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Biomedical subjects

L W Doyle

Publications and source records attributed to L W Doyle.

At least 19 recordsLinked to original sources

Magnesium sulphate for preventing preterm birth in threatened preterm labour.

BACKGROUND: Magnesium sulphate is used to inhibit uterine activity in women in preterm labour to prevent preterm birth. OBJECTIVES: To assess the effectiveness and safety of magnesium sulphate therapy given to women in threatened preterm labour with the aim of preventing preterm birth and its sequelae. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (May 2002) and the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2002). SELECTION CRITERIA TYPES OF PARTICIPANTS: Women thought to be in preterm labour. Types of interventions: Magnesium sulphate as the only tocolytic, administered intravenously or orally, compared with either placebo, no treatment or alternative tocolytic therapy. Types of outcome measures: Measures of effectiveness, complications, women's satisfaction with their care and health service use. DATA COLLECTION AND ANALYSIS: Assessments of trial eligibility, quality and data extractions were done by at least two of the reviewers. MAIN RESULTS: Over 2000 women were recruited into the 23 included trials. Only nine trials were rated of high quality for the concealment of allocation. In the magnesium sulphate versus control (all studies) no difference was seen for the risk of birth within 48 hours of treatment for women given magnesium sulphate compared with controls when using a random effects model (relative risk (RR) 0.85, 95% confidence interval (CI) 0.58-1.25, 11 trials, 881 women). No benefit was seen for magnesium sulphate on the risk of giving birth preterm (<37 weeks) or very preterm (<34 weeks). The risk of death (fetal and paediatric) was higher for infants exposed to magnesium sulphate (RR 2.82, 95% CI 1.20-6.62, 7 trials, 727 infants). There were only two fetal deaths, both in the magnesium sulphate group in one study. The six other trials reported there were no fetal deaths. No differences for total paediatric mortality were shown in the six trials with data. No beneficial effect was seen from using magnesium sulphate on the risk of other neonatal morbidity. A non-significant reduction in the risk of cerebral palsy was reported at follow up at 18 months corrected age (RR 0.14, 95% CI 0.01-2.60, 1 trial, 99 children). REVIEWER'S CONCLUSIONS: Magnesium sulphate is ineffective at delaying birth or preventing preterm birth, and its use is associated with an increased mortality for the infant. Any further trials should be of high quality, large enough to assess serious morbidity and mortality, compare different dose regimens, and provide neurodevelopmental status of the child.

Female↗

Sepsis in neonatal intensive care in the late 1990s.

AIM: To determine the incidence and clinical characteristics of sepsis in ventilated infants from an Australian neonatal intensive care unit (NICU) in the late 1990s. METHODS: Demographic data was collected from babies requiring assisted ventilation (AV) over the 6-month period from 1 July to 31 December 1998. Sepsis was divided into early onset sepsis (EOS; " 72 h of age) and late onset sepsis (LOS; >72 h of age), including both definite (culture-proven + abnormal markers) and probable (culture negative + abnormal markers) episodes. RESULTS: Two hundred and eleven babies required AV over this period. Of these, 64 (30.3%) had at least one infection, with 85 episodes of sepsis (40.3 episodes per 100 admissions requiring AV). There were 22 babies with 22 episodes of EOS, and 45 with 63 episodes of LOS. Three babies had both EOS and LOS. The rate of EOS was 10.4 infected infants (10.4 infections per 100 admissions requiring AV). The rate of LOS was 21.3 infected infants (29.9 infections per 100 admissions requiring AV). The rates of both EOS and LOS were higher than previously reported by Australian studies in the early 1990s. In both EOS and LOS, risk factors for infection were common. Group B streptococcus was the commonest cause of definite EOS. The mortality rate from sepsis in the EOS group was 14% (3/22). Coagulase-negative staphylococci were the commonest cause of LOS. The mortality rate from sepsis in the LOS group was 11% (5/45). CONCLUSIONS: EOS and LOS are significant problems in ventilated NICU infants in the late 1990s.

