Neonatal neutropenia associated with maternal hypertension poses a risk for nosocomial infection

One hundred and six neonates of 24–32 weeks gestation born to hypertensive mothers and 106 concurrent control infants of normotensive mothers were evaluated to determine the relationship between maternal hypertension and neonatal neutropenia and the risk of nosocomial infection developing in neutropenic infants.. Complete blood counts were performed on both cohorts and retrospectively evaluated. Neutropenia was diagnosed using published reference ranges for infants with birth weight ≤1500 g and >1500 g. Evidence of nosocomial infection based on a positive blood culture with supportive clinical signs of sepsis was documented. The incidence of neutropenia among infants of hypertensive mothers was not significantly different from that among infants of normotensive mothers (21% vs 24%), but the duration of neutropenia was significantly longer in the infants of hypertensive mothers (P = 0.0001). Nosocomial infection was more frequent in neutropenic than the non-neutropenic hypertensive mothers' infants (55% vs 12%, P = 0.0002). Conclusion Although there is no difference in the incidence of neonatal neutropenia between infants of hypertensive mothers and those of normotensive mothers, the former group has an increased risk of nosocomial infection in neutropenic infants of hypertensive mothers. This may be related to prolonged neutropenia which was found in these infants in the present study. Received: 24 August 1997 and in revised form: 30 March 1998 / Accepted: 1 April 1998     

Granulocyte colony stimulating factor treatment for alloimmune neonatal neutropenia.

Granulocyte colony stimulating factor (G-CSF) treatment was successfully used in three preterm infants with alloimmune neonatal neutropenia (AINN). Two infants had persistent neutropenia despite treatment with intravenous immunoglobulin and random donor granulocyte transfusions for presumed sepsis. Neutrophil counts returned to normal with G-CSF treatment; the response was least convincing in one infant with fulminant necrotising enterocolits. It is suggested that treatment with G-CSF be considered early for the treatment of infants with AINN.     

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.     

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.     

Treatment of aplastic anemia with antithymocyte globulin,cyclosporin A,methylprednisolone, danazole and recombinant human granulocyte-colony stimulating factor

The main purpose of the present study was to determine the response rate to immunosuppressive therapy combined with recombinant human granulocyte-colony stimulating factor (rhG-CSF) and its efficacy for preventing infections in patients with severe aplastic anemia. The treatments included one course of antithymocyte globulin, cyclosporin A, methylprednisolone, danazole and rhG-CSF. Three patients had very severe aplastic anemia and two had moderate aplastic anemia. One patient relapsed 13 months following the first course of therapy and received a second course. Five patients received six courses of treatment and the response rate at 6 months was 83.3%. All patients achieved an absolute neutrophil count of greater than 1.0 × 10⁹/L within 40 days. All patients with a complete response are transfusion-free and doing well. All five patients are currently alive and have not had any episode of infection for 17–53 months. The results of the study indicate that this therapy may improve the poor prognosis of young patients with severe aplastic anemia. It has a good response rate and induces a rather rapid increase in the neutrophil count, which protects against life-threatening bacterial and fungal infections.     

Effect of maternal hypertension on neonatal neutropenia and risk of nosocomial infection.

Neonatal neutropenia occurs in approximately 50% of newborns delivered by women with pregnancy-induced hypertension. It is thought to be transient, independent of birth weight and gestational age, and unassociated with significant risks, including infection. It recently was suggested that neonatal neutropenia occurs primarily in smaller, younger neonates, is related to the severity of pregnancy-induced hypertension, and importantly, may be associated with an increased risk for nosocomial infection. We examined these points in a large inborn population in consecutive years, performing retrospective (n = 110, 1989) and prospective (n = 151, 1990) studies in low birth weight (less than or equal to 2200 g) neonates delivered by women with pregnancy-induced hypertension. Overall, 40% to 50% of neonates studied developed neonatal neutropenia, and they were younger and smaller (P less than .01) than non-neutropenic neonates. In the prospective study, neutropenic neonates were more likely to have mothers with severe pregnancy-induced hypertension (P less than .001), and the incidence of neonatal neutropenia was primarily among neonates less than 30 weeks of gestation and less than 1500 g birth weight, approximately 80% vs 35% to 45% in older, larger neonates or infants (P less than .001). Although nosocomial infection occurred more frequently among the group of neutropenic neonates in the prospective study (P less than .02), the incidence was similar to that in matched non-neutropenic controls delivered of normotensive women. Thrombocytopenia (less than 100,000/mm3) was not more frequent in neutropenic neonates.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neonatal nosocomial infection at a pediatric resuscitation and intensive care unit

During 1989, a nosocomial infection rate of 3.15% was observed among the 412 neonates hospitalised for more than 2 days in the paediatric intensive care unit and a special care baby unit in the medical centre of Nice. Certain factors only partially explain the above, and it is probable that the non-invasive methods of monitoring and care and the experienced nursing staff contribute to a great extent to this low frequency of infection.     

