Short-term mortality and implementation of antiretroviral treatment for critically ill HIV-infected children in a developing country

Objective

To describe the short‐term outcome of critically ill HIV‐infected children with access to highly active antiretroviral therapy (HAART) in a developing region.

Methods

Prospective observational study conducted in a paediatric teaching hospital in Cape Town, South Africa. All children admitted to the paediatric intensive care unit (PICU) with suspected HIV infection were screened. Data are n (%) with 95% confidence intervals.

Results

Sixty eight of 96 HIV antibody‐positive children, median age 3 months, were confirmed HIV‐infected. Predicted PICU mortality was 0.42. Fifty one children (75%; 95% CI 65 to 85%) survived to PICU discharge, but hospital survival was only 51% (95% CI 40 to 63%). Limitation of intervention (LOI) decisions were a factor in the majority of PICU and ward deaths. Twenty one PICU survivors (31%; 95% CI 20 to 42%) commenced HAART, and two children were already on treatment. Nineteen children (28%) were considered to be established on HAART after 1 month. Thirteen HIV‐infected children (19%; 95% CI 10 to 28%), representing 25% (95% CI 14 to 37%) of all PICU survivors, and 68% (95% CI 48 to 89%) of those PICU survivors who were established on HAART remain well on treatment after median 350 days.

Conclusion

The majority of HIV‐infected children survived to discharge from PICU, but only half survived to hospital discharge. LOI decisions, usually made in PICU, directly influenced short‐term survival and the opportunity to commence HAART. Although few critically ill HIV‐infected children survived to become established on HAART, the long‐term outcome of children on HAART is encouraging and warrants further investigation.UNAIDS (the Joint United Nations Programme on HIV/AIDS) estimated that in 2003 almost 38 million people were living with HIV, including 2.1 million children, and approximately 630 000 children were newly infected in that year.¹ In developed countries, prevention‐of‐mother‐to‐child‐transmission (PMTCT) programmes have led to a reduction in vertical transmission rates from 15–20% to less than 2%.^2,3,4 However, the incidence of perinatal HIV infection remains high in developing countries, where large numbers of undiagnosed, antiretroviral‐naïve children continue to present to state health services.^5,6,7HIV‐infected infants frequently present to health services for the first time with a life‐threatening critical illness.⁸ This problem is magnified several fold in high‐prevalence developing regions, where rationing of resources for those who might derive maximal benefit is an inescapable necessity.⁹ One hundred and thirty six HIV antibody‐positive children were admitted to the paediatric intensive care unit (PICU) at this institution in 2002, prior to the availability of highly active antiretroviral therapy (HAART) in the public sector. Seventy three per cent of children survived to PICU discharge, 46% to hospital discharge, but only 14% were known to be alive one year later (personal communication, AA).The high incidence of HIV infection and lack of access to HAART, coupled with resource constraints, led to debate over whether the public health service could afford a deontological approach to health care for critically ill HIV‐infected children. In a recent review of these ethical issues, it has been suggested that “pragmatic adherence to a policy of refusing to offer ventilation [to HIV‐infected children] … has to be followed”, in order to avoid overwhelming the regional paediatric critical care services.⁹HAART has become available in developing and transitional countries, but the success of HAART programmes in regions with adequate healthcare resources, and relatively low incidence of paediatric HIV infection, cannot be taken for granted in developing regions with a much greater burden of HIV disease.^10,11,12,13 Data are urgently required to guide policy, resource allocation, and ethical decision‐making in this setting. The decision to offer intensive care, as for any complex medical intervention, would depend partly on available resources and partly on the likelihood of successful outcome.⁹ In the case of critically ill HIV‐infected children, successful outcome would be defined as survival to become established on long‐term HAART, not merely survival to PICU discharge.This prospective observational study was conducted to describe the short‐term outcome of HIV‐infected children, who were admitted to intensive care with the intention of starting HAART on resolution of their critical illness; to identify obstacles to successful implementation of long‐term HAART for such children; and to guide the allocation of critical care resources for HIV‐infected children in a developing or transitional region     

Comparison of standard versus double dose of amoxicillin in the treatment of non-severe pneumonia in children aged 2-59 months: a multi-centre, double blind, randomised controlled trial in Pakistan

Introduction

WHO pneumonia case management guidelines recommend oral amoxicillin as first line treatment for non‐severe pneumonia. Increasing treatment failure rates have been reported over a period of time, which could possibly be due to increasing minimum inhibitory concentrations of Streptococcus pneumoniae and Haemophilus influenzae for amoxicillin. Microbiological data show that this resistance can be overcome by increasing amoxicillin dosage. Based on this data, we examined whether we can improve the clinical outcome in non‐severe pneumonia by doubling the dose of amoxicillin.

Methods

A double blind randomised controlled trial was conducted in the outpatient departments of four large hospitals in Pakistan. Children aged 2–59 months with non‐severe pneumonia were randomised to receive either standard (45 mg/kg/day) or double dose (90 mg/kg/day) oral amoxicillin for 3 days and then followed up for 14 days. Final outcome was treatment failure by day 5.

Results

From September 2003 to June 2004, 876 children completed the study. 437 were randomised to standard and 439 to double dose oral amoxicillin. 20 (4.5%) children in the standard and 25 (5.7%) in the double dose group had therapy failure by day 5. Including the relapses, by day 14 there were 26 (5.9%) cumulative therapy failures with standard and 35 (7.9%) with double dose amoxicillin. These differences were not statistically significant (p = 0.55 and p = 0.29, respectively).

Conclusion

Clinical outcome in children aged 2–59 months with non‐severe pneumonia is the same with standard and double dose oral amoxicillin. Non‐severe pneumonia can be treated effectively and safely with a 3 day course of a standard dose.The WHO acute respiratory infection (ARI) standard case management guidelines recommend oral cotrimoxazole or oral amoxicillin for the treatment of non‐severe pneumonia¹ and have effectively reduced deaths from pneumonia.² Several clinical efficacy studies have demonstrated an increase in treatment failure rates with oral amoxicillin from 12% in 1991–92 to 19% in 2000–01 in Pakistan.^3,4,5 Similar trends have been reported from India,⁶ Bangladesh and Indonesia.⁷ The reasons for this increase in failure rate are not entirely clear, but antimicrobial resistance could be one possibility. In vitro resistance of Streptococcus pneumoniae and Haemophilus influenzae, the commonest bacteria causing childhood pneumonia, has been reported from Pakistan^8,9,10,11,12; however, for pneumonia the direct relationship of laboratory resistance to clinical failure is debatable.^3,13,14,15Increasing the amoxicillin dose to achieve higher minimum inhibitory concentrations can result in a more complete eradication of bacteria.^16,17 A high‐dose 3 day amoxicillin course was reportedly as effective as a 5 day standard dose course for the treatment of otitis media.¹⁸ The American Academy of Pediatrics believes that by recommending empiric initial treatment of acute otitis media with high‐dose oral amoxicillin (80–90 mg/kg/day), antimicrobial resistance to pneumococci can be overcome.¹⁹To our knowledge, no clinical trial has studied this issue as regards the clinical outcome in childhood pneumonia. Thus, in a multi‐centre, double blind, randomised controlled trial we compared a standard dose (45 mg/kg/day) course of oral amoxicillin with a double dose (80–90 mg/kg/day) course for the treatment of non‐severe pneumonia in children less than 5 years of age.     

Sudden infant death syndrome in infants born to HIV-infected and opiate-using mothers

Objective

This study was undertaken to determine the role of opiate use during pregnancy as a predisposing factor for sudden infant death syndrome (SIDS) in infants born to HIV‐infected mothers.

