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.     

Nosocomial infection in small for gestational age newborns with birth weight <1500 g: a multicentre analysis

Objective

To investigate whether preterm newborns who are small for gestational age are at increased risk of nosocomial infections and necrotising enterocolitis.

Design, setting and subjects

The German national surveillance system for nosocomial infection in very low birthweight infants uses the US Centers for Disease Control and Prevention criteria. 2918 newborns (24–28 weeks), born between 2000 and 2004, were selected after application of predefined inclusion criteria to ensure similar proportions of small and appropriate weight for gestational age newborns across gestational age groups.

Main outcome measures

The outcome criterion was at least one episode of nosocomial sepsis, pneumonia or necrotising enterocolitis. Adjusted odds ratios and corresponding 95% CIs were calculated based on general estimating equation models.

Results

The study population consisted of 13% (n = 392) small and 87% (n = 2526) appropriate weight for gestational age infants. 33% (n = 950) of the infants experienced at least one episode of sepsis: 42% (n = 163) of small and 31% (n = 787) of appropriate weight for gestational age newborns (adjusted OR 1.41, 95% CI 1.05 to 1.89). Pneumonia was diagnosed in 6% (n = 171) of infants: 8.4% (n = 33) of small and 5.5% (n = 138) of appropriate weight for gestational age newborns (adjusted OR 1.57, 95% CI 1.19 to 5.57). Necrotising enterocolitis was documented in 5.2% (n = 152) of infants: 7.1% (n = 28) of small and 4.9% of (n = 124) appropriate weight for gestational age newborns (adjusted OR 1.20, 95% confidence interval 0.75 to 1.94).

Conclusions

Growth‐retarded preterm infants seem to be at increased risk of nosocomial infection, irrespective of the responsible pathogen. Future immunological research should elucidate potential causal associations.Very low birthweight (VLBW, <1500 g) newborns are at increased risk of morbidity and mortality. Besides their immaturity, risk profiles can vary due to a multitude of factors. Growth retardation is one factor conferring additional risk. Recent studies have consistently shown an increased mortality risk for small for gestational age (SGA) infants,1,2,3 but results regarding morbidity are conflicting.4,5,6Nosocomial infection has a large impact on neonatal survival and has important cost implications,7,8 affecting up to 40% of babies in neonatal intensive care units (NICUs).9,10,11,12,13 Immunological immaturity (eg, poor phagocytosis or hypogammaglobinaemia), exposure to invasive procedures and prolonged hospitalisation predispose VLBW newborns to nosocomial infection.7,14,15 However, little is known about nosocomial infection in SGA newborns.4,11,16,17,18,19We addressed this issue in a large, multicentre analysis to investigate the association of being SGA and being at increased risk of nosocomial infection—that is, sepsis and pneumonia. In addition, necrotising enterocolitis (NEC) was considered as an outcome criterion.     

Selective ambulatory management of Plasmodium falciparum malaria in paediatric refugees

Background

Plasmodium falciparum (Pf) malaria is a leading cause of childhood mortality and morbidity. In developed countries, it is widely recommended that even patients with uncomplicated Pf malaria are hospitalised for at least 24 h, whereas ambulatory treatment is usual for uncomplicated infections in developing countries. This observational study assessed the safety of selective admission of paediatric refugees with Pf malaria in Australia.

Methods

Data were collected on African humanitarian refugee children (<16 years of age) presenting with malaria between February 2005 and April 2006. Children were treated as outpatients if they fulfilled specific criteria devised to maximise the safety of outpatient management of this potentially life‐threatening condition.

Results

Ninety paediatric refugees were infected with P falciparum, of whom 56 were treated as outpatients. Of the 34 children admitted to hospital, four had parasite loads ⩾4%. Most children were treated with oral atovaquone‐proguanil. Eighty eight patients attended follow‐up; all were compliant and none reported side‐effects. One infant failed treatment and was subsequently readmitted; he did not meet criteria for severe malaria on either occasion and had been initially treated as an inpatient.

