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Year of Publication
1.  Safety of new medicines in young children 
Archives of Disease in Childhood  2011;96(9):872-873.
doi:10.1136/archdischild-2011-300450
PMCID: PMC3198508  PMID: 21836178
2.  Corrections 
doi:10.1136/adc.2010.170118
PMCID: PMC3859681
3.  Evaluation of temperature–pulse centile charts in identifying serious bacterial illness: observational cohort study 
Archives of Disease in Childhood  2011;96(4):368-373.
Background
Distinguishing serious bacterial infection (SBI) from milder/self-limiting infections is often difficult. Interpretation of vital signs is confounded by the effect of temperature on pulse and respiratory rate. Temperature–pulse centile charts have been proposed to improve the predictive value of pulse rate in the clinical assessment of children with suspected SBI.
Objectives
To assess the utility of proposed temperature–pulse centile charts in the clinical assessment of children with suspected SBI.
Study design and participants
The predictive value for SBI of temperature–pulse centile categories, pulse centile categories and Advanced Paediatric Life Support (APLS) defined tachycardia were compared among 1360 children aged 3 months to 10 years presenting with suspected infection to a hospital emergency department (ED) in England; and among 325 children who presented to hospitals in the UK with meningococcal disease.
Main outcome measure
SBI.
Results
Among children presenting to the ED, 55 (4.0%) had SBI. Pulse centile category, but not temperature–pulse centile category, was strongly associated with risk of SBI (p=0.0005 and 0.288, respectively). APLS defined tachycardia was also strongly associated with SBI (OR 2.90 (95% CI 1.60 to 5.26), p=0.0002). Among children with meningococcal disease, higher pulse and temperature–pulse centile categories were both associated with more severe disease (p=0.004 and 0.041, respectively).
Conclusions
Increased pulse rate is an important predictor of SBI, supporting National Institute for Health and Clinical Excellence recommendations that pulse rate be routinely measured in the assessment of febrile children. Temperature–pulse centile charts performed more poorly than pulse alone in this study. Further studies are required to evaluate their utility in monitoring the clinical progress of sick children over time.
doi:10.1136/adc.2010.183129
PMCID: PMC3158667  PMID: 21233079
4.  Monitoring head size and growth using the new UK-World Health Organization growth standard 
Archives of disease in childhood  2011;96(4):386-388.
In order to assess the extent to which children in the United Kingdom (UK) will follow the UK-WHO head circumference standard, we used head circumference data from the Southampton Women’s Survey (SWS; n=3159) and the Avon Longitudinal Study of Parents and Children (ALSPAC; n=15,208) in children age 0-36 months, converted into z-scores using both the UK-WHO or UK1990 references. Rapid head growth was defined as crossing upwards through 2 major centile bands (1.33 SD). The UK-WHO standard identified many more infants with heads above the 98th centile compared to the UK1990 reference (UK-WHO 6% to 16% of infants at various ages, UK1990 1% to 4%). Rapid head growth in the first 6 to 9 months was also much more common using the UK-WHO standard (UK-WHO: 14.6% to 15.3%; UK1990: 4.8% to 5.1%). Practitioners should be aware of these findings to avoid unnecessary referrals.
doi:10.1136/adc.2010.200030
PMCID: PMC3685130  PMID: 21285227
ALSPAC; head circumference; growth charts; macrocephaly; microcephaly; hydrocephalus
5.  Distinguishing infant prolonged crying from sleep-waking problems 
Archives of disease in childhood  2011;96(4):340-344.
Objective
Infants who cry a lot, or are unsettled in the night, are common sources of concern for parents and costly problems for health services. The two types of problems have been linked together and attributed to a general disturbance of infant regulation. Yet the infant behaviours involved present differently, at separate ages and times of day. To clarify causation, this study aims to assess whether prolonged crying at 5–6 weeks (the peak age for crying) predicts which infants are unsettled in the night at 12 weeks of age (when most infants become settled at night).
Methods
Data from two longitudinal studies are analysed. Infant crying data were obtained from validated behaviour diaries; sleep-waking data from standard parental questionnaires.
