Timing of surfactant treatment.
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Humans↗
Biomedical subjects
H L Halliday
Publications and source records attributed to H L Halliday.
Incidence of molecular forms of bile salt-stimulated lipase in preterm and term human milk.
Preterm and term human milk samples obtained at various times after delivery were analyzed for the presence of molecular forms of the human milk enzyme, bile salt-stimulated lipase (BSSL). Thirty-five percent of both the preterm and term milk samples contained two molecular forms of BSSL, of variable molecular mass. The remainder contained only one molecular species of either 115 kD (50%) or 120 kD (15%). The number of molecular forms present was not related to length of lactation, maternal age, gestation, or maternal blood group. The specific activity of BSSL purified from term milk was similar to that purified from preterm milk, and there was no difference in specific activity whether one or two molecular forms were present. This study demonstrates heterogeneity of both molecular mass and molecular forms. We conclude that preterm babies fed their own mother's milk are unlikely to be disadvantaged with respect to fat digestion as BSSL secreted in preterm milk appears to be very similar to that produced in term milk, although we cannot exclude other functional differences.
Adult↗
Which interventions for neonatal respiratory failure are effective?
AIM: To review the evidence from clinical trials of various interventions to treat and prevent respiratory failure in the neonate and to determine which interventions are effective and which require further study. METHODS: Randomized controlled trials and/or meta-analyses of trials of interventions for neonatal respiratory failure were sought from databases including the Cochrane Collaboration. The results were synthesized as typical relative risks and typical risk differences, with 95% confidence intervals (CI). RESULTS: The following interventions were effective: conventional mechanical ventilation (absolute reduction in mortality 12%, 95% CI 4-21%), continuous positive airway pressure (absolute reduction in mortality 15%, 95% CI 1-28%), surfactant therapy (absolute reduction in mortality 4 to 9%, 95% CI 1-13%), and extracorporeal membrane oxygenation (absolute reduction in mortality 29%; 95% CI 15-42%). High frequency oscillatory ventilation with a volume recruitment strategy and inhaled nitric oxide appeared promising, but have not yet reduced mortality. Prenatal corticosteroids (absolute reduction in mortality 4%; 95% CI 2-6%) and amnioinfusion (effect on mortality not yet possible to estimate) prevented respiratory failure, but routine endotracheal intubation and suctioning of the airways at birth in vigorous meconium-stained term babies did not prove effective. CONCLUSIONS: Assisted ventilation, surfactant therapy, and extra-corporeal membrane oxygenation are effective, but it is uncertain how each should be applied in an individual infant. More research is needed to evaluate combinations of effective interventions, and effectiveness of high frequency oscillation and inhaled nitric oxide. Routine intubation and suctioning of the airways at birth in meconium-stained vigorous neonates is not recommended.
Humans↗
Lyso-phosphatidylcholine and outcome of preterm babies with respiratory distress syndrome treated with surfactant.
Phosphatidylcholine (PC) is the predominant phospholipid in natural surfactant preparations. A metabolic intermediate, lyso-PC, is potentially injurious to the lungs. In the present study, tracheal aspirates from preterm babies with respiratory distress syndrome treated with surfactant were examined for the presence of lyso-PC to determine if there was any correlation with outcome. Eighteen babies were assigned to receive initially either 100 or 200 mg/kg Curosurf followed by up to three further 100-mg/kg doses if required. Lyso-PC was present in aspirates taken 12-24 h after the last treatment from nine of 11 infants who initially received 200 mg/kg but in only one from seven receiving 100 mg/kg initially, and was dependent on the total dose of phospholipid administered. Three babies in the low-dose group developed bronchopulmonary dysplasia, whereas two in the high-dose group were non-survivors, however we could not correlate the presence of lyso-PC with adverse long-term outcome in this group of preterm infants.
Biological Products↗
Behavioural adjustment in school of very low birthweight children.
The school-based behavioural adjustment at 7-8 years of a cohort of 243 prematurely born, very low birthweight (< 1501 g) children and their normal birthweight controls is reported. The findings indicate that the children born preterm (both male and female) were rated by their teachers as expressing more behaviour problems than their controls, and were less well adjusted to the school environment. The deficits noted in the preterms applied across the social classes, with no amelioration noted in preterms of higher social class. It is speculated that the problem behaviours reflect a failure in self-regulatory functions.
Attention Deficit Disorder with Hyperactivity↗
Synthetic or natural surfactants.