Methods

In order to identify all infant deaths and their cause and association with maternal opiate use, the data of a nationwide prospective cohort study of HIV‐infected mothers and their children were extracted and analysed for a 13‐year period.

Results

24 (5.1%) infant deaths were observed out of 466 infants followed up until death or at least 12 months of life. 3 (0.6%) of them were due to non‐accidental trauma and were not associated with maternal opiate use. 7 (1.5%) died due to SIDS, which was confirmed by autopsy. All SIDS cases occurred in infants born to mothers reporting use of opiates during pregnancy (n = 124). The relative risk of SIDS compared to the general population was 18 (95% CI 9 to 38) for all infants of HIV‐infected mothers, and 69 (95% CI 33 to 141) for those with intrauterine opiate exposure (p<0.001).

Conclusions

Compared to the Swiss general population, the risk for SIDS in this cohort of infants born to HIV‐infected mothers was greatly increased, but only for mothers reporting opiate use during pregnancy. This effect appeared not to be mediated by prematurity, low birth weight, perinatal HIV infection or antiretroviral drug exposure.The evidence for a link between opiate use and sudden infant death syndrome (SIDS) in the general infant population is inconsistent.^1,2,3,4 In infants of HIV‐infected mothers, an increased rate of verified SIDS possibly related to maternal opiate use was noted in several cohorts, namely 5/1000 live births in the European Collaborative Study,⁵ 6/1000 in France⁶ and 14/1000 in Switzerland.⁷ Thus, a detailed analysis of this link in the Swiss cohort was thought to be worthwhile.This study was undertaken to determine the frequency and causes of non‐HIV‐related infant deaths in the Swiss Mother & Child HIV Cohort (MoCHiV), with special attention given to SIDS and the role of maternal heroin and/or methadone consumption during pregnancy. In addition, the role of non‐accidental trauma and of potential risk factors such as prematurity, low birth weight, maternal HIV infection and antiretroviral medication, were explored.     

Decline in pneumococcal meningitis after the introduction of the heptavalent-pneumococcal conjugate vaccine in northern France

Background

The impact of the heptavalent‐pneumococcal conjugate vaccine on the incidence of pneumococcal meningitis in Europe has not yet been assessed.

Objective

To determine whether heptavalent‐pneumococcal conjugate vaccine implementation in northern France has resulted in a decrease in the incidence of pneumococcal meningitis in children.

Design

Multicentre retrospective cohort study from 2000 through 2005.

Settings

All paediatric departments of the 18 hospitals in northern France.

Patients

Patients <18 years of age, admitted for laboratory‐confirmed pneumococcal meningitis during the study period, were included.

Interventions

Data were collected from medical files and the microbiological laboratories of each hospital and compared with the regional hospital discharge codes, using a capture–recapture method.

Main outcome measures

The study assessed and compared global and age‐related incidence rates of pneumococcal meningitis in 2001 (pre‐vaccine era) and 2005.

Results

77 cases were found through the capture–recapture method. The incidence rate of pneumococcal meningitis varied from 1.65/100 000 children <18 years in 2001 to 0.80/100 000 children in 2005 (53% reduction, 95% CI 31 to 74; p = 0.08). This has so far been significant only for children <2 years of age (8.9/100 000 in 2001 to 1.8/100 000 in 2005; 82% reduction, 95% CI 52 to 95; p = 0.03).

Conclusion

A decline in pneumococcal meningitis has been observed in infants since heptavalent‐pneumococcal conjugate vaccination began in our area.In the United States, Streptococcus pneumoniae has been considered to be the principal pathogen for bacterial meningitis (47%) since Haemophilus influenzae type b vaccination became widespread during the 1990s and before the implementation of vaccination with the heptavalent‐pneumococcal conjugate vaccine (PCV7, Prevenar).¹ In Western Europe, the mean incidence rate of pneumococcal meningitis has averaged 8.7 cases/100 000 in children <2 years old with incidence rates varying from 3.8 to 14.6/100 000 between countries.² Between 2001 and 2004, the French Bacterial Meningitis Surveillance Network reported that S pneumoniae caused 42% of all cases of bacterial meningitis in children, 70% of these occurring in children <2 years old.³ The case‐fatality rate for this disease is estimated at 8–12% in children and has not dramatically changed for 20 years despite progress in diagnosis and treatment.^1,4 Sequelae occur in 20–35% of cases and include deafness, motor deficits, learning disorders linked with concentration disorders, and memory problems.^5,6PCV7, first approved in the US in 1999, targets the seven serotypes involved most frequently in the invasive pneumococcal diseases of young children.^7,8 Serotypes 6B, 9V, 14, 18C and 23F, all present in this vaccine, account for most cases of pneumococcal meningitis today.⁹ PCV7 received marketing authorisation in Europe in February 2001, was available in France in April 2001 and was recommended in March 2002 for children with a disease at high risk of invasive pneumococcal infections (immunosuppression, sickle cell disease, etc),¹⁰ and children aged 2–24 months with risk factors for pneumococcal infection (ie, children cared for more than 4 h/week with more than two other children, children with breast‐feeding duration <2 months, children with at least two siblings), criteria which covered between 79 and 89% of children <2 years of age.¹¹ The vaccination schedule uses a four‐dose regimen, at 2, 3 and 4 months of age and a booster dose during the second year of life. The impact of the PCV7 on the incidence of meningitis and other invasive pneumococcal diseases has been clearly demonstrated in North America and Australia,^{12,13,14,15,16} whose vaccination schedules are different from those in France.The aim of this study was to determine whether PCV7 implementation in a large area of northern France affected the incidence of pneumococcal meningitis in children.     

Prevalence of nasopharyngeal carriage of pneumococcus in preschool children attending day care in London

Objective

To estimate the prevalence of nasopharyngeal (NP) carriage of pneumococcus (Streptococcus pneumoniae) and describe the antibiotic resistance patterns and serotypes in young children attending group day care in London.

Design and subjects

Cross‐sectional survey of attendees at a sample of registered child day care centres (CDCCs) in a London borough.

Setting

Urban setting with a socially and culturally diverse population.

Methods and outcomes

19 CDCCs (13% of total) participated between March and November 2003. A single NP swab was required from each child, and parents completed a questionnaire about their child''s health and attendance at day care. WHO methodology for pneumococcal carriage studies was followed.

Results

30% of parents consented. 234 swabs were collected from children aged 6 months to 5 years. 53% were boys and 81% were white. 120 children (51%, 95% CI 45% to 58%) carried pneumococci in their nasopharynx. None of the isolates were resistant to penicillin (upper CL 3%). 21 isolates were resistant to erythromycin (17.5%, 95% CI 11% to 25.5%). 68 isolates (57%) were serotypes included in the 7‐valent conjugate vaccine. Non‐white children had a lower prevalence of carriage (27% vs 58%).Conclusion: The prevalence of pneumococcal NP carriage was high. The penicillin resistance rate is lower than in many other countries and may reflect a decrease in community antibiotic prescribing in the UK. Monitoring circulating serotypes is important in the context of recent changes to the vaccination policy. Further study is required to explore the association with ethnicity and risk factors for antibiotic resistance.Out‐of‐home group childcare is associated with an increased risk of infectious illnesses^1,2,3 including invasive pneumococcal disease (IPD).⁴ Carriage studies in child day care centres (CDCCs) have shown increased risk of pneumococcal nasopharyngeal (NP) colonisation⁵ leading to concerns that CDCCs may act as foci for the emergence and transmission of antibiotic resistant organisms.^6,7Universal childhood vaccination against pneumococcal infection has been adopted in the US, and some European countries include attendance at day care as one of the risk factors for pneumococcal disease in their targeted vaccination strategies. The UK vaccination policy has recently changed to include universal vaccination.⁸ Previously only children who fell into certain clinical risk groups were recommended to be vaccinated either with the 7‐valent conjugate pneumococcal vaccine (under 5 years of age) or the 23‐valent polysaccharide vaccine and attendance at group day care was not regarded as a risk factor.Social changes in recent years have already led to many more children under the age of 5 attending group day care⁹ and a huge expansion of pre‐school day care provision is underway in England.¹⁰There are few UK data on pneumococcal carriage in the day care setting and this study was set up to address this gap. The aim was to determine the prevalence of pneumococcal carriage and resistance, and to describe the prevalent serotypes.     

