Sudden unexpected death in infancy: place and time of death.

In recent years, many babies who die of Sudden Unexpected Death in Infancy (SUDI) in Northern Ireland are found dead in bed--i.e. co-sleeping--with an adult. In order to assess its frequency autopsy reports between April 1996 and August 2001 were reviewed and linked to temporal factors. The day and month of death, and the place where the baby was found were compared to a reference population of infant deaths between one week of age and the second birthday. Although the rate of SUDI was lower than the UK average, 43 cases of SUDI were identified, and two additional deaths with virtually identical autopsy findings that were attributed to asphyxia caused by suffocation due to overlaying. Thirty-two of the 45 (71%) were less than four months of age. In 30 of the 45 cases (67%) the history stated that the baby was bed sharing with others; 19 died sleeping in an adult bed, and 11 on a sofa or armchair. In 16 of the 30 (53%) there were at least two other people sharing the sleeping surface, and in one case, three. SUDI was twice as frequent at weekends (found dead Saturday-Monday mornings) compared to weekdays (p<0.02), and significantly more common compared to reference deaths (p<0.002). Co-sleeping deaths were also more frequent at weekends. Almost half of all SUDI (49%) occurred in the summer months--more than twice the frequency of reference deaths. While sharing a place of sleep per se may not increase the risk of death, our findings may be linked to factors such as habitual smoking, consumption of alcohol or illicit drugs as reported in case-control studies. In advising parents on safer childcare practices, health professionals must be knowledgeable of current research and when, for example, giving advice on co-sleeping this needs to be person-specific cognisant of the risks within a household. New and better means of targeting such information needs to be researched if those with higher risk life-styles are to be positively influenced.

Social deprivation and childhood injuries in North and West Belfast.

Injuries in childhood represent a major public health concern. North and West Belfast is an area in which a high rate of emergency department attendance due to injury has been observed, and in which social deprivation is widespread. We carried out a cross sectional survey of 479 injuries in children aged 0-12 years presenting to four emergency departments serving North and West Belfast. Injury rates were compared between the most deprived and least deprived areas, selected on the basis of Noble Economic Deprivation scores. A significant correlation between economic deprivation and injury rate was demonstrated (r = 2.14, p < or = 0.001). Children living within the most deprived areas were particularly likely to be involved in road traffic accidents (relative risk RR = 3.25, p = 0.002). We conclude that children living within the most deprived areas of North and West Belfast are at greater risk of injury than those in less deprived areas. Specific causes of injury, for example burns and scalds, high falls, and motor vehicle accidents are particularly associated with deprivation. Targeting should be taken into account when injury prevention strategies are being developed.

A long-term follow-up of cognitive, emotional, and behavioural sequelae to Reye syndrome.

Eighteen adolescents who had survived Reye syndrome (RS) in early childhood were assessed on cognitive, emotional, and behavioural variables in a second follow-up study tracking this group. Siblings were used as controls. The entire group with RS had survived with no obvious neurological damage at the first follow-up study. Indeed, current findings suggested that long-term cognitive, emotional, and behavioural functioning was comparable to siblings in approximately half of the group with RS. However, two factors were associated with a less favourable outcome. Cognitive, emotional, and behavioural functioning were significantly poorer in the subgroup of survivors whose illness had occurred in the first year of life. In addition, loss of consciousness, although the association with poor outcome was not as noticeable, was also associated with relative deficits on some scales of cognitive ability. Many of these deficits had not been obvious at the first follow-up and the importance of neurodevelopmental factors are considered. Finally, the implications of these findings for research and interventions in RS and other such encephalopathies are discussed.

The mechanism of inhibition of beta-oxidation by aspirin metabolites in skin fibroblasts from Reye's syndrome patients and controls.

The effects of aspirin metabolites on beta-oxidation were studied in skin fibroblasts from eight typical Reye's syndrome (RS) patients and controls. RS patients' cells did not differ from controls in rates of palmitate oxidation or in the three component activities of the mitochondrial trifunctional enzyme (MTE), indicating no inherited beta-oxidation defect. Aspirin metabolites salicylate, hydroxyhippurate and gentisate, but not aspirin, directly inhibited palmitate oxidation in control and RS cells. RS cells were significantly more sensitive to inhibition than controls at 0.5 to 5 mM salicylate. Inhibition was concentration-dependent and reversible. Inhibition did not occur in fibroblasts lacking activity of the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activity of MTE. Salicylate was therefore inhibiting beta-oxidation at this step. Hydroxyhippurate and salicylate reversibly inhibited HAD activities in extracts of control and RS cells. Studies with pure short-chain HAD and LCHAD (MTE) showed hydroxyhippurate and salicylate were competitive inhibitors of the former but mixed (not competitive) inhibitors of the latter. Both compounds inhibited the combined, three-step, MTE reaction measured in the physiological direction. We conclude that (1) salicylate and hydroxyhippurate decrease beta-oxidation in intact cells by reversible inhibition of LCHAD activity of the MTE, and (2) beta-oxidation in RS cells is inherently more sensitive to inhibition by low concentrations of salicylate than controls.

