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Biomedical subjects

H L Halliday

Publications and source records attributed to H L Halliday.

At least 73 records · Page 4Linked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

Intracerebral haemorrhages in surfactant treated neonates with severe respiratory distress syndrome: age at diagnosis, severity and risk factors.

UNLABELLED: Within a randomized European multicentre trial the time of onset, severity and progression of intracerebral haemorrhages (ICH) were investigated prospectively by serial cranial ultrasonography in 343 ventilated infants with severe respiratory distress syndrome (RDS) following instillation of single or multiple doses of a natural porcine surfactant (Curosurf). In 148/343 infants (43%) ICH was diagnosed (grade I or II: 22%, grade III or IV: 21%). In 26 cases (8%) ICH was present on the ultrasound scan prior to surfactant instillation at a median age of 6 h. Incidence and severity of ICH was similar after single- or multiple-dose surfactant treatment. Using a logistic regression model the following risk factors predictive of ICH were defined: low birth weight, allocation to certain hospitals, vaginal delivery, Apgar score < or = 6, rectal temperature on admission < or = 36 degrees C, primary anaemia, acidosis prior to treatment, RDS grade IV in pre-treatment chest films and poor response to surfactant treatment. CONCLUSION: Our study provides supportive evidence that multiple doses of Curosurf do not increase the risk for ICH as compared to single-dose administration.

Biological Products↗
PubMed1994

Predictive value of soluble immunological mediators in neonatal infection.

1. Infection in the neonatal period is difficult to diagnose and is a significant cause of morbidity and mortality in preterm infants. 2. We investigated prospectively the predictive value of plasma measurement of bacterial endotoxin (lipopolysaccharide), tumour necrosis factor-alpha, interleukin-6, interleukin-8, intercellular adhesion molecule-1 and C-reactive protein in 60 consecutive newborn infants suspected of having neonatal infection. Plasma samples were taken at the time of acute clinical deterioration. Sixty-two cord blood samples were studied as controls taken at elective Caesarean section. 3. Forty-three infants had confirmed infections, 25 with positive blood cultures. Tumour necrosis factor-alpha and bacterial endotoxin levels were not significantly elevated over controls, whereas interleukin-6, interleukin-8 and intercellular adhesion molecule-1 levels were all significantly increased in the infected group compared with controls (all P < 0.001). 4. Increased plasma intercellular adhesion molecule-1 levels were a highly sensitive (88%) indicator of clinical infection and were independent of C-reactive protein. Use of these two assays in combination improved the diagnostic sensitivity to 95% and gave a negative predictive value of 97%. addition of interleukin-6 or interleukin-8 measurements failed to further significantly enhance the prediction of infection. 5. Measurement of intercellular adhesion molecule-1 level may have a clinical role in rapidly confirming, or predicting, the likely diagnosis in cases of suspected neonatal infection.

Bacterial Infections↗
PubMed1994

Neonatal infection does not affect the immunoreactive trypsinogen screening test for cystic fibrosis.

We aimed to discover whether neonatal infection affected levels of the immunoreactive trypsin (IRT) assay, which is used as a screening test for cystic fibrosis. Forty babies who had clinical features suggesting infection had blood spot specimens for IRT taken at the same time as blood for culture. Of 27 babies believed clinically to have infection, 19 had positive blood cultures and eight had negative culture. In retrospect, 13 were not thought to have infection. The mean (SD) IRT results in these three groups were 15 (8), 11 (4), and 16 (6) micrograms/L, respectively. The mean (SD; range) IRT result for all 40 babies was 14 (7; 10-39). Not only did no babies have elevated IRT results at routine neonatal screening, but none have presented with clinical features suggestive of cystic fibrosis since hospital discharge. Neonatal infection does not appear to cause elevated IRT levels and should therefore not cause false-positive results in mass neonatal screening.

C-Reactive Protein↗
PubMed1994

Comparison of surface properties and physiological effects of a synthetic and a natural surfactant in preterm rabbits.

AIMS: To compare the physical and physiological properties of a synthetic surfactant (Exosurf, Wellcome Foundation) and a natural surfactant (Curosurf, Chiesi Farmaceutici). METHODS: Surface properties of the surfactant suspensions (10 mg phospholipid/ml) were evaluated using the pulsating bubble surfactometer. Lung-thorax compliance was determined in 47 immature newborn rabbits with a gestational age of 27 days, treated with recommended clinical doses of either surfactant (Exosurf 67.5 mg/kg; Curosurf 200 mg/kg). The lungs were examined histologically. RESULTS: The mean (SD) contractile forces of the surface at maximum and minimum bubble size were significantly lower for Curosurf than for Exosurf: 31 (2) and 0 (0) mN/m v 53 (5) and 29 (4) mN/m, respectively. Mean (SD) lung-thorax compliance after one hour of ventilation was significantly higher in rabbits treated with Curosurf compared with animals receiving Exosurf or those serving as controls: 0.60 (0.15) ml/cm H2O.kg v 0.44 (0.03) and 0.34 (0.18) ml/cm H2O.kg, respectively. Both surfactants increased alveolar volume density compared with results for control animals, but only Curosurf significantly reduced the incidence of moderate or severe bronchiolar epithelial disruption. CONCLUSIONS: The natural surfactant, Curosurf, reduced the contractile force at an air-liquid interface to a greater extent than the synthetic surfactant, Exosurf, and led to a greater improvement in compliance and less airway epithelial damage when given in clinical treatment doses to immature rabbits.