High prevalence of asymptomatic vitamin D and iron deficiency in East African immigrant children and adolescents living in a temperate climate

Objectives

Vitamin D deficiency (VDD) is common in immigrant children with increased skin pigmentation living in higher latitudes. We assessed the pattern of and risk factors for VDD in immigrant East African children living in Melbourne (latitude 37°49′ South).

Study design

A prospective survey of 232 East African children attending a clinic in Melbourne. Data were collected by questionnaire, medical assessment and laboratory tests.

Results

Low 25‐hydroxyvitamin D (25‐OHD) levels (<50 nmol/l) occurred in 87% of children, and VDD (25‐OHD <25 nmol/l) in 44%. Risk factors included age <5 years, female gender, increased time in Australia, decreased daylight exposure and winter/spring season. Anaemia (20%), vitamin A deficiency (20%) and iron deficiency (19%) were also identified.

Conclusions

Asymptomatic VDD is common in East African immigrant children residing at a temperate latitude. Risk factors for VDD limit endogenous vitamin D production. Screening of immigrant children with increased skin pigmentation for VDD, anaemia, iron and vitamin A deficiency is appropriate. VDD in adolescent females identifies an increased risk of future infants with VDD.Severe vitamin D deficiency (VDD) causes rickets in infants and children, and osteomalacia in adolescents and adults due to decreased bone mineralisation.¹ VDD in pregnancy is associated with restricted fetal and infant growth,^2,3 and predisposes to neonatal VDD and hypocalcaemia.⁴ Vitamin D status in childhood and adolescence may play a role in the prevention of osteoporosis.⁵ Adequate status may reduce the adult risk of diabetes, ischaemic heart disease, hypertension and tuberculosis.⁶In Melbourne, nutritional rickets was documented during the 1960s; 70% of the affected children were migrants of Mediterranean origin.⁷ More recently, VDD has been documented in veiled or dark skinned pregnant women,⁸ and in immigrant infants from different backgrounds presenting with rickets.⁹In the absence of supplementation, skin pigmentation and exposure to solar ultraviolet B (UVB) irradiation determine serum levels of 25‐hydroxyvitamin D (25‐OHD) through endogenous production.¹ Adults and adolescents living in climates with reduced UVB exposure are at increased risk of VDD,^10,11 particularly those individuals with dark skin,¹² with reduced sun exposure¹³ or wearing covering clothing for socio‐cultural reasons.¹⁴ Knowledge of the risk factors in specific populations is important in preventing VDD in pregnant women and infants,⁸ and may also contribute to the prevention of osteoporosis.¹⁵The increased rates of VDD in adult East African immigrants living in Melbourne, Australia¹⁶ suggested that their immigrant offspring are also at risk of VDD. We aimed to prospectively assess the prevalence, severity, pattern of and risk factors for VDD in these children. Malnutrition, iron and vitamin A deficiency are prevalent in African children,¹⁷ and VDD is associated with underweight¹⁸ and with iron deficiency anaemia.¹⁹ We aimed to determine if VDD was part of a broader nutritional problem in these children.     

The significance of isolated elevation of serum aminotransferases in infants and young children

Introduction

The aim of this study was to assess the clinical significance and prognosis of a prolonged isolated elevation of serum aminotransferases without cholestasis (>3 months) in infants and young children, investigated for a variety of conditions, and to determine a protocol for their follow‐up and investigation.

Methods

A combined prospective‐retrospective analysis of apparently healthy babies and young children with isolated elevation of serum aminotransferases of at least 1.5 times above the norm for age which persisted for at least 3 months and whose creatine phosphokinase (CK), gamma glutamyltransferase (GGT), alkaline phosphatase and bilirubin levels remained normal throughout the study duration. The children underwent the following investigations: abdominal ultrasound and infectious, metabolic and/or immunological investigation depending on the duration of the abnormality.

Results

Six children were eliminated following the finding of positive cytomegalovirus (CMV) antigen in the urine. 72 children were investigated (47 males and 25 females). The duration of serum aminotransferases elevation was 3–36 months (average 12.4, median 11.5 months). The initial, maximal and final alanine aminotransferase (ALT) values were 85.5, 140.5 and 39.8 IU/l, respectively. Of seven children who had liver biopsies performed, three (42.8%) were suspected of having a glycogen storage disease which was not confirmed enzymatically. Four biopsies revealed non‐specific histological changes.

Conclusions

Isolated elevation of serum aminotransferases in healthy looking young children is mostly a benign condition that usually resolves within a year. If no pathology is found during routine investigation, these children can be followed conservatively. Liver biopsy does not contribute much to the diagnosis and is probably unnecessary.There is a plethora of literature on the investigation of the infant or child with cholestasis.^1,2,3,4 In the adult literature much attention is devoted to evaluation of the asymptomatic patient with abnormal liver enzymes.^{5,6,7,8,9,10,11,12,13,14} On the other hand, there are few if any studies on the investigation and prognosis of the asymptomatic infant or child with isolated elevation of serum aminotransferases. In most cases increased enzyme levels resolve within a few weeks and need no further evaluation. However, some of these apparently healthy subjects continue to exhibit high enzyme levels for several months.Therefore, the aim of the present study was to assess the clinical significance and prognosis of isolated elevation of serum aminotransferases without cholestasis (>3 months) in infants and young children, and to establish a protocol for their investigation and follow‐up.     

Sleep-disordered breathing in overweight and obese children and adolescents: prevalence, characteristics and the role of fat distribution

Aims

To determine the prevalence of sleep‐disordered breathing (SDB) in a clinical sample of overweight and obese children and adolescents, and to examine the contribution of fat distribution.

Methods

Consecutive subjects without chronic lung disease, neuromuscular disease, laryngomalacia, or any genetic or craniofacial syndrome were recruited. All underwent measurements of neck and waist circumference, waist‐to‐hip ratio, % fat mass and polysomnography. Obstructive apnoea index ⩾1 or obstructive apnoea–hypopnoea index (OAHI) ⩾2, further classified as mild (2⩽OAHI<5) or moderate‐to‐severe (OAHI⩾5), were used as diagnostic criteria for obstructive sleep apnoea (OSA). Central sleep apnoea was diagnosed when central apnoeas/hypopnoeas ⩾10 s were present accompanied by >1 age‐specific bradytachycardia and/or >1 desaturation <89%. Subjects with desaturation ⩽85% after central events of any duration were also diagnosed with central sleep apnoea. Primary snoring was diagnosed when: snoring was detected by microphone and normal obstructive indices and saturation.

Results

27 overweight and 64 obese subjects were included (40 boys; mean (standard deviation (SD)) age 11.2 (2.6) years). Among the obese children, 53% were normal, 11% had primary snoring, 11% had mild OSA, 8% had moderate‐to‐severe OSA and 17% had central sleep apnoea. Half of the patients with central sleep apnoea had desaturation <85%. Only enlarged tonsils were predictive of moderate‐to‐severe OSA. On the other hand, higher levels of abdominal obesity and fat mass were associated with central sleep apnoea.

