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.     

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

Objective

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

Methods

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

Results

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

Conclusions

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

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.     

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.     

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.     

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.     

Chest computed tomography findings in bronchopulmonary dysplasia and correlation with lung function

Objective

With changes in the predominant pathogenic factors in the new form of bronchopulmonary dysplasia (BPD), a different pattern of CT findings may be expected. This study aimed to (1) describe CT findings in infants with BPD and (2) correlate the CT findings with lung function abnormalities.

Study design and method

Retrospective review of 41 very low birthweight infants with BPD, who were referred for pulmonary investigations at between 10 and 20 months after birth because of persistent respiratory symptoms, and underwent CT and lung function tests.

Results

None of the infants had normal CT findings. The most frequent abnormalities were hyperlucent areas (n = 36; 88%), linear opacities (n = 39; 95%), and triangular subpleural opacities (n = 26; 63%). Bronchiectasis was not seen. None of the CT abnormalities correlated with the maximum expiratory flow at functional residual capacity (VmaxFRC). In contrast, increased number of subpleural opacities and limited linear opacities were associated with low FRC and longer duration of neonatal oxygen exposure. The numbers of triangular subpleural opacities also correlated with duration of mechanical ventilation.

Conclusions

Despite advances in neonatal care, many CT findings in infants with BPD are similar to those observed in the pre‐surfactant era, and are still associated with duration of supplemental oxygen and mechanical ventilation. The absence of bronchial involvement in the present study was the most striking difference from previous studies.Despite considerable obstetric and neonatal advances in the care of very low birthweight infants, bronchopulmonary dysplasia (BPD) continues to occur in 25–30% of surviving infants.1 BPD was initially described in premature infants who were supported with only supplemental oxygen and mechanical ventilation. As new treatment options became available, the characteristics of BPD changed. Before the surfactant treatment era, airway injury, inflammation and parenchymal fibrosis were the prominent findings in BPD.2,3 The “new” BPD seems to be a result of arrested lung development, characterised by abnormal alveolar septation and microvascular maturation. Husain and colleagues characterised this “new” BPD on the basis of autopsy lung specimens from surfactant‐treated infants with BPD.4 The consistent findings were negligible epithelial changes in the airways and a simplified distal lung due to impaired alveolarisation.4,5 The reduced risk of severe airway injury and the primary importance of arrested lung growth are associated with modifications in long‐term alterations in lung function tests. Small lung volumes are now a characteristic feature of infants with BPD whereas severe chronic airway obstruction is no longer seen.6,7 Similar to the changes seen in lung function tests, a different pattern of CT findings may be expected with changes in the main pathogenic factors of BPD. Previous CT findings included reticular opacities, multifocal areas of reduced density and marked bronchial wall thickening.8,9,10No recent study has reported both the results of lung function tests and CT evaluation in infants with BPD. Here we report on CT lesions in 1–2‐year‐old infants with BPD who were born before 32 weeks'' gestation and underwent investigations for persistent respiratory symptoms. We also correlated the CT findings with lung function abnormalities and examined the relative contributions of birth weight, gestational age and neonatal respiratory illness to the CT and lung function test findings.     

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.     

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.     

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.     

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.     

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.     

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 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.     

Zinc, copper, selenium and manganese blood levels in preterm infants

Objective

To measure the zinc, copper, selenium and manganese blood levels in a cohort of 68 preterm infants, and to establish any associations with growth and/or dietary intake.

Design

Blood samples were collected at an infant''s expected date of delivery (term) and 6 months later. Serum zinc, plasma copper and whole blood manganese were analysed by atomic absorption spectrometry, plasma and red cell selenium were determined by mass spectrometry. Growth and dietary intake determinations have been previously published.

Setting

Hampshire, England.

Results

Mean (SD) birth weight of the infants was 1.47 (0.434) kg and mean gestation was 31.4 (2.9) weeks. Mean blood levels at term and 6 months were: serum zinc 12.0 (2.6) µmol/l and 13.8 (2.5) µmol/l; plasma copper 10.1 (2.6) µmol/l and 19.2 (3.6) µmol/l; plasma selenium 0.49 (0.15) µmol/l and 0.72 (0.14) µmol/l; red blood cell selenium 1.68 (0.40) µmol/l and 1.33 (0.19) µmol/l; and blood manganese 320 (189) nmol/l and 211 (68) nmol/l, respectively. There were no significant associations between levels of zinc and copper and dietary intakes of those nutrients at either age (dietary intakes of selenium and manganese were not determined). Only copper levels at term were significantly associated (r = 0.31; p = 0.05) with a growth parameter (head circumference).

