Increased granulocyte-colony stimulating factor (G-CSF) levels in neonates with perinatal complications

We have investigated cord blood granulocyte-colony stimulating factor (G-CSF) levels in neonates with or without neonatal complications to examine some changes in the G-CSF levels in the neonatal period. The G-CSF levels were measured in 613 neonates by enzyme immunoassay. The results showed that G-CSF levels were distributed in a broad range from the level under the cutting point (31 pg/mL) to over the measurable range (2000 pg/mL). Normal neonates without perinatal complications were 322. In normal neonates, the G-CSF level correlated with the gestational age (r = 0.255, P < 0.01) and cord blood leukocyte count (r = 0.210, P < 0.01). The G-CSF values were under 100 pg/mL in 95% of normal neonates with a median of 35.0 pg/mL. We divided the neonates into two groups: a lower (< 100 pg/mL) and a higher (≥ 100 pg/mL), based on the G-CSF level. The percentage of neonates with higher G-CSF levels (≥ 100 pg/mL) was greater in neonates with perinatal complications than in normal neonates (< 100 pg/mL; P < 0.01). Compared with normal neonates, the percentages of the higher group were greater in neonates with infections (P < 0.01), fetal distress (P < 0.01), premature rupture of membranes (P < 0.05), neonatal asphyxia (P < 0.01) and meconium staining of amniotic fluid (P < 0.01). Neonates with higher G-CSF levels had larger numbers of peripheral leukocytes (P < 0.05) than did those with the lower G-CSF levels. Counts of leukocytes were parallel with those of neutrophils. In conclusion, cord G-CSF levels in neonates can be increased in response to, not only infections, but also to such stress states as fetal distress, premature rupture of membranes, neonatal asphyxia and meconium staining of the amniotic fluid, which may result in increased numbers of neutrophils.     

Granulocyte macrophage-colony stimulating factor (GM-CSF) in neonatal neutropenia

Neutropenia in neonates is often associated with sepsis, prematurity and maternal hypertension with increased risk of mortality. We describe two neonates with neutropenia treated with granulocyte macrophage colony stimulating factor. The total and absolute neutrophil counts showed a marked response and led to a favourable outcome. Human granulocyte macrophage colony stimulating factor may be used as an adjuvant therapy for neonatal neutropenia of different aetiologies.     

Myocardial ischaemia in neonates with perinatal asphyxia

In asphyxiated neonates, hypoxia is often responsible for myocardial ischaemia. To evaluate cardiac involvement in neonates with respiratory distress, ECG and echocardiographic recordings were performed, and cardiac enzymes determined. These data were related to clinical presentation and patient outcome. Three groups of neonates were studied: 22 healthy newborn infants (group I) with 5 min Apgar scores >9 and pH >7.3; 15 neonates with moderate respiratory distress (group II) which had Apgar scores ranging between 7 and 9, and pH between 7.2 and 7.3; and 13 neonates with severe asphyxia, Apgar scores <7, and pH <7.2 (group III). The ECGs were evaluated according to the 4-grade classification proposed by Jedeikin et al. [8]. On the echocardiograms, fractional shortening and aortic flow curve parameters were taken into account. Serum creatine kinase (CK), creatine kinase-MB isoenzyme (CK-MB) and lactate dehydrogenase were determined. All of groups I and II survived, but 5 out of 13 in group III died within the 1st week. Grade 3 or 4 ECG changes were observed only in group III patients, while all group II and 3 patients of group I showed grade 2 ECG changes. Fractional shortening, peak aortic velocity and mean acceleration were significantly reduced in group III, whereas the only abnormality found in group II was a reduced fractional shortening. CK, CK-MB, CK-MB/CK ratio and lactate dehydrogenase were all increased in group III, while in group II only CK-MB and the CK-MB/CK ratio were abnormal. Conclusion Severely asphyxiated newborn infants reflect relevant ischaemic electro- cardiographic changes, depressed left ventricular function and marked cardiac enzyme increase. These alterations are far less pronounced in neonates with mild respiratory distress. Received 5 May 1998 / Accepted in revised form: 11 January 1999     