Conclusion

SDB is very common in this clinical sample of overweight children. OSA is not associated with abdominal obesity. On the contrary, higher levels of abdominal obesity and fat mass are associated with central sleep apnoea.Obese children and adolescents are at risk of sleep‐disordered breathing (SDB). Several studies, using polysomnography, have documented the prevalence of obstructive sleep apnoea (OSA) in this group, ranging from 13% to 66%.^1,2,3,4,5 This wide range is probably due to factors such as ethnic predisposition, different inclusion criteria and diagnostic criteria for both obesity and OSA. Marcus et al⁴ also reported on the occurrence of central apnoeas of abnormal duration or followed by desaturation in 4 of 22 children studied. More objective data on the prevalence of these pathological central apnoeas are still lacking.In adults, studies have shown a strong correlation between central adiposity and OSA.^6,7,8,9,10 This association has not yet been studied in childhood obesity. We therefore determined the prevalence and characteristics of OSA and central sleep apnoea in a clinical sample of overweight and obese children and adolescents, and examined the association with fat distribution.     

Prevalence of asthma among schoolchildren in Patras, Greece: four questionnaire surveys during 1978-2003

Background

The prevalence of asthma and wheezing has risen during the past four decades. Recent reports suggest that the “asthma epidemic” has reached a plateau.

Objective

To examine further trends in the prevalence of childhood diagnosed asthma and wheezing in an urban environment in Greece.

Methods

A population‐based cross‐sectional parental questionnaire survey was repeated among third‐grade and fourth‐grade school children (8–10 years) of public primary schools in 2003 in the city of Patras, Greece, by using methods identical to that of surveys conducted in 1978 (completed questionnaires, n = 3003), 1991 (n = 2417) and 1998 (n = 3076).

Results

2725 questionnaires were completed in the 2003 survey. The prevalence rates of current asthma and/or wheezing in 1978, 1991, 1998 and 2003 were 1.5%, 4.6%, 6% and 6.9%, respectively (p for trend <0.001). The lifetime prevalence of asthma and/or wheezing in the three more recent surveys was 8%, 9.6% and 12.4%, respectively (p for trend <0.001). The male:female ratios of current asthma and/or wheezing in the four surveys were 1.14:1, 1.15:1, 1.16:1 and 1.22:1, respectively. The proportion of those with wheezing diagnosed with asthma has increased during the study period, more so among non‐current children with asthma.

Conclusions

Our findings show a continuous increase in the prevalence of asthma and wheezing among preadolescent children in Patras, Greece, over 25 years, albeit at a decelerating rate. There seems to be a true increase in wheezing, despite some diagnostic transfer, particularly among younger children. The male predominance of the disease has persisted in the population of this study.Several studies have reported a rise in the prevalence of childhood asthma in Western countries over the past 3–4 decades. This increase can be, at least partially, explained by changes in diagnostic criteria and increased public awareness of the disease.¹ Those few serial studies that have used identical methods support the impression of a true increase in the prevalence of childhood asthma.^2,3,4,5,6,7 However, recently reported trends show no further increase in the prevalence of asthma, suggesting that the asthma epidemic may have reached a plateau.^8,9,10,11Using a standard parental questionnaire, the increasing prevalence of asthma was shown among 8–10‐year‐old school children in Patras, Greece, in 1978, 1991 and 1998.⁶ In this study, we hypothesised that a plateau in the prevalence of asthma has been reached in the city of Patras as well. To test this hypothesis, we performed another survey in 2003 using the same method as in the previous years and reanalysed the data, including sex analysis of the prevalence of asthma over the whole 25‐year surveillance period.     

Derivation of the children's head injury algorithm for the prediction of important clinical events decision rule for head injury in children

Background

A quarter of all patients presenting to emergency departments are children. Although there are several large, well‐conducted studies on adults enabling accurate selection of patients with head injury at high risk for computed tomography scanning, no such study has derived a rule for children.

Aim

To conduct a prospective multicentre diagnostic cohort study to provide a rule for selection of high‐risk children with head injury for computed tomography scanning.

Design

All children presenting to the emergency departments of 10 hospitals in the northwest of England with any severity of head injury were recruited. A tailor‐made proforma was used to collect data on around 40 clinical variables for each child. These variables were defined from a literature review, and a pilot study was conducted before the children''s head injury algorithm for the prediction of important clinical events (CHALICE) study. All children who had a clinically significant head injury (death, need for neurosurgical intervention or abnormality on a computed tomography scan) were identified. Recursive partitioning was used to create a highly sensitive rule for the prediction of significant intracranial pathology.

Results

22 772 children were recruited over 2½ years. 65% of these were boys and 56% were <5 years old. 281 children showed an abnormality on the computed tomography scan, 137 had a neurosurgical operation and 15 died. The CHALICE rule was derived with a sensitivity of 98% (95% confidence interval (CI) 96% to 100%) and a specificity of 87% (95% CI 86% to 87%) for the prediction of clinically significant head injury, and requires a computed tomography scan rate of 14%.

Conclusion

A highly sensitive clinical decision rule is derived for the identification of children who should undergo computed tomography scanning after head injury. This rule has the potential to improve and standardise the care of children presenting with head injuries. Validation of this rule in new cohorts of patients should now be undertaken.One million patients with head injuries attend emergency departments each year in the UK, of whom as many as 50% are children^1,2,3; this proportion is similar in the US, where there are 95 000 hospital admissions from childhood head injuries, at a cost of over US$ 1 billion per year.^4,5,6 In contrast with the high incidence of head injury, mortality is comparatively low (6–10 per 100 000), and as few as 1 in 500 of all people attending the emergency department have a fatal outcome.^7,8 Thus, although emergency physicians see a large number of patients with head injury, they rarely see patients who have life‐threatening intracranial complications after the injury.Over the past decade, several decision rules have been derived and validated using high‐quality methods to identify adults with a head injury who require computed tomography scanning.^{9,10,11,12,13,14} Although children account for as many as half of all head injuries, no such well‐derived multicentre clinical decision rules exist for children. The American Academy of Pediatrics in 1999^14a concluded that they could not advocate an evidence‐based computed tomography scanning strategy because of the poor quality of studies on children.¹⁵ In 2003, The National Institute of Clinical Excellence in the UK found that the quality of studies on childhood head injuries was so poor that they issued a clinical decision rule for children that was derived and validated only in adults.¹⁶Our aim was to derive a sensitive clinical decision rule for the management of children presenting with an acute head injury, which would identify children at high risk so as to undergo computed tomography scanning and allow the remaining patients to be discharged with no investigation.     

Severe complications of chickenpox in hospitalised children in the UK and Ireland

Aims

To estimate the annual incidence of hospitalisations due to severe complications of varicella, describe the complications and estimate annual mortality.

Methods

Active surveillance throughout the UK and Ireland for 13 months by paediatricians notifying cases to the British Paediatric Surveillance Unit and completing a questionnaire. The case definition was any child aged <16 years hospitalised with complicated varicella, as defined by a list of conditions, or admitted to ICU/HDU with varicella.

Results

188 cases were notified for the surveillance period, of which 112 (0.82/100 000 children/year) met the case definition and were not duplicates. Confirmed cases had a median age of 3 years (range 0–14). The complications were: bacteraemia/septic shock (n = 30), pneumonia (n = 30), encephalitis (n = 26), ataxia (n = 25), toxic shock syndrome/toxin‐mediated disease (n = 14), necrotising fasciitis (n = 7), purpura fulminans/disseminated coagulopathy (n = 5), fulminant varicella (n = 5) and neonatal varicella (n = 3). 52 children (46%) had additional bacterial infections. Six deaths were due, or possibly due, to varicella, including one intrauterine death. Four of the other five children who died (ages 2–14 years) had a pre‐existing medical condition. Sequelae on discharge were reported for 41 cases (40%), most frequently ataxia or skin scarring. The median length of hospital stay was 7 days (range 1–68).