Conclusion

These results provide new information about trace element status in this vulnerable population.Trace elements are essential nutrients for metabolism, growth, and neurological and immunological function.1,2,3 Zinc is an important micronutrient that supports normal growth.2 Preterm infants are especially vulnerable to zinc deficiency.4,5 Selenium is an essential component of selenoproteins including the antioxidant glutathione peroxidase. At birth, blood levels of selenium are lower in preterm infants than in term infants and continue to fall until weaning is commenced.6,7,8 Copper is a cofactor in several metalloproteins, essential for oxidative metabolism, myelination and the metabolism of several steroid hormones.2 Clinical copper deficiency is a recognised hazard among preterm infants.9 Manganese is an essential micronutrient component of several enzymes including pyruvate carboxylase, mitochondrial superoxide dismutase and enzymatic systems of matrix turnover in skeletal growth.10,11 The measurement of the variation in trace element blood levels in preterm infants throughout infancy, and the range of levels associated with good development are important areas of research.We have previously reported a randomised clinical trial of a specially devised nutritional strategy in preterm infants.12 The trial aimed to analyse blood mineral levels at term (expected date of delivery) and 6 months'' gestation corrected age (GCA), and assess dietary intake and growth at these ages. As we did not find any significant differences in the blood levels of trace elements in the two arms of the trial, in this paper we report on the combined results of all infants enrolled in the trial to provide information on zinc, selenium, copper and manganese blood levels in a healthy population of UK preterm infants. The interaction between growth and dietary intake and blood biochemistry is also explored.     

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.     

MMR: marginalised,misrepresented and rejected? Autism: a focus group study

Objective

To explore how the measles, mumps, and rubella (MMR) vaccine controversy impacted on the lives of parents caring for children with autism.

Design

Qualitative focus group study.

Setting

United Kingdom.

Patients

A purposively selected sample of 38 parents took part in 10 focus group discussions between March 2003 and May 2005.

Results

Many parents felt that the MMR vaccine could be too potent for children who are susceptible to developing autism. Of the parents whose children received the MMR vaccine, many felt guilty that they may have caused or contributed to their child''s autism. Some parents felt frustrated by health professionals'' lack of understanding of the negative impact the MMR controversy has had on them. Some parents were anxious about subsequent MMR decision‐making for their children.

Conclusions

The controversy has had a negative impact on some parents of children with autism. This has implications for health professionals, who need to be particularly aware of the issues these parents face in future MMR decision‐making for their affected child and younger siblings. It is anticipated that these findings will raise awareness among health professionals of the difficulties faced by such parents. More generally, there is a need to promote a greater awareness of the important role health visitors can play in parental decision‐making and for research examining whether health professionals feel they receive sufficient training in communication skills. It is also essential that the latest scientific research findings are disseminated quickly to these parents and to those health professionals advising parents on matters of vaccine safety.The combined measles, mumps, and rubella (MMR) vaccine was introduced in the United Kingdom (UK) into the routine childhood immunisation programme in 1988, replacing the monocomponent measles vaccine, in order to eliminate measles, mumps and rubella and its associated congenital rubella syndrome.^1,2,3 By the early 1990s, MMR coverage for 2 year old children exceeded 90% nationally.⁴ However, just as rates of measles notification were reaching an all time low, speculation about the safety of the vaccine began to emerge. In February 1998, a paper was published postulating a link between the MMR vaccine, bowel disease and autism.⁵ Wakefield and colleagues hypothesised that the vaccine caused inflammation of the gut making it more permeable, permitting peptides to leak out, which in turn were said to act as toxins on the brain causing serious developmental disorders (including autism). The paper sparked immediate criticism and concern,^6,7,8,9 and researchers were quick to test Wakefield''s hypothesis. However, subsequent scientific support has been absent,^10,11 and further experiments designed to identify the measles virus in intestinal tissue¹² or blood¹³ have failed to find vaccine viruses. Furthermore, researchers have been unable to identify significant intestinal inflammation post‐vaccination¹⁴; large epidemiological studies have found no evidence of a new form of autism associated with MMR^15,16; there is no evidence of an increased incidence of autism related to the uptake of the MMR or measles vaccines^17,18; studies investigating severe adverse reactions to the MMR vaccine conducted in Finland^19,20 have failed to identify bowel problems or autism following vaccination; and a recent Cochrane review concluded that exposure to MMR was unlikely to be associated with autism.²¹