The in vivo effect of recombinant human granulocyte-colony stimulating factor in neutropenic neonates with sepsis

The effects of recombinant granulocyte-colony stimulating factor (rhG-CSF) in neonatal neutropenia with presumed sepsis, which has a poor prognosis, were investigated. The study involved 14 neonates with presumed sepsis and neutropenia. Findings were compared with those from 24 historical controls. rhG-CSF (5 μg/kg/day i.v. for 5 days) was administered immediately following diagnosis. Complete blood counts were obtained before and 24, 48, 72, 96 and 120 h after initiation of treatment. Neutrophil storage pool (NSP) was assessed (in 4 patients) before and after treatment. Statistical analysis was performed using one way analysis of variance. Treatment led to an increase in absolute neutrophil count (ANC) levels in 13/14 patients. At the end of treatment, the mean ANC was higher than that of controls (P = 0.007). There was a marked increase in the NSP of between 32% and 65% (P = 0.005). There were two clinical failures, one of whom was considered to have died from his underlying condition. There were no reports of clinical or haematological toxicity during treatment or follow up. Received: 14 June 1996 / Received in revised form and accepted: 15 November 1996     

Effect of perinatal factors on cord blood thyroid stimulating hormone levels

OBJECTIVE: To study the influence of perinatal factors on cord blood (CB) TSH levels. INFANTS AND METHODS: In a prospective cross-sectional study, CB TSH levels were measured in 1,590 live-born infants using IRMA. The effect of various perinatal factors on the CB TSH levels was analyzed statistically. RESULTS: The mean TSH level in the study group was 10.6 +/- 6.7 microU/ml (range 0.01-66.4 microU/ml). A significant fall in CB TSH levels was noted with increasing gestational age. A similar decline was noted in TSH levels with increase in birth weight. No significant difference in TSH levels was noted between males and females, or AGA and SGA (n = 296) infants. Infants with birth asphyxia (Apgar score < 4 at 5 min) had significantly higher CB TSH levels (mean 31 microU/ml, n = 18) as compared to those without (mean 10.4 microU/ml) (p < 0.01). The highest TSH levels were noted in neonates delivered by forceps extraction (mean 29.4 microU/ml, n = 17) and lowest levels in infants born by elective Caesarian section (mean 8.7 microU/ml, n = 149). CONCLUSION: CB TSH levels fall with increase in gestational age while birth asphyxia and difficult deliveries tend to elevate them.     

新生儿高胆红素血症对远期预后的影响

目的探讨新生儿血清胆红素水平及其对远期预后的影响。方法 对120例新生儿高胆红素血症患儿在5-10岁时进行智力、听力及神经系统随访。结果31例有智力缺陷,其中9例干预治疗后恢复正常;25例听力损失;5倒有神经系统改变,其中脑性瘫痪3例,单侧肢体(左上肢)运动障碍、语言障碍各1例。智力、听力及神经系统异常率与血清总胆红素峰值均无显著相关(P均>0.05)溶血组与非溶血组异常率无显著差异(P>0.05)结论除重度高胆红素血症外,轻中度高胆红素血症也可对新生儿产生神经损害,致神经精神发育异常,仅凭血清总胆红素水平并不能确切判断远期预后 对所有高胆红素血症新生儿均应积极治疗,尽量减少后遗症     

