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Biomedical subjects

R W Cooke

Publications and source records attributed to R W Cooke.

At least 19 recordsLinked to original sources
PubMed1995

Randomised controlled trial of allopurinol prophylaxis in very preterm infants.

Allopurinol, an inhibitor of xanthine oxidase (an enzyme capable of generating superoxide radicals following hypoxiaischaemia), was investigated in preterm infants to determine its ability to prevent the complications of neonatal intensive care which may be associated with oxidative injury. Four hundred infants of between 24 and 32 weeks' gestation were randomly allocated to receive enteral allopurinol (20 mg/ml) or an equivalent dose of placebo for seven daily doses. At admission, plasma hypoxanthine concentrations were significantly higher in infants who subsequently developed periventricular leucomalacia (PVL), bronchopulmonary dysplasia (BPD), or retinopathy of prematurity (ROP), but there was no difference in the primary endpoint (PVL) between the treated and control groups. The failure of allopurinol prophylaxis in this group of infants is probably related to the complex nature of the pathological processes and to the timing of treatment. If oxidant injury is an important mechanism of cellular injury in these preterm infants, an alternative biochemical modulator would be required, or a combination of agents might be effective.

Allopurinol↗
PubMed1995

Motor impairment in children 12 to 13 years old with a birthweight of less than 1250 g.

AIM: To determine whether poor motor skills, previously identified in a cohort of very low birthweight (< 1250 g) children, born in 1980-1, have persisted or improved. Previous assessments had shown significant improvement between the ages of 6 and 8 years. METHODS: The original cohort were traced and were assessed using the Movement Assessment Battery for Children, an update of the Test Of Motor Impairment, used at 6 and 8 years. Where possible the classroom-matched controls from the original studies were assessed, otherwise new controls were selected. Teachers were also asked to identify those children whom they considered clumsy. Forty seven of the original cohort of 53 children, all but one still attending mainstream school, and 40 original and 20 new classroom-matched controls were studied. RESULTS: Fifty one per cent of the cohort showed clinically important or borderline impairment. More of these children had significant impairment (16/47, 34%) than the controls (3/60, 5%). The improvement seen by 8 years of age was maintained but there was no further improvement. Girls had significantly higher overall impairment scores (median 16; interquartile range 10-21.5) than the boys (5.5 (1.5-12.5)), and on a wider variety of subtests (5/8) than the boys (3/8). CONCLUSIONS: Many very low birthweight children have impaired motor skills. Despite early improvement it persists into adolescence and the deficit remains. Interventional studies may help to see if these problems can be alleviated.

Adolescent↗
PubMed1994

Clinical and subclinical deficits at 8 years in a geographically defined cohort of low birthweight infants.

OBJECTIVE: To determine the prevalence of subclinical deficits in cognitive and motor function in low birthweight infants. DESIGN: Children of birth weight < or = 2000 g born to mothers resident in Merseyside in 1980-1 assessed using the Wechsler Intelligence Scale for Children (WISC), the Neale analysis of reading ability, and the Stott-Moyes-Henderson test of motor impairment (TOMI). Children attending normal schools assessed with controls matched for age, sex, and class in school. Children attending special schools were assessed unmatched. SUBJECTS: 233 matched index case-control pairs attending normal primary schools and 46 unmatched children attending special schools. SETTING: Primary and special schools. MAIN OUTCOME MEASURES: IQ score, reading age in months, and TOMI score. RESULTS: Index cases when compared with controls had a lower WISC score (mean IQ difference 8.8; 95% confidence interval (CI) 6.8 to 10.7), a lower reading age (mean difference 6.5 months; 95% CI 4.0 to 9.0), and poorer motor performance as shown by the TOMI score (mean difference 1.4; 95% CI 1.1 to 1.8). Of the children attending special schools, 23/46 (50%) had a WISC score < or = 50. CONCLUSIONS: Low birthweight children have significant subclinical deficits of cognitive and motor function and extra resources, especially in education, may be required to meet their needs.

Birth Weight↗
PubMed1992

Annual audit of neonatal morbidity in preterm infants.

Annual odds ratios, standardised for known confounding variables, were used to examine trends in major neonatal morbidities among 3220 preterm infants of less than 35 weeks' gestation admitted to a regional referral centre between 1980 and 1991. Despite improved survival, the risk of major cerebral haemorrhage, ventriculoperitoneal shunt insertion, and necrotising enterocolitis was unchanged. A recent reduction in risk of pneumothorax and persistence of the arterial duct was noted. An increased risk for chronic lung disease over time could be accounted for by increased survival, although a similar increase in risk for infection remained unexplained.

