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Biomedical subjects

N J Shaw

Publications and source records attributed to N J Shaw.

At least 55 records · Page 3Linked to original sources

Improved survival and neurodevelopmental outcome after prolonged ventilation in preterm neonates who have received antenatal steroids and surfactant.

AIMS: To assess survival and neurodevelopmental outcome following prolonged ventilation beyond 27 or 49 days of postnatal life in neonates treated with antenatal steroids and surfactant. METHODS: The medical records of 84 babies born in 1994-1996 requiring ventilation after 27 postnatal days at Liverpool Women's Hospital were reviewed to determine the duration of mechanical ventilation, survival, and neurodevelopmental outcome at 3 years of age. RESULTS: Fifty six babies were mechanically ventilated after 27 postnatal days but for less than 50 days; 48 (86%) survived to 3 years. Twenty six (54%) of the survivors had normal neurodevelopment at 3 years and seven (15%) had only mild disability. Twenty eight babies were ventilated after 49 postnatal days; 14 survived to 3 years. Five of these survivors were neurodevelopmentally normal at 3 years and two had mild disability. CONCLUSIONS: Survival decreases with more prolonged ventilation. When antenatal steroids and postnatal surfactant are used, there appears to be improved survival and neurodevelopmental outcome in preterm babies who require prolonged ventilation.

Developmental Disabilities↗

Dependency level of babies on the neonatal unit: a comparison of two different classification systems.

BACKGROUND: Monitoring activity on the neonatal unit is important for planning service provision and as part of monitoring quality of care. The dependency level of the patients cared for must be taken into account as well as the number of patients. Two different systems for determining dependency level are in common use. AIM: To develop a system that would allow the accurate determination of dependency level for babies in our care using both the British Association for Perinatal Medicine and Neonatal Nurses Association definitions and the Northern Neonatal Network definitions and to perform a comparison between these two systems. METHOD: Forty details relating to current clinical status and treatment being given were recorded daily for every patient on two neonatal units over a 17 month period. These details were recorded in a computer database, and dependency levels were calculated for each patient day using both systems. RESULTS: A total of 21 905 patient days were recorded for 1555 patients. There was good agreement between the two systems on what constituted the highest level of dependency, but overall comparability was poor, with the two systems assigning comparable dependency levels to only 76% of patient days. CONCLUSIONS: There is limited comparability in dependency levels between these two widely used systems. There is a need for a standardisation of definitions to allow meaningful comparisons to be made between units.

Algorithms↗

Respiratory distress in heavier versus lighter twins.

UNLABELLED: We performed a retrospective study of twin pairs under 36 weeks gestation admitted to a regional neonatal unit over a three year period to determine if the larger twin of a twin pair is at increased risk of respiratory distress in the immediate postnatal period compared to the smaller twin. Gestation, gender, birth weight, mode and reason for delivery, birth order, and Apgar at 5 minutes were correlated with the need for added oxygen at 4 hours, the need for ventilation, oxygen requirement at 28 days and mortality. One hundred and twenty-four twin pairs were analyzed with a median gestation of 31 weeks (range 23-35). There were 47 female-female pairs, 40 male-male pairs and 37 mixed pairs. Multiple logistic regression revealed no significant increased risk for ventilation in male, heavier or second twins. The need for oxygen at 4 hours was strongly associated with being male and being the second twin, but not with being the heavier twin. However, on analysis of twins of 28 weeks gestation or above a significant association was found between a persisting oxygen requirement at 4 hours and being male (OR 2.2; 95% CI 1.15-4.16), being the heavier twin (OR 1.9; 95% CI 1.03-3.46), and being the second twin (OR 2.7; 95% CI 1.48-4.99). No association was found between mortality and being male, and being the second or smaller twins. CONCLUSION: Heavier twins above 28 weeks gestation are at increased risk of short term mild respiratory problems following delivery compared to lighter twins at the same gestation. This is not as strong a factor as birth order or male gender, but it is important to be aware of this in antenatal counselling of the parents as the smaller twin is usually perceived to be at greater risk of morbidity.

Apgar Score↗

Neurodevelopmental outcome in high-risk preterm infants treated with inhaled nitric oxide.

