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26.  Generalized joint hypermobility in childhood is a possible risk for the development of joint pain in adolescence: a cohort study 
BMC Pediatrics  2014;14(1):302.
Background
There is some evidence that indicates generalized joint hypermobility (GJH) is a risk factor for pain persistence and recurrence in adolescence. However, how early pain develops and whether GJH without pain in childhood is a risk factor for pain development in adolescence is undetermined. The aims for this study were to investigate the association between GJH and development of joint pain and to investigate the current GJH status and physical function in Danish adolescents.
Methods
This was a longitudinal cohort study nested within the Copenhagen Hypermobility Cohort. All children (n = 301) were examined for the exposure, GJH, using the Beighton test at baseline at either 8 or 10 years of age and then re-examined when they reached 14 years of age. The children were categorized into two groups based on their number of positive Beighton tests using different cut points (i.e. GJH4 defined as either < 4 or ≥ 4, GJH5 and GJH6 were similarly defined). The outcome of joint pain was defined as arthralgia as measured by the Brighton criteria from the clinical examination. Other outcome measures of self-reported physical function and objective physical function were also collected.
Results
Children with GJH had three times higher risk of developing joint pain in adolescence, although this association did not reach statistical significance (GJH5: 3.00, 95% [0.94-9.60]). At age 14, the adolescents with GJH had significantly lower self-reported physical function (for ADL: GJH4 p = 0.002, GJH5 p = 0.012; for pain during sitting: GJH4 p = 0.002, GJH5 p = 0.018) and had significantly higher body mass index (BMI: GJH5 p = 0.004, GJH6 p = 0.006) than adolescents without GJH. There was no difference in measured physical function.
Conclusion
This study has suggested a possible link between GJH and joint pain in the adolescent population. GJH was both a predictive and a contributing factor for future pain. Additional studies with larger sample sizes are needed to confirm our findings.
doi:10.1186/s12887-014-0302-7
PMCID: PMC4305244  PMID: 25492414
Joint laxity; Chronic pain; Joint pain; Rheumatic diseases; Pediatrics; Musculoskeletal system
27.  Management of neonatal sepsis at Muhimbili National Hospital in Dar es Salaam: diagnostic accuracy of C – reactive protein and newborn scale of sepsis and antimicrobial resistance pattern of etiological bacteria 
BMC Pediatrics  2014;14(1):293.
Background
We determined the accuracy of Rubarth’s newborn scale of sepsis and C- reactive protein in diagnosing neonatal sepsis and assessed antimicrobial susceptibility pattern of etiological bacteria.
Methods
This cross sectional study was conducted at Muhimbili National Hospital in Dar es Salaam, Tanzania between July 2012 and March 2013. Neonates suspected to have sepsis underwent physical examination using Rubarth’s newborn scale of sepsis (RNSOS). Blood was taken for culture and antimicrobial sensitivity testing, full blood picture and C – reactive protein (CRP) performed 12 hours apart. The efficacy of RNSOS and serial CRP was assessed by calculating sensitivity, specificity, negative and positive predictive values, receiver operating characteristics (ROC) analysis as well as likelihood ratios (LHR) with blood culture result used as a gold standard.
Results
Out of 208 blood samples, 19.2% had a positive blood culture. Single CRP had sensitivity and specificity of 87.5% and 70.9% respectively, while RNSOS had sensitivity of 65% and specificity of 79.7%. Serial CRP had sensitivity of 69.0% and specificity of 92.9%. Combination of CRP and RNSOS increased sensitivity to 95.6% and specificity of 56.4%. Combination of two CRP and RNSOS decreased sensitivity to 89.1% but increased specificity to 74%. ROC for CRP was 0.86; and for RNSOS was 0.81.
For CRP the LHR for positive test was 3 while for negative test was 0.18, while for RNSOS the corresponding values were 3.24 and for negative test was 0.43.
Isolated bacteria were Klebsiella spp 14 (35%), Escherichia coli 12 (22.5%), Coagulase negative staphlococci 9 (30%), Staphylococcus aureus 4 (10%), and Pseudomonas spp 1 (2.5%). The overall resistance to the WHO recommended first line antibiotics was 100%, 92% and 42% for cloxacillin, ampicillin and gentamicin, respectively. For the second line drugs resistance was 45%, 40%, and 7% for ceftriaxone, vancomycin and amikacin respectively.
Conclusions
Single CRP in combination with RNSOS can be used for rapid identification of neonates with sepsis due to high sensitivity (95.6%) but cannot exclude those without sepsis due to low specificity (56.4%). Serial CRP done 12hrs apart can be used to exclude non-cases. This study demonstrated very high levels of resistance to the first-line antibiotics.
doi:10.1186/s12887-014-0293-4
PMCID: PMC4262228  PMID: 25475836
C – Reactive protein; Newborn scale of sepsis; Hematological markers; Neonatal sepsis
28.  The Health Initiative Program for Kids (HIP Kids): effects of a 1-year multidisciplinary lifestyle intervention on adiposity and quality of life in obese children and adolescents - a longitudinal pilot intervention study 
BMC Pediatrics  2014;14(1):296.