Bacterial Infections↗
PubMed1992

Plasma hypoxanthine: a marker for hypoxic-ischaemic induced periventricular leucomalacia?

Cerebral ischaemia of the immature brain may result in cavitating periventricular leucomalacia (PVL), an important association of cerebral palsy. Hypoxanthine measured by high performance liquid chromatography was used as a marker of peripartum hypoxia and ischaemia in 116 infants at risk of PVL. PVL was detected by ultrasound. The 81 infants who were unaffected had median (range) gestation of 30 weeks (24-32), weight of 1336 g (724-3790), and a plasma hypoxanthine concentration of 7.8 mumol/l (2.4-48.9). The seven infants who had cavitating PVL had a median gestation of 28 weeks (26-30), weight of 1165 g (682-1860), and a hypoxanthine concentration of 31.9 mumol/l (7.1-149). Cavitating PVL was significantly dependent only on hypoxanthine when controlling for the effects of weight and gestation. This suggests that peripartum hypoxia-ischaemia may be one of the aetiological factors in cavitating PVL. Oxidation of hypoxanthine during reperfusion generates free radicals which may contribute to the tissue destruction of PVL. The association of hypoxia-ischaemia with PVL suggests that PVL may be modified by reducing free radical activity.

Biomarkers↗
PubMed1992

Receiver operating characteristic curves for comparison of serial neutrophil band forms and C reactive protein in neonates at risk of infection.

The performance of indirect indices of infection in the newborn vary because of differences in techniques, including diagnostic cut off levels. We have compared serial neutrophil band cell counts with C reactive protein measured by rate nephelometry. The 'gold standard' was a positive culture and the performance of the tests was compared by the technique of receiver operating characteristics (ROC) as well as sensitivity and specificity. A total of 172 septic screens were performed in 56 patients. The operational diagnostic cut off values were: C reactive protein greater than 8 mg/l, immature:total neutrophil ratio (I:T ratio) greater than 0.2, and band count greater than 5%. Compared with the sensitivity of C reactive protein (71%), I:T ratio (34%) was significantly different but band count (69%) was not. The specificity of C reactive protein (72%) was better than band count (39%) but no better than I:T ratio (73%). ROC curves were constructed for all possible diagnostic cut off values of the tests and superior performance was demonstrated for C reactive protein compared with band count and I:T ratio. We conclude that C reactive protein is a useful early indicator of infection in neonates and that ROC curves permit comprehensive and graphic comparison between tests and the calculation of optimal diagnostic cut off values.

Bacteria↗
PubMed1991

Predicting costs and outcomes of neonatal intensive care for very low birthweight infants.

A geographically determined cohort of all infants of less than 1,500 g born in 1980 and 1981 were clinically followed up to age four to determine their disabilities which were classified as mild, moderate or severe. A quality adjustment coefficient, determined by the severity of the disability, was used to calculate the number of quality adjusted lives produced. The total cost of care for these children was assessed as the sum of hospital costs to age four (which were specifically determined) and an estimate of the life-time costs of care of disabled children from information provided by the Education and Social Service departments. A very poor predictive power of birthweight with cost was obtained with the ungrouped birthweight data, whereas clinical factors explained up to 60% of the variance of the initial hospital costs for survivors and up to 30% of the variance of life-time costs and the cost of quality adjusted lives produced. Rules for the allocation of resources based on discrimination by birthweight are flawed but the application of clinical discretion is important.

Birth Weight↗
PubMed1991

Prolonged low dose indomethacin for persistent ductus arteriosus of prematurity.

A total of 121 infants who required indomethacin for persistent ductus arteriosus in Liverpool and Cambridge over a four year period were randomised to receive either 0.1 mg/kg daily for six days or 0.2 mg/kg every 12 hours for three doses. The groups were of similar birth weight and gestational and postnatal age, though those treated with a low dose were by chance receiving a higher percentage of oxygen at the start of treatment and there were more deaths from bronchopulmonary dysplasia in this group. Of 59 infants treated with the prolonged course 53 (90%) responded initially to indomethacin compared with 48 of 62 (77%) treated conventionally--a difference of 13% (95% confidence interval for the difference 0 to 26%). Of the 53 responders 11 (21%) relapsed after low dose indomethacin, whereas after the shorter course 19 of 48 (40%) relapsed. This difference was significant (95% confidence intervals 3 to 37%). Side effects, mainly gastrointestinal haemorrhage, were similar in both groups. Significantly fewer infants experienced a rise in serum creatinine or urea concentration after treatment with low dose indomethacin. A prolonged low dose course of indomethacin offers advantages over conventional treatment.

