺氧缺血性脑病 (HIE)、感染性疾病及早产儿血清白细胞介素 2 (IL 2 )、白细胞介素 6(IL 6)检测值的变化及临床意义 ,间接了解新生儿部分特异性及非特异性免疫功能。 方法 　选择 3 3 1例住院新生儿 ,分为HIE组、感染组、早产儿组 ,与 3 0例健康新生儿对照 ,采用酶联免疫吸附法 (ELISA)检测血清IL 2、IL 6的水平 ,进行对比分析。 结果 　①患病新生儿IL 2明显低于正常新生儿 ,P <0 0 1,有高度显著性差异 ,其中早产儿组最低仅为 1 3 5pg/ml;②感染组IL 6增高最为明显 ,与健康对照组相比 ,P <0 0 1,有高度显著性差异 ,其中 2 5例败血症患儿的IL 6均 >5 0pg/ml。 结论 　①新生儿感染性疾病、HIE及早产儿的免疫方面受到不同程度的损伤 ,介导特异性免疫的IL 2检测值低于健康新生儿 ;②本文首次报道早产儿IL 2检测值 ;③感染组介导天然免疫的IL 6高于健康新生儿 ,认为可作为早期诊断新生儿败血症的指标。     

Cord blood levels of cytokines as predictors of early neonatal sepsis

AIM: To investigate whether cord blood levels of C-reactive protein, interleukin-1beta, interleukin-6, interleukin-8, tumour necrosis factor-alpha and the soluble receptor of interleukin-2, are useful markers in the diagnosis of early neonatal sepsis. DESIGN: Umbilical cord blood samples were obtained at birth from 261 neonates, but 5 of these newborns were excluded from the study. Group I included 10 newborns that developed early neonatal sepsis with a positive blood culture; Group II included 11 newborns with non-infectious perinatal diseases; Group III, which served as the control group, included 10 randomly selected patients, matched for gestational age, among the 235 healthy newborn babies. RESULTS: There were no differences among the three study groups in levels of C-reactive protein. interleukin-1beta, tumour necrosis factor-alpha and the soluble receptor of interleukin-2. Interleukin-6 was significantly elevated in Group I (360.4+/-157.8 pg/ml) and Group II (158.8+/-122.3 pg/ml), when compared with Group III (8.6+/-3.12 pg/ml) (p < 0.01), whereas interleukin-8 was significantly elevated in Group I (389.3+/-115.9 pg/ml) compared with Groups II (30.2+/-5.1 pg/ml) (p < 0.05) and III (33.9+/-8.6 pg/ml) (p < 0.05). A cut-off of 100.8 pg/ml for interleukin-6 obtained by the ROC (receiver operating characteristic) method gave a sensitivity of 50% and a specificity of 87%, and a cut-off of 111.7 pg/ml for interleukin-8 showed a sensitivity of 78% and a specificity of 91%. CONCLUSION: While cord blood levels of interleukin-6 appear to be related to pathological conditions in the perinatal period (infectious and non-infectious), interleukin-8 seems to be a good predictor of early bacterial neonatal infection.     

Neutrophil CD64 is a sensitive diagnostic marker for early-onset neonatal infection

This prospective study aimed to evaluate the diagnostic utilities of neutrophil CD64 expression for the identification of early-onset clinical infection and pneumonia in term infants and to define the optimal cutoff value so that it may act as a reference with which future studies can be compared. Term newborns in whom infection was suspected when they were <72 h of age were recruited into the study. C-reactive protein (CRP) and expression of CD64 on neutrophils were measured at 0 h (at the time of sepsis evaluation) and 24 h. The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of CRP, CD64, and the combination of these two markers for predicting neonatal sepsis were determined. A total of 338 infants with suspected clinical sepsis were investigated, 115 of whom were found to be clinically infected. CRP and CD64 in infected infants were both significantly elevated at 0 and 24 h compared with noninfected infants (p < 0.001). The calculated optimal cutoff value for CD64 was 6136 antibody-phycoerythrin molecules bound/cell. CD64 has a very high sensitivity (96%) and NPV (97%) at 24 h. The addition of CRP only marginally enhanced the sensitivity and NPV (97 and 98%, respectively). In conclusion, neutrophil CD64 is a very sensitive diagnostic marker for the identification of early-onset clinical infection and pneumonia in term newborns. The results strongly suggest that measurement of neutrophil CD64 may allow neonatal clinicians to discontinue antibiotic treatment at 24 h in infants who are clinically stable and whose CD64 expressions are below the optimal cutoff level.     

Evaluation of interleukin-6, tumour necrosis factor-α and interleukin-1β for early diagnosis of neonatal sepsis

The objective of this study was to assess the contribution of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) to an early diagnosis of early-onset neonatal sepsis. A cohort of 117 newborn infants delivered during a 1-y period had IL-6, TNF-alpha and IL-1beta, blood and cerebrospinal fluid (CSF) cultures, leucocyte and platelet count collected on the initial evaluation of possible early-onset sepsis. They were divided into four groups: I, positive blood and/or CSF cultures; II, probably infected with clinical sepsis but negative cultures; III, same as group II but mother received antibiotic antepartum; and IV, newborn infants that did not receive any antibiotic therapy. There were no differences among the four groups with respect to mean gestational ages and birthweights, median Apgar scores, type of delivery, or number of newborn infants with leucocyte count <5000 mm(-3) or >25000 mm(-3), platelet count <100000 mm(-3), immature/total neutrophil ratio >0.2, absolute neutrophil count <1000mm(-3) and median IL-1beta levels. Median IL-6 and TNF-alpha levels were significantly higher in groups with patients with a diagnosis of clinical sepsis than in controls. The optimal cut-off point was 32 pg ml(-1) for IL-6 and 12 pg ml(-1) for TNF-alpha. The combination of both provided a sensitivity of 98.5%. In conclusion, the combination of IL-6 and TNF-alpha is a highly sensitive marker of sepsis in the immediate postnatal period.     