Background
Though recent data suggest that multidisciplinary outpatient interventions can have a positive effect on childhood obesity, it is still unclear which program components are most beneficial and how they affect quality of life (QoL). The aim of this study was to determine if a 1-year multidisciplinary, family-centered outpatient intervention based on social cognitive theory would be effective in (i) preventing further increases in BMI and BMI z-score, and (ii) improving QoL in obese children and adolescents.
Methods
Obese children and adolescents 8–17 years of age and their families participated in this 1-year longitudinal pilot intervention study. The intervention consisted of fifteen 90-minute educational sessions led by a dietitian, exercise specialist, and social worker. Anthropometric measures, body composition, and QoL (Pediatric Quality of Life Inventory 4.0), were assessed at baseline, 3 months, and 12 months. Laboratory values were measured at baseline and 12 months. The primary outcome measures were change in BMI and BMI z-score, secondary outcome measures included change in QoL and body composition. A paired sample t-test was used to assess within-group differences and 95% confidence intervals were reported for the mean differences.
Results
42 obese children and adolescents (21 girls) completed the 1-year intervention (mean age 12.8 ± 3.14 years). Mean baseline BMI was 31.96 ± 5.94 kg/m2 and BMI z-score was +2.19 ± 0.34. Baseline QoL (self-assessments and parental assessments) was impaired: mean baseline scores were 74.5 ± 16.5 and 63.7 ± 19.4 for physical functioning and 69.0 ± 14.9 and 64.0 ± 18.3 for emotional functioning, respectively. At 12 months, BMI z-score had decreased (−0.07 ± 0.11, 95% CI: −0.11 to −0.04). BMI (0.80 ± 1.57 kg/m2, 95% CI 0.31 to 1.29) and fat-free mass (4.02 ± 6.27 kg, 95% CI 1.90 to 6.14) increased, but % body fat and waist circumference did not. Both the parent-reported physical (11.3 ± 19.2, 95% CI 4.7 to 17.9) and emotional (7.7 ± 15.7, 95% CI 2.3 to 13.0) functioning QoL scores and the children's self-reported physical (5.3 ± 17.1, 95% CI 0.5 to 11.1) and emotional (7.9 ± 14.3, 95% CI 3.2 to 12.7) functioning scores significantly improved.
Conclusions
Following a 1-year intervention, the participants’ BMI z-scores and QoL improved, while other adiposity-related measures of body composition remained unchanged.
Trial registration
UMIN Clinical Trials Registry UMIN000015622.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0296-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s12887-014-0296-1
PMCID: PMC4263062  PMID: 25475951
Obesity; Overweight; Behavior modification; Family-centered; BMI z-score; Nutrition; Pediatric; Outpatient; Childhood; Youth
29.  The impact of hospital-based and community based models of cerebral palsy rehabilitation: a quasi-experimental study 
BMC Pediatrics  2014;14(1):301.
Background
Cerebral palsy requires appropriate on-going rehabilitation intervention which should effectively meet the needs of both children and parents/care-givers. The provision of effective support is a challenge, particularly in resource constrained settings. A quasi-experimental pragmatic research design was used to compare the impact of two models of rehabilitation service delivery currently offered in Harare, Zimbabwe, an outreach-based programme and the other institution-based.
Method
Questionnaires were distributed to 46 caregivers of children with cerebral palsy at baseline and after three months. Twenty children received rehabilitation services in a community setting and 26 received services as outpatients at a central hospital. The Gross Motor Function Measurement was used to assess functional change. The burden of care was measured using the Caregiver Strain Index, satisfaction with physiotherapy was assessed using the modified Medrisk satisfaction with physiotherapy services questionnaire and compliance was measured as the proportion met of the scheduled appointments.
Results
Children receiving outreach-based treatment were significantly older than children in the institution-based group. Regression analysis revealed that, once age and level of severity were controlled for, children in the outreach-based treatment group improved their motor function 6% more than children receiving institution-based services.
There were no differences detected between the groups with regard to caregiver well-being and 51% of the caregivers reported signs consistent with clinical distress/depression. Most caregivers (83%) expressed that they were overwhelmed by the caregiving role and this increased with the chronicity of care. The financial burden of caregiver was predictive of caregiver strain.
Caregivers in the outreach-based group reported greater satisfaction with services and were more compliant (p < .001) as compared to recipients of institution-based services.