Conclusions

This study provides a minimum estimate of severe complications and death resulting from varicella in children in the UK and Ireland. Most complications, excluding deaths, occur in otherwise healthy children and thus would be preventable only through a universal childhood immunisation programme.Varicella‐zoster virus causes varicella (chickenpox) on primary infection and herpes zoster upon reactivation. Varicella is generally mild, but there is an increased risk of complications in immunocompromised individuals and neonates if maternal varicella is temporally close to birth. Nevertheless, severe complications can occur even in previously healthy children, including secondary bacterial infections, central nervous system manifestations and death.¹ Approximately 90% of UK varicella cases occur in children less than 15 years of age, with the highest incidence in the 1–4‐year‐old age group.^2,3,4A safe and effective live‐attenuated vaccine against varicella was developed in the 1970s.¹ It is universally recommended in several countries, including the United States, Canada, Australia and Finland. The vaccine prevents varicella in 85% of immunised children, with 97% protection against severe disease.¹ However, childhood varicella immunisation is not carried out routinely in the UK or Ireland, although two vaccines are licensed and recommended for seronegative healthcare workers, and certain high risk individuals and their seronegative contacts.⁵ There are few data on complicated varicella in either country and routine hospitalisation records cannot provide sufficiently detailed or accurate information.^2,3,6 Therefore, the publication of data on severe complications of varicella will make a valuable contribution to the epidemiological and economic data available and help determine the advisability of current selective, or future universal, immunisation policies. The data also provide a baseline against which any policy change may be evaluated.     

Tacrolimus ointment does not affect the immediate response to vaccination, the generation of immune memory, or humoral and cell-mediated immunity in children

Background

Concern exists that the prolonged application of immunomodulators to treat atopic dermatitis may cause systemic immunosuppression.

Aims

In a 7‐month, multicentre, randomised, controlled trial, we investigated the equivalence of response to vaccination against meningococcal serogroup C disease with a protein‐conjugate vaccine in children (2–11 years) with moderate to severe atopic dermatitis, by applying either 0.03% tacrolimus ointment (TAC‐O; n = 21) or a hydrocortisone ointment regimen (HC‐O; n = 111).

Methods

TAC‐O was applied twice daily (bid) for 3 weeks, and thereafter daily until clearance. 1% hydrocortisone acetate (HA) for head/neck and 0.1% hydrocortisone butyrate ointment for trunk/limbs was applied bid for 2 weeks; thereafter HA was applied bid to all affected areas. At week 1, patients were vaccinated with protein‐conjugate vaccine against meningococcal serogroup C, and challenged at month 6 with low dose meningococcal polysaccharide vaccine. The control group (44 non‐atopic dermatatits children) received the primary vaccination and challenge dose. Assessments were made at baseline, weeks 1 and 5, and months 6 and 7. The primary end point was the percentage of patients with a serum bactericidal antibody (SBA) titre ⩾8 at the week 5 visit.

Results

The response rate (patients with SBA titre ⩾8) was 97.5% (confidence interval (CI) approximately 97.3 to 100), 99.1% (94.8 to 100) and 97.7% (93.3 to 100) in the TAC‐O, HC‐O and control groups, respectively.

Conclusions

The immune response to vaccination against meningococcal serogroup C in children with atopic dermatitis applying either 0.03% TAC‐O or HC is equivalent. Ointment application does not affect the immediate response to vaccination, generation of immune memory or humoral and cell‐mediated immunity.Atopic dermatitis is a chronic, pruritic, inflammatory skin disease that can seriously affect the health and quality of life of the patient. Intense itching is the predominant symptom and excessive scratching can cause damaging excoriations, erosions and lichenification of the skin.¹ The disease is most common during childhood, with 80–90% of children having onset before 5 years of age,² and is likely to persist into adulthood in those who are severely affected.³ The exact pathogenesis of atopic dermatitis is unknown, but it is recognised that T cell‐mediated reactions⁴ and increased eosinophil levels⁵ are involved in the inflammatory response.Atopic dermatitis usually has a relapsing course, and requires long‐term continuous or intermittent treatment. Emollients provide symptomatic relief by reducing the intense itching and inflammation. However, for the treatment of acute exacerbations, most patients require topical treatment with either corticosteroids or calcineurin inhibitors such as tacrolimus or pimecrolimus. Children with moderate to severe atopic dermatitis have large affected body surface areas, often with open and weeping lesions, and this raises concerns that the prolonged application of topical immunomodulators may cause systemic immunosuppression. Current evidence is that the percutaneous absorption of tacrolimus and pimecrolimus is minimal.^6,7,8,9 Nonetheless, as atopic dermatitis often occurs in young children who are undergoing childhood immunisation programmes, it is important to determine whether topical immunomodulators have an effect on the humoral and cell‐mediated immune response to vaccination.Information about the immune response to vaccination of patients with atopic dermatitis treated with topical immunomodulators is scarce. Several studies, however, have investigated the immune response to vaccination of children with corticosteroid‐dependent asthma. It seems that children receiving short‐term low to moderate daily maintenance doses of systemic corticosteroids can receive live virus vaccines without marked suppression of the antibody response.¹⁰ Hanania et al¹¹ found that children with asthma receiving high‐dose inhaled corticosteroids had a normal response to A antigens of the inactivated influenza vaccine. Other studies on children with asthma found no association between inhaled corticosteroid use and varicella vaccine failure,¹² or an impaired immune response to pneumococcal vaccines.¹³ With regard to children with atopic dermatitis applying topical immunomodulators, Papp et al¹⁴ reported that treating children with 1% pimecrolimus cream for up to 2 years did not affect the seropositivity rates for tetanus, diphtheria, measles or rubella after vaccination. In a small US study of 23 children with atopic dermatitis, the application of 0.03% tacrolimus ointment (TAC‐O) for 7 weeks had no effect on the serological response to pneumococcal polysaccharide vaccine.¹⁵To increase our knowledge of the immune response to vaccination of children with atopic dermatitis treated with topical immunomodulators, we investigated whether the application of a hydrocortisone regimen or 0.03% TAC‐O had any effect on the immune response after vaccination against meningococcal serogroup C disease.     

The natural history of Noonan syndrome: a long-term follow-up study

Objective

To define better the adult phenotype and natural history of Noonan syndrome.

Design

A prospective observational study of a large cohort.

Results

Data are presented for 112 individuals with Noonan syndrome (mean age 25.3 (range 12–71) years), who were followed up for a mean of 12.02 years. Mutations in PTPN11 were identified in 35% of probands. Ten subjects died during the study interval; three of these deaths were secondary to heart failure associated with hypertrophic cardiomyopathy. Pulmonary stenosis affected 73 (65%) subjects; 42 (58%) required no intervention, nine underwent balloon pulmonary valvuloplasty (three requiring further intervention) and 22 surgical valvuloplasty (three requiring further intervention). Hypertrophic cardiomyopathy affected 21 (19%) patients, which had remitted in two cases, but one subject required cardiac transplant. No subjects died suddenly or had symptoms suggestive of arrhythmia. The mean final adult height was 167.4 cm in males and 152.7 cm in females. Feeding problems in infancy were identified as a predictor of future outcome. The mean age of speaking in two‐word phrases was 26 months for those with no feeding difficulties, compared with 39 months for those with severe problems requiring nasogastric feeding. Attendance at a school for children with special needs for the same groups was 12.5% and 58%, respectively. A statement of special educational need had been issued in 44% overall; however, academic achievement was broadly similar to that of the general population.

