Showing papers by "Peter Brocklehurst published in 2008"

The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: A randomised controlled trial

Abstract: A hypoxic-ischaemic insult occurring around the time of birth may result in an encephalopathic state characterised by the need for resuscitation at birth, neurological depression, seizures and electroencephalographic abnormalities. There is an increasing risk of death or neurodevelopmental abnormalities with more severe encephalopathy. Current management consists of maintaining physiological parameters within the normal range and treating seizures with anticonvulsants. Studies in adult and newborn animals have shown that a reduction of body temperature of 3–4°C after cerebral insults is associated with improved histological and behavioural outcome. Pilot studies in infants with encephalopathy of head cooling combined with mild whole body hypothermia and of moderate whole body cooling to 33.5°C have been reported. No complications were noted but the group sizes were too small to evaluate benefit. TOBY is a multi-centre, prospective, randomised study of term infants after perinatal asphyxia comparing those allocated to "intensive care plus total body cooling for 72 hours" with those allocated to "intensive care without cooling". Full-term infants will be randomised within 6 hours of birth to either a control group with the rectal temperature kept at 37 +/- 0.2°C or to whole body cooling, with rectal temperature kept at 33–34°C for 72 hours. Term infants showing signs of moderate or severe encephalopathy +/- seizures have their eligibility confirmed by cerebral function monitoring. Outcomes will be assessed at 18 months of age using neurological and neurodevelopmental testing methods. At least 236 infants would be needed to demonstrate a 30% reduction in the relative risk of mortality or serious disability at 18 months. Recruitment was ahead of target by seven months and approvals were obtained allowing recruitment to continue to the end of the planned recruitment phase. 325 infants were recruited. Combined rate of mortality and severe neurodevelopmental impairment in survivors at 18 months of age. Neurodevelopmental impairment will be defined as any of: • Bayley mental developmental scale score less than 70 • Gross Motor Function Classification System Levels III – V • Bilateral cortical visual impairments Current Controlled Trials ISRCTN89547571

A prospective national study of acute fatty liver of pregnancy in the UK

Abstract: Objectives: To identify a national, population-based cohort of women with AFLP, to evaluate proposed diagnostic criteria and to document accurately the incidence, management and outcomes of the condition. Design: A population-based descriptive study using the UK Obstetric Surveillance System. Setting: All 229 hospitals with consultant-led maternity units in the UK. Participants: 57 women in the UK diagnosed with AFLP between February 2005 and August 2006 in an estimated cohort of 1,132,964 maternities. Main outcome measures: Rates with 95% confidence intervals (95%CI). Results: The estimated incidence of AFLP was 5.0 cases per 100,000 maternities (95%CI 3.8-6.5/100,000). Fifty-five cases (90%) were confirmed by diagnostic criteria and clinical assessment, 2 (3%) by clinical assessment alone, representing 97% agreement (kappa statistic=0.78). 18% of women had twin pregnancies and 20% were underweight (BMI Conclusions: We have identified the largest population-based cohort of women with AFLP to date. Diagnostic criteria previously proposed agree substantially with clinical diagnosis. The incidence estimate from this study is lower than documented by earlier hospital-based studies, but maternal and neonatal outcomes are better than previously reported, possibly related to improved ascertainment. Women with twin pregnancies appear to be at higher risk but further studies are needed to investigate the risk associated with low BMI.

MRC ORACLE Children Study. Long term outcomes following prescription of antibiotics to pregnant women with either spontaneous preterm labour or preterm rupture of the membranes.

Abstract: The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate. The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents. National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England. This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age. The ORACLE Trial and Children Study is registered in the Current Controlled Trials registry. ISCRTN 52995660

The INIS Study. International Neonatal Immunotherapy Study: Non-specific intravenous immunoglobulin therapy for suspected or proven neonatal sepsis: An international, placebo controlled, multicentre randomised trial

Abstract: Background: Sepsis is an important cause of neonatal death and perinatal brain damage, particularly in preterm infants. While effective antibiotic treatment is essential treatment for sepsis, resistance to antibiotics is increasing. Adjuvant therapies, such as intravenous immunoglobulin, therefore offer an important additional strategy. Three Cochrane systematic reviews of randomised controlled trials in nearly 6,000 patients suggest that non-specific, polyclonal intravenous immunoglobulin is safe and reduces sepsis by about 15% when used as prophylaxis but does not reduce mortality in this situation. When intravenous immunoglobulin is used in the acute treatment of neonatal sepsis, however, there is a suggestion that it may reduce mortality by 45%. However, the existing trials of treatment were small and lacked long-term follow-up data. This study will assess reliably whether treatment of neonatal sepsis with intravenous immunoglobulin reduces mortality and adverse neuro-developmental outcome. Methods and design: A randomised, placebo controlled, double blind trial. Babies with suspected or proven neonatal sepsis will be randomised to receive intravenous immunoglobulin therapy or placebo. Eligibility criteria - Babies must be receiving antibiotics and have proven or suspected serious infection AND have at least one of the following: birthweight less than 1500 g OR evidence of infection in blood culture, cerebrospinal fluid or usually sterile body fluid OR be receiving respiratory support via an endotracheal tube AND there is substantial uncertainty that intravenous immunoglobulin is indicated. Exclusion criteria - Babies are excluded if intravenous immunoglobulin has already been given OR intravenous immunoglobulin is thought to be needed OR contra-indicated. Trial treatment - Babies will be given either 10 ml/kg of intravenous immunoglobulin or identical placebo solution over 4–6 hours, repeated 48 hours later. Primary outcome - Mortality or major disability at two years, corrected for gestational age. Data collection - Data will be collected at discharge from hospital and at 2 years of age (corrected for gestation) using a parental questionnaire and a health status questionnaire completed during a face-to-face follow-up appointment with the child's paediatrician. Trial registration: Current Controlled Trials ISCRTN94984750.