Conclusions

Using this protocol, outpatient management of refugee children with Pf malaria appears safe, with minimal complication and treatment failure rates. This approach has rationalised management of paediatric malaria in this carefully selected population and substantially reduced utilisation of hospital resources.Malaria is responsible for considerable global mortality and morbidity and accounts for up to 20% of childhood deaths in Africa.¹Plasmodium falciparum (Pf) malaria has a significant case‐fatality rate even when managed appropriately.² Prompt recognition and treatment is essential in the non‐immune patient and in young children, who are at increased risk of rapid deterioration and death.³ In Australia, as in the US⁴ and Canada,⁵ there has been a increase in the incidence of malaria in recently resettled African refugees.^6,7,8Current guidelines generally advocate mandatory admission to hospital of all children with Pf malaria in developed countries,^9,10,11 but there is little evidence to support this recommendation. This study evaluated the safety of selective ambulatory management of African refugee children with Pf malaria in Australia.     

Selective fluconazole prophylaxis in high-risk babies to reduce invasive fungal infection

Objectives

To evaluate the impact of selective fluconazole prophylaxis on incidence of invasive fungal infection and emergence of fluconazole resistance in neonatal intensive care.

Design

Retrospective study of very low birthweight (VLBW) babies (<1500 g birth weight) admitted to a neonatal intensive care unit (NICU) in the period 1 year before and after the implementation of an antifungal prophylaxis guideline.

Patients

VLBW babies with an additional risk factor: colonisation of Candida species from surface sites with a central venous catheter; third generation cephalosporin treatment; or total duration of antibiotic treatment >10 days.

Fluconazole protocol

Fluconazole 6 mg/kg for 3 weeks. Dose interval is every 72 h during the first 2 weeks of life. Thereafter, dose interval is reduced to every 48 h until 3 weeks old when daily fluconazole is given. Fluconazole is administered orally when enteral feeding achieved.

Results

121 and 107 VLBW babies were admitted to the NICU in the year before and after the guideline was implemented, respectively. Data were available in 110 and 102 charts. 33/110 and 31/102 babies were eligible for fluconazole prophylaxis in the period before and after guideline implementation. 6/33 babies eligible for prophylaxis developed culture proven Candida sepsis before compared with no (0/31) babies after the guideline was implemented (p = 0.03). One baby (1/31) did develop probable Candida sepsis in the post guideline implementation period. During both study periods all Candida isolates remained fully susceptible to fluconazole.

Conclusions

Selective antifungal prophylaxis has reduced invasive fungal sepsis in one NICU without evidence of fluconazole resistance emerging.Invasive fungal infection, most commonly due to Candida species, is increasingly common in preterm babies in neonatal intensive care.1,2,3,4,5,6 The estimated incidence in very low birthweight (VLBW) babies is between 2% and 4%, but it may be as high as 10% in extremely low birthweight (ELBW) babies. Fungal sepsis has much higher mortality, 21–32%, than bacteraemia, and it is also associated with markedly higher rates of adverse neurodevelopmental outcomes.6,7,8,9,10Fluconazole prophylaxis reduces the incidence and mortality from invasive fungal infection,11,12,13,14,15,16,17,18,19 but widespread use of antifungals might increase the emergence of resistance.3,10,20,21,22,23 Studies to date are too short to fully assess the potential for fluconazole resistance and there remain reservations about treating all babies to protect a few.12 Fluconazole seems to be well tolerated in prophylactic doses,11,12,13,14,15,16,17,18,19 but there are associations with rise in liver transaminases, cholestasis, toxic epidermal necrolysis and Steven–Johnson syndrome, and interactions with other medications.2,13,24,25,26 Selective use of antifungal prophylaxis in the subset of VLBW babies at very high risk of fungaemia may be preferable to minimise the risk of adverse effects.2,12 Although comparatively little data are available on selective antifungal prophylaxis, two recent studies reported reductions in invasive fungal infection with a fluconazole prophylaxis policy targeting VLBW babies with additional risk factors.16,17 Recognised additional risk factors for acquiring fungal sepsis in preterm infants include third generation cephalosporin use, fungal colonisation, prolonged broad spectrum antibiotic use, parenteral nutrition with lipids, endotracheal intubation, male gender, central venous catheter use and number of days in situ, previous bacterial blood stream infections, postnatal steroids, gastrointestinal pathology, H₂‐receptor antagonists, shock and coagulopathy.2,25,27,28,29,30In October 2003, the neonatal intensive care unit (NICU) at the Royal Maternity Hospital, Belfast, developed a guideline for antifungal prophylaxis in VLBW babies with additional risk factors for fungal sepsis. We conducted this retrospective study to determine if the use of selective fluconazole prophylaxis was effective in reducing invasive fungal infection in high‐risk babies. We also wanted to establish if there has been an increase in fluconazole resistance.     