Surfactant replacement therapy is one of the most studied interventions in neonatal medicine, with many thousands of infants having been enrolled in randomized clinical trials. It is clear that surfactant therapy reduces neonatal mortality and the risk of pulmonary air leaks in babies with or at risk of developing respiratory distress syndrome. Yet some doubts linger over other aspects of this therapy, despite it having been an acceptable and proven therapy for the past 7-10 years. As regards timing of treatment, the earlier the better, with true prophylaxis being reserved for babies of less than 28 week's gestation. Natural surfactant preparations containing surfactant proteins B and C act more rapidly than their synthetic protein-free counterparts and probably also have a greater impact on reducing neonatal mortality and pulmonary air leaks. Fears raised about immunological effects, prion transmission and chemical contamination of natural surfactants have not been substantiated. Long-term follow-up studies do not show any differences in outcome between treated and non-treated infants, except that the incidence and severity of retinopathy of prematurity might be reduced by treatment with natural surfactant. Further research is needed and this will include more detailed follow-up studies, newer indications for surfactant therapy and the testing of newer preparations with synthetic peptides or protein analogues added.
Humans↗
Randomised controlled trial of an aggressive nutritional regimen in sick very low birthweight infants.
AIMS: To improve energy intake in sick very low birthweight (VLBW) infants; to decrease growth problems, lessen pulmonary morbidity, shorten hospital stay, and avoid possible feeding related morbidity. Morbidity in VLBW infants thought to be associated with parenteral and enteral feeding includes bronchopulmonary dysplasia, necrotising enterocolitis, septicaemia, cholestasis and osteopenia of prematurity. METHODS: A prospective randomised controlled trial (RCT) comparing two types of nutritional intervention was performed involving 125 sick VLBW infants in the setting of a regional neonatal intensive care unit. Babies were randomly allocated to either an aggressive nutritional regimen (group A) or a control group (group B). Babies in group B received a conservative nutritional regimen while group A received a package of more aggressive parenteral and enteral nutrition. Statistical analysis was done using Student's t test, the Mann-Whitney U test, the chi 2 test and logistic regression. RESULTS: There was an excess of sicker babies in group A, as measured by initial disease severity (P < 0.01), but mean total energy intakes were significantly higher (P < 0.001) in group A at days 3 to 42 while receiving total or partial parenteral nutrition. Survival and the incidences of bronchopulmonary dysplasia, septicaemia, cholestasis, osteopenia and necrotising enterocolitis were similar in both groups. Growth in early life and at discharge from hospital was significantly better in babies in group A. There were no decreases in pulmonary morbidity or hospital stay. CONCLUSION: Nutritional intake in sick VLBW infants can be improved without increasing the risk of adverse clinical or metabolic sequelae. Improved nutritional intake resulted in better growth, both in discharge, but did not decrease pulmonary morbidity or shorten hospital stay.
Bacterial Infections↗
Clinical trials of surfactant replacement in Europe.
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Clinical Trials as Topic↗
Rhesus haemolytic disease of the newborn, complicating a quadruplet pregnancy.
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Adult↗
Treatment of severe meconium aspiration syndrome with porcine surfactant. Collaborative Surfactant Study Group.
UNLABELLED: This study is based on clinical data from a retrospective series of 54 infants with meconium aspiration syndrome treated with porcine surfactant at a median age of 14 h (range 1-176 h). Median arterial/ alveolar oxygen tension ratio (a/A PO2 ratio) before treatment was 0.08 (range 0.02-0.23) and oxygenation index 25 (range 6-110). After treatment with surfactant at an initial dose of 50-200 mg/kg there was a modest but statistically significant increase in a/APO2 ratio associated with a reduction of oxygenation index. Ten (18%) babies showed a 3-4 fold increase in a/APO2 ratio within 1-2 h of treatment. Twenty-four (44%) babies showed little or no response by 1-2 h with the remaining infants showing modest improvement in oxygenation. One third of babies required repeated doses of surfactant. Twenty-eight day survival was 81%, with two babies requiring extracorporeal membrane oxygenation. CONCLUSION: Natural surfactant treatment of severe meconium aspiration may prove to be a useful intervention and randomised controlled clinical trials should be undertaken.
Biological Products↗
Controversies: synthetic or natural surfactant. The case for natural surfactant.