UNLABELLED: Inhaled nitric oxide (iNO) is used to treat preterm infants with hypoxaemic respiratory failure. In this study we describe the long-term survival and neurodevelopmental status of high-risk preterm infants enrolled into a randomized controlled trial of iNO therapy. Information regarding long-term outcome was available for all 25 children enrolled in the original trial who survived until discharge from hospital. Formal, blinded, developmental assessment and neurological examinations were performed in 21 out of 22 children still alive at 30 mo of age, corrected for prematurity. No significant differences were found in long-term mortality (12/20 vs 8/22, RR 1.65, 95% CI 0.87-3.3), neurodevelopmental delay (4/7 vs 9/14, RR 0.89, 95% CI 0.37-1.75), severe neurodisability (0/7 vs 5/14, p = 0.12) or cerebral palsy (0/7 vs 2/14, p = 0.53) between iNO-treated and control infants. CONCLUSION: In this study there was no evidence of a significant effect on either survival or long-term neurodevelopmental status in infants treated with iNO.

Administration, Inhalation↗

GATA3 haplo-insufficiency causes human HDR syndrome.

Terminal deletions of chromosome 10p result in a DiGeorge-like phenotype that includes hypoparathyroidism, heart defects, immune deficiency, deafness and renal malformations. Studies in patients with 10p deletions have defined two non-overlapping regions that contribute to this complex phenotype. These are the DiGeorge critical region II (refs 1, 2), which is located on 10p13-14, and the region for the hypoparathyroidism, sensorineural deafness, renal anomaly (HDR) syndrome (Mendelian Inheritance in Man number 146255), which is located more telomeric (10p14-10pter). We have performed deletion-mapping studies in two HDR patients, and here we define a critical 200-kilobase region which contains the GATA3 gene. This gene belongs to a family of zinc-finger transcription factors that are involved in vertebrate embryonic development. Investigation for GATA3 mutations in three other HDR probands identified one nonsense mutation and two intragenic deletions that predicted a loss of function, as confirmed by absence of DNA binding by the mutant GATA3 protein. These results show that GATA3 is essential in the embryonic development of the parathyroids, auditory system and kidneys, and indicate that other GATA family members may be involved in the aetiology of human malformations.

Amino Acid Sequence↗

Pumactant and poractant alfa for treatment of respiratory distress syndrome in neonates born at 25-29 weeks' gestation: a randomised trial.

BACKGROUND: Exogenous surfactant preparations vary in their constitution and biophysical properties. Synthetic and animal-derived preparations lower the rate of death compared with controls. No significant differences in mortality or important long-term clinical outcomes have been shown between them in randomised trials. We did a randomised controlled trial to compare pumactant, a synthetic surfactant, with poractant alfa, an animal-derived surfactant, both of which are widely used in the UK. METHODS: We enrolled 212 neonates born between 25 weeks' and 29 weeks and 6 days' gestation who were intubated for presumed surfactant deficiency and were free from life-threatening malformations. We randomly assigned 105 neonates poractant alfa, and 107 pumactant. The primary outcome was duration of high-dependency care and mortality was a secondary outcome. Analysis was by intention to treat. FINDINGS: Outcome data were analysed for 199 babies. The trial was stopped on the recommendation of the data and safety monitoring committee because mortality assumed a greater importance than the primary outcome. Predischarge mortality differed significantly between groups, in favour of poractant alfa (14.1 vs 31.0%, p=0.006; odds ratio 0.37 [95% CI 0.18-0.76). This difference was sustained after adjustment for centre, gestation, birthweight, sex, plurality, and use of antenatal steroids. INTERPRETATION: Mortality was unexpectedly lower among neonates who received poractant alfa than among those who received pumactant, and was independent of all the variables we investigated. Stopping the trial early may have widened the difference between the treatment groups.

Cause of Death↗

Outcome of congenital diaphragmatic hernia.

The outcome of congenital diaphragmatic hernia (CDH) differs for different stages of the fetus or infant's life (i.e., antenatal, immediate postnatal, and postoperative). Assessing combined data from nonrandomized studies is technically difficult. Following recognized methods of reviewing such trials, we aimed to review the available literature on the outcome of CDH to provide a guide to clinicians when counselling parents who have a fetus/infant with this condition. Thirty-five studies reporting data for CDH from 1985 to March 1998 were identified using a high sensitive search strategy, hand-searching journals, and reviewing references of relevant studies. These were systematically reviewed. The median overall mortality was 58% (interquartile range (IQR), 43-65%) for babies diagnosed in utero, 48% (IQR, 35-55%) if born alive, and 33% (IQR, 18-54%) postoperatively. Diagnosis before 25 weeks of gestation is not a uniformly bad prognostic indicator (median mortality, 60%). Outcome was worse for those fetuses with other anomalies (median mortality, 93%). The median percentage mortality for all infants born alive and treated in extracorporeal membrane oxygenation (ECMO) centers was 34% (IQR, 26-47%). Median percentage mortality for all ECMO-treated infants was 44% (IQR, 35-50%). Different treatment strategies may have a variable impact on outcome. These figures, together with local data, may help in parental counselling on prognosis for fetuses/infants with CDH.