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.     

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.     

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).     

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.     

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     

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.     

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.     

Failure to thrive: the prevalence and concurrence of anthropometric criteria in a general infant population

Background

Failure to thrive (FTT) in early childhood is associated with subsequent developmental delay and is recognised to reflect relative undernutrition. Although the concept of FTT is widely used, no consensus exists regarding a specific definition, and it is unclear to what extent different anthropometric definitions concur.

Objective

To compare the prevalence and concurrence of different anthropometric criteria for FTT and test the sensitivity and positive predictive values of these in detecting children with “significant undernutrition”, defined as the combination of slow conditional weight gain and low body mass index (BMI).

Methods

Seven criteria of FTT, including low weight for age, low BMI, low conditional weight gain and Waterlow''s criterion for wasting, were applied to a birth cohort of 6090 Danish infants. The criteria were compared in two age groups: 2–6 and 6–11 months of life.

Results

27% of infants met one or more criteria in at least one of the two age groups. The concurrence among the criteria was generally poor, with most children identified by only one criterion. Positive predictive values of different criteria ranged from 1% to 58%. Most single criteria identified either less than half the cases of significant undernutrition (found in 3%) or included far too many, thus having a low positive predictive value. Children with low weight for height tended to be relatively tall.

Conclusions

No single measurement on its own seems to be adequate for identifying nutritional growth delay. Further longitudinal population studies are needed to investigate the discriminating power of different criteria in detecting significant undernutrition and subsequent outcomes.Failure to thrive (FTT) is regarded as an indicator of physical or psychosocial problems in early childhood and is associated with subsequent growth delay and cognitive deficiencies.^1,2,3 Although the concept of FTT is widely used, no consensus exists regarding a specific definition.⁴ Thus, FTT has been used to cover a broad range of different anthropometric indicators, usually based on centile charts for weight or height.^5,6 Criteria involving behavioural characteristics of the child or quality of the mother–child relationship were proposed in early work, which linked the condition to emotional deprivation,^7,8 but a consensus in 1985 concluded that the diagnosis should be based solely on anthropometric parameters.⁹ Reviews further recognised that the unifying characteristic in FTT was relative undernutrition,^10,11 thus approaching the concept of “protein energy malnutrition” (PEM), a term used to describe nutritional deprivation among children in developing countries.⁴ However, FTT and PEM are described in different literatures, with FTT mainly comprising children in more affluent societies.Most early studies on FTT used criteria based on attained low weight or, sometimes, height with a cut‐off around the 3rd or 5th centile.⁵ Dynamic measures of weight gain are now increasingly being used,⁶ including fall from a normal birth weight below a given cut‐off, dropping through major centile spaces and, recently, slow conditional weight gain, taking into account the normal phenomenon of regression to the mean, with small children tending to move upwards through the centiles and large children tending to cross downwards.^12,13,14,15 Although FTT and PEM both refer to paediatric undernutrition resulting in growth deviation,⁴ different criteria are often used in developing societies. Thus, weight may be expressed as a percentage of the median weight for age, like the Gomez criterion, whereas severe undernutrition is often assessed using weight for height, which has the advantage of not requiring age to be known. Thus, Waterlow''s criterion expresses weight as a percentage of the median weight for measured height.^16,17 However, weight for height has not been used much to diagnose FTT in affluent countries, but recently published age‐specific body mass index (BMI; weight (kg)/height (m²)) standards for childhood^18,19,20 could make this method more feasible.Thus, several definitions of FTT are in use, but it is unclear to what extent these definitions concur, hampering comparison between studies. The few studies that have compared different definitions found poor concordance, but were performed in highly selected clinical cohorts.^21,22 To our knowledge, no such comparison has been carried out in a whole population of children from affluent societies.In this study, we compare the prevalence and concurrence of different anthropometric criteria of FTT when applied to a birth cohort of Danish infants.     