The changing clinical pattern of Reye's syndrome 1982-1990.

OBJECTIVE: To describe trends in the clinical pattern of Reye's syndrome in the British Isles between 1982 and 1990; and to determine the relation between any changes and the June 1986 warnings against the use of aspirin in children. DESIGN: Development, and application to reported cases, of a scoring system designed such that patients showing the typical clinical and pathological features of 'classical' Reye's syndrome scored highly. The relations between 'Reye scores' and a number of explanatory variables were explored using multivariable analysis. SETTING: British Isles. SUBJECTS: 445 cases fulfilling the Reye's syndrome case definition reported to the surveillance scheme between January 1982 and December 1990. MAIN OUTCOME MEASURE: Individual 'Reye score'. RESULTS: Cases with high scores were more likely to have occurred in the 4 1/2 year period before June 1986 compared with the subsequent period (p < 0.006). Numbers of cases in the low and intermediate score categories declined by about 50% after June 1986, whereas those in the high category fell by 79%. High scorers were more likely to have received aspirin (p < 0.0001) and were older than intermediate and low scorers (p < 0.008). No relation was identified between score and season of onset. CONCLUSIONS: The decline in Reye's syndrome after the aspirin warnings cannot be explained entirely, as has been proposed, by improved diagnosis of 'Reye-like' inherited metabolic and other disorders: this would not account for the greater decline of the high scoring subgroup which also contained those cases most likely to resemble 'classical' Reye's syndrome and to have received aspirin. This study provides further evidence for the role of aspirin in a subset of cases meeting the standard diagnostic criteria for Reye's syndrome and supports the need to consider this disorder as a heterogeneous group of conditions including Reye-like inherited metabolic disorders.

Metabolism of paracetamol in children with chronic liver disease.

OBJECTIVE: To study the metabolism of single doses of paracetamol in paediatric patients with chronic liver disease admitted to a hospital liver disease clinic. RESULTS: Thirteen paediatric patients, aged 7 months to 12 years, with chronic liver disease of varying severity were studied. In these children, paracetamol elimination half-life was negatively correlated with serum albumin and positively with prothrombin time, as previously reported in adults with liver disease. The rate constant of glucuronide formation was higher in the children with liver disease compared to the value reported in healthy children of similar ages. The rate constant of the formation of paracetamol sulphate was no different from that in normal children. The 36 h urinary paracetamol glucuronide to sulphate ratio was 1.4 (95% CI 0.8 to 1.7). This mean ratio was higher than in healthy children (0.81 and 0.75) but not significantly so, probably because of a Type 1 error due to the inevitable small sample size arising from the nature of the population being studied. CONCLUSION: The present study provides reassuring additional data to indicate that, at least for single doses, there is no cause for concern in the use of paracetamol in children with chronic liver disease.

Assay of paracetamol and its metabolites in urine, plasma and saliva of children with chronic liver disease.

A high-performance liquid chromatographic (HPLC) assay of paracetamol and its metabolites is described. The method for quantifying the metabolism of paracetamol in children with chronic liver disease and the good correlation between plasma and salivary concentrations of paracetamol is demonstrated. Despite an increasing bias between the two methods with increasing concentration of paracetamol, it is concluded that salivary assay is satisfactory for characterising paracetamol pharmacokinetics in the group of patients studied.

Paediatric consultation patterns in general practice and the accident and emergency department.

The age, sex, source of referral and diagnosis of children brought to a paediatric accident and emergency department by their parents were compared to those consulting their general practitioner. A simultaneous, prospective review of these consultations was carried out over a six-week period in an inner-city paediatric teaching hospital and a group practice in a socially deprived urban area. 730 children less than 13 years of age who presented for a new consultation were seen. 629 (86%) presented initially to the general practitioner, who dealt with all but 25 (4.0%) without onward referral to the accident and emergency department. 127 consultations took place at the accident and emergency department, of which 104 (82%) were parental referrals. There was no sex difference in children seen by the general practitioner. There was a decreasing trend with increasing age in the proportion of children who consulted the general practitioner, perhaps due to the higher frequency of injury in the older children. Over three quarters (77%) of injured children were brought directly to the accident and emergency department, compared with only 4% of children without injuries (p < 0.001). Of 22 children with injuries who presented to the general practitioner, only 4 (18%) required onward referral. General practitioners met the great majority of the paediatric workload generated by the practice. Audit between primary and secondary care gives a more reliable picture than data from only one source. Injured children are more likely to be taken to the accident and emergency department. Further study of the severity of injury in children is required to determine if there is potential to reduce parental referrals to accident and emergency departments.