Neonatal neutropenia. Clinical manifestations, cause, and outcome

Neutropenia, defined as an absolute neutrophil count that falls below 2.0 x 10(9)/L, is being identified more frequently in the newborn intensive care unit and significantly influences clinical decisions regarding therapy. We prospectively identified 119 episodes of neutropenia in 87 infants (6% of admissions). Less than half of the episodes could be attributed to infections. The majority of noninfectious neutropenia episodes were related to specific perinatal events or were of unknown cause. Infants weighing less than 2500 g were more likely to have neutropenia than term infants (13% vs 3%, respectively) and less likely to have neutropenia related to bacterial infections. Short-term survival (89% vs 95%) and long-term survival (74% vs 77%) were not different in infants with infectious diseases compared with those with noninfectious diseases. Mortality was highly correlated with the need for assisted ventilation (20%) or with an absolute neutrophil count of 0.5 x 10(9)/L (24%). We conclude that the cause of neutropenia and the clinical condition must be carefully evaluated before instituting aggressive therapy for infection.     

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     

Plerixafor plus granulocyte-colony stimulating factor for autologous hematopoietic stem cell mobilization in patients with metastatic neuroblastoma

Current therapies for high-risk neuroblastoma (NB) necessitate the availability of several aliquots of autologous peripheral blood stem cells to reverse-associated myelosuppression. Priming with the CXCR4 inhibitor plerixafor plus G-CSF was associated with successful stem cell harvest in 5/7 heavily prior-treated patients with stage 4 NB who had previously failed G-CSF priming. Minimal residual disease was not detected in harvested cells from any patient despite the presence of disease in bone/bone marrow in 6/7. Hematopoietic reconstitution was achieved in all three patients receiving plerixafor-primed stem cells after myeloablative therapy. Plerixafor is an effective and safe agent for stem cell collection in patients with NB.     

粒细胞集落刺激因子对移植的人神经干细胞体内分化的影响

目的 观察缺氧缺血性脑损伤(HIBD)新生大鼠应用粒细胞集落刺激因子(G-CSF)对移植的人神经干细胞(hNSCs)体内分化成星形胶质细胞的影响.方法 新生1周的Wistar大鼠建立HIBD模型后分成2组:NSC移植组(A组,n ＝ 16)和NSC移植 + G-CSF治疗组(B组,n ＝ 16),其中B组建模后1 h即开始皮下注射G-CSF,1次/d,移植前后连续5 d注射G-CSF.两组均于建模后第2天经脑室移植hNSCs.移植后1、2周分别用免疫荧光法检测植入细胞在大鼠脑内向星形胶质细胞分化的情况.结果 移植后1周,B组植入细胞分化的星形胶质细胞数量较A组多,差异有统计学意义(t ＝ 4.83,P ＜ 0.01).移植后2周,两组植入细胞分化的星形胶质细胞数量上差异无统计学意义(t ＝ 1.59,P ＞ 0.05).结论 G-CSF能在移植后早期促进植入的外源性NSCs向星形胶质细胞分化.     

Neonatal neutropenia and thrombocytopenia following maternal hypertension

Objective : To assess the relationship between the subtypes of hypertension in pregnancy and subsequent neonatal haematology.
Methodology : Retrospective review of the haematology of newborns of hypertensive mothers at a tertiary neonatal unit
Results : Over a 2 year period. 249 infants had full blood examinations. Nineteen (7.6%) were neutropenic and 35 (14.1%) thrombocytopenic, including 11 (4.4%) who were both neutropenic and thrombocytopenic. Neutropenia occurred only in infants whose mothers had severe pre-eclampsia and eclampsia or pre-eclampsia with pre-existing hypertension, whereas thrombocytopenia complicated all maternal hypertension subtypes. Two (10%) of the neutropenic infants developed nosocomial infection while seven (20%) of the thrombocytopenic infants bled. Thirteen (68%) of the neutropenic infants compared with 15 (43%) of the thrombocytopenic infants developed their haematological abnormality within 24 h of birth. All but two infants developed the haematological abnormality by the 5th day of life.
Conclusions : Although haematological abnormalities in infants born to hypertensive mothers are uncommon, serious neonatal complications can occur and therefore early haematological screening of these infants is recommended.     

Transient erythroblastopenia and neutropenia revealing human parvovirus B19 infection]

The authors report on a pediatric case of transient neutropenia with erythroblastopenia secondary to human parvovirus infection occurring in a child without underlying hemolytic disease. The heterogeneity of hematologic manifestations in such infections is discussed.     