Australia↗

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Australia↗

Perinatal glucocorticoid therapy and neurodevelopmental outcome: an epidemiologic perspective.

A relatively brief course of antenatal glucocorticoids (ACS), given to reduce the severity of respiratory distress syndrome in preterm infants, improves survival and appears to protect against brain damage. In clinical trials as well as observational studies, ACS have been associated with a decreased risk of intraventricular haemorrhage and cerebral palsy. In observational studies a decreased risk of white-matter damage, identified with cranial ultrasound, has been observed. There is some evidence, from observational studies, that repeated courses of ACS (typically given at weekly intervals) can reduce the rate of fetal head growth, and experiments in animals provide further support for this possibility. In contrast to the effects of a brief course of ACS, postnatal glucocorticoids (PCS), given to preterm infants to reduce the severity of chronic lung disease have been associated with an increased risk of neurologic impairment. Available evidence suggests that PCS does not improve survival. Further study is needed of the neurodevelopmental consequences of both multiple courses of ACS, as well as PCS.

Betamethasone↗

Interleukin-6 and interleukin-8 in newborn bacterial infection.

The objective of this study is to determine the plasma concentrations and diagnostic accuracy of interleukin-6 (IL-6) and interleukin-8 (IL-8) in newborn infection. One hundred and one newborn infants with clinical signs of infection during their primary hospitalization were investigated with the minimum of a blood culture, C-reactive protein (CRP), full blood examination (FBE), and cytokine concentrations (IL-6 and IL-8). Infection in infants was classified without knowledge of cytokine levels into four groups-definite (n = 11), probable (n = 12), uncertain (n = 52), and nil (n = 26). The median concentrations of IL-6 and IL-8 were significantly higher in the definitely infected group compared with the other three groups (p <0.05). At the cut-off concentration of highest accuracy, IL-6 (>175 pg/mL) and IL-8 (>28 pg/mL) had similar sensitivities (80 and 82%, respectively) and specificities (91 and 81%, respectively). Cut-off concentrations could be identified with improved sensitivities (90% for IL-6 and 100% for IL-8) that maintained specificity >50%. However, the confidence intervals were wide for all sensitivities and specificities. IL-6 and IL-8 had little diagnostic accuracy in infants with probable infection. IL-6 and IL-8 concentrations increase early in newborn infants with definite infection.

C-Reactive Protein↗

Cognition, academic progress, behavior and self-concept at 14 years of very low birth weight children.

The aim of this study was to compare cognition, academic progress, behavior, and self-concept children of very low birth weight (VLBW, birth weight < 1501 g) born in the period 1980 to 1982 with randomly selected children of normal birth weight (NBW, birth weight > 2,499 g). At 14 years of age, 130 (84.4%) of 154 VLBW and 42 (70.0%) of 60 NBW children were assessed. Ten VLBW children and one NBW child who had cerebral palsy were excluded. VLBW children scored at a significantly lower level on all three composite scales of the Wechsler Intelligence Scale for Children, 3rd Edition. VLBW children were also significantly disadvantaged on more specific cognitive processes, including tests of visual processing and visual memory and on subtests reflecting learning and problem solving. Only in arithmetic was a difference between the groups discerned on tests of achievement. Significantly more VLBW children were rated by teachers as socially rejected and by their parents as having learning problems at school. VLBW children had significantly reduced self-esteem. VLBW children had more cognitive, academic, and behavioral problems and lower self-esteem at 14 years of age than NBW control subjects.

Achievement↗

Birth weight <1501 g and respiratory health at age 14.