Animals↗
PubMed1993

Reduction in the risk of bronchopulmonary dysplasia from 1980-1990: results of a multivariate logistic regression analysis.

A retrospective analysis (1980-1990) of normally formed low birthweight (< 2500 g) infants surviving to at least 28 days following intermittent positive pressure ventilation (IPPV) for longer than 12 h was performed. Bronchopulmonary dysplasia (BPD) was defined as oxygen dependency at 28 days with characteristic radiographic findings. Logistic regression analysis of risk factors, before and after the initiation of IPPV was performed on 412 infants. Decreasing birth weight (BW) and gestational age (GA) were associated with an increased risk of BPD. When controlled for these variables, predictive factors prior to IPPV were gender, age at IPPV, respiratory diagnosis, and year of birth. Following IPPV, duration of peak inspiratory pressure > 25 cm H2O, duration of fraction of inspired oxygen (FiO2) > 0.60 (DO2), maximum peak inspiratory pressure (MPIP), maximum FiO2, patent ductus arteriosus, bacteraemia and either pneumothorax or pulmonary interstitial emphysema were associated with an increased risk of BPD. Adjusting for BW and GA, there was a significant reduction in BPD risk from 1980-1990 (relative odds of 0.88 for each year compared to the previous year). This trend could be largely accounted for by decreases in MPIP and DO2 during the study period. Surfactant treatment was not independently associated with a significant change in the risk of BPD. Based on this analysis, we developed a scoring system for predicting the risk of BPD in the neonatal period which we evaluated in a random sample of infants. This predicted infants at risk of BPD with a sensitivity of 65% and a specificity of 88%.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1993

Perinatal predictors of ocular morbidity in school children who were very low birthweight.

Two hundred children from one neonatal intensive care unit (NICU), who were very low birthweight (VLBW), were examined at approximately 9 years of age and compared with a control group of normal birthweight children. Visual morbidity was significantly higher among children who were very low birthweight. Binocular visual acuity of 6/9 or worse was noted in 21 (10.5%), strabismus in 38 (19%) and regressed retinopathy of prematurity (ROP) in 13 (6.7%) of these children. A history of seizures in the perinatal period was highly correlated with poor visual acuity. Independently significant factors associated with strabismus included clinically diagnosed intraventricular haemorrhage, a maternal history of neonatal death, transfer from another hospital, bronchopulmonary dysplasia and necrotising enterocolitis. Perinatal variables that correlated with regressed ROP included birthweight, time from birth to admission to the NICU, necrotising enterocolitis and a history of maternal smoking during the pregnancy. When screening for ocular abnormalities among children who were born preterm, particular attention should be given to children with these risk factors.

Child↗
PubMed1993

Multicentre randomised trial comparing high and low dose surfactant regimens for the treatment of respiratory distress syndrome (the Curosurf 4 trial).

A randomised trial was conducted in 82 centres using the porcine surfactant extract, Curosurf, to compare two regimens of multiple doses to treat infants with respiratory distress syndrome and arterial to alveolar oxygen tension ratio < 0.22. Infants were randomly allocated to a low dosage group (100 mg/kg initially, with two further doses at 12 and 24 hours to a maximum cumulative total of 300 mg/kg; n = 1069) or a high dosage group (200 mg/kg initially with up to four further doses of 100 mg/kg to a maximum cumulative total of 600 mg/kg; n = 1099). There was no difference between those allocated low and high dosage in the rates of death or oxygen dependency at 28 days (51.1% v 50.8%; difference -0.3%, 95% confidence interval (CI) -4.6% to 3.9%), death before discharge (25.0% v 23.5%; difference -1.5%, 95% CI -5.1% to 2.2%), and death or oxygen dependency at the expected date of delivery (32.2% v 31.0%; difference -1.2%, 95% CI -5.2% to 2.7%). For 14 predefined secondary measures of clinical outcome there were no significant differences between the groups but the comparison of duration of supplemental oxygen > 40% did attain significance; 48.4% of babies in the low dose group needed > 40% oxygen after three days compared with 42.6% of those in the high dose group. The total amount of surfactant administered in the low dose regimen (mean 242 mg phospholipid/kg) was probably enough to replace the entire pulmonary surfactant pool. Adopting the low dose regimen would lead to considerable cost savings, with no clinically significant loss in efficacy.

Biological Products↗