Respiratory distress syndrome in very low birth weight infants with occasionally normal surfactant phospholipids

Lung effluent phospholipids were analysed in 120 very lwo birth weight (560–1500g) infants within 12 h from birth. The phospholipid profile accurately predicted the presence or absence of respiratory distress syndrome (RDS). However, in three of the 72 RDS cases, the phospholipids revealed no biochemical abnormality as compared to lung effluent from newborns without RDS. In RDS with normal phospholipids, only the lipid-rich fractions of the aspirate were surface active, whereas the protein-rich fraction of the aspirate inhibited the surface activity of lung effluent from normal newborns, suggesting the presence of a surfactant inhibitor. The pathogenesis and treatment of RDS with normal surfactant phospholipids may prove to be different from classical RDS.Supported by the Finnish Heart Foundation, the Paulo Foundation, and the Foundation for Pediatric Research (Finland)     

Care of very low birth weight infants with respiratory distress syndrome: an evidence-based review

Since 1959, when it was reported that many preterm infants had surfactant deficiency, there has been a remarkable improvement in the prevention of respiratory distress syndrome (RDS) and in the care of infants who develop RDS. Antenatal corticosteroids and surfactant replacement have improved the care of very low birth weight infants.     

肺表面活性制剂治疗新生儿呼吸窘迫综合征多中心临床观察

目的　评价肺表面活性制剂 (PS)在治疗新生儿呼吸窘迫综合征 (NRDS)的疗效和安全性。方法　对 4个医院的 42例NRDS患儿用curosurf (PS的一种 )治疗 ,观察治疗前后患儿肺功能和肺泡充气程度的变化及早产儿部分常见并发症的发生率。结果　用药后 30min患儿PaO2 和动脉 肺泡氧分压比值 (a/APO2 )明显上升 ,分别从 (44± 14)mmHg (1mmHg =0 .133kPa)上升至 (10 2± 5 9)mmHg和从 0 .11± 0 .0 5上升至 0 .2 8± 0 .18。用药后 1h、6h、12h、2 4h、3d和 10d的PaO2 和a/APO2 仍在较高水平 ,与用药前比较 ,差异均有非常显著意义 (P均 <0 .0 1)。用药后 30min ,患儿PaCO2 从用药前的 (5 4± 17)mmHg下降至 (45± 13)mmHg (P <0 .0 5 )。用药后 12h ,胸部X线片显示 ,患儿肺野透亮度明显改善 ,与用药前比较 ,差异有非常显著意义。用药后患儿颅内出血、气胸、动脉导管开放和肺炎等并发症的发生率分别为 2 8%、7%、35 %和 79%。结论　curosurf治疗能快速、安全、有效地改善NRDS患儿的肺功能和肺泡充气程度。     

Nasal high flow therapy in very low birth weight infants with mild respiratory distress syndrome: a single center experience

Background

Pulmonary disorders and respiratory failure represent one of the most common morbidities of preterm newborns admitted to neonatal intensive care units (NICUs). The use of nasal high-flow therapy (nHFT) has been more recently introduced into the NICUs as a non-invasive respiratory (NIV) support.

Methods

We performed a retrospective study to evaluate safety and effectiveness of nHFT as primary support for infants born <?29 weeks of gestation and/or VLBW presenting with mild Respiratory Distress Syndrome (RDS).The main outcome was the percentage of patients that did not need mechanical ventilation. Secondary outcomes were rate of bronchopulmonary dysplasia (BDP), air leaks, nasal injury, late onset sepsis (LOS), intraventricular hemorrhage (IVH), retinopathy (ROP), necrotizing enterocolitis (NEC), hemodynamically-significant patent ductus arteriosus (PDA) and death.

Results

Sixty-four preterm newborns were enrolled. Overall, 93% of enrolled patients did not need mechanical ventilation. In a subgroup analysis, 88.5% of infants <?29 weeks and 86.7% of infants ELBW (<?1000 g BW) did not need mechanical ventilation.BPD was diagnosed in 26.6% of preterms enrolled (Mild 20%, Moderate 4.5%, Severe 1.5%). In subgroup analysis, BPD was diagnosed in 53.9% of newborns with GA <?29 weeks, in 53.3% of ELBW newborns and in 11.1% of small for gestational age (SGA) newborns.Neither air leaks nor nasal injury were recorded as well as no exitus occurred. LOS, IVH, ROP, NEC and PDA occurred respectively in 16.1%, 0%, 7.8%, and 1.6% of newborns.