AIMS: To determine the respiratory health in adolescence of children of birth weight <1501 g, and to compare the results with normal birthweight controls. METHODS: Prospective cohort study of children born in the Royal Women's Hospital, Melbourne. Two cohorts of preterm children (86 consecutive survivors 500-999 g birth weight, and 124 consecutive survivors 1000-1500 g birth weight) and a control group of 60 randomly selected children >2499 g birth weight were studied. Children were assessed at 14 years of age. A paediatrician determined the clinical respiratory status. Lung function was measured according to standard guidelines. RESULTS: Of 180 preterm children seen at age 14, 42 (23%) had bronchopulmonary dysplasia (BPD) in the newborn period. Readmission to hospital for respiratory ill health was infrequent in all groups and the rates of asthma were similar (15% in the 500-999 g birth weight group, 21% in the 1000-1500 g birth weight group, 21% in controls; 19% BPD, 18% no BPD). Overall, lung function was mostly within the normal range for all cohorts; few children had lung function abnormalities in clinically significant ranges. However, the preterm children had significantly lower values for variables reflecting flow. Lung function in children of 500-999 g birth weight was similar to children of 1000-1500 g birth weight. Preterm children with BPD had significantly lower values for variables reflecting flow than children without BPD. CONCLUSIONS: The respiratory health of children of birth weight <1501 g at 14 years of age is comparable to that of term controls.

Adolescent↗

Outcome at 14 years of extremely low birthweight infants: a regional study.

OBJECTIVES: To determine the neurosensory outcome at 14 years of age of a regional cohort of extremely low birthweight (ELBW) children, to contrast their prognosis with normal birthweight (NBW) controls, and to determine the predictive value of assessments earlier in childhood. DESIGN: Geographically determined cohort study. SETTING: The state of Victoria, Australia. PATIENTS: Consecutive ELBW survivors of birth weight 500-999 g (n = 88) born during 1979-1980, and 60 randomly selected contemporaneous NBW (birth weight > 2499 g) controls. MAIN OUTCOME MEASURES: Rates of neurosensory impairments and disabilities at 14 years of age, and earlier in childhood. RESULTS: Of 351 ELBW consecutive live births, 88 (25%) survived and 79 (90%) of the survivors were assessed at 14 years of age. Of the 79 ELBW children assessed, eight (10%) had cerebral palsy, five (6%) had bilateral blindness, four (5%) were deaf requiring hearing aids, and 36 (46%) had an intelligence quotient (IQ) < -1 SD compared with the mean for the NBW controls. Overall 11 (14%) ELBW children were severely disabled, 12 (15%) were moderately disabled, 20 (25%) were mildly disabled, and 36 (46%) had no disability. In contrast, only one (2%) of 42 NBW children assessed had a severe disability, six (14%) had a mild disability, and the remaining 35 (83%) were not disabled. Comparing psychological test scores for ELBW children with those for NBW controls, rather than test norms, avoided bias in the assessment of disability earlier in childhood. Relative to assessments earlier in childhood, the prediction of disability at 14 years of age was highly significant at each of 2, 5, and 8 years of age, but the accuracy progressively increased with age. CONCLUSIONS: ELBW children have substantially higher rates of neurosensory impairments and disabilities at 14 years of age than NBW controls. Comparison of ELBW children with NBW controls avoids bias in the assessment of disability. Early childhood assessments are highly predictive of disability at 14 years of age.

Adolescent↗

Outcome at 5 years of age of children 23 to 27 weeks' gestation: refining the prognosis.

OBJECTIVES: To determine the changes with postnatal age for survival, with and without major sensorineural disability, to 5 years of age in very preterm infants and to contrast their prognosis with normal birth weight (NBW) control participants. METHODS: A geographically determined cohort study was conducted in Victoria, Australia. Consecutive live births of 23 to 27 weeks' gestational age born during 1991 to 1992 and randomly selected contemporaneous NBW control participants were studied. The main outcome measures were survival and rates of major disability at 5 years of age, determined for those offered intensive care, after day 7, after day 28, and at hospital discharge. RESULTS: Of 401 live births of 23 to 27 weeks' gestation, 225 (56.1%) survived to 5 years of age. The survival rate rose significantly with increasing gestational age at birth in those offered intensive care and by day 7 but not by day 28. The survival rate free of major disability rose significantly with increasing gestational age at all postnatal ages but was not an independent predictive variable by day 28; other adverse events were more important. In the absence of adverse events, the rate of survival free of major disability for very preterm infants who had survived to discharge was 93.2%, similar to the rate of 95.5% for NBW control participants. CONCLUSIONS: The prognosis for very preterm infants changes substantially with postnatal age. Counseling of families should be repeated at intervals, and the advice offered should vary with perinatal events.