Extracorporeal Membrane Oxygenation↗

Dopamine versus dobutamine for hypotensive preterm infants.

BACKGROUND: Inotropes are widely used in preterm infants to treat systemic hypotension. The most commonly used drugs are dopamine and dobutamine. These agents have different modes of action which may result in different haemodynamic effects. OBJECTIVES: To compare the effectiveness and safety of dopamine and dobutamine in the treatment of systemic hypotension in preterm infants. SEARCH STRATEGY: The standard search method of the Cochrane Neonatal Review Group was used. Searches of electronic and other databases were performed. Previous reviews were searched for references to relevant trials and leading authors in the field were contacted for information about other published and unpublished studies. SELECTION CRITERIA: Randomised controlled trials where short and/or long term effects of treatment with dopamine and dobutamine for the treatment of systemic arterial hypotension were compared were selected for this review. Trials studying newborn infants born before 37 completed weeks gestation and less than 28 days of age were eligible for inclusion. Systemic arterial hypotension was not defined specifically, but accepted as defined in individual studies. Studies were not limited by birthweight, lower gestational age threshold or by route or duration of administration of inotropic agents. Study quality and eligibility were assessed independently by each reviewer. DATA COLLECTION AND ANALYSIS: The standard method of the Cochrane Collaboration described in the Cochrane Collaboration Handbook was used to perform this systematic review. Data extraction was performed independently by each reviewer, with differences being resolved by discussion. The following outcomes were determined: mortality in the neonatal period, long term neurodevelopmental outcome, radiological evidence of severe neurological injury, short term haemodynamic changes and incidence of adverse effects. The effect of interventions is expressed either as Relative Risk (RR), Risk Difference (RD) or as Weighted Mean Difference (WMD) with their 95% Confidence Interval (CI). MAIN RESULTS: Four trials met the pre-defined criteria for inclusion in this review. There was no evidence of a significant difference between dopamine and dobutamine in terms of neonatal mortality (RD 0.02 95% CI -0.12 to 0.16), incidence of periventricular leukomalacia (RD -0.08, 95% CI -0.19 to 0.04), or severe periventricular haemorrhage (RD -0.02, 95% CI -0.13 to 0.09). Dopamine was more successful than dobutamine in treating systemic hypotension, with fewer infants having treatment failure (RD -0.29, 95% CI -0.42 to -0.17; NNT = 3.5, 95% CI 2.4 to 5.9). There was no evidence of a significant difference in change in left ventricular output when dopamine was compared with dobutamine (WMD -83 ml/kg/min, 95% CI -174 to 8 ml/kg/min). There was no evidence of a significant difference between the two agents with respect to the incidence of tachycardia (RD -0.06, 95% CI -0.25 to 0.14). None of the studies reported the incidence of adverse long term neurodevelopmental outcome. REVIEWER'S CONCLUSIONS: Dopamine is more effective than dobutamine in the short term treatment of systemic hypotension in preterm infants. There was no evidence of an effect on the incidence of adverse neuroradiological sequelae (severe periventricular haemorrhage and/or periventricular leucomalacia), or on the incidence of tachycardia. However, in the absence of data confirming long term benefit and safety of dopamine compared to dobutamine, no firm recommendations can be made regarding the choice of drug to treat hypotension.

Cardiotonic Agents↗

Type 2 diabetes mellitus in UK children--an emerging problem.

AIMS: Type 2 diabetes mellitus has never previously been described in UK children, although an increasing incidence in childhood is recognized in international studies. The prevalence of obesity in UK children is increasing and is a recognized risk factor for the development of diabetes. The aim of this study was to identify and characterize children with Type 2 diabetes in the West Midlands and Leicester. METHODS: Children were identified by contacting paediatricians responsible for diabetes in five hospitals. Details were collected on demographics, mode of presentation, investigations and treatment on a standard proforma. RESULTS: Eight girls were identified with Type 2 diabetes, aged 9-16 years and who were of Pakistani, Indian or Arabic origin. They were all overweight (percentage weight for height 141-209%) and had a family history of diabetes in at least two generations. They presented insidiously with hyperglycaemia and glycosuria without ketosis and five were asymptomatic. Islet cell antibodies measured in seven patients were negative. Four had acanthosis nigricans which is a cutaneous marker of insulin resistance and the other four had high plasma levels of insulin and/or C peptide. These patients are distinct from those with maturity-onset diabetes of the young (MODY). All were initially managed with dietary measures, seven have been treated with oral anti-diabetic agents of whom two have subsequently required insulin. CONCLUSIONS: These are the first UK case reports of Type 2 diabetes in children. Paediatricians need to be aware of the risk of Type 2 diabetes developing in childhood in high-risk ethnic groups, particularly in association with obesity and a positive family history.