Results
A significant, weak relationship was found between crying at 5–6 weeks and 12-week night waking and signalling in one study, but not the other. Most infants who met the definition for prolonged crying/colic at 5–6 weeks were settled during the night at 12 weeks of age; they were not more likely than other infants to be unsettled.
Conclusions
Most infants who cry a lot at 5–6 weeks of age ‘sleep through the night’ at 12 weeks of age. This adds to evidence that the two types of problematic behaviour have different causes, and that infant sleep-waking problems usually involve maintenance of signalling behaviours rather than a generalised disturbance.
doi:10.1136/adc.2010.200204
PMCID: PMC3202670  PMID: 21220260
6.  What clinical signs best identify severe illness in young infants aged 0–59 days in developing countries? A systematic review 
Archives of disease in childhood  2011;96(11):1052-1059.
Despite recent overall improvement in the survival of under-five children worldwide, mortality among young infants remains high, and accounts for an increasing proportion of child deaths in resource-poor settings. In such settings, clinical decisions for appropriate management of severely ill infants have to be made on the basis of presenting clinical signs, and with limited or no laboratory facilities. This review summarises the evidence from observational studies of clinical signs of severe illnesses in young infants aged 0–59 days, with a particular focus on defining a minimum set of best predictors of the need for hospital-level care. Available moderate to high quality evidence suggests that, among sick infants aged 0–59 days brought to a health facility, the following clinical signs—alone or in combination—are likely to be the most valuable in identifying infants at risk of severe illness warranting hospital-level care: history of feeding difficulty, history of convulsions, temperature (axillary) ≥37.5°C or <35.5°C, change in level of activity, fast breathing/respiratory rate ≥60 breaths per minute, severe chest indrawing, grunting and cyanosis.
doi:10.1136/adc.2010.186049
PMCID: PMC3081806  PMID: 21220263
8.  What causes attention deficit hyperactivity disorder? 
Archives of Disease in Childhood  2011;97(3):260-265.
Attention deficit hyperactivity disorder (ADHD) affects around 1–3% of children. There is a high level of comorbidity with developmental and learning problems as well as with a variety of psychiatric disorders. ADHD is highly heritable, although there is no single causal risk factor and non-inherited factors also contribute to its aetiology. The genetic and environmental risk factors that have been implicated appear to be associated with a range of neurodevelopmental and neuropsychiatric outcomes, not just ADHD. The evidence to date suggests that both rare and multiple common genetic variants likely contribute to ADHD and modify its phenotype. ADHD or a similar phenotype also appears to be more common in extreme low birth weight and premature children and those exposed to exceptional early adversity. In this review, the authors consider recent developments in the understanding of risk factors that influence ADHD.
doi:10.1136/archdischild-2011-300482
PMCID: PMC3927422  PMID: 21903599
9.  Feather bedding and childhood asthma associated with house dust mite sensitisation: a randomised controlled trial 
Archives of Disease in Childhood  2011;96(6):541-547.
Introduction
Observational studies report inverse associations between the use of feather upper bedding (pillow and/or quilt) and asthma symptoms but there is no randomised controlled trial (RCT) evidence assessing the role of feather upper bedding as a secondary prevention measure.
Objective
To determine whether, among children not using feather upper bedding, a new feather pillow and feather quilt reduces asthma severity among house dust mite (HDM) sensitised children with asthma over a 1-year period compared with standard dust mite avoidance advice, and giving children a new mite-occlusive mattress cover.
Design
RCT.
Setting
The Calvary Hospital in the Australian Capital Territory and the Children's Hospital at Westmead, Sydney, New South Wales.
Patients
197 children with HDM sensitisation and moderate to severe asthma.
Intervention
New upper bedding duck feather pillow and quilt and a mite-occlusive mattress cover (feather) versus standard care and a mite-occlusive mattress cover (standard).
Main outcome measures
The proportion of children reporting four or more episodes of wheeze in the past year; an episode of speech-limiting wheeze; or one or more episodes of sleep disturbance caused by wheezing; and spirometry with challenge testing. Statistical analysis included multiple logistic and linear regression.