Case-Control Studies↗

Auditory function at 14 years of age of very-low-birthweight.

The aim of the study was to determine audiological function at 14 years of age of very-low-birthweight (VLBW < or = 1500 g) children compared with a cohort of normal birthweight (NBW > 2499 g) children. Participants were consecutive surviving preterm children of birthweight < 1000 g born between 1977 and 1982 (n=86) and of birthweight 1000 to 1500 g born between 1980 and 1982 (n=124) and randomly selected NBW children born between 1981 and 1982 (n=60). Audiometric tests included pure tone audiometry, tympanometry, stapedius muscle reflexes, and measures of central auditory processing. Psychometric tests included measures of IQ, academic achievement, and behaviour. There were no significant differences in rates of hearing impairment, abnormal tympanograms, figure-ground problems, or digit recall between VLBW children and NBW control children. VLBW children had higher rates of some central auditory processing problems, which in turn were associated with poorer intellectual, academic, and behavioural progress.

Adolescent↗

Very low birth weight and growth into adolescence.

OBJECTIVE: To compare the growth and pubertal development of very low-birth-weight (VLBW) children (birth weight <1500 g) and normal-birth-weight (NBW) children (birth weight >2499 g) to adolescence to determine if, and at what age, VLBW children "catch up." DESIGN: Inception cohort study to age 14 years. SETTING: Royal Women's Hospital, Melbourne, Australia. PATIENTS: Eighty-six consecutive survivors with a birth weight less than 1000 g, 120 consecutive survivors with a birth weight of 1000 to 1499 g, and 60 randomly selected NBW controls. Children with cerebral palsy at age 14 years were excluded. MAIN OUTCOME MEASURES: Weight, height, and head circumference measurements at birth and ages 2, 5, 8, and 14 years converted to z (SD) scores. RESULTS: At age 14 years, pubertal development was similar in NBW and VLBW children. At ages 2, 5, 8, and 14 years, VLBW children were significantly shorter and lighter and had smaller head circumferences than NBW children. The differences in height and weight between VLBW and NBW children were less apparent as SD scores improved in VLBW children over time. Within the VLBW group, compared with children with a birth weight of 1000 to 1499 g, those with a birth weight less than 1000 g had significantly lower weight z scores earlier in childhood but not at age 14 years, significantly lower height z scores only at age 2 years, and significantly lower head circumference z scores throughout childhood. CONCLUSION: This group of VLBW children experienced late catch-up growth to age 14 years but remain smaller than their NBW peers. Arch Pediatr Adolesc Med. 2000;154:778-784

Adolescent↗

Moderately early (7-14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants.

