Trends in imported childhood malaria in the UK: 1999-2003

Objective

To describe the epidemiology of imported malaria in children in the UK.

Methods

Surveillance data on children with imported malaria, collected through an enhanced surveillance network set up by the Malaria Reference Laboratory (London, UK), diagnosed between January 1999 and December 2003 were analysed.

Results

Over the 5‐year study period, 9238 cases were reported to the Malaria Reference Laboratory, and children accounted for 1456 (14.8%) cases. The number of imported paediatric malaria cases fell from 326 in 1999 to 241 in 2003. Malarial infection occurred in children of all ages and the number of patients increased gradually with age. Visiting family and relatives was the most common reason for travel (59.5%), with only 7.2% travelling to an area endemic to malaria on holiday. Most infections (88.4%) were acquired in Africa, and mainly in Nigeria (49.7%). Plasmodium falciparum was responsible for 81.7% of all cases, followed by P vivax (11.1%). The number of both P falciparum and P vivax cases fell gradually from 262 and 45 cases in 1999 to 196 and 20 cases in 2003, respectively. Malaria prophylaxis was taken by 39% of 500 children with malaria who had travelled to a country endemic to malaria. The proportion of children with malaria who had taken malaria prophylaxis decreased steadily from 53% in 1999 to 29% in 2003. Two (0.14%) children died compared with 62 (0.76%) adults over the 5‐year study period (p = 0.007).

Conclusions

Although the incidence of malaria has started to decline, a considerable number of children are still diagnosed with malaria in the UK. In addition, the proportion of children with malaria who had taken malaria prophylaxis is falling. Although it is reassuring to note the low mortality, there is an urgent need to improve preventive measures among families travelling to high‐risk countries.Malaria remains a major cause of morbidity and mortality in adults and children worldwide.¹ The UK has one of the highest rates of imported malaria among non‐endemic countries, second only to France, with around 2000 cases reported every year (http://data.euro.who.int/CISID/?TABID = 98149).^2,3 The number of cases due to Plasmodium falciparum, the species responsible for most of the morbidity and mortality associated with malaria,⁴ continues to rise and is now responsible for >75% of all malaria cases in almost all European countries.^2,3,5,6 Children under the age of 16 years account for a considerable proportion (10–20%) of imported malaria cases.^7,8 Compared with adults, they are more likely to present with non‐specific febrile illnesses and their condition can deteriorate rapidly with rapid increases in blood parasite densities, particularly if they have not been exposed to malaria previously.⁷ Despite this, the diagnosis of malaria continues to be missed, mainly because a travel history is not obtained and malaria is not suspected.⁹ Studies in adults and children have consistently shown that delays in initiating appropriate treatment for malaria is one of the most important risk factors for the development of serious complications or death.^5,10,11We describe recent trends in the epidemiology, the Plasmodium species responsible, uptake of malaria prophylaxis and outcome in children with imported malaria in the UK over a 5‐year period. It is hoped that this study will increase the awareness of imported malaria in children.     

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.     

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.     

Effects of dietary management of phenylketonuria on long-term cognitive outcome

Background

Phenylketonuria (PKU) is associated with dopaminergic depletion in the dorsolateral prefrontal cortex and abnormalities of myelination. Both mechanisms may lead to deficits in cognitive functioning. Studies of cognitive outcome in children treated with PKU at an early stage have suggested that there are benefits in remaining on diet into adolescence.

Aim

To assess the nature and extent of any cognitive deficits in adults treated at an early stage with PKU who had discontinued their diets in adolescence.

Method

25 patients (aged 18–38 years) who were diagnosed early and had discontinued their diets in adolescence were compared with 25 adults (aged 18–38 years) with PKU on continuous diet, and with a healthy control group (n = 45).

Results

The groups differed significantly on accuracy (p = 0.007) and speed (p = 0.001) of performance on an n‐back working memory task and on speed of performance (p = 0.001) on a flanker inhibitory task, but not on flanker accuracy, object alternation learning or perceptual judgement tasks (all p>0.05). The off‐diet group performed significantly below the on‐diet group on n‐back accuracy (p = 0.007) and flanker speed (p = 0.05), and significantly below the control group on n‐back speed (p = 0.002) and flanker speed (p = 0.001).