Conclusions

According to our results, n-HFT seems to be effective as first respiratory support in preterm newborns with mild RDS. Further studies in a larger number of preterm newborns are required to confirm nHFT effectiveness in the acute phase of RDS.

     

两种无创呼吸支持治疗极低出生体重儿呼吸窘迫综合征疗效分析

目的 探讨早期应用经鼻间歇正压通气（NIPPV）与加温湿化经鼻导管高流量通气（HHHFNC）治疗极低出生体重呼吸窘迫综合征（RDS）早产儿的临床疗效。方法 89例极低出生体重RDS早产儿依据初始呼吸支持治疗方式随机分为NIPPV组（46例）和HHHFNC组（43例）。分析两组患儿初始治疗失败率、肺表面活性物质（PS）使用率、呼吸支持治疗相关数据及各种并发症的发生率。结果 NIPPV组治疗72 h内气管插管率、PS使用率、有创辅助通气时间、无创辅助通气时间及总用氧时间、严重呼吸暂停发生率、肺炎发生率与HHHFNC组的差异无统计学意义（P > 0.05）;NIPPV组支气管肺发育不良、颅内出血、早产儿视网膜病、坏死性小肠结肠炎、动脉导管未闭、气漏的发生率与HHHFNC组的差异均无统计学意义（P > 0.05）;NIPPV组鼻损伤的发生率高于HHHFNC组（P < 0.05）。结论 对于极低出生体重RDS早产儿的初始呼吸支持治疗,HHHFNC与NIPPV疗效相当,是可供临床选择的另一种安全和有效的无创辅助通气治疗方式。     

A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants

This study was carried out to assess the feasibility of late cord clamping of 45 s in preterm infants delivered mainly by caesarean section and the effects on post-partal adaptation and anaemia of prematurity. Prior to delivery, 40 infants of <33 gestational weeks were randomised to either 20 s or 45 s of late cord clamping. After the first shoulder was delivered, oxytocin was given intravenously to the mother in order to enhance placento-fetal transfusion while the infant was held below the level of the placenta. The 20 infants in group 1 (20 s) had a mean birth weight of 1070 g and a mean gestational age of 29 + 4/7 weeks versus 1190 g and 30 weeks in group 2 (45 s). On day 42 of life there were ten infants without transfusions in group 2 versus three in group 1 (P < 0.05). Out of the 20 infants in group 1, 19 and 15/19 in group 2 were delivered by caesarean section. There were no significant differences in Apgar scores, temperature on admission, heart rate, blood pressure and requirements for artificial ventilation. Conclusion Delayed cord clamping of 45 s is feasible and safe in preterm infants below 33 weeks of gestation. It is possible to perform the procedure at caesarean section deliveries and it should be performed whenever possible. It reduces the need for packed red cell transfusions during the first 6 weeks of life. Received: 10 February 2000 / Accepted: 12 April 2000     

呼吸窘迫综合征极低出生体重儿解脲脲原体感染与支气管肺发育不良的关系

目的 探讨并发新生儿呼吸窘迫综合症（RDS）的极低出生体重儿下呼吸道分泌物解脲脲原体（UU）感染与支气管肺发育不良（BPD）的关系。方法 选取73例诊断为RDS、早期使用机械通气治疗且至少应用1剂肺表面活性物质的极低出生体重儿,采用荧光定量聚合酶链反应法检测气管内吸出物UU核酸,分为UU感染组（n=21）和非感染组（n=52）,比较两组临床特点及BPD的发生率。结果 UU感染组阴道产百分率及反复院内肺部感染、胎膜早破发生率均高于非感染组;胎膜早破持续时间长于非UU感染组;且吸氧时间及住院时间均长于非UU感染组。UU感染组生后3 h内血浆免疫球蛋白IgM、白细胞计数、中性粒细胞绝对值显著高于非UU感染组。73例患儿中,发生BPD 45例,其中UU感染组BPD发生率（90%,19/21）显著高于非UU感染组（50%,26/52）,差异有统计学意义（P结论 下呼吸道UU感染可增加RDS 极低出生体重儿BPD的发生率。     

Risk factors for early sepsis in very low birth weight neonates with respiratory distress syndrome