窒息围产儿血液阴离子间隙状态的探讨

该文对 6 5例出生时窒息的围产儿复苏后同步作血气分析、血清电解质及阴离子间隙 (AG)测定。结果高AG 47例、正常AG 1 6例、低AG 2例。代谢性酸中毒 5 8例 ,发生率为 89% ,高AG代酸、三重性酸碱失衡分别占代谢性酸中毒的 81 %及 2 4%。分析表明 :窒息复苏后有严重的酸碱紊乱 ,以高AG状态为主 ,代谢性酸中毒发生率高 ;高AG代射性酸中毒与窒息的程度无关 (P >0 .0 5 ) ;高AG组血Cl-,HCO3 -比正常AG组、低AG组明显降低 (P <0 .0 5 )。因此强调除作血气分析外 ,须作AG分析 ,以便对酸碱紊乱作出更准确的诊断。除治疗原发病外 ,还应保证通气 ,改善微循环。     

新生儿肺炎患儿内皮素和表皮生长因子水平的变化

目的 探讨内皮素(ET)与表皮生长因子(EGF)在新生儿肺炎发病中的作用和临床意义。方法 应用放免法测定38例新生儿肺炎患儿血浆ET及26例患儿尿EGF水平。结果 肺炎急性期血浆ET及尿EGF水平均明显高于对照组(P值均<0<01);8例重症新生儿肺炎,恢复期血浆ET及尿EGF水平较急性期明显下降（P值均<0.01）。血浆ET与尿EGF水平在病程中的变化规律一致,两者呈正相关关系(r=0.481,P<0.05)。结论 ET和EGF对新生儿肺炎的发生发展可能有一定的促进作用,测定血浆ET及尿EGF可作为判断新生儿肺炎病情变化的参考指标。     

休克新生儿血浆内皮素和心钠素变化及其临床意义

目的：研究新生儿休克时血浆内皮素(ET-1)和心钠素(ANF)水平的变化及其与临床病程的关系。方法：以放射免疫分析法分别测定29例休克新生儿治疗前后血浆ET-1和ANF水平,并与18例对照组新生儿对比。结果：休克时血浆ET-1和ANF水平均明显高于对照组(P<0.01);休克纠正后ANF水平迅速下降,但ET-1水平下降不明显;感染性与非感染性休克患儿之间其ET-1和ANF水平无明显差异;休克合并心力衰竭时ET-1和ANF水平下降均较缓慢;休克时ET-1和ANF水平呈显著正相关关系(r=0.76,P<0.05)。结论：血浆ET-1和ANF均可能参与了新生儿休克的发病机制和病理经过,并可作为判断休克转归的重要参考指标。     

新生儿窒息后血浆褪黑素水平变化的临床研究

目的 研究新生儿窒息后血浆褪黑素(MT)水平的变化,阐明褪黑素在新生儿窒息及缺氧缺血性脑病(HIE)发生发展过程中的作用,并为临床应用提供依据.方法 选择正常足月新生儿12名的脐动脉血标本为对照组.足月新生儿窒息病例36例为观察组,其中轻度窒息12例,重度窒息24例,重度窒息中并发HIE 12例;分别于急性期(生后24 h内)和恢复期(生后第7天)采股静脉血标本,用酶联免疫分析法检测血浆褪黑素水平.结果 窒息急性期、恢复期与正常对照组相比,褪黑素水平升高有统计学意义(P<0.05和P<0.01);窒息恢复期与急性期相比,褪黑素水平升高有统计学意义(P<0.01).无HIE组急性期与对照组相比.褪黑素水平变化无统计学意义(P>O.05);其余各组与对照组相比,褪黑素水平升高均有统计学意义(P<0.01).无HIE组恢复期与急性期相比及急性期HIE组与无HIE组相比,褪黑素水平升高有统计学意义(P0.05).结论 新生儿窒息后及并发HIE时血浆褪黑素水平均升高,提示对机体有一定的保护作用.     

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.     

围生期新生儿B族链球菌感染

曹云教授 受<中国循证儿科杂志>编辑部委托,在第三届上海国际新生儿医学论坛会议期间,很荣幸邀请到美国哈佛大学波士顿儿童医院Michael Wessels教授和上海市(复旦大学附属)公共卫生临床中心妇产科蒋佩茹教授就围生期新生儿B族链球菌（GBS）感染进行讨论.     

