Granulocyte colony-stimulating factor receptor expression on neutrophils of term and preterm neonates with and without signs of infection

Neutrophils are an essential component of the human host defence system against infection. Recombinant human granulocyte colony-stimulating factor induces neutrophilia and enhances effector functions of mature neutrophils. Since the biological effects of granulocyte colony-stimulating factor (G-CSF) are mediated by its receptor, we investigated the expression of G-CSF receptor on the surface of neutrophils of term and preterm neonates (n = 22) with and without signs of infection and of healthy adults (n = 13) by flow cytometry. In healthy adults, the percentage of neutrophils expressing G-CSF receptor was higher compared to cord blood of term and preterm neonates (87% vs 53%, P < 0.05). Between 2 and 32 h of life, neonates with signs of infection showed lower values of G-CSF receptor expression compared to neonates without signs of infection (32% vs 54%, P < 0.05). No correlation was detectable between expression of G-CSF receptor and gestational age. Conclusion Expression of granulocyte colony-stimulating factor receptor on neutrophils is lower than in adults. This may adversely affect granulopoiesis and neutrophil function during the neonatal period. Moreover, granulocyte colony-stimulating factor receptor expression seems to be down-regulated during neonatal infection. Received: 8 June 1998 / Accepted in revised form: 13 October 1998     

Congenital malaria in a preterm infant

Abstract:   A case of congenital malaria in a preterm newborn infant is presented. The case illustrates the difficulty of early diagnosis, and the atypical nature of presentation in a preterm infant.     

Hyperglycaemia as a possible marker of invasive fungal infection in preterm neonates

AIM: The incidence of invasive fungal infection in preterm newborns is rising steadily. Early recognition and treatment are imperative, but diagnosis is difficult as data from microbiological investigations are often poor, and clinical and laboratory signs do not help in differentiating bacterial from fungal infections. We evaluated whether glucose intolerance could represent a possible surrogate marker predictor of invasive fungal infection in preterm neonates. METHODS: We performed a case-control study on neonates with birthweight less than 1250 g admitted to our tertiary-level unit during the years 1998-2004 (n = 383), comparing those with invasive fungal infection (n = 45, group A) to matched controls with late-onset sepsis caused by bacterial agents (n = 46, group B). We investigated in both groups the occurrence of hyperglycaemia (serum glycaemia > 215 mg/dl, i.e. 12 mmol/l) in the first month of life, and its temporal relationship with the episodes of sepsis. RESULTS: Hyperglycaemia occurred significantly more often in group A (21/45, 46.6%) than in group B neonates (11/46, 23.9%) (OR 1.95, 95% CI 1.235-4.432, p = 0.008). Moreover, in 19 of 21 (90.4%) neonates with hyperglycaemia in group A, the carbohydrate intolerance episode typically occurred 72 h prior to the onset of invasive fungal infection; in contrast, no temporal relationship was found in neonates with bacterial sepsis (p = 0.002). Correction of hyperglycaemia was successfully achieved in all neonates of both groups, with no significant differences in the number of days of insulin treatment needed to normalize glycaemia (p = 0.15). CONCLUSIONS: Hyperglycaemia is significantly more frequent in neonates who subsequently develop fungal rather than bacterial late-onset sepsis, with a typical 3-d interval. We suggest that a preterm neonate whose birthweight is less than 1250 g in its first month of life should be carefully evaluated for systemic fungal infection whenever signs of carbohydrate intolerance occur.     

烟雾病患儿粒细胞集落刺激因子的变化

目的：探讨粒细胞集落刺激因子（G-CSF）在烟雾病发病机制中的作用。方法：采用酶联免疫吸附法(ELISA)检测20例有症状的烟雾病患儿及20例健康对照儿童的血清G-CSF浓度。结果：健康对照组的血清G-CSF 浓度平均值为23.5±3.8 pg/mL, 烟雾病组平均值为35.7±10.3 pg/mL。烟雾病组的血清G-CSF平均浓度明显高于健康对照组,P<0.01。结论：烟雾病组的血清G-CSF浓度比健康对照组明显升高, 提示G-CSF在烟雾病的发病机制中可能具有重要作用。［中国当代儿科杂志,2010,12（2）：117-119］     