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.     

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.     

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.     

Pancreatic phenotype in infants with cystic fibrosis identified by mutation screening

Objective

To determine the pancreatic phenotype of infants with cystic fibrosis (CF) diagnosed in the first week of life by a combined immunoreactive trypsin/mutation screening program.

Design

A prospective evaluation of pancreatic function in infants with CF at the time of neonatal diagnosis and up to the age of 12.

Setting

Two different centres (Verona, Italy and Westmead, Australia) to enable comparison of results between two regions where <60% or ⩾90% of patients, respectively, have at least one single ΔF508 a mutation.

Patients

315 children with CF including 149 at Verona and 166 at Westmead.

Interventions

Fat balance studies over 3–5 days and pancreatic stimulation tests with main outcome measures being faecal fat or pancreatic colipase secretion. Patients with malabsorption are pancreatic insufficient (PI) or with normal absorption and pancreatic sufficient (PS).

Results

34 infants (23%) at Verona and 46 (28%) at Westmead were PS at diagnosis. 15% of those with two class I, II or III “severe” mutations and 26/28 (93%) of those with class IV or V mutations were PS at this early age. Of the 80 infants with PS, 20 became PI before the age of 12. All 20 had two severe mutations.

Conclusion

Neonatal mutational screening programs for CF are less likely to detect PS patients with non‐ΔF508 mutations. Of PS patients who are detected, those with two severe class I, II or III mutations are at particularly high risk of becoming PI during early childhood.Neonatal screening for cystic fibrosis (CF) began in the early 1980s with measurement of immunoreactive trypsin (IRT) assays on dried blood spots obtained from infants in the first 4–6 weeks of life.^1,2 Questions were raised about the reliability of these programs as they had not been validated for the 10%–15% of patients with normal fat absorption (pancreatic sufficient or PS).³ Subsequently however, 37% of screened infants were found to be PS,^4,5 that is 2–3 times the 10%–15% observed in older patients.³ Furthermore, follow‐up studies demonstrated that nearly 50% of the infants with PS near birth developed fat malabsorption (pancreatic insufficient or PI) in later childhood, thus accounting for the lower proportion of PS patients at an older age. It is significant that all those who transitioned from being PS to PI had two “severe” class I, II or III cystic fibrosis transmembrane conductance regulator (CFTR) mutations,⁶ as defined previously,^7,8 whereas those with persistent PS had at least one class IV or V “mild” mutation.Following the discovery of the CFTR gene,⁹ most screening programs have modified their screening strategy.¹⁰ In regions where more than 90% of patients with CF have at least one ΔF508 mutation, analysis for ΔF508 is performed on week 1 neonatal blood spots with an elevated IRT level.¹¹ This strategy has been further modified in regions (particularly southern Europe) where ΔF508 is only present in 40%–60% of patients, by screening for an extended panel of non‐ΔF508 mutations (usually severe class I, II or III) common to that region.^12,13 These IRT/DNA screening strategies are, however, not without problems. For instance, in regions where ΔF508 is responsible for CF in over 90% of cases, up to 10% of patients have non‐ΔF508 mutations with a preponderance of PS patients¹⁴ and therefore screening for ΔF508 alone would not detect such patients.Currently, only limited data are available on the pancreatic phenotype of infants with CF diagnosed by IRT/DNA screening from a study¹⁵ restricted to 27 infants with only class I or II mutations. The present study was thus undertaken, firstly to determine the pancreatic phenotype of infants in either a ΔF508 predominant or non‐dominant region, and secondly, to determine what proportion of infants initially with PS later transitioned to being PI and whether this was determined by the presence of two severe mutations.     

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.     

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.     

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.     

Evaluating the CSAPPA subscales as potential screening instruments for developmental coordination disorder

Objective

In this study, we assess the potential of three subscales of the Children''s Self‐Perceptions of Adequacy in and Predilection for Physical Activity (CSAPPA), a measure of generalised self‐efficacy, as possible screens for developmental coordination disorder (DCD).