AIM: To identify maternal and neonatal factors that increase suspicion of early sepsis in Very Low Birth Weight neonates with respiratory distress syndrome. METHODS: The cohort included 282 neonates born at Soroka Medical Centre 1996-2000. Definitions of 'high' and 'low'-suspicion groups for early sepsis were based on comparison between neonates with early sepsis and the remaining cohort. Univariate analysis and logistic regression were used to compare between groups. RESULTS: The incidence of early sepsis in the cohort was 1.8%, and 94% received antibiotics following delivery. Comparing with the remaining cohort, the five neonates with early sepsis had increased incidence of positive maternal cultures, use of antenatal antibiotics, lower 1 min Apgar scores and tendency to leucopenia. A 'low-suspicion' group comprised 38% of the cohort and did not include any neonates with early sepsis. This group were more frequently treated with antenatal steroids and delivered by Caesarean section compared to the 'high-suspicion' group, but otherwise there were no clinical and laboratory differences. CONCLUSION: Although the incidence of early sepsis is low almost all neonates received antibiotics. A 'low-suspicion' group was defined and the role of antibiotic treatment in this group needs to be determined.     

A randomised controlled trial of early insulin therapy in very low birth weight infants, "NIRTURE" (neonatal insulin replacement therapy in Europe)

Background

Studies in adult intensive care have highlighted the importance of insulin and improved glucose control on survival, with 32% reduction in mortality, 22% reduction in intensive care stay and halving of the incidence of bacteraemia. Very low birth weight infants requiring intensive care also have relative insulin deficiency often leading to hyperglycaemia during the first week of life. The physiological influences on insulin secretion and sensitivity, and the potential importance of glucose control at this time are not well established. However there is increasing evidence that the early postnatal period is critical for pancreatic development. At this time a complex set of signals appears to influence pancreatic development and β cell survival. This has implications both in terms of acute glucose control but also relative insulin deficiency is likely to play a role in poor postnatal growth, which has been associated with later motor and cognitive impairment, and fewer β cells are linked to risk of type 2 diabetes later in life.

Methods

A multi-centre, randomised controlled trial of early insulin replacement in very low birth weight babies (VLBW, birth weight < 1500 g). 500 infants will be recruited from 10 centres in the UK and Europe. Babies will be randomised to receive a continuous insulin infusion (0.05 units/kg/h) or to receive standard neonatal care from the first day of life and for the next 7 days. If blood glucose (BG) levels fall infants will receive 20% dextrose titrated to maintain normoglycaemia (4–8 mmol/l). If BG is consistently above 10 mmol/l babies will receive standard treatment with additional insulin infusion. The primary end point will be mortality on or before expected date of delivery, secondary end points will be markers of morbidity and include episodes of sepsis, severity of retinopathy, chronic lung disease and growth.

Trial Registration

Current Controlled Trials ISRCTN78428828. EUDRACT Number 2004-002170-34     

Phosphorus deficiency syndrome in very low birth weight infants

Inadequate dietary phosphorus intake is a contributing factor to the occurrence of metabolic bone disease in very low birth weight infants. This article reviews the clinical presentation and the pathophysiology of the phosphorus deficiency syndrome in premature infants. Recommendations for therapy and prevention of phosphorus deficiency are presented.     

Two-year follow-up of infants enrolled in a randomized trial of surfactant replacement therapy for prevention of neonatal respiratory distress syndrome

A randomized clinical trial of the use of bovine surfactant for the prevention of neonatal respiratory distress syndrome was completed at our Institution in 1984 (Pediatrics 1985;76:145-153). All infants entering the trial were enrolled in our follow-up clinic and seen at regular intervals for assessment of growth and development, neurologic and sensory status, and incidence of respiratory disease and allergic conditions. Infants have now been followed-up for at least 2 years. Of those infants for whom follow-up is complete, two of 32 (6.3%) surfactant-treated infants died, five (15.6%) had major neuro-developmental handicaps, and five had minor neurodevelopmental handicaps. In the control group, eight of 33 (24%) infants died, whereas only two (6.1%) survived with major neurodevelopmental handicaps, and four (12.1%) were left with minor handicaps. Except for an increased neonatal death rate in the control group, other differences were not statistically significant. The groups were also comparable in terms of the incidence of late respiratory or allergic disease as assessed by history. Treatment with bovine surfactant at birth of premature infants at high risk for respiratory distress syndrome appears to be safe and of short-term benefit, although no decrease in neurodevelopmental handicap at 2 years' follow-up can be demonstrated.     