Conclusion

The findings suggest that although discontinuing diet in adolescence appears disadvantageous compared with remaining on continuous diet, any deficits are relatively subtle.Phenylketonuria (PKU) is caused by the deficiency of phenylalanine hydroxylase, which converts phenylalanine (Phe) into the dopamine precursor tyrosine. Without treatment, PKU generally results in severe learning and behavioural disturbances.¹ Early screening and effective dietary treatment have considerably improved outcomes,² such that children treated early can now expect to lead relatively normal lives, although mean IQ scores for children with PKU in the UK have been shown to be below the population means.³ Relationships have been reported between IQ and factors such as treatment initiation, duration and severity of exposure to Phe in early childhood.^3,4 A minority of adults with PKU showed increased psychosocial morbidity,⁵ and this has been linked to poorer performance on measures of intellectual and executive functioning.Two main hypotheses were proposed regarding the possible mechanisms leading to cognitive impairment in PKU—namely, slowed information processing resulting from deficient white matter myelination, and selective executive deficits associated with prefrontal cortex (PFC) dysfunction resulting from neurotransmitter abnormalities. Both white matter abnormalities and PFC dysfunction may occur together in PKU.⁶ Abnormalities of myelination have been linked to PKU,^2,6 particularly in posterior and periventricular white matter. Neurotransmitter abnormalities have also been identified. Tyrosine deficiency may lead to deficiency of dopamine; and increased Phe impedes transport of other amino acids into the brain. Indeed, dopamine neurones in the ventral tegmental area projecting to PFC may be differentially depleted through this process.^7,8 The frontal lobes, particularly the PFC, are believed to be central to executive functions, which control our ability to respond adaptively to the environment by orchestrating necessary cognitive processes to achieve specific goals.⁹ Dopamine plays a central role in functions linked with the lateral PFC.¹⁰ These include working memory, attentional control and inhibition of habitual responses.Available evidence for children with PKU does not differentiate clearly between these two hypotheses. Studies have varied considerably in terms of methods, making comparisons difficult. White et al⁶ described reduced processing speed in children treated early with PKU, and linked this to white matter abnormalities. Several studies have examined the executive deficit hypothesis using measures involving working memory, sustained attention or inhibition. Some reported executive dysfunction despite a normal IQ, even with continuous dietary treatment.^{6,8,11,12,13,14} Other studies have failed to find deficits.^15,16,17,18 Welsh¹⁹ noted it was not clear whether executive impairment continued into adulthood, or simply showed a developmental lag that eventually disappeared with continued treatment.Little work has been performed examining the outcome in adult patients who were adequately treated from an early age, and little is known about the possible benefits of lifelong treatment. There are two key questions: what mechanisms underpin any cognitive deficits in adults with PKU; and are there continuing benefits in staying on a lifelong diet? Some support has been provided for selective executive deficits,¹⁸ but other findings have been mixed. Ris et al²⁰ studied a group of adults on and off diet and reported deficits compared with controls in IQ, attention and visuoconstructional ability, but not on an executive task. Impairment was found both on executive and non‐executive clinical tasks in adults with PKU who were off diet or poorly controlled.²¹ In two previous studies, we examined the outcome in adults with PKU who were treated early and put on lifelong diet, and found only mild impairment in aspects of cognitive functions, with little evidence of a selective executive deficit on either clinical²² or computerised experimental²³ tasks. The present study was designed to investigate outcomes in off‐diet adults with PKU who were diagnosed early and treated. It was hypothesised that they would show subtle cognitive impairments, but that these would not reflect selective executive deficits.     

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.     

Intravenous pamidronate treatment of infants with severe osteogenesis imperfecta

Objective

Children with the severe forms of osteogenesis imperfecta have in several studies been treated with intravenous pamidronate, but there are only few reports of the effect of early treatment.