Results
No differences between groups were found for primary end points – frequent wheeze (OR 1.51, 95% CI 0.83 to 2.76, p=0.17), speech-limiting wheeze (OR 0.70, 95% CI 0.32 to 1.48, p=0.35), sleep disturbed because of wheezing (OR 1.17, 95% CI 0.64 to 2.13, p=0.61) or for any secondary end points. Secondary analyses indicated the intervention reduced the risk of sleep being disturbed because of wheezing and severe wheeze to a greater extent for children who slept supine.
Conclusion
No differences in respiratory symptoms or lung function were observed 1 year after children with moderate–severe asthma and HDM sensitisation were given a mite-occlusive mattress cover and then received either feather upper bedding (pillow and quilt) or standard bedding care.
doi:10.1136/adc.2010.189696
PMCID: PMC3093241  PMID: 21451166
10.  Maternal smoking during pregnancy and offspring growth in childhood: 1993 and 2004 Pelotas cohort studies 
Archives of Disease in Childhood  2011;96(6):519-525.
Objective
To explore the effects of maternal smoking during pregnancy on offspring growth using three approaches: (1) multiple adjustments for socioeconomic and parental factors, (2) maternal–paternal comparisons as a test of putative intrauterine effects and (3) comparisons between two birth cohort studies.
Methods
Population-based birth cohort studies were carried out in Pelotas, Brazil, in 1993 and 2004. Cohort members were followed up at 3, 12, 24 and 48 months. Multiple linear regression analysis was used to examine the relationships between maternal and paternal prenatal smoking and offspring anthropometric indices. In the 2004 cohort, the association of smoking with trunk length, leg length and leg-to-sitting-height ratio at 48 months was also explored.
Results
Maternal smoking during pregnancy was associated with reduced z scores of length/height-for-age at each follow-up in both cohorts and reduced leg length at 48 months in the 2004 cohort. Children older than 3 months born to smoking women showed a higher body mass index-for-age z score than children of non-smoking women.
Conclusions
The results of this study strongly support the hypothesis that maternal smoking during pregnancy impairs linear growth and promotes overweight in childhood.
doi:10.1136/adc.2010.191098
PMCID: PMC3093240  PMID: 21377989
11.  Detection of child abuse in emergency departments: a multi-centre study 
Archives of Disease in Childhood  2011;96(5):422-425.
Objective
This study examines the detection rates of suspected child abuse in the emergency departments of seven Dutch hospitals complying and not complying with screening guidelines for child abuse.
Design
Data on demographics, diagnosis and suspected child abuse were collected for all children aged ≤18 years who visited the emergency departments over a 6-month period. The completion of a checklist of warning signs of child abuse in at least 10% of the emergency department visits was considered to be compliance with screening guidelines.
Results
A total of 24 472 visits were analysed, 54% of which took place in an emergency department complying with screening guidelines. Child abuse was suspected in 52 children (0.2%). In 40 (77%) of these 52 cases, a checklist of warning signs had been completed compared with a completion rate of 19% in the total sample. In hospitals complying with screening guidelines for child abuse, the detection rate was higher (0.3%) than in those not complying (0.1%, p<0.001).
Conclusion
During a 6-month period, emergency department staff suspected child abuse in 0.2% of all children visiting the emergency department of seven Dutch hospitals. The numbers of suspected abuse cases detected were low, but an increase is likely if uniform screening guidelines are widely implemented.
doi:10.1136/adc.2010.202358
PMCID: PMC3075563  PMID: 21278429
12.  Prevalence, profile and predictors of malnutrition in children with congenital heart defects: a case–control observational study 
Archives of Disease in Childhood  2011;96(4):354-360.
Objective
To investigate the prevalence, profile and predictors of severe malnutrition in children with congenital heart defects (CHDs).
Design
Case–control, observational study.
Setting
Tertiary teaching hospital in Lagos, Nigeria (March 2006 to March 2008).
Participants
Children aged 3–192 months with uncorrected symptomatic CHD and healthy controls, frequency matched for age and sex.