BACKGROUND: Corticosteroids have been used late in the neonatal period to treat chronic lung disease (CLD) in preterm babies and early to try to prevent it. CLD is likely to be the result of persisting inflammation in the lung and the use of powerful anti-inflammatory drugs like dexamethasone has some rationale. Early use tends to be associated with increased adverse effects so that studies of moderately early treatment (7-14 days postnatal) might have the dual benefits of fewer side effects and onset of action before chronic inflammation is established. OBJECTIVES: To determine if moderately early (7-14 days) postnatal corticosteroid treatment vs control (placebo or nothing) is of benefit in the prevention and/or treatment of early chronic lung disease in the preterm infant. SEARCH STRATEGY: Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, Cochrane Database of Controlled Trials, Medline, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. SELECTION CRITERIA: Randomised controlled trials of postnatal corticosteroid treatment from 7-14 days of birth in high risk preterm infants were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality up to 28 days and before discharge, failure to extubate, mortality and / or chronic lung disease at 28 days and 36 weeks, CLD at 28 days and 36 weeks, infection, hyperglycaemia, hypertension, severe retinopathy of prematurity (ROP), pneumothorax, necrotizing enterocolitis (NEC), gastrointestinal bleeding, severe intraventricular hemorrhage (IVH), hypertrophic cardiomyopathy, late rescue with dexamethasone and abnormal neurological examination at follow-up were abstracted and analysed using Revman 4.0.4. MAIN RESULTS: Moderately early steroid treatment (vs placebo or nothing) reduced mortality by 28 days, chronic lung disease at 28 days and 36 weeks, and death or chronic lung disease at 28 days or 36 weeks. Earlier extubation was facilitated. There was no significant effect on the rates of pneumothorax, severe ROP, and NEC. Adverse effects included hypertension, hyperglycaemia, gastrointestinal bleeding, hypertrophic cardiomyopathy and infection. Steroid-treated infants were less likely to need late rescue with dexamethasone. There was only one small study of longterm follow-up and it did not show any increase in adverse neurological outcome. REVIEWER'S CONCLUSIONS: Moderately early corticosteroid therapy (started at 7-14 days) reduces neonatal mortality and CLD, but at the cost of important short term adverse effects. No reliable evidence concerning long term effects is provided by the trials included in this review. In view of the evidence of an important increase in cerebral palsy and other adverse neurodevelopmental outcomes from trials in which postnatal steroid was begun either earlier or later than 7-14 days, there are reasonable grounds for extending this concern to moderately early initiation of steroid therapy. More research is urgently needed, including long term follow-up of survivors included in previous and any future trials, before the benefits and risks of postnatal steroid treatment, including initiation at 7-14 days, can be reliably assessed.

Anti-Inflammatory Agents↗

Delayed (>3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants.

BACKGROUND: Many preterm babies who survive, having had respiratory distress syndrome (RDS) or not, go on to develop chronic lung disease (CLD). This is probably due to persistence of inflammation in the lung. Corticosteroids have powerful anti-inflammatory effects and have been used to treat established CLD. However it is unclear whether any beneficial effects outweigh the adverse effects of these drugs. OBJECTIVES: To determine if late (> 3 weeks) postnatal corticosteroid treatment vs control (placebo or nothing) is of benefit in the treatment of chronic lung disease (CLD) in the preterm infant. SEARCH STRATEGY: Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, the Cochrane Database of Controlled Trials, Medline, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. SELECTION CRITERIA: Randomised controlled trials of postnatal corticosteroid treatment initiated at > 3 weeks of age in preterm infants with CLD were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality before discharge, failure to extubate, infection, hyperglycaemia, hypertension, severe retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), gastrointestinal bleeding, bowel perforation, echodensities on ultrasound scan of brain, need for home oxygen, glycosuria, need for late rescue with dexamethasone, cerebral palsy in survivors and blindness in survivors were abstracted and analysed using Revman 4.0.4. MAIN RESULTS: Delayed steroid treatment had no effect on mortality. The only beneficial effects were reductions in failure to extubate by 7 or 28 days, need for late rescue treatment with dexamethasone, chronic lung disease at 36 weeks, and discharge to home on oxygen therapy. There was no increase in risk of infection, necrotising enterocolitis, or gastrointestinal bleeding. Short-term adverse affects included hyperglycaemia, glycosuria and hypertension. There was an increase in severe retinopathy of prematurity, but no effect on blindness. There were increases in long-term neurologic sequelae including abnormal neurologic examination and cerebral palsy, the latter of borderline statistical significance. REVIEWER'S CONCLUSIONS: The benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. There is a worrying increase in adverse neurological outcomes in infants treated with postnatal steroids (see also Review of Early Postnatal corticosteroids). Corticosteroids should be reserved for infants who cannot be weaned from mechanical ventilation. The dose of dexamethasone and the duration of any course of treatment should be minimised.

Anti-Inflammatory Agents↗