An audit of dermatology in a paediatric accident and emergency department.

Two studies were undertaken of patients with dermatological disorders who attended the Accident and Emergency (A&E) Department of the Royal Belfast Hospital for Sick Children during 1990-1991. The aims were to review diagnostic accuracy and assess the benefits of an open-access consultant dermatology clinic. A retrospective survey of 14,340 new attendances at the A&E department over a 7-month period found that 540 of these (4%) had a primary dermatological disorder. In 26% no diagnosis had been made although only 10% were referred for a specialist opinion. A 2-month prospective study of patients who attended the department and were referred to a consultant dermatology open-access clinic revealed overall diagnostic accuracy of 66% (+/- 2 SEM). Individual rates of diagnostic concordance between junior doctor and consultant were 59% for skin infections and 77% for papulosquamous disorders. The open-access clinic allowed prompt referral for correct diagnosis and initiation of appropriate management.

Current concepts in Reye's syndrome.

Reye's syndrome is an acute metabolic encephalopathy largely affecting children and adolescents. Its aetiopathogenesis, although controversial, is at least partially understood. Its study has helped to create a greater awareness of inherited disorders of intermediary metabolism. Although these are individually rare, when combined they constitute a significant cause of morbidity and mortality.

Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency--diagnosis, plasma carnitine fractions and management in a further patient.

Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD), the third enzyme of the mitochondrial beta-oxidation pathway, carries out the dehydrogenation of 3-hydroxyacyl-CoA compounds of 12-18 carbon length. To date only nine cases of LCHAD deficiency have been documented. We report a further patient who as a neonate developed non-specific gastrointestinal symptoms and at 5 months of age cardiomyopathy, recurrent hypoketotic hypoglycaemia and gross alterations of plasma carnitine fractions. Dietary management with medium chain triglycerides led rapidly to clinical improvement. There was a close correlation between the clinical condition, plasma carnitine fractions and cardiac function. At 2 years of age she is developing normally.

The phenylpropionic acid load test: experience with 72 children at-risk for beta-oxidation disorders.

The urinary excretion of metabolites of orally administered phenylpropionic acid (PPA) in 72 children, aged 2 days to 16 years, thought to be at-risk of medium acyl CoA dehydrogenase deficiency has been studied. Forty had presented as Reye Syndrome, 9 as a Reye-like syndrome and 24 were sibs of decreased RS, sibs of RLS cases or sibs of infants who had died suddenly and without explanation where an autopsy revealed the presence of very heavy fatty infiltration of the liver. These studies demonstrated that PPA metabolites are maximally excreted during the 3 hours following the oral load and that this urine collection should be diagnostic. PPA loading is a relatively simple, safe test which is part of the investigation of a patient suspected of having an inborn error of metabolism.

A sibling-controlled study of intelligence and academic performance following Reye syndrome.

The authors compared the intellectual, cognitive and academic abilities of 22 survivors of Reye syndrome attending normal schools with the sibling nearest in age as control. The British Ability Scales, visual and verbal IQ, short-term memory scales and attainment tests were administered to all children. Reye syndrome children as a group differed significantly from the controls only on the basic number skills test. However, children with severe encephalopathy and those whose illness occurred in infancy had significant deficits on many of the tests. 18 children recovered without requiring 'additional educational provision'; the mean IQ of the 22 Reye syndrome children was 101. Nonetheless, these children's poor performance on the basic number skills test has important implications for teachers, and careful monitoring of future educational performance is essential.

Trends in the incidence of Reye's syndrome and the use of aspirin.

In 1986 there was a public warning in the United Kingdom about a link between the consumption of aspirin and Reye's syndrome. To find out if the use of aspirin and paracetamol in children had altered, and whether the incidence of Reye's syndrome had changed since a previous study, parents were interviewed in Belfast and London, and the British Reye's Syndrome Surveillance System data were reviewed. Children with febrile illnesses were 17 times more likely to have received aspirin before admission to hospital in 1985/6 compared with 1988/9. Only 21 Belfast parents (40%) and 13 London parents (27%) had heard of Reye's syndrome and only 12 in Belfast (23%) and seven in London (15%) knew of its association with aspirin, suggesting a continuing need for public education. Cases of Reye's syndrome declined both in numbers (from a peak of 79 in 1983/4 to 19 in 1988/9) and in median age. Of the 418 reported cases, the diagnosis was subsequently revised in 89, most often (in 31 of 89, 36%) to 'inborn errors of metabolism'.