Acanthosis Nigricans↗

Intravenous pamidronate in juvenile osteoporosis.

AIMS: To investigate the use of the aminobisphosphonate, disodium pamidronate, in children with vertebral osteoporosis. METHODS: Five children (aged 10-15 years) with vertebral osteoporosis who developed compression fractures in the thoracic and/or lumbar spine as a consequence of five different conditions, received treatment with intravenous disodium pamidronate in doses ranging from 0.5 to 12 mg/kg/y. RESULTS: Each child had rapid pain relief following the first treatment, followed by large increments in lumbar spine bone density over one year; the change in bone density standard deviation score ranged from 0.5 to 2.5 with percentage increments of 26% to 54%. CONCLUSION: Intravenous pamidronate appears to be a useful therapeutic option in childhood osteoporosis, but its use in children must still be regarded as experimental and therefore closely monitored.

Absorptiometry, Photon↗

Respiratory syncytial virus infection in high risk infants and the potential impact of prophylaxis in a United Kingdom cohort.

BACKGROUND: Bronchiolitis caused by respiratory syncytial virus (RSV) is an important cause of morbidity in ex-premature infants. In a randomised placebo controlled trial monoclonal antibody prophylaxis showed a 55% reduction in relative risk of hospital admission for these high risk infants, against a background incidence of 10.6 admissions per 100 high risk infants. AIMS: To follow a cohort of high risk infants in order to assess hospitalisation rate from RSV and the potential impact of prophylaxis for these patients in a UK local health authority. METHODS: A cohort of high risk infants from a local health authority were followed over the 1998/99 and 1999/2000 RSV seasons. The high risk population was defined as infants who, at the beginning of the seasons studied, were: (1) under 6 months old and born prior to 36 weeks gestation with no domiciliary oxygen requirement; or (2) under 24 months of age and discharged home in supplemental oxygen. All admissions with bronchiolitis during the season were identified. RESULTS: A total of 370 high risk infants were identified for the 1998/99 season and 286 for the following year. Over the two years there were 68 admissions. Significantly more admissions occurred from group 2 infants. RSV was identified in 27 cases (four admissions per hundred high risk infants). Prophylaxis may have saved up to pound 195,134 in hospital costs over the two years, but would have cost pound 1.1 million in drug acquisition costs. CONCLUSIONS: Careful consideration of risk factors is needed when selecting infants for RSV prophylaxis.

Antibodies, Monoclonal↗

Randomised controlled trial of patient triggered and conventional fast rate ventilation in neonatal respiratory distress syndrome.

AIM: To compare patient triggered, with conventional fast rate, ventilation in a randomised controlled trial using the incidence of chronic lung disease as the primary outcome measure. METHODS: Three hundred and eighty six preterm infants with birthweights from 1000 to 2000 g, and requiring ventilation for respiratory distress syndrome within 24 hours of birth, were randomised to receive either conventional or trigger ventilation with the SLE 2000 ventilator. RESULTS: There were no significant differences in the incidence of chronic lung disease (28 day and 36 week definitions), death, pneumothorax, intraventricular haemorrhage, number of ventilator days, or length of oxygen dependency between groups. CONCLUSIONS: Patient triggered ventilation in preterm infants with respiratory distress syndrome is feasible. No significant differences, when compared with conventional fast rate ventilation in important medium and longer term outcome measures, were evident.

Cause of Death↗

Severe retinopathy of prematurity and its association with different rates of survival in infants of less than 1251 g birth weight.