Aim

To evaluate the effect of treatment started in infancy.

Methods

In a prospective observational study, with a historic control group, intravenous disodium pamidronate (APD) was given as monthly infusions to 11 children with osteogenesis imperfecta aged 3–13 (median 3.6) months, who had severe osteogenesis imperfecta with congenital bowing of the femora and vertebral compression fractures.

Results

During treatment of children aged between 3 and 6 (median 4.5) years, dual‐energy x ray absorptiometry measurements of the lumbar spine showed a gradual increase in bone density. Bone metabolism parameters in serum (alkaline phosphatase, osteocalcin, procollagen 1 carboxy‐terminal peptide, collagen 1 teleopeptide) and in urine (deoxypyridinoline) indicated a decrease in bone turnover. An improvement of mobility was seen and at the latest recording, at the age of 3.3–6.5 (median 4.8) years, the children could all walk. Vertebral remodelling was seen, with increased vertebral height, and no child developed scoliosis, kyphosis or basilar impression. All children required femoral intramedullar rods for fractures, and five needed tibial rodding for extreme curvatures that prevented functional standing and walking. No adverse effects were seen on growth, fracture healing or blood chemistry.

Conclusions

APD is an efficient symptomatic treatment for infants with severe osteogenesis imperfecta, but additional orthopaedic surgery is often needed. Early treatment may prevent scoliosis and basilar impression. Long‐term follow‐up is important.Osteogenesis imperfecta is a disease that shows a large variation in phenotype, ranging from very mild bone fragility (type I) through intermediate severity (types IV and III) to the most severe lethal form (type II). This clinical classification into four major subgroups was designed by Sillence in 1979^1,2 and describes most cases. Recent modifications encompass additional, even less common, forms of the disease. In most cases, there are mutations in the COLIA1 or COLIA2 genes localised to chromosomes 17 and 7, respectively. This leads either to a reduced production of normal collagen type I or to the synthesis of collagen type I with abnormal structure and function. In general, the genotype is an unreliable predictor of phenotype and severity, and no new classification based on the different mutations has yet been devised.Intravenous disodium pamidronate (APD) treatment of children with osteogenesis imperfecta has been used since 1991, and we presented the first case at the Fifth International Conference on Osteogenesis Imperfecta in 1993. The rationale for bisphosphonate treatment in osteogenesis imperfecta is that the complex function of bisphosphonate, with a predominantly inhibitory effect on osteoclasts, might lead to a net effect of increased bone mass, especially as growing children with osteogenesis imperfecta have thin bone with few trabeculae, thin cortices and high remodelling rates.^3,4,5,6,7 We have previously published long‐term results in 3 adolescents and 28 children aged 0.6–18 years.^8,9 The few reports of bisphosphonate treatment of infants with osteogenesis imperfecta are mainly, a mix of toddlers and infants, few under the age of 15 months.^{9,10,11,12,13,14,15,16} Here we present very promising results of APD treatment in a group of 11 infants with severe but not lethal forms of osteogenesis imperfecta.     

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.     

Determinants of neuropsychological and behavioural outcomes in early childhood survivors of congenital heart disease

Aims

To evaluate the relative effect of cyanosis, surgical interventions and family processes on neuropsychological and behavioural outcomes in 4‐year‐old survivors of serious congenital heart disease (CHD).

Methods

90 children with a range of cyanotic and acyanotic conditions, who underwent either corrective or palliative surgery, completed a neuropsychological and behavioural evaluation. Families of participants were also profiled by evaluation of maternal mental health, worry, social support, parenting style and family functioning.

Results

Compromised neuropsychological outcomes were associated with a combination of cyanotic conditions and open‐heart surgery, but this was not exacerbated by having a complex, palliative, status. Both cyanotic and acyanotic conditions were associated with specific sensorimotor delays, regardless of method of the correction. Only children with complex conditions and palliative interventions seemed at risk of poor behavioural outcomes; indeed, children with cyanosis with complete repair showed favourable behavioural outcomes compared with controls. Multivariate analyses highlighted the sometimes greater relevance of family processes (eg parenting style, maternal mental health and worry), rather than disease or surgical factors, in predicting especially behavioural outcomes.