Implications

Although the morbidity for some patients with Noonan syndrome is low, early predictors of poorer outcome have been identified, which will help ascertain those most in need of intervention.Noonan syndrome (MIM 163950) is a relatively common multiple congenital abnormality syndrome characterised by a typical facial appearance, short stature (50–60%) and heart defects, most commonly pulmonary stenosis (50–62%) and hypertrophic cardiomyopathy (HCM, 10–20%). Expression is variable and other recognised aspects of the phenotype include cryptorchidism in males (60–77%), pectus deformities (70–95%) and bleeding diatheses (20%).^1,2 Incidence is estimated to be between 1 in 1000 and 1 in 4000, and Noonan syndrome may be inherited in an autosomal dominant manner, although 60% of cases are sporadic. Linkage was established to a 5‐cM region on 12q24 in 1994 and heterogeneity was shown, as not all the families studied linked to this locus.³ In 2001, mutations were found in PTPN11 in 6 of the 12 patients studied.⁴ This gene encodes the intracellular messenger SHP‐2, which is a ubiquitously expressed protein tyrosine phosphatase that is implicated in many developmental pathways.⁵ Studies of larger cohorts have found a mutation prevalence of 29–60% and have disclosed a genotype–phenotype correlation, with those carrying mutations in PTPN11 exhibiting a higher incidence of pulmonary stenosis and a lower incidence of HCM than patients with Noonan syndrome but no mutation.^6,7,8,9Although the clinical spectrum seen in children with the condition is well recognised,^1,2,10 studies of the adult phenotype have been limited to specific aspects of the condition such as facial features¹¹ or final height,¹² and have been mostly cross‐sectional in nature. There have been no studies to date looking prospectively at long‐term outcome in Noonan syndrome to establish the natural history of the overall phenotype.     

Objective measurement of levels and patterns of physical activity

Objective

To measure the levels and patterns of physical activity, using accelerometers, of 11‐year‐old children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC).

Design

Cross‐sectional analysis.

Setting

ALSPAC is a birth cohort study located in the former county of Avon, in the southwest of England. This study used data collected when the children were 11 years old.

Participants

5595 children (2662 boys, 2933 girls). The children are the offspring of women recruited to a birth cohort study during 1991–2. The median age (95% CI) of the children is now 11.8 (11.6 to 11.9) years.

Methods

Physical activity was measured over a maximum of 7 consecutive days using the MTI Actigraph accelerometer.

Main outcome measures

Level and pattern of physical activity.

Results

The median physical activity level was 580 counts/min. Boys were more active than girls (median (IQR) 644 (528–772) counts/min vs 529 (444–638) counts/min, respectively). Only 2.5% (95% CI 2.1% to 2.9%) of children (boys 5.1% (95% CI 4.3% to 6.0%), girls 0.4% (95% CI 0.2% to 0.7%) met current internationally recognised recommendations for physical activity. Children were most active in summer and least active in winter (difference = 108 counts/min). Both the mother and partner''s education level were inversely associated with activity level (p for trend <0.001 (both mother and partner)). The association was lost for mother''s education (p for trend = 0.07) and attenuated for partner''s education (p for trend = 0.02), after adjustment for age, sex, season, maternal age and social class.

Conclusions

A large majority of children are insufficiently active, according to current recommended levels for health.Regular physical activity in children is associated with improved health.^1,2,3 A recent systematic review of the evidence relating physical activity to health concluded that children should spend at least 60 min in moderate to vigorous physical activity (MVPA) each day, in order to promote a broad range of health improvements.³ Few studies^4,5,6 worldwide have collected objective physical activity data in large samples of children and we lack population‐based objective data describing levels and patterns of children''s activity. Nevertheless, physical activity is frequently implicated in the escalating levels of type 2 diabetes⁷ and obesity^8,9,10,11,12 in children. We report here on objectively measured physical activity levels and patterns in a large contemporary cohort of 11‐year‐old children—the Avon Longitudinal Study of Parents and Children (ALSPAC).     

Recent trends in visual impairment and blindness in the UK

Objective

To study recent trends in the cumulative incidence of visual impairment in childhood over a 15‐year period and to assess progress against WHO goals for prevention.

Design, setting and participants

Data from a population‐based register of visual impairment in southern England were used to estimate cumulative incidence and trends in visual impairment (VI) and severe visual impairment/blindness (SVI/BL) for children born in 1984–1998. Causes were classified by anatomical site(s), timing of insult(s) and whether the visual impairment was potentially preventable or treatable.

Results

Of 691 eligible children, 358 (53%) had VI and 323 (47%) SVI/BL. The cumulative incidence of VI to age 12 years was 7.1 (95% CI 6.4 to 7.8) per 10 000 live births and for SVI/BL was 6.2 (95% CI 5.6 to 6.9); the incidence of both decreased significantly over time. There was an inverse relationship with gestational age and birth weight, although the risk of visual impairment associated with prematurity and low birth weight decreased substantially over time. 55% of children with VI and 77% with SVI/BL had other impairments; the proportion of associated impairments among children with VI decreased over time. 130 (19%) of the children have died, with over half dying before the age of 5.

Conclusions

There is evidence of a temporal decline in the incidence of VI and SVI/BL in births from 1984 to 1998 especially in very preterm and low birthweight infants. Early childhood mortality was high. The causes of visual impairment in UK children are numerous, complex and often part of a wider picture of childhood disability.Visual impairment in childhood has important effects on development and can have serious economic implications for both the family and society.¹ In the long term it affects employment and many other opportunities in life. In developed countries most visual impairments in children are present from birth or early childhood and a substantial proportion of these children have other impairments and disabilities as well.^2,3The prevention of avoidable visual impairment in children is one of the goals of the World Health Organization''s (WHO) Global initiative for the elimination of avoidable blindness by 2020, known as VISION 2020.⁴ Comparative data are needed to assess progress towards this goal,⁵ but with a few exceptions such information is scarce worldwide.^3,6,7,8 In the UK the most recent data come from the study of severe visual impairment and blindness newly diagnosed in 2000, conducted through the British Ophthalmological and British Paediatric Surveillance Units.³ The latter found a higher incidence of severe visual impairment/blindness than expected based on rates from blindness registers.^3,6We report trends in the incidence of visual impairment in children born over a 15‐year period from 1984, the relationship with birth weight and gestational age, the distribution of specific and potentially preventable or treatable visual impairment, and the risk of death.     

Improving infant sleep and maternal mental health: a cluster randomised trial

Objectives

To determine whether a community‐delivered intervention targeting infant sleep problems improves infant sleep and maternal well‐being and to report the costs of this approach to the healthcare system.

Design

Cluster randomised trial.

Setting

49 Maternal and Child Health (MCH) centres (clusters) in Melbourne, Australia.

Participants

328 mothers reporting an infant sleep problem at 7 months recruited during October–November 2003.

Intervention

Behavioural strategies delivered over individual structured MCH consultations versus usual care.

Main outcome measures

Maternal report of infant sleep problem, depression symptoms (Edinburgh Postnatal Depression Scale (EPDS)), and SF‐12 mental and physical health scores when infants were 10 and 12 months old. Costs included MCH sleep consultations, other healthcare services and intervention costs.

Results

Prevalence of infant sleep problems was lower in the intervention than control group at 10 months (56% vs 68%; adjusted OR 0.58 (95% CI: 0.36 to 0.94)) and 12 months (39% vs 55%; adjusted OR 0.50 (0.31 to 0.80)). EPDS scores indicated less depression at 10 months (adjusted mean difference −1.4 (−2.3 to −0.4) and 12 months (−1.7 (−2.6 to −0.7)). SF‐12 mental health scores indicated better health at 10 months (adjusted mean difference 3.7 (1.5 to 5.8)) and 12 months (3.9 (1.8 to 6.1)). Total mean costs including intervention design, delivery and use of non‐MCH nurse services were £96.93 and £116.79 per intervention and control family, respectively.