Conclusion
Long term caregiving leads to strain in caregivers and there is a need to design interventions to alleviate the burden. The study was a pragmatic, quasi-experimental study thus causality cannot be inferred. However findings from this study suggest that the provision of care within a community setting as part of a well-structured outreach programme may be preferable method of service delivery within a resource-constrained context. It was associated with a greater improvement in functioning, greater satisfaction with services and better compliance.
doi:10.1186/s12887-014-0301-8
PMCID: PMC4265462  PMID: 25476072
Cerebral palsy; Community based rehabilitation; Institution based intervention; Rehabilitation; Zimbabwe
30.  Intensive training of motor function and functional skills among young children with cerebral palsy: a systematic review and meta-analysis 
BMC Pediatrics  2014;14(1):292.
Background
Young children with cerebral palsy (CP) receive a variety of interventions to prevent and/or reduce activity limitations and participation restrictions. Some of these interventions are intensive, and it is a challenge to identify the optimal intensity. Therefore, the objective of this systematic review was to describe and categorise intensive motor function and functional skills training among young children with CP, to summarise the effects of these interventions, and to examine characteristics that may contribute to explain the variations in these effects.
Methods
Ten databases were searched for controlled studies that included young children (mean age less than seven years old) with CP and assessments of the effects of intensive motor function and functional skills training. The studies were critically assessed by the Risk of bias tool (RoB) and categorised for intensity and contexts of interventions. Standardised mean difference were computed for outcomes, and summarised descriptively or in meta-analyses.
Results
Thirty-eight studies were included. Studies that targeted gross motor function were fewer, older and with lower frequency of training sessions over longer training periods than studies that targeted hand function. Home training was most common in studies on hand function and functional skills, and often increased the amount of training. The effects of constraint induced movement therapy (CIMT) on hand function and functional skills were summarised in six meta-analyses, which supported the existing evidence of CIMT. In a majority of the included studies, equal improvements were identified between intensive intervention and conventional therapy or between two different intensive interventions.
Conclusions
Different types of training, different intensities and different contexts between studies that targeted gross and fine motor function might explain some of the observed effect variations. Home training may increase the amount of training, but are less controllable. These factors may have contributed to the observed variations in the effectiveness of CIMT. Rigorous research on intensive gross motor training is needed.
Systematic review registration number
CRD42013004023.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0292-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s12887-014-0292-5
PMCID: PMC4265534  PMID: 25475608
Young children; Cerebral palsy; Intensive training; Motor function; Functional skills; Systematic review
31.  Infant and child feeding index reflects feeding practices, nutritional status of urban slum children 
BMC Pediatrics  2014;14(1):290.
Background
Infant and child feeding index (ICFI) an age-specific index, can be used to assess child feeding practices. We used the ICFI to assess feeding practices for urban slum children and the association between ICFI and child nutritional status.
Methods
446 children aged 6 to 24 months from urban slums of Mumbai, India were studied. We used the 24-hour diet recall to study dietary diversity and a food frequency questionnaire for consumption of food groups during the preceding week. ICFI was computed using five components, namely, breastfeeding, use of bottle, dietary diversity score (DDS), food group frequency score (FGFS) and feeding frequency scores (FFS). Weight, height and Mid-Upper Arm Circumference (MUAC) were measured, and z scores were calculated. Association between ICFI scores and nutritional status was examined.
Results
The mean total ICFI score for all was 5.9 ± 1.9. Among the five components, FGFS and FFS differed between children <12 months of age and >12 months and by breast feeding status. In contrast, there were no differences vis-à-vis dietary diversity scores (DDS), breast feeding, and use of bottle. Non-breastfed children had significantly higher DDS scores than did breastfed children. The mean feeding frequency score (FFS) for children <12 months of age was slightly but not significantly lower than scores for children >12 months of age. Mother’s age and child’s age were significant determinants of ICFI. Multivariate analysis indicated that ICFI was significantly associated with Length-for-Age z scores (LAZ) and BMI-for-Age z scores (BAZ). Sensitivity of ICFI was lower than its specificity.
Conclusions
The results of the present study confirmed that the ICFI can be used to collect information on key components of young child feeding practices and be incorporated into public-health programmes. Further, it could be used to determine the influence of complementary feeding practices on nutritional status of children.
doi:10.1186/s12887-014-0290-7
PMCID: PMC4256801  PMID: 25433391
Infant and child feeding index; Dietary diversity; Complementary feeding practices; Nutritional status; Urban slums; India
32.  Differential low uptake of free vitamin D supplements in preterm infants: the Quebec experience 
BMC Pediatrics  2014;14(1):291.
Background
Vitamin D is essential for bone mineralization, particularly in premature infants. For nearly 20 years, Quebec has offered a program of free vitamin D supplements via its public medication insurance plan Régie de l’Assurance Maladie du Québec (RAMQ). The objective of this study is to evaluate the number of preterm infants that obtained at least one bottle (50 doses) of vitamin D supplement through this program and to determine if uptake varied by gestational age.