Increased levels of circulating adhesion molecules in neonates with congenital diaphragmatic hernia complicated by persistent pulmonary hypertension

The aim of this study was to determine circulating levels of adhesion molecules in serum from patients with congenital diaphragmatic hernia (CDH) to investigate the relationship between soluble ICAM-1, ELAM-1, and VCAM-1 liberated by activated vascular endothelium and the development of persistent pulmonary hypertension (PPH) in patients with CDH. We measured serum levels of ICAM-1, ELAM-1, and VCAM-1 in 20 high-risk neonates with CDH at the time of diagnosis (11 with PPH and 9 without PPH) and 7 age-matched controls using ELISA system. We further examined the lungs of 5 patients with CDH complicated by PPH who died during resuscitation and stabilization, and three control lung specimens for the expression of adhesion molecules using immunohistochemistry. The mean serum ICAM-1 levels in CDH patients with PPH (227.0±98.9 ng/ml) were increased compared with levels in CDH patients without PPH (140.29±37.4 ng/ml; p<0.05) and controls (130.0±23.8 ng/ml; p<0.05). Mean serum ELAM-1 levels in CDH patients with PPH (116.5±19.2 ng/ml) were significantly increased compared with levels in CDH patients without PPH (79.3±27.9 ng/ml; p<0.01) and controls (58.4±14.5 ng/ml; p<0.001). Mean serum VCAM-1 levels in CDH patients with PPH (1596.9±460.4 ng/ml) were significantly higher compared with levels in CDH patients without PPH (1069.3±444.6 ng/ml; p<0.01) and controls (838.0±171.2 ng/ml; p<0.001). But serum adhesion molecule levels in CDH patients without PPH were no different from controls statistically. Pulmonary vascular endothelial cells from CDH lung with PPH had strong expression of adhesion molecules compared with controls. Up-regulated expression of adhesion molecules on the endothelium of pulmonary vessels and high circulating levels of adhesion molecules in CDH patients with PPH suggest that adhesion molecules may play a role in the development of PPH in CDH.     

Auditory brainstem response in neonates with hypoxic-ischemic-encephalopathy following perinatal asphyxia.

The technique of auditory brainstem evoked responses testing (ABR) was applied to twenty four new born infants with asphyxia complicated by hypoxic-ischemic-encephalopathy (HIE) in an attempt to study potential influence of HIE on hearing impairment. Twenty normal term neonates with no apparent neurological disorder, were also examined for comparison. Twenty two per cent (n = 5) of the patients with HIE showed some abnormality in the ABR pattern, the major one being a transient elevation in threshold of wave V (n = 4; 16.6%). ABR abnormalities, however, were found with greater frequency in neonates with Stage II HIE (75% vs 10%, p less than 0.001). Further ABR abnormalities were found in Stage II HIE only when duration of neurological abnormalities was greater than 5 days. There was no difference, however, between the ABR latencies of the asphyxiated and non-asphyxiated newborn infants (p greater than 0.05). One neonate (4%) with severe HIE, however, had persistent ABR abnormality in the form of bilateral absence of all waves in the later part of the ABR with preservation of wave I. This implied only cochlear functions and absence of any brainstem conduction. These results indicate that birth asphyxia complicated by HIE is a significant high risk factor for hearing impairment in the affected neonates. This justifies ABR testing of neonates with HIE (particularly Stage III), at the time of their discharge, as a screening procedure for early detection of permanent hearing loss.     

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.     