Conclusions

Implementing this sleep intervention may lead to health gains for infants and mothers and resource savings for the healthcare system.

Trial registration

Current Controlled Trial Registry, number ISRCTN48752250 (registered November 2004).Maternal depression impacts adversely on maternal quality of life, mother–child relationships and child development.^1,2 Despite a prevalence of 15% in the first year postpartum,³ depression often remains undiagnosed and, even if detected, many mothers reject the diagnosis, the treatment or both.⁴Maternal depression is linked to poor infant sleep. Problems with frequent night waking and difficulties settling to sleep are reported by over a third of parents in the second 6 months of life^5,6 and are consistently associated with poor maternal health.^7,8,9In a previous efficacy trial, we demonstrated that treating infant sleep problems (simple behavioural techniques delivered in local well‐child centres over two to three sessions) significantly reduced maternal reports of depression symptoms as well as infant sleep problems.¹⁰ However, efficacy and generalisability may be limited by the predominantly middle‐class status of participating families and the fact that the intervention was delivered by a single paediatrician (HH). In another randomised trial,¹¹ a single, nurse‐led consultation emphasising ways to help very young infants settle to sleep independently resulted in intervention infants sleeping more than controls at age 12 weeks but in no change in maternal depression. All other sleep intervention trials have been limited by selection bias, small sample sizes, short follow‐up and/or lack of randomisation.¹²The trial reported here was conducted within an existing universally available, state‐wide primary health care service, training the well‐child care providers themselves to manage infant sleep problems in families from a broad sociodemographic sample. We hypothesised that a brief behavioural intervention designed to reduce infant sleep problems would result in improved infant sleep and maternal well‐being. We also documented the costs of the intervention and costs to the healthcare system.     

Predictors of abdominal pain in schoolchildren: a 4-year population-based prospective study

Background

Chronic abdominal pain (CAP) is common among schoolchildren, but risk factors for its onset are still largely unknown.

Aims

To determine the frequency of onset of CAP in schoolchildren and investigate risk factors for its development.

Methods

1411 schoolchildren aged 11–14 years were recruited from schools in North West England. Information was collected on recent pain symptoms and potential risk factors for developing CAP. Participants were followed up 1 and 4 years later and new episodes of CAP were identified.

Results

22% reported new‐onset abdominal pain at 1‐year follow‐up which persisted at 4‐year follow‐up (CAP). CAP was almost three times higher in girls than boys (34% vs 13%; χ²: 26.0; p<0.001). In girls, reporting headache at baseline was the only predictive factor for CAP onset: those reporting headaches experienced a doubling in the risk of symptom onset (relative risk: 2.1; 95% confidence interval: 0.95 to 4.7). In contrast, in boys, development of CAP was independently predicted by daytime tiredness (3.0; 1.2 to 7.6), lack of school enjoyment (2.0; 0.95 to 4.2), adverse psychosocial exposures (2.3; 1.2 to 4.5) and taller stature (1.9; 0.8 to 4.5).

Conclusion

Our results suggest that over 20% of adolescent schoolchildren experience new‐onset non‐self‐limiting abdominal pain over a 1‐year period. Future abdominal pain is predicted by previous somatic symptom reporting in girls and both somatic symptom reporting and psychosocial factors in boys. These risk factors indicate a possible mechanism for understanding the development of CAP, and might have important implications for both primary and secondary preventive strategies.Abdominal pain is common in children, with 12‐month prevalence ranging from 20% in population samples¹ to 44% in primary care attendees.² On physical examination, most children display no abnormalities and this has led to the long‐held belief that most abdominal pain is “functional” in origin.³ In the long term, some researchers have demonstrated an increased risk of irritable bowl syndrome among adults with a history of childhood abdominal pain,⁴ while others have not detected such an association but found that persistent abdominal pain in childhood is associated with adult psychiatric disorders.¹ Such findings have raised speculation that childhood abdominal pain might be a precursor of gastrointestinal and/or psychiatric disorders in adults. Thus, studying its determinants is important in understanding the origin of common and disabling adult illnesses.Previous studies have focused on children with “recurrent abdominal pain” defined as at least three bouts of pain over a period of not less than 3 months. This term, first introduced by Apley and Naish in 1958,⁵ has received criticism for being too general and unclear. Recently, the Subcommittee on Chronic Abdominal Pain of the American Academy of Pediatrics recommended that this term should be retired. Instead, they proposed that “chronic abdominal pain” (CAP) should be used to describe long‐lasting intermittent or constant abdominal pain.⁶Abdominal pain in children often coexists with other somatic pain conditions. A recent study demonstrated that one quarter of children reported pain within the previous 3 months in more than one site, the most common combination being headache and abdominal pain.⁷ Behavioural symptoms are also commonly linked with abdominal pain. Children with such pain have been described as compulsive, highly strung and perfectionist.⁵ In addition, these children experience sleep disturbances and are more prone to suffer from depression.²A major limitation of previous studies is that they have been cross‐sectional or retrospective in design and, therefore, have been unable to establish the temporal nature of any associations. It is clear, therefore, that longitudinal studies are required. Thus, the aims of the current study were to determine the frequency of onset of CAP and to identify risk factors for its development.     

Randomised controlled trial of the efficacy of a metered dose inhaler with bottle spacer for bronchodilator treatment in acute lower airway obstruction

Background

Inhaled bronchodilator treatment given via a metered dose inhaler (MDI) and spacer is optimal for relief of bronchoconstriction. Conventional spacers are expensive or unavailable in developing countries, but there is little information on the efficacy of low‐cost spacers in young children.

Objective

To compare the response to bronchodilator treatment given via a conventional or a low‐cost bottle spacer

Methods

A randomised controlled trial of the efficacy of a conventional spacer compared with a bottle spacer for bronchodilator treatment in young children with acute lower airway obstruction. Bronchodilator treatment was given from an MDI via an Aerochamber or a bottle spacer. Clinical score and oximetry recording were carried out before and after 15 min of treatment. MDI–spacer treatment was repeated up to three times, depending on clinical response, after which nebulisation was used. The primary outcome was hospitalisation.

Results

400 children, aged (median (25th–75th centile)) 12 (6–25) months, were enrolled. The number of children hospitalised (n = 60, 15%) was identical in the conventional and bottle spacer groups (n = 30, 15% in each). Secondary outcomes including change in clinical score (−2 (−3 to −1)), oxygen saturation (0 (−1 to 1)) and number of bronchodilator treatments (2 (1 to 3)) were similar in both groups. Oral corticosteroids, prescribed for 78 (19.5%) children, were given to a similar number in the conventional (37 (18.5%)) and bottle spacer groups (41 (20.5%)).