Main outcome measures
Prevalence of malnutrition based on WHO/National Center for Health Statistics/Centers for Disease Control and Prevention z score ≤−2; weight for age, weight for height/length and height for age; proportions of underweight, wasting and stunting in cases and controls, and in acyanotic and cyanotic CHD; and predictors of malnutrition using multivariate logistic analysis.
Results
90.4% of cases and 21.1% of controls had malnutrition (p=0.0001), and 61.2% and 2.6%, respectively, had severe malnutrition (p=0.0001). Wasting, stunting and underweight were identified in 41.1%, 28.8% and 20.5%, and 2.6%, 3.9% and 14.5% of cases and controls, respectively. Wasting was significantly higher (58.3%) in acyanotic CHD (p=0.0001), and stunting (68.0%) in cyanotic CHD (p=0.0001). Age at weaning was significantly lower in cases than controls (3.24±0.88 and 7.04±3.04 months, respectively; p=0.0001) and in acyanotic than cyanotic CHD (2.14±0.33 and 5.33±1.22 months, respectively; p=0.004). Predictors of malnutrition in CHD were anaemia, moderate to severe congestive heart failure (CHF), poor dietary intake of fat and prolonged unoperated disease.
Conclusion
Severe malnutrition in association with anaemia and moderate to severe CHF is highly prevalent in CHD preoperatively in these children. Early weaning may be a marker of feeding difficulties in heart failure.
doi:10.1136/adc.2009.176644
PMCID: PMC3056291  PMID: 21266339
13.  Ciprofloxacin safety in paediatrics: a systematic review 
Archives of Disease in Childhood  2011;96(9):874-880.
Objective
To determine the safety of ciprofloxacin in paediatric patients in relation to arthropathy, any other adverse events (AEs) and drug interactions.
Methods
A systematic search of MEDLINE, EMBASE, CINAHL, CENTRAL and bibliographies of relevant articles was carried out for all published articles, regardless of design, that involved the use of ciprofloxacin in any paediatric age group ≤17 years. Only articles that reported on safety were included.
Results
105 articles met the inclusion criteria and involved 16 184 paediatric patients. There were 1065 reported AEs (risk 7%, 95% CI 3.2% to 14.0%). The most frequent AEs were musculoskeletal AEs, abnormal liver function tests, nausea, changes in white blood cell counts and vomiting. There were six drug interactions (with aminophylline (4) and methotrexate (2)). The only drug related death occurred in a neonate who had an anaphylactic reaction. 258 musculoskeletal events occurred in 232 paediatric patients (risk 1.6%, 95% CI 0.9% to 2.6%). Arthralgia accounted for 50% of these. The age of occurrence of arthropathy ranged from 7 months to 17 years (median 10 years). All cases of arthropathy resolved or improved with management. One prospective controlled study estimated the risk of arthropathy as 9.3 (OR 95% CI 1.2 to 195). Pooled safety data of controlled trials in this review estimated the risk of arthropathy as 1.57 (OR 95% CI 1.26 to 1.97).
Conclusion
Musculoskeletal AEs occur due to ciprofloxacin use. However, these musculoskeletal events are reversible with management. It is recommended that further prospective controlled studies should be carried out to evaluate the safety of ciprofloxacin, with particular focus on the risk of arthropathy.
doi:10.1136/adc.2010.208843
PMCID: PMC3155117  PMID: 21785119
14.  Increased protein-energy intake promotes anabolism in critically ill infants with viral bronchiolitis: a double‑blind randomised controlled trial 
Archives of Disease in Childhood  2011;96(9):817-822.
Objective
The preservation of nutritional status and growth is an important aim in critically ill infants, but difficult to achieve due to the metabolic stress response and inadequate nutritional intake, leading to negative protein balance. This study investigated whether increasing protein and energy intakes can promote anabolism. The primary outcome was whole body protein balance, and the secondary outcome was first pass splanchnic phenylalanine extraction (SPEPhe).