Ductus Arteriosus, Patent↗
PubMed1991

Trends in preterm survival and incidence of cerebral haemorrhage 1980-9.

The annual survival rates and incidence of cerebral haemorrhage in 2618 preterm infants of 34 weeks' gestation or less were examined in one referral centre over a 10 year period from January 1980 to December 1989. Survival was independently related to weight, gestation, sex, and inborn delivery. When these variables had been taken into account, survival was 56% greater at the end of the decade compared with 1980. The incidence of cerebral haemorrhage (diagnosed by cranial ultrasound scanning) was related to birth weight, gestation, sex, inborn delivery, and caesarean section, but there was no significant trend in the incidence with time. Rates of caesarean section in this group increased from 31% in 1980 to over 50% more recently. Haemorrhage affecting the brain parenchyma was related to gestation and inborn delivery, and showed a small but significant decline over time. The lack of association between changes in survival rates and rates of cerebral haemorrhage may indicate that factors associated with both neonatal mortality and the incidence of cerebral haemorrhage may not be causally related as previously assumed.

Analysis of Variance↗
PubMed1991

The incidence of renal calcification in preterm infants.

A total of 79 infants born at less than 32 weeks' gestation were studied with serial renal ultrasound scans to assess the incidence of nephrocalcinosis. Twenty one infants developed renal calcification giving an overall incidence of 26.6% in the study group. Affected infants were significantly smaller (mean (SD) birth weight 940 (323) g) and significantly less mature (mean (SD) gestation 26.9 (1.9) weeks). In 17 patients the calcification was represented by hyperechogenic renal pyramids alone, and in four patients renal calculi were demonstrated. Factors associated with renal calcification included hypophosphataemia, hypercalcaemia, hypercreatininaemia, and prolonged oxygen requirement during the first month of life. Multivariate analysis showed that the strongest clinical indicator of calcification was duration of oxygen treatment. Infants who still required oxygen treatment at 28 days had a 62% chance of developing renal calcification.

England↗
PubMed1991

Factors associated with chronic lung disease in preterm infants.

Among 659 infants of 30 weeks' gestation or less born in a regional perinatal centre between 1983 and 1989, 195 were ventilated for four days or more and survived to 28 days, and 87 of these developed chronic lung disease. There was a sevenfold increase in the annual incidence of chronic lung disease over time. During the same period there were significant increases in the number of infants who survived, the incidence of septicaemia, and the use of parenteral lipid emulsions. Chronic lung disease was significantly associated with low birth weight, shorter gestation, duration of ventilation, vaginal delivery, sepsis, and the use of lipid. Respiratory and physiological measurements at 96 hours were significantly worse in infants who subsequently developed chronic lung disease. Initial logistic regression showed that gestation, arterial carbon dioxide tension (PaCO2), and ventilation rate at 96 hours; and birth in 1988 or 1989, were independently associated with chronic lung disease, but when septicaemia and use of lipid during the first 21 days were included, only gestational age (odds ratio 0.64, 95% confidence interval (CI), 0.49 to 0.81 for each week) and use of lipid (odds ratio 8.1, 95% CI, 2.32 to 28.0) remained significantly associated with chronic lung disease. The observed increase in incidence of chronic lung disease in this population was associated with earlier use of parenteral lipids in infants of very low gestation rather than with changes in population, survival, or ventilator treatment of respiratory distress syndrome.

Birth Weight↗
PubMed1990

Cerebral palsy in very low birthweight infants.

Eighty one very low birthweight survivors with cerebral palsy were matched with controls by sex, gestational age, and place of birth. Using discriminant analysis, the perinatal profiles for infants with cerebral palsy and their controls were shown to differ significantly. When infants with various types of cerebral palsy were analysed with their controls the discriminating variables differed. Diplegic infants could be differentiated from controls on antenatal variables alone, but significant discrimination of hemiplegic and quadriplegic infants required the addition of postnatal variables. Cranial ultrasound appearances differed appreciably between types of cerebral palsy. Future studies should differentiate between types of cerebral palsy and include ultrasound data. Cerebral palsy in very low birthweight infants is unlikely to prove a useful outcome indicator for neonatal intensive care.

Brain↗
PubMed1990

Five year outcome of preterm sextuplets related to size at birth.

Preterm sextuplets were studied to examine whether growth retardation affects long term outcome. All were growing normally at 5 years. Intelligence quotients (IQ) ranged from 105-116 and motor impairment scores from 1.0-7.0. No neurological or behavioural abnormalities were found. The largest sextuplet has maintained her position for growth and IQ. No relation between test scores and birth weight or perinatal variables was found in the remaining siblings.

Birth Weight↗