Conclusions

The findings (1) suggest a more complex relationship between cyanosis, surgical methods of correction, neuropsychological and behavioural outcomes than previously charted, (2) highlight that family processes may be aetiologically more important than disease and surgical factors, and (3) indicate specific targets for secondary prevention programmes for this at‐risk population.An emerging view suggests that children with cyanotic congenital heart disease (CHD) who have undergone surgical procedures involving circulatory arrest are at particular risk of both neuropsychological and behavioural problems.^1,2,3,4,5 However, some studies have found no such evidence or indeed, in terms of behavioural adjustment, suggested better outcomes than controls.^6,7,8 Moreover, where statistically significant differences have been found, clinical significance is sometimes dubious. Indices of intellectual functioning and behavioural adjustment in some studies have often been well within the normal range, with statistical significance sometimes determined by above‐average scores in control groups.^3,9,10Contributing to this ambiguity, studies have often used restricted samples of children with CHD (eg cases of transposition of great arteries) and have neglected to examine the mediating effects of maternal and family factors, which can covary with CHD.^6,8,11,12,13 This study includes measures of maternal adaptation and family functioning, in addition to cyanosis and surgical factors, in examining determinants of neuropsychological and behavioural outcomes in 4‐year‐old survivors of severe congenital heart defects. Children with cyanosis are divided into subgroups of those who had corrective versus palliative surgery only. These subgroups have often been merged in previous studies, but important differences are likely. Children without acyanosis are also subgrouped into those who underwent open or closed surgery. In this way, the importance of surgical procedures involving cardiopulmonary bypass, independent of cyanosis, may be considered. Neuropsychological and behavioural profiles across groups are first considered, followed by multivariate analyses of outcome determinants.     

Car seat test for preterm infants: comparison with polysomnography

Objectives

To monitor preterm infants in a cot and a car seat and compare an observed car seat trial with polysomnography (PSG).

Design

Non‐randomised controlled trial.

Setting

Regional neonatal unit.

Patients

Preterm infants before discharge.

Interventions

Nap PSG respiratory and sleep variables were measured including gastro‐oesophageal pH. Nurse observations included respiratory distress, apnoea measured by apnoea alarm, oxygen saturation and heart rate. Infants were studied supine in a cot and then in a car seat. Nursing observations were compared with PSG during the car seat trial only. Criteria for failure of the PSG and observed tests were predefined.

Main outcome measures

Difference in respiratory instability between cot and car seat. Concurrence regarding failure of the car seat trial between nurse‐observed data and PSG.

Results

20 infants (median gestation 33 weeks (range 28–35 weeks; median postmenstrual age (PMA) at study 36.5 weeks (range 35–38 weeks)) were studied. There were sufficient car seat data on 18 infants for comparison. There were fewer central apnoeas and arousals in the cot than the car seat (p = 0.047 and p = 0.024, respectively). Airway obstruction was not more common in the car seat. Younger PMA at time of study predicted failure in both car seat (p = 0.022) and cot (p = 0.022). The nurse‐observed test had low sensitivity for predicting PSG failure but more accurately predicted airway obstruction on PSG.

