Biomedical subjects
Publications and source records attributed to G McClure.
Advances in neonatal intensive care have resulted in increasing survival of very small babies, who often require prolonged periods of mechanical ventilation. These babies have limited nutritional reserves, and are difficult to feed by either parenteral or enteral routes. This review article discusses the interaction between undernutrition and respiratory muscle function in the critically ill preterm baby.
The postnatal growth, respiratory status and neurodevelopmental outcome of surviving babies enrolled in the first European multicentre trial of porcine surfactant (Curosurf) replacement for severe neonatal respiratory distress syndrome, were assessed at corrected ages of 1 and 2 years. Follow up rates of survivors were 93% at 1 year and 89% at 2 years. Treated and control groups were similar at both 1 and 2 years in terms of physical growth, the prevalence of persistent respiratory symptoms and the occurrence of major and minor disability. Serum antibodies recognising Curosurf and surfactant-anti-surfactant immune complexes were detected in both treated and control babies, the titres showing no difference between groups. Examination of histological lung sections from non-survivors revealed a higher incidence of severe pulmonary interstitial emphysema in control babies than in those treated with surfactant. Surfactant treatment for severe respiratory distress syndrome reduces neonatal mortality and air leaks and is not associated with an increase in disability 2 years later.
OBJECTIVE: To determine whether the predictive value of Doppler ultrasonography extends beyond the perinatal period. DESIGN: Descriptive follow-up study. SETTING: Specially designated paediatric clinic in Royal Maternity Hospital. SUBJECTS: 40 children who as high risk fetuses had had assessment of umbilical artery flow velocity waveforms. INTERVENTIONS: Parental history, physical examination, anthropometry, Denver developmental screening test. OUTCOME MEASURES: Weight, height, head circumference, neurological impairment, Denver development screening test RESULT: Abnormal waveforms were an accurate predictor of neonatal outcome, with significant differences in birthweight, gestational age, need for nursery admission, and frequency of intrauterine growth retardation between normal and abnormal waveform groups. However, abnormal Doppler studies were not predictive of long-term adverse sequelae. There were no significant differences in height, head circumference, proportion with neurological impairment, or results of Denver developmental screening test at a median age of five years. CONCLUSION: The predictive value of Doppler ultrasonography is less for long-term growth and neurodevelopment than for perinatal outcome in the high risk fetus.
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In an international multicenter trial infants with clinical and radiological signs of severe RDS (age 2-15 h, birthweight 700-2,000 g, mechanical ventilation, FiO2 greater than or equal to 0.6, no complicating disease) were randomized to receive either a single dose (n = 176) or up to three subsequent doses (n = 167) of a natural porcine surfactant (Curosurf). Using a logistic regression model, the effects of therapy, birthweight, sex, hospital and other clinical factors on survival and various outcome parameters were evaluated. Mortality (13 vs. 21%, p less than 0.05) and the incidence of pneumothorax (9 vs. 18%, p less than 0.01) were significantly lower in the multiple-dose group. Low birthweight, hospital allocation, low Apgar score and initial disease severity were associated with an increased mortality. Low birthweight, hypothermia (admission temperature less than 36 degrees C) and acidosis (pH less than 7.25) prior to surfactant treatment could be identified as risk factors for the development of intracranial hemorrhage.
There is now convincing evidence that the severity of neonatal respiratory distress syndrome can be reduced by surfactant replacement therapy; however, the optimal therapeutic regimen has not been defined. This randomized European multicenter trial was designed to determine whether the beneficial effects of a single large dose of Curosurf (200 mg/kg) in babies with severe respiratory distress syndrome (arterial to alveolar oxygen tension ratio approximately 0.10) could be enhanced by using multiple doses of surfactant. Preterm neonates (birth weight 700 to 2000 g) with severe respiratory distress syndrome requiring artificial ventilation with fraction of inspired oxygen greater than or equal to 0.6 were randomized into two groups at an age of 2 to 15 hours. Both groups received the usual dose of Curosurf (200 mg/kg) immediately after randomization. In neonates randomized to receive multiple-dose treatment, two additional doses of Curosurf (100 mg/kg each) were instilled into the airways (12 and 24 hours after the initial dose) provided that the patients still needed artificial ventilation with fraction of inspired oxygen greater than 0.21. In both groups (single dose: n = 176, multiple doses: n = 167) there was a rapid improvement in oxygenation as reflected by a threefold increase in arterial to alveolar oxygen tension ratio within 5 minutes after surfactant instillation (P less than .001), and peak inspiratory pressure and mean airway pressure could be reduced significantly during the first 6 hours after surfactant treatment. In addition, ventilatory requirement (peak inspiratory pressure, ventilatory efficiency index) was reduced in the multiple-dose group 2 to 4 days after randomization (P less than .05 to .01).(ABSTRACT TRUNCATED AT 250 WORDS)
VNTR regions are informative genetic markers for linkage mapping and individual identification. Using PCR, we have developed a procedure for the enzymatic amplification of the VNTR located in the 16th intron of the human retinoblastoma (RB1) gene. We have also prepared a nonisotopically labeled oligonucleotide probe which facilitates detection of the amplification products. In examining 250 individuals from four different populations, we have detected 11 alleles ranging from 650 to 1,800 bp in size. The core repeat is approximately 50 bp in length. On the basis of the observed allele frequencies for Caucasian, African-American, and Hispanic populations from the United States and for the Mexican Hispanic population, the heterozygosities have been calculated to be 62%, 75%, 61%, and 50%, respectively. The observed genotype frequencies do not deviate from the values expected under Hardy-Weinberg equilibrium. The effect of varying primer sequences, annealing temperature, and cycle number on the amplification are also discussed. Amplification of this marker may also prove useful for detecting the heterozygosity loss that is associated with tumor formation in retinoblastoma.