早产儿医院感染的危险因素

目的 探讨早产儿医院感染的发病情况及危险因素,为医院感染的监控和干预提供理论依据.方法回顾性调查本院2008年1月-2010年1月本院NICU 516例早产儿的临床资料,分析医院感染的危险因素.结果 1.早产儿516例中,74例发生医院感染,发生率为14.3%,共发生医院感染98例次,平均每例发生1.32次,医院感染的住院日相关发生率为8.9‰;感染部位以呼吸道为主(51.0%),其中呼吸机相关性肺炎最为多见(占36.0%),其次为皮肤软组织(26.5%)和消化道(14.3%).2.共培养出病原菌69株,革兰阴性杆菌占71.0%,以肺炎克雷伯菌最为多见(17.4%);革兰阳性球菌占18.8%,以草绿色链球菌最为多见;真菌占10.1%,主要为白色念珠菌.3.胎龄≤32周、出生体质量≤1.5 kg、羊水胎粪污染、胎膜早破≥48 h、糖尿病母亲儿、吸痰次数≥10次、气管插管次数≥3次、机械通气时间≥3 d、置胃管、静脉营养、应用抗生素时间≥2周及住院时间≥2周与医院感染率显著相关,多元Logistic回归方程显示胎龄≤32周、静脉营养、机械通气时间≥3 d及住院时间≥2周是医院感染发生的独立危险因素.结论 NICU早产儿医院感染的危险因素众多,尽量减少侵入性操作次数、缩短静脉营养及住院的时间、合理应用抗生素可有效降低医院感染发生率.     

急性感染时血清粒细胞集落刺激因子的检测

目的探讨急性感染时血清粒细胞集落刺激因子（Ｇ－ＣＳＦ）水平的变化规律，为急性感染的诊断提供依据。方法肺部感染、消化道感染及全身感染患者共７０例，入院当天均作血清Ｇ－ＣＳＦ血培、养及血常规检测。Ｇ－ＣＳＦ的测定采用双抗体夹心酶联免疫法。对测定结果进行统计学处理。结果７０例急性感染患者，Ｇ－ＣＳＦ阳性者４４例，阳性率为６２．８５％，细菌培养３４例阳性，阳性率为４８．５７％。肺部感染、消化道感染及全身感染，Ｇ－ＣＳＦ的阳性率分别为３０％、６９％、８３％。７０例患者血培养阳性者１８例（２５．７％）。与Ｇ－ＣＳＦ阳性率相比，差异非常显著（Ｐ＜０．００１）。４４例Ｇ－ＣＳＦ阳性患者抗感染治疗前后中性粒细胞绝对值（ＡＮＣ）分别为（８．３８±３．３９）×１０９／Ｌ和（４．１２±１．４７）×１０９／Ｌ（ｔ＝７．６１，Ｐ＜０．００１）。结论急性感染患者血清中Ｇ－ＣＳＦ水平显著升高。测定血清Ｇ－ＣＳＦ可作为判断细菌感染的敏感指标，与血培养及血常规检查相比，其敏感度、阳性率高，但特异性较差。     

Evaluation of infectious episodes in neonates using a new procedure for the nitroblue tetrazolium test

A new procedure for the NBT slide test for peripheral blood neutrophils has been tested. 255 neonates were studied of which 63 served as control cases. Among the 114 term infants, 37 were patently infected, 30 suspicious and 47 non-infected. The latter did not significantly differ from control cases, whereas suspicious and infected infants were credited with significantly higher NBT scores.78 infants were preterm, 31 of which were patently infected, 22 suspicious and 25 non-infected. NBT scores of infected and suspicious infants were significantly higher than those of non-infected infants, but, as previously reported, scores of preterm infants were systematically and significantly lower than those of full-term infants of the same bacteriological class.Threshold values are suggested; they could represent an accurate diagnostic aid in the early differentiation of healthy infants from high-risk infants regarding bacterial infections.     

Reducing discomfort while measuring crown-heel length in neonates

AIM: To assess the degree of discomfort caused by length measurement in neonates, performed with one or both lower limbs extended, on the first and second day after birth, with either one or both lower limbs extended. METHODS: Healthy full-term neonates were systematically sampled during the months of February and March 2004. Crown-heel length was measured, using a 1-mm precision neonatometer, at approximately 8 h and 32 h after birth, with one and both lower limbs extended. The Neonatal Facial Coding System was used to assess discomfort during measurements. Data were analysed by parametric and non-parametric tests as appropriate. RESULTS: Whatever the measurement technique, discomfort scores are significantly higher during the length measurement than at baseline. Whenever length measurements are performed, discomfort scores are significantly higher when extending both lower limbs rather than one lower limb (p < 0.006). The measured length is greater with one lower limb extended; however, the difference decreases over time, being 0.19 cm (95% CI 0.1-0.3; p < 0.001) at approximately 32 h of age. No significant differences in length were found between measurements at approximately 8 or 32 h, regardless of the technique used. The best correlation between length measurements with one or both lower limbs extended was observed at approximately 32 h after birth (r = 0.98). CONCLUSION: Measuring crown-heel length is a distressful procedure for the neonate. Measurements with one lower limb extended result in less discomfort than when both lower limbs are extended, without decreasing the accuracy.     