Conclusions

Immature infants exhibit respiratory instability in cots and car seats. A car seat test does not accurately detect all adverse events during sleep in the seat.Since concerns were first raised about the vulnerability of preterm infants during transportation,1,2 several studies have attempted to quantify the respiratory compromise experienced by these infants while in car seats.3,4,5,6,7,8,9,10,11,12,13 Many of these studies had methodological limitations as not all measured the sleep state, or used a supine position for comparison or airflow measures to detect obstructive apnoea, or allowed for differences in postmenstrual age (PMA) at study.Although car seat trial before discharge has been incorporated into many neonatal discharge practices it has not been universally accepted as the gold standard test for assessing risk of respiratory compromise in a car seat after discharge.14,15,16 Despite many neonatal nurseries implementing variations of the practice,14 criteria defining how premature infants should be monitored, how long to monitor or what constitutes failure of the test are lacking.15,17,18 Neonatal unit car seat testing programmes therefore vary in equipment type, quality, time and outcome data.14The present study aimed to examine respiratory variables during active and quiet sleep in preterm infants ready for discharge and compare variables recorded supine in a cot with those recorded supine in a car seat, in particular, to determine whether more obstructive events occurred after transfer to the car seat. A second aim was to compare car seat testing before discharge with concurrent polysomnography (PSG) recording to determine if a nurse‐observed test was a sensitive enough predictor of respiratory instability, and in particular airway obstruction, found on PSG.     

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.     

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.     

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.     

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.     

New height, weight and head circumference charts for British children with Williams syndrome

Aim

To produce a growth reference for British children with Williams syndrome.

Methods

The children and adults recruited into the study were all affiliated to the Williams Syndrome Foundation, a parent support group founded in 1979. They have all been shown to have a deletion of chromosome 7q11.23. One growth nurse (WRS) prospectively measured the weight, height and head circumference of individuals from 19 regions in Great Britain including Scotland, England and Wales. 169 children and adults were measured on up to four occasions between 2001 and 2004 (275 measurements). In addition, retrospective data were obtained from the hospital notes of 67 of these individuals (586 measurements). Centile curves were constructed using Cole''s LMS method.

Results

The centile charts differ from charts previously derived in the USA and Germany and provide more appropriate standards for the British population.

Conclusions

We propose that these charts be adopted for routine clinical practice as abnormalities in growth are an important feature of this syndrome.Short stature is a recognised feature of Williams syndrome. This syndrome was first described in 1961 as a triad of supravalvular aortic stenosis, learning difficulties and unusual facial features.¹ It was quickly recognised as being linked with infantile hypercalcaemia and in 1993, Ewart et al demonstrated the presence of a micro deletion on chromosome 7 (del 7q11.23) in all children with this syndrome.^2,3 To date, 28 genes have been detected within this region, including the elastin gene. The genes responsible for the developmental abnormalities and hypercalcaemia remain to be determined. A number of large cohort studies have described the presence of low birth weight, failure to thrive in infancy, short stature and precocious puberty.^4,5,6 In addition to congenital heart disease and infantile hypercalcaemia, children with Williams syndrome have been described as having hypothyroidism,⁷ growth hormone insufficiency^8,9 and coeliac disease.¹⁰ These diverse conditions make accurate assessment of growth an essential requirement of health surveillance.Morris et al produced growth charts for children with Williams syndrome in 1988 from retrospective, cross‐sectional data collected from American children attending either their clinic in Salt Lake City, Utah or a Williams Syndrome National Association meeting in 1986.¹¹ The mean adult heights of males and females were 167 and 157 cm, respectively. Pankau et al published retrospective data from a cohort of German children with Williams syndrome and in this population mean adult heights for males and females were 168 and 154 cm, respectively.¹² Both these studies were published before the gene deletion had been identified. Partsch et al subsequently documented a prospective study of a cohort of the same German children in 1999 but again the diagnosis was only confirmed genetically in 44% of cases.⁶ Mean adult heights for this cohort of males and females were 165 and 152 cm, respectively. The most recent British data were published by Martin et al in 1984 and in that cohort mean adult heights for males and females were 159 and 147 cm, respectively. Therefore, we identified the need for a contemporary British growth reference for children with genetically diagnosed Williams syndrome.⁴     

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.     

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.     

Is there an intrauterine influence on obesity? Evidence from parent–child associations in the Avon Longitudinal Study of Parents and Children (ALSPAC)

Background

It has been suggested that increasing obesity levels in young women lead to intrauterine environments that, in turn, stimulate increased obesity among their offspring, generating an intergenerational acceleration of obesity levels. If this mechanism is important, the association of maternal body mass index (BMI) with offspring BMI should be stronger than the association of paternal with offspring BMI.