Inflammatory chemokine expression in the peripheral blood of neonates with perinatal asphyxia and perinatal or nosocomial infections

AIM: The inflammatory response induced by perinatal infections and asphyxia is considered to participate in neonatal brain damage. Inflammatory responses are characterized by the expression of chemokines. Although chemokine levels have been investigated in healthy newborns, their role during neonatal pathological conditions has not been studied. The aim of our study was to examine chemokine serum levels in asphyxiated and infected neonates. METHODS: Peripheral blood samples were obtained from perinatally asphyxiated and infected neonates during the first days of life and from neonates who developed nosocomial infections. Serum levels of interleukin-8 (IL-8), interferon-gamma-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), and regulated upon activation, normal T cells expressed and secreted (RANTES) were determined. RESULTS: In perinatally asphyxiated neonates, IL-8 levels were significantly elevated on the 1st day of life. In perinatally infected neonates, IL-8 and IP-10 levels were significantly increased on the 1st day of life, while RANTES levels were significantly lower and remained so until the 4th day. In nosocomially infected neonates, IL-8, IP-10 and MIP-1alpha levels were significantly increased on diagnosis of infection. CONCLUSION: The neonatal immune system is able to produce chemokines for the induction of an inflammatory response during perinatal asphyxia and perinatal or nosocomial infections. Blockade of inflammatory chemokines could possibly contribute to the prevention of brain damage.     

Increased renal medullary echogenicity in neonates

The prevalence of increased renal medullary echogenicity in healthy neonates was looked for. A group of 178 neonates underwent renal ultrasound on the first and second days of life. On the first day of life 58 % had hypereochoic material in their renal collecting system, whereas on the second day only 33% were found to have ultrasonographically demonstrable increased echogenicity in their kidneys. Urinary protein concentrations in infants with increased renal echogenicity were significantly higher than in those without increased renal echogenicity.

     

Plasma platelet-activating factor levels in newborn infants with and without perinatal asphyxia: Is it an additional marker of perinatal asphyxia?

Abstract Background: Hypoxic-ischemic encephalopathy (HIE) is still a very important cause of neonatal mortality and morbidity. Recently platelet-activating factor (PAF) has been accused of being responsible for the neuronal damage in hypoxic-ischemic brain.
Methods: Therefore, we conducted a study in newborns with perinatal asphyxia to try to show the relationship between the clinical severity and plasma PAF levels.
Results: Mean plasma levels of 19 asphyxiated infants (997.8 ± 363.5 pg/mL) were significantly higher than that of 20 healthy infants (410.2 ± 148.6 pg/mL, P< 0.0001). Patients with clinically severe HIE had significantly higher levels of PAF (1494.2 ± 386.6 pg/mL) when compared with patients with mild HIE (815 ± 114.5 pg/mL) and with moderate HIE (828.3 ± 61.1 pg/mL). There was a significant correlation between plasma PAF concentration and arterial pH and base deficit, but no correlation with platelet and leukocyte counts.
Conclusions: Plasma PAF levels correlating with the severity of HIE is interpreted to mean that high PAF levels may be an indicator of clinical severity and probably the poorer prognosis of patients with HIE.     

Plasma transforming growth factor beta1 levels in thrombocytopenic and nonthrombocytopenic neonates

In this study, we determined the plasma TGF-beta1 levels in healthy and thrombocytopenic and nonthrombocytopenic neonates who had perinatal risk factors and examined the association between plasma TGF-beta1 levels and platelet counts in these newborns to investigate the role of TGF-beta1 in the pathogenesis of neonatal thrombocytopenia. Three groups were defined in this prospective study: group 1, thrombocytopenic neonates (n=22) who had perinatal risk factors; group 2, nonthrombocytopenic neonates who had similar perinatal risk factors for thrombocytopenia (n=20); group 3, healthy and nonthrombocytopenic neonates without any risk factors (n=20). Plasma TGF-beta1 levels were measured with ELISA. Plasma TGF-beta1 levels of the thrombocytopenic neonates were significantly lower than those of healthy nonthrombocytopenic neonates but did not differ significantly from nonthrombocytopenic neonates who had similar perinatal risk factors for thrombocytopenia. There was a significant positive correlation between plasma TGF-beta1 levels and platelet counts. Further studies are needed to determine the cause of low plasma TGF-beta1 levels in thrombocytopenic neonates and to investigate the role of plasma TGF-beta1 levels in the pathogenesis of neonatal thrombocytopenia.