Ultrasound grading of cerebral ventricular dilatation in preterm neonates

OBJECTIVE: To compare three grading systems previously described for the measurement of cerebral ventricular dilatation in preterm neonates using ultrasound scans and then to compare these with expert clinical judgement. METHODS: Eighty-one preterm neonates <1500 g birthweight or < 32 weeks' gestation, with normal, mild, moderate or severely dilated ventricles recorded predominantly during the first 2 weeks of life were selected to ensure a broad representation of ventricular size. Their cranial ultrasound scans obtained nearest to 6 weeks of age were studied. The ventricular index, the diagonal width in the coronal plane and the ventricular height in the parasagittal plane were measured adjacent to the foramen of Monro and were used to grade the degree of dilatation. In 20 of these neonates, this grading was compared with grading based on expert clinical judgement. RESULTS: Grading according to the ventricular index defined 79% of the scans as normal. However, only 44% and 39% were considered to be normal according to vertical height and diagonal width, respectively. There was a high level of correlation between expert clinical judgement and grading based on ventricular height measurement (r = 0.812; area under receiver operating characteristic (ROC) curve = 0.922) and the diagonal width (r = 0.806; area under ROC curve = 0.935). Ventricular index correlated poorly with clinical judgement (r = 0.298; area under ROC curve = 0.604). CONCLUSIONS: The measurement of ventricular height and the measurement of diagonal width correlated well with expert clinical judgement. The ventricular index correlated poorly and was less sensitive to mild dilatation. There was no correlation between the ventricular index and the other two measures. The ventricular height and the diagonal width are more appropriate for assessing ventricular dilatation in preterm neonates.     

Improvement of neutropenia and neutrophil dysfunction by granulocyte colony-stimulating factor in a patient with glycogen storage disease type Ib

Patients with glycogen storage disease type Ib (GSD Ib) suffer from recurrent bacterial infections due to neutropenia and neutrophil dysfunction. To improve the quality of life in a 9-year-old boy with GSD Ib, we subeutaneously administered recombinant human granulocyte colony-stimulating factor (G-CSF). Daily injections of 100 g/m² of G-CSF significantly increased absolute neutrophil counts and augmented neutrophil mobility. The patient was then treated with 70 and 100 g/m² of G-CSF daily and twice-weekly. The treatment maintained absolute neutrophil counts at significantly higher levels than those without treatment for 22 months and markedly decreased the frequency of infections and the necessity for hospitalisation. No adverse effects were observed during treatment. These findings indicate that daily and twice-weekly treatment with G-CSF of long duration are safe and effective for patients with GSD Ib. G-CSF may be a useful therapeutic agent in patients with neutrophilic impairment as a consequence of a metabolic disorder.     

血小板活化因子在新生儿缺氧缺血性脑病中的变化及意义

为探讨血小板活化因子（PAF）与新生儿缺氧缺血性脑病（HIE）之间的关系，应用改良的Henson法测定30例HIE患儿和20例正常新生儿血清PAF。结果表明，30例HIE患儿血清PAF明显增高，与正常对照组比较差异有显著性（P＜0．001）。提示：PAF与HIE有密切的相关性，PAF可作为判断HIE病情轻重程度和预后的重要指标。     

Studies of Peripheral Blood Toxic Neutrophils as a Predictor of Coronary Risk in Kawasaki Disease—the Pathogenetic Role of Hematopoietic Colony-Stimulating Factors (GM-CSF, G-CSF)

Many toxic neutrophils, characterized by cytoplasmic swelling, vacuolization and toxic granulation, can be seen in the acute phase of Kawasaki Disease (KD; mucocutaneous lymph node syndrome). Polymorphonuclear neutrophils (PMNs) of 36 patients with acute and convalescent phase KD were studied with reference to their morphological characteristics. The percentage of toxic neutrophils in the acute phase tended to be higher in the group with coronary artery lesions (CAL) than in the group without CAL. The results suggest that observation of toxic neutrophils in the acute phase of KD may be useful in predicting a high risk of CAL. In vitro cultivation studies of PMNs from healthy persons, in the presence of diverse hematopoietic colony-stimulating factors (CSF), revealed that GM-CSF (granulocyte-macrophage-CSF) and G-CSF (granulocyte-CSF) participated in the induction of cytoplasmic vacuolization of PMNs, and that the healthy PMNs morphologically mimicked peripheral PMNs seen in the acute phase of KD.     