Surfactant replacement therapy for respiratory distress syndrome (RDS) is not new, the first trials having been performed over 30 years ago. These early trials used synthetic protein-free surfactants administered as aerosols and were unsuccessful. Since 1980 a variety of natural and synthetic surfactant preparations have been used to treat or prevent RDS, and both demonstrate clinical effects. I have used evidence derived from 3 areas to demonstrate the superiority of natural surfactants: in vitro physical properties, in vivo physiological effects and the results of comparative clinical trials. using the pulsating bubble surfactometer, the surface tension at maximum and minimum bubble size are significantly lower for natural compared to synthetic surfactants (31 and 0 mN/m versus 53 and 29 mN/m respectively). Physiological effects of surfactants have been compared in immature rabbits and lambs and both models demonstrate the superiority of natural surfactants. For example in immature rabbits lung compliance values after 60 minutes of ventilation are 0.60 ml/cmH2O in natural surfactant treated animals, 0.44 ml/cmH2O in synthetic surfactant treated animals and 0.34 ml/cmH2O in controls (p < 0.01). The technique of meta-analysis was used to analyse the outcome of 6 comparative clinical trials of natural and synthetic surfactants. These 6 studies included 3536 babies and 5 of them compared Survanta (a bovine natural surfactant) and Exosurf (a synthetic protein-free surfactant). One study compared Infasurf (another bovine natural surfactant with Exosurf). Meta-analysis shows a 19% reduction in the odds of neonatal death for natural compared to synthetic surfactant treated babies (OR, 0.81; 95% CI 0.66-0.98). For bronchopulmonary dysplasia there was a non-significant reduction in risk for Survanta-treated babies (OR, 0.93; 95% CO 0.78-1.10). In summary, there is now clear evidence of physiological and clinical superiority of natural compared to synthetic surfactants. Surfactant proteins B and C are needed to facilitate rapid adsorption and spreading of phospholipids. They also account for the more rapid clinical action allowing oxygen and ventilator pressures to be lowered soon after administration. The odds of neonatal mortality are reduced by about 20% if natural surfactants are preferred to their synthetic protein-free counterparts. Long-term follow-up studies of babies treated with both types of surfactant should be a top priority.
Animals↗
Natural vs synthetic surfactants in neonatal respiratory distress syndrome.
This review examines the 11 randomised clinical trials that have compared different surfactant preparations. Seven trials, enrolling 2488 infants with respiratory distress syndrome (RDS), compared the natural surfactant beractant (Survanta) with the synthetic surfactant colfosceril palmitate (Exosurf Neonatal). Infants treated with beractant had lower oxygen requirements for at least 3 days than those treated with colfosceril palmitate. The infants treated with beractant also had lower risks of neonatal mortality [odds ratio (OR) 0.81; 95% confidence interval (CI) 0.65 to 1.01], retinopathy of prematurity (OR 0.81; 95% CI 0.66 to 0.99), and the combined endpoint of death or bronchopulmonary dysplasia (OR 0.86; 95% CI 0.75 to 0.99), compared with those treated with colfosceril palmitate. Calf lung surfactant extract (CLSE; Infasurf), another natural surfactant, has been compared with colfosceril palmitate in 2 studies: in one as prophylaxis and in the other as rescue therapy. Similar, although nonsignificant, advantages were found for the natural surfactant compared with the synthetic surfactant. In 6 of these 9 trials there was a significant reduction in the odds of pulmonary air leaks (OR 0.53; 95% CI 0.41 to 0.64) for infants treated with natural compared with synthetic surfactants. In 7 trials (3554 infants) comparing natural and synthetic surfactants to treat RDS (6 comparing beractant and colfosceril palmitate, and one CLSE and colfosceril palmitate), there was a significantly reduced risk of neonatal mortality (OR 0.80; 95% CI 0.66 to 0.97) with natural compared with synthetic surfactant treatment. In 2 further trials, different natural surfactant preparations have been compared. Reduced oxygen needs for 24 hours after treatment were found for CLSE and Curosurf (porcine-derived lung surfactant, PLS) when each was compared with beractant. Apparent longer term benefits from these surfactants were not statistically proven. Further trials are needed to be certain of the differences between the various surfactant preparations.
Humans↗
Surfactant replacement therapy.
Surfactant replacement therapy for treatment or prevention of the respiratory distress syndrome (RDS) has been studied intensively over the past decade. Randomized controlled trials have demonstrated a reduction in the odds of neonatal death of about 40% and of pulmonary air leaks of 35 to 70% depending upon the type of surfactant used. Prophylaxis or very early treatment is superior to later treatment, especially for the very preterm (< 28 week) infant. Natural (derived from animal lungs) surfactants have a more rapid onset of action than synthetic surfactants and may also provide better long-term benefits, but further comparative trials will be needed to demonstrate this conclusively. Surfactant treatment should not be viewed as a substitute for prenatal steroid therapy to enhance fetal lung maturity; the treatments are synergistic.
Clinical Trials as Topic↗
Percutaneous central venous catheter use in the very low birth weight neonate.