Diagnosis of late onset neonatal sepsis with cytokines,adhesion molecule,and C-reactive protein in preterm very low birthweight infants

AIMS—To evaluate the commonly used markers—namely IL-6, TNFα, IL-1β, C-reactive protein and E-selectin for identification of late onset neonatal sepsis; to define the optimal cutoff value for each marker in preterm neonates; to assess whether these markers could assist in early discontinuation of antibiotics in non-infected cases; and to delineate the profile of these markers during systemic infection and in relation to successful treatment.METHODS—Very low birthweight infants in whom clinical sepsis was suspected when they were >72 hours of age were eligible for study. A full sepsis screen was performed in each episode. Cytokines, C-reactive protein, and E-selectin were serially measured on days 0 (at the time of sepsis evaluation), 1, 2, 4 and 7. The optimal cutoff value for each marker was calculated after minimising the number of misclassified episodes over all possible cutoff values for days 0 and 1. The sensitivity, specificity, positive and negative predictive values for each test and combination of tests for predicting systemic infection were also determined.RESULTS—One hundred and one episodes of suspected clinical sepsis were investigated in 68 infants. Forty five episodes were proved to be infections. The optimal cutoff values were IL-6 31 pg/ml, TNFα 17 pg/ml, IL-1β 1 pg/ml, C reactive protein 12 mg/l and E-selectin 174 ng/ml. IL-6 had the highest sensitivity (89%) and negative predictive value (91%) for detecting late onset infection on day 0. However, between 24 and 48 hours of onset, C-reactive protein was the best single marker, with an overall sensitivity and specificity of 84% and 96%, respectively. The use of serial and multiple markers in the first 48 hours further enhanced the sensitivity and specificity of these tests. Performing IL-6 and C-reactive protein on day 0, together with either TNFα on day 1 or C-reactive protein on day 2, showed the best overall sensitivity (98%) and specificity (91%) for the diagnosis of late onset infection.CONCLUSIONS—Optimal cutoff values for these markers in detecting late onset systemic infection in very low birthweight infants have been defined. Withholding antibiotic treatment at the onset of infection could be fatal and is not recommended, but the concomitant use of IL-6 and C-reactive protein or TNFα should allow antimicrobial treatment to be discontinued at 48 hours without waiting for microbiological results, provided that the infants are in good clinical condition.     

Circulating thrombopoietin levels in neonates with infection

Thrombocytopenia is a commonly encountered hematologic complication in neonates with sepsis. Thrombopoietin (TPO) is the principal physiologic regulator of megakariocytopoiesis and platelet production. This study was carried out to determine whether variations in circulating TPO levels would occur in infected neonates and/or if they would correlate with platelet counts. In a prospective study of 36 sick neonates (gestational age 24-42 wk) admitted to a regional Neonatal Intensive Care Unit (NICU), blood was collected for TPO measurements and platelet counts on admission to the NICU, if infection was inferred, and at recovery before discharge. An additional group of 15 apparently healthy neonates was also studied (median postnatal age at the time of blood sampling for TPO assessment: 4 d, range 1-10) as control. TPO was measured on plasma samples using a commercially available enzyme-immunosorbent assay (ELISA). On admission, the majority (21/36) of the sick neonates had non-infectious diseases, 2 had early onset sepsis, and 13 had infection (defined as the presence of clinical signs of sepsis, abnormal leukocyte counts or C-reactive protein values, and positive results on local cultures, but negative blood culture results). During the hospital stay, 5 neonates developed sepsis (positive blood culture) and 6 had infection (as previously defined) or necrotizing enterocolitis (NEC). The median TPO level (1704 pg/ml, range 51-3912) was higher during sepsis (either early or late) than during infection (included NEC) (198 pg/ml, range 21-2504), or non-infectious disease (659 pg/ml, range 0-2533), while platelet counts (median value 37,000 cells/microl, range 15,000-486,000) were lower than during either infection (included NEC) (median value 238,000 cells/microl, range 49,000-655,000) or non-infectious disease (median value 110,000 cells/microl, range 45,000-549,000). When infants had recovered from these illnesses, TPO concentrations markedly dropped (median value 59 pg/ml, range 0-825). These values were similar to those found in the control neonates (median TPO level 85 pg/ml, range 43-620). In infected neonates (sepsis plus infection), TPO levels inversely correlated with platelet counts (r = -0.634, p = 0.001) as did those of infants with non-infectious disease (r = -0.574, p = 0.006), while there was no significant correlation between TPO levels and platelet counts in the samples obtained after recovery or in the control infants. We conclude that infected neonates have high circulating TPO levels in the face of low platelet counts. Whether larger TPO concentrations following exogenous administration of recombinant TPO would restore the number of circulating platelets warrants further investigation.