小剂量粒细胞-集落刺激因子在血液系统肿瘤疾病中的疗效观察

目的　观察小剂量粒细胞 集落刺激因子 (G CSF)对小儿急性白血病及恶性肿瘤联合化疗后中性粒细胞减少的疗效及毒副作用。方法　急性白血病或恶性肿瘤化疗后外周血中性粒细胞绝对值减少者 ,给予G CSF 1～ 2 μg/(kg·d) ,皮下注射 (sc) ,共 3～ 5d。 结果　小剂量G CSF短期内可使中性粒细胞升高 ,有效率达83 .3 % ,显著高于对照组 (P <0 .0 1)。结论　小剂量G CSF可有效缩短化疗后骨髓抑制期 ,预防感染 ,且副作用小 ,可作为临床大剂量化疗的辅助治疗手段     

Induction of necrotizing funisitis by fetal administration of intravenous granulocyte-colony stimulating factor and intra-amniotic endotoxin in premature fetal sheep

The purpose of the present study was to determine whether experimental intrauterine inflammation could induce necrotizing funisitis, a severe, chronic inflammation of the umbilical cord. Fetuses, randomly divided into four groups (n = 4 each), were infused with 50 mug/d of granulocyte-colony stimulating factor (G-CSF) intravenously on d 125-129 of gestation (G-CSF group), 20 mg of endotoxin into the amniotic cavity on d 127 gestation (endotoxin group), both G-CSF and endotoxin (G-CSF + endotoxin group), or only saline (control group). On d 130 of gestation, the umbilical cords were processed for histologic analysis, scored for degree of inflammation, and compared statistically. At birth, the blood polymorphonuclear leukocyte counts in G-CSF and G-CSF + endotoxin groups were significantly higher than those in endotoxin and control groups (p < 0.05). The inflammatory score of the umbilical cord in G-CSF + endotoxin group was significantly higher than those in the other three groups (p < 0.05). All the fetuses in G-CSF + endotoxin group had necrotizing funisitis, but none of the fetuses in the other three groups developed this condition. An increase in blood polymorphonuclear leukocytes before their activation in the umbilical cord is probably essential for experimentally inducing necrotizing funisitis.     

Granulocyte colony stimulating factor in neonatal alloimmune neutropenia: A possible association with induced thrombocytopenia

Neonatal alloimmune neutropenia (NAIN) is a rare cause of congenital neutropenia seen in <1% of births. Significant morbidity, usually infections, may result from this disease. The pathophysiology of NAIN, mediated by maternal antibodies crossing the placenta to destroy fetal cells expressing paternal antigens, is similar to that of neonatal alloimmune thrombocytopenia, as well as Rh/ABO hemolytic disease of the newborn. The use of high‐dose granulocyte colony stimulating factor in patients with NAIN may cause a reversible thrombocytopenia in some patients. Pediatr Blood Cancer 2010;54:1014–1016 © 2010 Wiley‐Liss, Inc.     

Sequential administration of interleukin-6 and granulocyte-colony stimulating factor in newborn rats: modulation of newborn granulopoiesis and thrombopoiesis.

During states of increased demand, neonatal host defense is characterized by dysregulation of granulopoiesis, resulting in a high incidence of neutropenia. This study investigated the modulation of neonatal rat hematopoiesis by 14-d administration of recombinant human (rh) IL-6, rh-granulocyte-colony stimulating factor (G-CSF), or sequential combination of rhIL-6 and rhG-CSF. Specifically, newborn Sprague-Dawley rats were treated with either rhIL-6 (5 micrograms/kg/d for 14 d), rhG-CSF (5 micrograms/kg/d for 14 d), rhIL-6 for 7 d followed by rhG-CSF for 7 d, PBS/BSA for 7 d followed by rhG-CSF for 7 d, or PBS/BSA for 14 d. RhIL-6 alone significantly increased the peripheral platelet count during the latter part of the 2nd wk of administration (d 13: 980 +/- 42 versus 716 +/- 23 x 10(3)/mm3) (p = less than 0.001) (mean +/- SEM). Treatment with rhIL-6 for 7 d followed by rhG-CSF significantly increased the peripheral neutrophil count compared with 7 d of PBS/BSA and 7 d of G-CSF (d 14 absolute neutrophil count 4888 +/- 12 versus 2720 +/- 317/mm3) (p = less than 0.05). Similarly, sequential rhIL-6/rhG-CSF significantly increased the d-14 bone marrow neutrophil storage pool (9873 +/- 882 versus 3564 +/- 159/mm3) (p = less than 0.005). Lastly, sequential rhIL-6/rhG-CSF induced the highest increase in bone marrow (p less than 0.01) and liver/spleen CFU-GM pool (p less than 0.001) compared with any other treatment group. These studies suggest that rhIL-6 alone is associated with a significant increase in the neonatal platelet count.(ABSTRACT TRUNCATED AT 250 WORDS)     

重症监护室院内感染的危险因素

院内感染 (ｎｏｓｏｃｏｍｉａｌｉｎｆｅｃｔｉｏｎ)又称医院内获得性感染 ,是随着医院的出现而出现的 ,随着近年来抗生素应用于临床 ,各种侵入性检查操作增多 ,院内感染已经成为一个突出的公共卫生问题。院内感染率与医院的规模、等级、科室设置、收治对象、管理水平和感染监测方法等因素有关。与传统的发病机制相比 ,院内感染多为内源性感染 ,接触性传染 ,侵袭对象系免疫功能低下和抵抗力差的病人。因此 ,院内感染的危险因素在院内感染中起着决定作用。1　危险因素在院内感染中的作用由于ＩＣＵ收治的患者病情危重 ,部分还存在免疫功能低…