Objective

To compare the relative strengths of association of maternal and paternal BMI with offspring BMI at age 7.5, taking into account the possible effect of non‐paternity.

Methods

We compared strength of association for maternal–offspring and paternal–offspring BMI for 4654 complete parent–offspring trios in the Avon Longitudinal Study of Parents and Children (ALSPAC), using unstandardised and standardised regression analysis. We carried out a sensitivity analysis to investigate the influence of non‐paternity on these associations.

Results

The strength of association between parental BMI and offspring BMI at age 7.5 was similar for both parents. Taking into account correlations between maternal and paternal BMI, performing standardised rather than unstandardised regression and carrying out a sensitivity analysis for non‐paternity emphasised the robustness of the general similarity of the associations. The associations between high parental BMI (top decile) and offspring BMI are also similar for both parents.

Conclusion

Comparison of mother–offspring and father–offspring associations for BMI suggests that intergenerational acceleration mechanisms do not make an important contribution to levels of childhood BMI within the population. Associations at later ages and for different components of body composition now require study.The increasing prevalence of obesity among children and adults in many countries constitutes a potentially serious threat to the future health of these populations.^1,2,3 The importance of a shift in the balance of energy intake to energy expenditure as the proximal determinant of rising obesity levels is generally recognised,¹ with changes in social organisation and local, national and international economic forces being seen to underlie this pattern.⁴ In addition, there is evidence to support a role for prenatal influences on childhood and adulthood obesity.^5,6,7 Maternal obesity may lead to greater placental transfer of nutrients during embryonic and fetal development, leading to permanent changes in appetite, metabolism and the neuroendocrine function of offspring.⁵ Studies in animal models have provided some support for the existence of such mechanisms.⁸The consequence of this influence of maternal body composition on offspring body composition, mediated through the intrauterine environment, would be an intergenerational acceleration in obesity levels.^1,7 Changes in the balance of energy intake and energy expenditure, leading to an increase in obesity in mothers, would, through such intrauterine processes, generate increases in obesity among offspring. When the female offspring in turn produce their own offspring, the latter will be destined to experience further increases in obesity through the influence of the obesity levels of their mothers on the intrauterine environment they encounter. This feed‐forward mechanism would lead to an intergenerational acceleration of obesity levels, over and above the acute effects of shifts in the balance between energy intake and energy expenditure within populations.There is clear evidence that mothers with gestational diabetes have offspring with increased obesity levels in childhood and adolescence,⁹ although the degree to which this persists into adulthood is uncertain.¹⁰ The strongest evidence for a specific effect of diabetes during pregnancy on offspring body mass index (BMI) comes from a study of siblings discordant for maternal diabetes during pregnancy.¹¹ At age 22, the sibling exposed to a maternal diabetic environment had, on average, higher BMI than the unexposed sibling. No influence of paternal diabetes was seen on offspring BMI, suggesting that the intrauterine environment, rather than a simple genetic mechanism, was responsible.Raised BMI will generate a lesser degree of metabolic disturbance than that seen with diabetes, and the influence of this more modest exposure on offspring BMI is not well delineated. One approach to this issue, that would allow estimation of the potential importance of any intergenerational acceleration in obesity levels, is to compare associations between maternal BMI and offspring BMI with those between paternal BMI and offspring BMI. If maternal BMI has an influence on offspring BMI through intrauterine effects, the expectation would be of a stronger correlation of maternal than paternal BMI with offspring BMI. Few studies have approached this issue, and the available data have not been presented in a way that allows formal comparison of the magnitude of associations. Existing studies have yielded conflicting findings, generally from small sample sizes.^{12,13,14,15,16,17} We have therefore examined this issue in the Avon Longitudinal Study of Parents and Children (ALSPAC), producing directly comparable estimates of maternal and paternal BMI associations with offspring BMI, while taking into account plausible degrees of non‐paternity.     

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.     

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).