UNLABELLED: A retrospective study was carried out comparing 61 very low birth weight infants (VLBW) with percutaneous central venous catheters with 92 infants managed with peripheral cannulae. Eighteen infants developed one or more episodes of catheter-associated bacteraemia. In 70% of cases the infection was successfully treated with the line in situ. Logistic regression analysis was performed to examine risk factors for bacteraemia. The duration of intravenous fluids and of intermittent positive pressure ventilation were both significant risks for infection (odds ratios and 95% confidence limits 4.4, 2.7-12.0 and 2.5, 1.0-6.1 respectively), but the presence of a silastic catheter was not an independent risk factor (odds ratio 0.6, 95% confidence limits 0.1-3.0). CONCLUSION: Percutaneous central venous catheters provide a satisfactory means of delivering parenteral nutrition with minimal disturbance to ill VLBW infants.
Bacteremia↗
Prediction of chronic lung disease (CLD)
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Chronic Disease↗
Update on surfactant therapy. Report from the 9th International Workshop on Surfactant Replacement, Jerusalem, May 22-25, 1994.
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Humans↗
Overview of clinical trials comparing natural and synthetic surfactants.
This overview summarizes the ten randomized clinical trials that have compared different surfactant preparations. Six trials, enrolling 2,450 babies with respiratory distress syndrome (RDS), compared Survanta and Exosurf. Babies treated with the natural surfactant had lower oxygen requirements for at least 3 days than those treated with the synthetic surfactant. The babies treated with Survanta had lower risks of neonatal mortality (odds ratio, OR, 0.80; 95% confidence interval, CI, 0.65-1.00), retinopathy of prematurity (OR 0.68; 95% CI 0.50-0.94), and death or bronchopulmonary dysplasia (OR 0.84; 95% CI 0.70-1.00) when compared to those treated with Exosurf. Infasurf has been compared with Exosurf in two studies: one as prophylaxis and the other a rescue trial. Similar, although non-significant benefits were found for the natural surfactant. When all eight trials were included in a meta-analysis, there was a significant reduction in the odds of pulmonary air leaks (OR 0.52; 95% CI 0.41-0.66) for babies treated with natural as compared with synthetic surfactants. For seven trials (3,576 babies) comparing natural and synthetic surfactants to treat RDS (six comparing Survanta and Exosurf and one Infasurf and Exosurf), there was a significantly reduced risk of neonatal mortality (OR 0.80; 95% CI 0.66-0.97) with natural as compared with synthetic surfactant treatment. In two further trials different natural surfactant preparations have been compared. Reduced oxygen needs for 24 h after treatment were found for Infasurf and Curosurf, respectively, when compared to Survanta. Apparent longer-term benefits from these surfactants were not statistically significant. Further trials are needed to be certain of the differences between various surfactant preparations.
Biological Products↗
The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants. European Multicentre Erythropoietin Study Group.
BACKGROUND: Anemia of prematurity is characterized by low reticulocyte counts and inadequate erythropoietin response, for which many very-low-birth-weight infants receive multiple blood transfusions. We investigated whether early treatment of such infants with recombinant human erythropoietin would reduce their need for transfusions. METHODS: We performed a controlled, blinded trial in 241 infants with very low birth weights at 12 centers in six European countries. When three days old, the infants were randomly assigned either to the epoetin group or to the control group. Those in the epoetin group received 250 IU of epoetin beta per kilogram of body weight subcutaneously three times a week from day 3 to day 42 (for a total of 17 doses); those in the control group did not receive this drug. Infants in both groups received oral iron (2 mg per day) from day 14 onward. RESULTS: The control infants needed a mean of 1.25 transfusions each, as compared with 0.87 transfusion for epoetin-treated infants (P = 0.013). The median cumulative volume of blood transfused per kilogram per day was 0.41 ml in the control group (first quartile, 0 ml; third quartile, 0.8 ml) and 0.09 ml in the epoetin group (first quartile, 0 ml; third quartile, 0.8 ml) (P = 0.044). The rate of success, defined as an absence of need for transfusions and a hematocrit that never fell below 32 percent, was 4.1 percent in the control group and 27.5 percent in the epoetin group (P = 0.008). Epoetin was most beneficial in boys with birth weights of 1200 g or more and a base-line hematocrit of 48 percent or more. No toxic effects were observed in the epoetin group; as compared with the control group, the epoetin group had an increased incidence of septicemia (14 vs. 7 episodes, P not significant) and reduced weight gain (520 vs. 571 g, P = 0.02). CONCLUSIONS: Infants with very low birth weights have less need of transfusions if given epoetin beta during the first six weeks of life (250 IU per kilogram three times a week). We recommend early epoetin treatment for all such infants, but further studies of nutrition and iron supplementation during treatment are needed.
Anemia, Neonatal↗