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Twenty two babies who developed bronchopulmonary dysplasia were compared with 22 babies matched for gestational age who did not. Those with bronchopulmonary dysplasia weighed less at birth and had lower energy intakes from day 7 to day 56. Undernutrition before and after birth is a major problem in babies who develop bronchopulmonary dysplasia.
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All 162 consecutive admissions to a multidisciplinary paediatric intensive care unit in the UK have been prospectively evaluated in terms of therapeutic intention, sickness levels, age, utilisation of resources, and outcome. For 101 (62.3%) of the children admitted the aim of treatment was to cure the condition but for 30 (18.5%) ultimately only a palliative option was available. Five children were admitted to avail of specialised monitoring facilities. One half of the children admitted were physiologically unstable. The majority (102, 62.9%) were age 12 months or less. Resource utilisation, which was not affected by therapeutic intention, was greatest for the sickest patients, those age 1 month or less and non-survivors. Mortality rate overall was 17.9%. Mortality was unaffected by age and therapeutic intention and was inversely related to level of sickness. The information provided by this study forms a basis for medical audit within the unit and is essential for meaningful comparisons of standards of care and outcome with other units.
Forty-five cases of systemic neonatal candidiasis were diagnosed over a 9-year period in a neonatal intensive care unit; 42 infants weighted less than 1.5 kg. All had been very ill with preceding bacterial sepsis and other complications of low birthweight. Where treatment was instituted the mortality was low (4 out of 39 dying) and complications of treatment were transitory. We therefore recommend diligent examination for the presence of this infection, and treatment with a combination of amphotericin B and 5-flucytosine.
A retrospective study of 17 babies admitted to the neonatal intensive care unit of the Royal Maternity Hospital, Belfast, was undertaken to determine the causes and prognosis of conjugated hyperbilirubinaemia (direct fraction greater than 20% of total) over a five year period. Mean gestational age was 29 weeks and mean birth weight was 1,240g with a 2:1 male preponderance. All babies had a complicated clinical course involving prolonged periods of parenteral nutrition and many episodes of sepsis. Liver damage was not found to be a contributory factor to death in any baby who died before the age of one year. Bilirubin levels in the survivors had returned to normal within one year. No permanent pathological cause of cholestasis, such as biliary atresia, was ascribable to any of the cases, indicating that extensive investigation to exclude anatomical causes in this population is unlikely to prove rewarding.
Ten thousand new out-patient referrals are made each year to the out-patient department of the Royal Belfast Hospital for Sick Children. A prospective study of a random sample of 295 (4%) of these children was undertaken to determine their reason for referral and the outcome of their attendance. The stated reason for referral was for investigation/diagnosis (45%), therapeutic advice (47%) or parental reassurance (6%). Non-attenders (10%) could not be predicted from the referral letter. Twenty-four per cent were found to have no abnormality. Significantly more children referred for parental reassurance and infants were included in this category. Less than half (45%) had investigations performed. These were mainly non-invasive with plain x-rays and urinalysis accounting for 44%. Consultant medical staff saw 53% of new referrals and requested more investigations but were less likely to review patients. The information obtained is used to suggest ways in which more rational use of hospital resources might be achieved without decreasing the standard of care to these children.
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Fetal hydrops (hydrops fetalis) remains a significant cause of fetal and neonatal mortality. The decreased incidence of rhesus iso-immunisation due to prophylaxis with rhesus immune globulin (anti-D), improved antenatal ultrasound screening, and advances in neonatal intensive care have greatly altered the clinical outlook in this condition. A retrospective review of all 27 liveborn cases of hydrops in the Royal Maternity Hospital, Belfast in the period 1974-89 showed that in the last five years 40% of cases were non-immune in origin. The mortality rate fell from 100% in the first part of the study to 50% in the second.
A 14 year review of meningitis in babies showed that overall mortality and survival without handicap has not improved. The failure to improve the prognosis of these babies during a period when overall perinatal mortality fell rapidly is because smaller babies are being affected and different organisms are being cultured.