Design

We used the Bruininks‐Oseretsky Test of Motor Proficiency short form (BOTMP‐SF) to identify probable cases of DCD. We administered the BOTMP‐SF and the CSAPPA to 590 children in grades 4–8 from four schools in the Niagara region of Ontario, Canada. We used receiver operator characteristic (ROC) analysis to assess and compare the performance of the subscales and the full instrument.

Results

The area under the receiving operating characteristic curve (AUC), a measure of the overall performance of the test against a diagnostic standard, was good for the full CSAPPA (AUC = 0.81, 95% CI 0.75 to 0.87). The adequacy (AUC = 0.79, 95% CI 0.73 to 0.85) and predilection (AUC = 0.80, 95% CI 0.74 to 0.87) subscales had performance statistically equivalent to the full scale. Since the adequacy subscale is shorter and has good content validity with respect to DCD, we ran additional analyses on this measure. A cut‐point of 24 on this subscale gives a sensitivity of 0.86 (95% CI 0.76 to 0.97) and a specificity of 0.47 (95% CI 0.43 to 0.51).

Conclusion

The adequacy subscale of the CSAPPA appears to be equivalent to the full measure for the purposes of screening for DCD. Further research should explore the possibility of adding further criteria to improve the CSAPPA''s modest specificity in this role.Developmental coordination disorder (DCD) is characterised by poor motor proficiency that results in a significant impairment in social and academic functioning and is not the result of another psychiatric, neurological or other medical condition.¹ DCD is common, with prevalence estimated at 5–6%.^1,2 The specific manifestations of the disorder are varied and pervasive, and include gross and/or fine motor skill impairment. These problems make day‐to‐day activities such as tying shoelaces, writing and participating in activities such as skipping or basketball extremely difficult. It is not surprising, therefore, that children with DCD tend to participate less in social activities than other children, as social activities in childhood often involve physical activity.³Despite its relatively high prevalence, most children with DCD are never diagnosed.³ Rather, teachers typically describe these children as clumsy, awkward or lazy.⁴ However, DCD is strongly associated with behavioural and emotional problems,^5,6 low self‐worth,^7,8,9 poor perceived competence,⁹ anxiety,^9,10 depression,^11,12 bullying⁸ and obesity.¹³ Cairney et al¹³ recently demonstrated that children with DCD tend not to participate in physical activities, increasing the likelihood of overweight/obesity and poor cardiorespiratory fitness.¹⁴If identified early, the physical health and academic and emotional needs of affected children can be addressed and negative experiences prevented.^15,16 The potential for improved quality of life justifies efforts to screen for and identify children with DCD in non‐clinical settings.¹⁷ However, existing screening measures are based either on parent¹⁸ or teacher¹⁹ reporting of motor coordination difficulties. To date, child self‐report measures have not been available.Previous work has examined the possibility that the Children''s Self‐Perceptions of Adequacy in and Predilection for Physical Activity scale (CSAPPA) may be useful as a screening instrument for DCD in children aged 9–14.^3,17 When compared with a standardised motor assessment, the Bruininks‐Oseretsky Test of Motor Proficiency short form (BOTMP‐SF),²⁰ sensitivity and specificity for boys (0.90 and 0.89, respectively) and girls (0.88 and 0.75, respectively) on the CSAPPA were moderate to high. The advantages of the CSAPPA over motor testing are: i) it can be administered to children in groups in 15–20 min (unlike motor testing, which is administered individually); ii) it is easy to score; and iii) it can be administered by teachers or research personnel. However, there are instances where the 19‐item CSAPPA measure is too demanding and a shorter screening instrument is required. In clinical settings, brief and effective screening instruments are preferable. Moreover, in population‐based studies, where multiple measures are being administered in a single survey, a premium is placed on shorter instruments that require little time to complete.The 19‐item CSAPPA is composed of three subscales: i) perceived adequacy (seven items); ii) predilection toward physical activity (nine items); and iii) enjoyment of physical education class (three items).²¹ The purpose of this study was to compare the CSAPPA with a standardised measure of motor proficiency which is often used to identify children with DCD and to evaluate the three CSAPPA subscales as possible short‐form screens for DCD.