Box 1 Examples of parents comparing the general health of their children with and without autism

“they''re like chalk and cheese, she''s a much stronger child, she, she never had a thing where he was just sickly from day one. He''s always been a sickly child… he was always covered in spots, he was always on antibiotics, he always had tonsillitis, erm… he''s always had bowel problems, em…. He''s always had loads and loads of antibiotics. He''s got asthma and eczema, erm, so he''s always been on creams and lotions and potions and God knows what else. He''s got food allergies.… He''s very, very sensitive to whatever goes in his body. But as for our daughter she''s a much stronger child.” (G3: P9)“… his immune system is shot to pieces…. He, he does seem to be one of these children who follows the, the path for antibiotics and then vaccinations and then autism. When he gets a cough or a cold he seems to have it much, much longer whereas my other son can carry on functioning and going to school. But he just gets really ill… it puts him into hospital…. I actually asked the consultant before he discharged him last time. I said ‘you know, he does seem to be poorly a lot of the time, you know and he does have autism and I think there''s a link between his autism and his immune system'' and the consultant said ‘no, that''s absolutely not true, there''s no correlation between autism and the immune, his immune system''. He dismissed it – so I said ‘well okay'' but I just felt that I had to say something.” (G10: P36)Despite government and public health officials acting quickly to reassure parents that the MMR vaccine was not associated with autism, vaccine uptake dropped following the widespread media coverage of the MMR vaccine controversy (see: http://www.hpa.org.uk/infections/topics_az/vaccination/071102_MMRpreferable.htm). Recent research has investigated parents'' reasons for refusing the MMR vaccine and their perceptions of the MMR controversy. Evans and colleagues suggested that for many parents it is easier to live with the risk of their child naturally contracting one of the diseases than with the risk of causing their child damage through vaccination,²² a finding reminiscent of previous work on omission bias.^23,24 Raithatha et al²⁵ highlighted how parents'' assessment of vaccine risk is influenced by their attitudes to the immunisation process as well as by the degree of trust they have in government and health professionals. They warned that the MMR controversy may have triggered a broader reappraisal of vaccine risk, and proposed that in order to address parents'' fears about a causal link between autism and the MMR vaccine, further research into the aetiology of autism should be conducted. This was echoed in the recommendations from the Medical Research Council''s (MRC) review of autism research.²⁶Despite this growing evidence base on parental views of decision‐making about MMR,^22,23,24 there is a notable absence of scientific research reporting the views of one crucial group of parents, namely those caring for children with autism. To date their stories have been represented by journalists^27,28 or through a few books in which parents offer their personal accounts.^29,30,31,32 Horton³³ asserted that parents of children with autism: “… have become an even more marginalized group in the high‐temperature debate over Wakefield''s work” (p 92).

Box 2 Example of a mother recalling an adverse reaction to MMR vaccination

“He was ill. You know, when they''re really, really poorly and they''ve a temperature and they''ve just got that look of, I''m not here, that''s scary as a parent, you''re scared. And then when he finally kind of awoke, you know, he had the deadest eyes, it was like all the life had gone from his eyes. It was like before he was like a wee boy, twinkly eyes and after it, it was like the same eyeballs but as if, the glare had been taken out of them or something.” (G1: P1)Since the putative link with autism was central to the MMR controversy, it is important to understand the views of parents of children with autism both in terms of the impact of the controversy on them, and in determining whether the controversy has given rise to particular needs for information and support. We undertook a study to elicit the views of this neglected group of parents to develop a better understanding of how the MMR controversy impacted upon their lives, and to discover whether their experience can provide lessons for future immunisation policy and practice.     

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.