A European multicenter randomized controlled trial of single dose surfactant therapy for idiopathic respiratory distress syndrome

We performed a multicenter prospective randomized controlled trial to determine the efficacy and safety of the surfactant preparation, Survanta (Abbott Laboratories, Chicago, USA), for 750–1750 g infants with idiopathic respiratory distress syndrome, (IRDS) receiving assisted ventilation with 40% or more oxygen. One hundred and six eligible infants from the eight participating centers were randomly assigned between March 1986 and June 1987 to receive either surfactant (100 mg phospholipid/kg, 4 ml/kg) or air (4 ml/kg) administered into the trachea within 8 h of brith (median time of treatment 6.2 h, range 3.2–9.1 h). The study was stopped before enrollment was completed at the request of the United States Food and Drug Administration when significant differences were observed in incidence of periventricular-intraventricular hemorrhage (PIH), between the surfactant treated and control infants. Surfactant treated infants had larger average increases in the arterial-alveolar oxygen ratio, (a/A ratio) (P<0.0001), and larger average decreases in FiO₂ (P<0.0001) and mean airway pressure, (MAP) (P<0.017) than controls over the 48 h following treatment. The magnitude of the differences between the surfactant and control groups were 0.19 (SE=0.03) for a/A ratio, –0.28 (SE=0.04) for FiO₂ and –1.7 cm H₂O (SE=0.70) for MAP. The clinical status on days 7 and 28 after treatment was classified using four predefined ordered categories: (1) no respiratory support; (2) supplemental O₂ with or without continuous positive airway pressure (CPAP); (3) intermittent mandatory ventilation; and (4) death. There were no statistically significant differences in the status categories on days 7 or 28 between surfactant and control infants. There were no significant differences between the groups with respect to the incidence of patent ductus arteriosus, bronchopulmonary dysplasia, necrotizing entero-colitis, air leaks or death. There was a statistically significant difference between treated and control infants in the frequency and severity of periventricular-intraventricular hemorrhage (PIH) (Cochran-Mantel-Haenszel ²adj=6.36,P=0.01). Hemorrhages occurred in 59.6% of surfactant treated infants and 26.9% of controls. Severe hemorrhages (grades 3 or 4) occurred in 38.5% of surfactant treated infants and 15.4% of controls ( ²adj=4.01,P=0.045). We conclude that the intratracheal administration of Survanta prior to 8 h of age to infants with IRDS receiving assisted ventilation with 40% or more oxygen results in a reduction in the severity of respiratory distress during the 48 h after therapy. Because of the difference in incidence of PIH between surfactant and control infants in this study, we recommend that future clinical trials of surfactant include more frequent prospective serial ultrasound evaluations for diagnosis of hemorrhage.     

经鼻持续气道正压通气在极低出生体质量儿呼吸支持中的应用价值

目的 评价经鼻持续气道正压通气(nCPAP)在极低出生体质量儿呼吸支持中的应用价值.方法 我院NICU从1999年1月至2008年12月共收治155例机械通气治疗的极低出生体质量儿,前5年只用有创通气,后5年采用无创通气、有创通气相结合的治疗方法.比较应用nCPAP前后5年通气策略改变后的治疗情况,包括平均通气时间、治愈率及并发症.结果 前5年机械通气53例,均为有创通气,平均通气时间(6.16±4.84)d.后5年机械通气102例:单纯ncPAP通气60例;有创通气结合nCPAP通气20例(10例在nCPAP治疗过程中病情有加重趋势,及时转为气管插管有创通气,10例在有创通气后改为nCPAP);单纯有创通气22例.平均有创通气时间(3.93±2.48)d,与前5年比较有下降,但差异无显著性(t=1.37,P＞0.05).前5年治愈率为27/53(50.9%),放弃治疗20例(37.7%),死亡6例(11.3%).后5年治愈率为85/102(83.3%),与前5年比较有明显上升,差异有非常显著性(x~2=18.25,P＜0.01);放弃治疗13例(12.8%),死亡4例(3.9%).应用nCPAP后,呼吸机相关性肺炎发生率有显著下降(x~2=6.08,P＜0.01),肺气漏、颅内出血及慢性肺部疾病的发生率无明显变化.结论 nCPAP是治疗极低出生体质量儿的一种安全有效的方法,可以减少有创通气的应用,降低呼吸机相关性肺炎发生率.