BACKGROUND: There is controversy over whether improved survival of preterm infants has resulted in a higher incidence of severe (grade 3 or greater) retinopathy of prematurity (ROP). AIM: To compare survival rates and rates of > or = stage 3 ROP-that is, with a high risk of sequelae-in preterm infants in five English cities where, anecdotally, the incidence of ROP is reported to show considerable variation. METHODS: All infants of birth weight < 1500 g and or gestational age < 32 weeks, born in 1994 in one of the cities or transferred in within 48 hours, were studied. The populations were adjusted for case mix variation using CRIB (clinical risk index for babies, a disease severity scoring system). The incidence of severe ROP, the actual death rate, and that adjusted for disease severity were determined. RESULTS: The rate of severe ROP per 1000 births was higher in city 1 than in all the other cities. This increase in comparison with city 2 and city 4 was significant (city 1, 167 (95% confidence interval (CI) 96 to 260); city 2, 24 (6 to 59); city 4, 16 (1 to 84)). A significant difference was not seen between city 1 and cities 3 (23 (1 to 120)) and 5 (74 (21 to 79)). The relative risk of developing severe ROP in city 1 compared with all the other cities was 5.5 (2.5 to 11.9). The actual death rate per 1000 births in city 1 was significantly lower than that predicted by modelling death against CRIB score (city 1: actual 270; predicted 385 (95% CI 339 to 431)). In contrast, the other cities had actual death rates as predicted, or worse than predicted, by CRIB. INTERPRETATION: A significantly higher incidence of severe ROP was identified in one of the five cities studied. Variation in survival rates among high risk infants may explain this observation.

England↗

Changes in pulmonary arterial pressure in preterm infants with chronic lung disease.

BACKGROUND: Pulmonary arterial pressure (PAP) is raised in preterm infants with respiratory distress syndrome who subsequently develop chronic lung disease. The natural history of pulmonary hypertension in infants with chronic lung disease is unknown. OBJECTIVES: To investigate changes in PAP, assessed non-invasively using Doppler echocardiography, in infants with chronic lung disease during the 1st year of life. METHODS: Serial examinations were performed in infants with chronic lung disease and healthy preterm infants. The Doppler derived acceleration time to right ventricular ejection time ratio (AT/RVET) was calculated from measurements made from the pulmonary artery velocity waveform. RESULTS: A total of 248 examinations were performed in 54 infants with chronic lung disease and 44 healthy preterm infants. The median AT/RVET was significantly lower in infants with chronic lung disease than in healthy preterm infants (0.31 v 0.37). AT/RVET significantly correlated with age corrected for prematurity in both infants with chronic lung disease (r = 0.67) and healthy infants (r = 0.55). There was no significant difference between the rate of change in AT/RVET between the two groups. In infants with chronic lung disease, multivariate analysis showed that AT/RVET was significantly independently associated with age and inversely with duration of supplemental oxygen treatment. Median AT/RVET was significantly lower in infants with chronic lung disease until 40-52 weeks of age corrected for prematurity. CONCLUSIONS: Although PAP falls with increasing age in both infants with chronic lung disease and healthy preterm infants, it remains persistently raised in infants with chronic lung disease until the end of the 1st year of life.

Age Factors↗

A comparison of indices of respiratory failure in ventilated preterm infants.

AIM: To compare indices of respiratory failure in terms of their ability to predict adverse respiratory outcomes in preterm infants. The indices evaluated were: (a) the alveolar-arterial oxygen tension difference (A-aDO(2)); (b) the ratio of arterial to alveolar oxygen tension (a/A ratio); (c) the oxygenation index (OI); (d) the fractional inspired oxygen concentration (FIO(2)). METHODS: Details of respiratory support and arterial blood gas data in the first 24 hours of life were collected in ventilated infants below 34 weeks gestation. The worst single value of a particular index in the first 24 hours was chosen to quantify the severity of respiratory failure in each infant. Receiver operating characteristic curves were constructed and areas under the curve (AUC) calculated to compare the performance of the indices in predicting death from respiratory failure and/or the development of chronic lung disease (CLD). RESULTS: A total of 155 preterm infants were studied, of whom 35 (23%) died primarily from respiratory failure and 53 of the 120 survivors (44%) developed CLD. The overall performance of the four indices in predicting death from respiratory failure ranged from 0. 77 (AUC for maximum FIO(2)) to 0.88 (AUC for minimum a/A ratio). The corresponding AUCs for gestational age and birth weight were 0.75 and 0.76 respectively. In contrast, demographic variables tended to perform better than indices of respiratory failure in predicting CLD/death. CONCLUSIONS: There was no evidence of a significant difference between the performance of the a/A ratio, A-aDO(2), and OI in predicting adverse respiratory outcomes. Use of the OI is recommended because of its ease of calculation.

Chronic Disease↗