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??Non-invasive high-frequency ventilation??NIHFV?? is a newer form of non-invasive ventilation??NIV?? which uses nasopharyngeal tubes??short nasal prongs or masks instead of endotracheal tube to deliver high frequency ventilation. NIHFV offers the advantages of invasive high frequency ventilation??no need for synchronisation??high CO2 removal??less volume/barotrauma?? and nasal CPAP??non-invasive interface??increase in functional residual capacity allowing oxygenation to improve??. Clinical pilot studies show NIHFV can be used as a rescue therapy after failure of other NIV modes to help prevent or delay intubation. However??the data is limited. Further multi-center??prospective??randomized??controlled trials are needed.     

Granulocyte-colony stimulating factor levels in cord blood and neonatal peripheral blood

We measured the granulocyte-colony stimulating factor (G-CSF) levels in cord blood and peripheral blood obtained from full-term or pre-term infants during the first 3 days of birth. The mean G-CSF level among cord blood (17.2pg/mL) was similar to that of peripheral blood on day 0 (18.3 pg/mL) and day 1 (13.6 pg/mL), while that of peripheral blood on day 0 was significantly higher than on day 2 (10.9 pg/mL) and day 3 (8.8 pg/mL; both P < 0.05). There was no correlation between neutrophil counts and G-CSF levels. No difference was found in neutrophil counts or G-CSF levels between infants who weighed more or less than 2500 g at birth. These results suggest that the neonatal neutrophil count depends on regulatory factors other than G-CSF.     

Neutrophil functions of Chinese neonates

OBJECTIVE: To delineate neutrophil function of preterm and full-term neonates of Chinese origin. METHODS: Chinese neonates admitted to two major Hong Kong neonatal units were randomly selected for the study. Candidacidal activity, phagocytosis, chemotaxis and nitroblue tetrazolium reduction scores were evaluated from blood. RESULTS: Except for chemotactic activity, the neutrophil functions of Chinese preterm neonates were similar to Chinese full-term neonates. The candidacidal activity of males was significantly lower when compared with female neonates. Compared with adult controls, both term and preterm infants had similar phagocytic activities although their candidacidal activities and chemotactic index were significantly decreased. Neutrophil function of Chinese infants was nearer to that of adult controls than historically reported for western infants. CONCLUSION:: Preterm Chinese neonates had similar neutrophil function to full-term infants. Neutrophil function of Chinese infants was more mature than that of western infants.     

Elevated immunoglobulin M levels in low birth-weight neonates with chronic respiratory insufficiency

Ten babies weighing less than 1500 g at birth subsequently developed chronic respiratory insufficiency and bubbly appearance on chest X-ray during their infancy. The clinical diagnoses were compatible with Wilson-Mikity syndrome. They were compared with very low birth-weight infants who did not show these signs and symptoms. On the first day (mean) of life significantly high serum immunoglobulin M levels were found in the study group. The possibility exists that the chronic respiratory insufficiency seen in these very low birth-weight infants may have been caused by intrauterine infection.     

Plasma fibronectin levels in extremely preterm infants in the first 8 weeks of life

Abstract Fibronectin has in the past been considered to function simply as a non-specific plasma opsonin. However, recent studies have demonstrated that this molecule plays an important role in fundamental components of the immune response, for example, neutrophil adhesion, T cell activation and endothelial function. Additionally, fibronectin is important in lung homeostasis where it contributes to alveolar epithelial integrity. In this study plasma fibronectin levels were measured longitudinally in a group of extremely preterm infants, mean gestational age 27 weeks.
Plasma fibronectin levels at birth were significantly lower in the preterm study group than in term controls (mean 91±33 μg/mL compared with 214±62 μg/mL in the term controls, P <0.0001). The preterm cohort demonstrated a more than two-fold rise in plasma fibronectin on days one and two; levels fell almost to baseline values by day three with a subsequent slow rise to a plateau by day 28. No further increase was seen by day 56. This sequence of early changes in fibronectin levels mirrored closely the time course of respiratory distress syndrome. Infants of mothers with pre-eclampsia had significantly lower peak fibronectin levels than in those without ( P = 0.016), and those infants with bronchopulmonary dysplasia showed a trend towards lower basal fibronectin levels ( P = 0.07) and a greater difference between peak and basal levels ( P = 0.05).
Neonates, particularly those born preterm, have blunted immunological responses to infection. Fibronectin plays a key role in immunological responsiveness. The significant changes in fibronectin levels after birth in the preterm neonate are likely to have important pathophysiological consequences. The relationship between alterations in fibronectin after birth, endothelial and epithelial cell function, and respiratory distress syndrome (RDS) remain to be explored.