Design
This was a double-blind randomised controlled trial. Infants (n=18) admitted to the paediatric intensive care unit with respiratory failure due to viral bronchiolitis were randomised to continuous enteral feeding with protein and energy enriched formula (PE-formula) (n=8; 3.1±0.3 g protein/kg/24 h, 119±25 kcal/kg/24 h) or standard formula (S-formula) (n=10; 1.7±0.2 g protein/kg/24 h, 84±15 kcal/kg/24 h; equivalent to recommended intakes for healthy infants <6 months). A combined intravenous-enteral phenylalanine stable isotope protocol was used on day 5 after admission to determine whole body protein metabolism and SPEPhe.
Results
Protein balance was significantly higher with PE-formula than with S-formula (PE-formula: 0.73±0.5 vs S-formula: 0.02±0.6 g/kg/24 h) resulting from significantly increased protein synthesis (PE-formula: 9.6±4.4, S-formula: 5.2±2.3 g/kg/24 h), despite significantly increased protein breakdown (PE-formula: 8.9±4.3, S-formula: 5.2±2.6 g/kg/24 h). SPEPhe was not statistically different between the two groups (PE-formula: 39.8±18.3%, S-formula: 52.4±13.6%).
Conclusions
Increasing protein and energy intakes promotes protein anabolism in critically ill infants in the first days after admission. Since this is an important target of nutritional support, increased protein and energy intakes should be preferred above standard intakes in these infants.
Dutch Trial Register number: NTR 515.
doi:10.1136/adc.2010.185637
PMCID: PMC3155119  PMID: 21673183
15.  Risk score to stratify children with suspected serious bacterial infection: observational cohort study 
Archives of Disease in Childhood  2011;96(4):361-367.
Objectives
To derive and validate a clinical score to risk stratify children presenting with acute infection.
Study design and participants
Observational cohort study of children presenting with suspected infection to an emergency department in England. Detailed data were collected prospectively on presenting clinical features, laboratory investigations and outcome. Clinical predictors of serious bacterial infection (SBI) were explored in multivariate logistic regression models using part of the dataset, each model was then validated in an independent part of the dataset, and the best model was chosen for derivation of a clinical risk score for SBI. The ability of this score to risk stratify children with SBI was then assessed in the entire dataset.
Main outcome measure
Final diagnosis of SBI according to criteria defined by the Royal College of Paediatrics and Child Health working group on Recognising Acute Illness in Children.
Results
Data from 1951 children were analysed. 74 (3.8%) had SBI. The sensitivity of individual clinical signs was poor, although some were highly specific for SBI. A score was derived with reasonable ability to discriminate SBI (area under the receiver operator characteristics curve 0.77, 95% CI 0.71 to 0.83) and risk stratify children with suspected SBI.
Conclusions
This study demonstrates the potential utility of a clinical score in risk stratifying children with suspected SBI. Further work should aim to validate the score and its impact on clinical decision making in different settings, and ideally incorporate it into a broader management algorithm including additional investigations to further stratify a child's risk.
doi:10.1136/adc.2010.183111
PMCID: PMC3158666  PMID: 21266341
16.  Assent for children's participation in research is incoherent and wrong 
Archives of Disease in Childhood  2011;96(10):960-962.
When children are considered for participation in research, British and international guidelines suggest that they should provide assent in addition to their parents' consent. However, examination of these guidelines shows there is confusion regarding the concept of assent. Furthermore, the need for assent may cause problems. The guidelines should be revised: the parents of incompetent children should consent for them and competent children should consent on their own behalf.
doi:10.1136/adc.2011.211342
PMCID: PMC3171745  PMID: 21775300
17.  What clinical signs best identify severe illness in young infants aged 0–59 days in developing countries? A systematic review 
Archives of Disease in Childhood  2011;96(11):1052-1059.