Conclusion

A low‐cost bottle spacer is as effective as a conventional spacer for bronchodilator treatment in young children with acute obstruction of the lower airways.Acute obstruction of the lower airway is common in young children. Inhaled bronchodilator treatment is recommended for relief of airway obstruction. In children, a pressurised metered dose inhaler (MDI) with spacer produces bronchodilation equivalent or superior to nebulised treatment even in the case of severe airway obstruction.^1,2,3 An MDI–spacer delivery system has many advantages over nebulisation, including shorter and easier administration of drug, transportability, no need for a power source and lower risk of nosocomial infection.⁴ Moreover, use of an MDI–spacer has been reported to be cost effective; the cost and time for MDI–spacer treatment has been calculated as 40–60% that for nebulised treatment.⁵ However, a spacer is essential to minimise dependence on the child''s inhalation technique and to optimise drug delivery.^1,4Various commercially produced spacers have been developed, but expense and unavailability have limited their use in developing countries. The development of low‐cost spacers has received relatively little attention; however, a modified plastic bottle spacer has been shown to have clinical efficacy in children >5 years.^6,7 A randomised trial of a plastic bottle compared with a conventional spacer in children >5 years with acute asthma found that bottle and conventional spacers produced similar bronchodilation as measured by improvements in clinical score and pulmonary function.⁷ Another study of children aged 5–15 years with acute asthma reported similar improvements in peak expiratory flow rates and clinical parameters in patients who used a bottle spacer compared with those using a commercially produced spacer.⁸ However, the clinical efficacy of a bottle spacer has not been tested in infants or young children.The potential efficacy of a modified plastic bottle as a spacer for young children has been suggested by aerosol deposition studies in which lung deposition of nebulised technetium 99m DTPA given via a bottle or a conventional spacer was measured.⁹ In children <5 years, lung deposition from a bottle was found to be twice that obtained with a conventional small‐volume spacer.⁹ The amount of lung deposition was dependent on age, with a marked reduction occurring at around 50 months; this pattern occurred with both conventional and bottle spacers.The aim of this study was to compare the response to bronchodilator given via an MDI with bottle or conventional spacer in young children with acute lower airway obstruction (LAO).     

Pertussis requiring intensive care

Objectives

To describe children with pertussis who require intensive care.

Design, setting and patients

An audit in Auckland, New Zealand, of pertussis admissions to the national paediatric intensive care unit (PICU) from 1991 to 2003.

Results

72 children, 97% of whom were <12 months old. The annual number of cases increased with time (p = 0.04). Forty patients (56%) were coughing for less than 8 days before admission. Apnoea or paroxysmal cough was present in 33 (83%) of these children. Thirty five (49%) received assisted ventilation. Four died. 19% were readmitted to PICU. Those readmitted presented with more atypical disease and had a shorter first admission but longer total PICU admission (9 vs 5 days, p = 0.009). Of the 58 children from Auckland, nine either died (three) or had subsequent respiratory or neurodevelopmental problems (six). There was an increased risk (relative risk, 95% CI) of death or disability associated with having a co‐morbidity (RR = 5.56, 1.50 to 8.15), an elevated lymphocyte count (RR = 5.75, 1.54 to 13.65), presenting with seizures/encephalopathy (4.87, 1.18 to 8.34) or shock (6.50, 1.89 to 8.94), having a PIM score of 1% or more (RR = 6.20, 1.22 to 21.72), any abnormal neurological signs (RR = 9.65, 3.32 to 15.23) or being readmitted to PICU (RR = 4.63, 1.44 to 8.82).

Conclusions

Apnoea and paroxysmal cough are key symptoms of pertussis in those with shorter cough duration. Death or disability are frequent. Clinical factors define children at increased risk of these poor outcomes. Early discharge from PICU is associated with an increased risk of readmission and poor outcome.Severe pertussis in young infants remains difficult to treat. The limited success of extra‐corporeal membrane oxygenation (ECMO) and oscillatory ventilation has been reported.^1,2Although the risk factors for fatal disease have been defined, the clinical course of the disease in children requiring intensive care for pertussis is incompletely described.^2,3,4 The largest reported series included 24 children in Sydney between 1978 and 1989, and 25 in London paediatric intensive care units (PICUs) between 1998 and 2000.^5,6New Zealand (NZ) has high pertussis hospitalisation rates. The average annual rates in the 1990s and 2000s for infants were 222 and 293 per 100 000 person‐years, respectively.⁷ In comparison, the rate (per 100 000) in the United States was 33 in 1990–2000 and 69 in England and Wales in 1995.^8,9,10The Starship Children''s Hospital PICU is the country''s sole PICU. It serves 850 000 children aged 0–14 years in NZ¹¹ and so has more experience with pertussis than most.This study aimed to describe our pertussis intensive care experience and to identify factors associated with death or subsequent disability.     

The incidence of inherited metabolic disorders in the West Midlands, UK

Background

Inherited metabolic disorders (IMDs) are a heterogeneous group of genetic conditions mostly occurring in childhood. They are individually rare but collectively numerous, causing substantial morbidity and mortality.

Aims

To obtain up‐to‐date estimates of the birth prevalence of IMDs in an ethnically diverse British population and to compare these estimates with those of other published population‐based studies.

Methods

Retrospective data from the West Midlands Regional Diagnostic Laboratory for Inherited Metabolic Disorders (Birmingham, UK) for the 5 years (1999–2003) were examined. The West Midlands population of 5.2 million is approximately 10% of the UK population. Approximately 11% of the population of the region is from black and ethnic minority groups compared with approximately 8% for the the UK.

Results

The overall birth prevalence was 1 in 784 live births (95% confidence interval (CI) 619 to 970), based on a total of 396 new cases. The most frequent diagnoses were mitochondrial disorders (1 in 4929; 95% CI 2776 to 8953), lysosomal storage disorders (1 in 5175; 95% CI 2874 to 9551), amino acid disorders excluding phenylketonuria (1 in 5354; 95% CI 2943 to 9990) and organic acid disorders (1 in 7962; 95% CI 3837 to 17 301). Most of the diagnoses (72%) were made by the age of 15 years and one‐third by the age of 1 year.

Conclusions

These results are similar to those of the comparison studies, although the overall birth prevalence is higher in this study. This is probably due to the effects of ethnicity and consanguinity and increasing ascertainment. This study provides useful epidemiological information for those planning and providing services for patients with IMDs, including newborn screening, in the UK and similar populations.Inherited metabolic disorders (IMDs) are a complex and heterogeneous group of monogenic disorders, usually resulting from deficient activity in a single pathway of intermediary metabolism.¹ Clinical consequences of IMDs are often severe, and they are an important cause of morbidity and mortality in clinical practice, especially in paediatrics.²Although each disorder is individually rare, their cumulative incidence is substantial; an incidence of 1 in 2500–5000 live births is often quoted.^2,3 However, most published studies have focused on specific disorders or groups of disorders, disorders that are screened for or diagnosed in specialist reference laboratories, or in selected populations at particularly high risk for certain conditions.^{4,5,6,7,8,9,10,11} Although the results of these studies have shown a high level of consistency, a lack of accurate epidemiological data creates difficulties for those seeking to plan and provide appropriate clinical services for these patients. This is becoming more relevant because of new laboratory technologies for diagnosis and screening and the availability of new (and often expensive) treatment options.^{8,12,13,14,15,16,17,18} As a result, more patients are now surviving into adulthood, with important consequences for their health and health services.We therefore aimed to obtain up‐to‐date estimates of the birth prevalence of IMDs in an ethnically diverse British population and to compare these with other published population‐based studies of their prevalence. Substantial changes in ethnic populations in the UK deem that those planning and providing services should have a comprehensive and recent estimate of the potential disease burden. A previous study in the West Midlands reported data that are now over 15 years old.¹¹ Since 1991 (the final year of data reported in the West Midlands ethnicity study), the proportion of people belonging to minority ethnic groups in the UK has risen by 53% (an increase of 1.6 million people) and that in the West Midlands by over 40% (an increase of 129 510 people). As the incidence of IMDs is around 10 times higher in these minority ethnic groups, this increase has important implications for service provision. Also, the previous study was incomplete because it included only a selection of disorders, excluding urea cycle, organic acid and glycogen storage disorders altogether. Specific “indicator” disorders were chosen to represent other IMD groups—for example, medium‐chain acyl coenzyme A dehydrogenase deficiency was used to represent fatty acid oxidation disorders. Thus, this new study provides more comprehensive and recent data than the previous study.