Despite recent overall improvement in the survival of under-five children worldwide, mortality among young infants remains high, and accounts for an increasing proportion of child deaths in resource-poor settings. In such settings, clinical decisions for appropriate management of severely ill infants have to be made on the basis of presenting clinical signs, and with limited or no laboratory facilities. This review summarises the evidence from observational studies of clinical signs of severe illnesses in young infants aged 0–59 days, with a particular focus on defining a minimum set of best predictors of the need for hospital-level care. Available moderate to high quality evidence suggests that, among sick infants aged 0–59 days brought to a health facility, the following clinical signs—alone or in combination—are likely to be the most valuable in identifying infants at risk of severe illness warranting hospital-level care: history of feeding difficulty, history of convulsions, temperature (axillary) ≥37.5°C or <35.5°C, change in level of activity, fast breathing/respiratory rate ≥60 breaths per minute, severe chest indrawing, grunting and cyanosis.
doi:10.1136/adc.2010.186049
PMCID: PMC3081806  PMID: 21220263
18.  Prevalence of wasting among under 6-month-old infants in developing countries and implications of new case definitions using WHO growth standards: a secondary data analysis 
Archives of Disease in Childhood  2011;96(11):1008-1013.
Objectives
To determine wasting prevalence among infants aged under 6 months and describe the effects of new case definitions based on WHO growth standards.
Design
Secondary data analysis of demographic and health survey datasets.
Setting
21 developing countries.
Population
15 534 infants under 6 months and 147 694 children aged 6 to under 60 months (median 5072 individuals/country, range 1710–45 398). Wasting was defined as weight-for-height z-score <−2, moderate wasting as −3 to <−2 z-scores, severe wasting as z-score <−3.
Results
Using National Center for Health Statistics (NCHS) growth references, the nationwide prevalence of wasting in infant under-6-month ranges from 1.1% to 15% (median 3.7%, IQR 1.8–6.5%; ∼3 million wasted infants <6 months worldwide). Prevalence is more than doubled using WHO standards: 2.0–34% (median 15%, IQR 6.2–17%; ∼8.5 million wasted infants <6 months worldwide). Prevalence differences using WHO standards are more marked for infants under 6 months than children, with the greatest increase being for severe wasting (indicated by a regression line slope of 3.5 for infants <6 months vs 1.7 for children). Moderate infant-6-month wasting is also greater using WHO, whereas moderate child wasting is 0.9 times the NCHS prevalence.
Conclusions
Whether defined by NCHS references or WHO standards, wasting among infants under 6 months is prevalent in many of the developing countries examined in this study. Use of WHO standards to define wasting results in a greater disease burden, particularly for severe wasting. Policy makers, programme managers and clinicians in child health and nutrition programmes should consider resource and risk/benefit implications of changing case definitions.
doi:10.1136/adc.2010.191882
PMCID: PMC3195296  PMID: 21288999
20.  Armed conflict and child health 
Summary
Armed conflict has a major impact on child health throughout the world. One in six children worldwide lives in an area of armed conflict and civilians are more likely to die than soldiers as a result of the conflict. In stark contrast to the effect on children, the international arms trade results in huge profits for the large corporations involved in producing arms, weapons and munitions. Armed conflict is not inevitable but is an important health issue that should be prevented.
doi:10.1136/adc.2009.178186
PMCID: PMC3237260  PMID: 21393303
21.  Herpes simplex serious neurological disease in young children: incidence and long-term outcome 
Archives of Disease in Childhood  2011;97(2):162-165.
Objective
To determine the contribution of herpes simplex virus (HSV) to serious neurological disease.
Setting and patients
A 3-year prospective survey of children aged 2–23 months in Britain and Ireland.
Results
19 children had HSV central nervous system (CNS) infection; 13 aged 2–11 months had focal neuroimaging abnormalities and 11 long-term neurological sequelae. Of six aged 12–35 months, one had abnormal neuroimaging and three long-term neurological sequelae. 17 of the 19 had serious neurological disease. HSV CNS infection accounted for 23% of serious neurological disease in children aged 2–11 months and 4.5% in older children.
Conclusions
The incidence of HSV-induced serious neurological disease in the UK was estimated at 1 in 64 000/year in younger children and 1 in 230 000 in older children. HSV CNS infection has clinical effects ranging from frank encephalitis to severe illness with fever and convulsions to milder disease lacking encephalopathy.
doi:10.1136/adc.2010.204677
PMCID: PMC3256733  PMID: 21685219

Results 1-21 (21)