Methods
This was a retrospective cohort study of preterm infants covered by RAMQ and born from 1998 to 2008; all infants had 1 year of follow-up data regarding supplement use. Data were extracted from the Quebec Pregnancy Cohort, a linked administrative database and were stratified by early (<34 weeks) or late gestational age premature infants. The number of infants obtaining supplements was the primary outcome and their characteristics were compared across gestational age groups. Predictors for participation (obtaining at least 1 bottle) or adherence (2 or more bottles) were identified via logistic regression (GEE).
Results
10288 infants were eligible; the percentage exposed to vitamin D was 24.5% (37.4%- early; 20.7%-late preterm infants, p < 0.001). The median number of bottles obtained was 2 for early and 1 for late preterms. For all premature infants, there was an apparent geometric decline in the infants obtaining subsequent bottles of supplements over the 12 month period. Additionally, there was a significant decline in program participation over time (OR = 0.90/year, 95% CI: 0.89-0.90) regardless of gestational age. Older or more educated mothers were positive predictors for participation. A prescription from a pediatrician significantly increased the odds of obtaining the supplement.
Conclusion
Early preterm infants were more likely to obtain the supplement post-discharge; uptake was low and decreased with time for both age categories. Specifically, targeting late preterm infants and young mothers with less education could improve vitamin D uptake.
doi:10.1186/s12887-014-0291-6
PMCID: PMC4260192  PMID: 25433491
Premature infants; Vitamin D; Supplementation; Mineralization; Fractures; Early preterm; Socioeconomic status; Education
33.  Early exposure of infants to natural rotavirus infection: a review of studies with human rotavirus vaccine RIX4414 
BMC Pediatrics  2014;14(1):295.
Background
Rotaviruses are the leading cause of severe acute gastroenteritis in children aged <5 years worldwide. A live attenuated human rotavirus vaccine, RIX4414 has been developed to reduce the global disease burden associated with rotavirus gastroenteritis. Serum anti-rotavirus immunoglobulin A (IgA) antibody measured in unvaccinated infants during clinical trials of RIX4414 reflects natural rotavirus exposure, and may inform the optimal timing for rotavirus vaccination.
Methods
We reviewed phase II and III randomized, placebo-controlled clinical trials conducted by GlaxoSmithKline Vaccines, Wavre, Belgium between 2000 and 2008 which used the commercial formulation of RIX4414 lyophilized vaccine. We included trials for which demographic data and pre-dose-1 and post-last-dose anti-rotavirus IgA antibody status were available from placebo recipients.
Results
Sixteen clinical trials met the inclusion criteria. The studies were conducted across Africa (N = 3), Asia (N = 4), Latin America (N = 4), Europe (N = 4) and North America (N = 1). Overall, 46,398 infants were enrolled and among these, 20,099 received placebo. The mean age at pre-dose-1 time point ranged from 6.4 − 12.2 weeks while the mean age at post-last-dose time point ranged from 13.5 − 19.6 weeks. The anti-RV IgA seropositivity rates at both time points were higher in less developed countries of Africa, Asia and Latin America (pre-dose-1: 2.1%-26.3%; post-last-dose: 6.3%-34.8%) when compared to more developed countries of Asia, Europe and North America (pre-dose-1: 0%-9.4%; post-last-dose: 0%-21.3%), indicating that rotavirus infections occurred at a younger age in these regions.
Conclusion
Exposure to rotavirus infection occurred early in life among infants in most geographical settings, especially in developing countries. These data emphasize the importance of timely rotavirus vaccination within the Expanded Program on Immunization schedule to maximize protection.
doi:10.1186/s12887-014-0295-2
PMCID: PMC4261882  PMID: 25433534
Rotavirus; Early protection; Gastroenteritis; Anti-rotavirus
34.  Clinical outcomes of children with acute asthma and pneumonia in Mulago hospital, Uganda: a prospective study 
BMC Pediatrics  2014;14(1):285.
Background
Little attention has been paid to asthma in ‘under-fives’ in Sub-Saharan Africa. In ‘under-fives’, acute asthma and pneumonia have similar clinical presentation and most children with acute respiratory symptoms are diagnosed with pneumonia according to the WHO criteria. The mortality associated with acute respiratory diseases in Uganda is high but improving, dropping from 24% in 2004 to 11.9% in 2012. We describe the immediate clinical outcomes of children with acute asthma and pneumonia and document the factors associated with prolonged hospitalization and mortality.
Methods
We enrolled 614 children aged 2 to 59 months with acute respiratory symptoms presenting at the emergency paediatric unit of Mulago hospital. Clinical histories, physical examination, blood and radiological tests were done. Children with asthma and bronchiolitis were collectively referred to as ‘Asthma syndrome’. Hospitalized children were monitored every 12 hours for a maximum of 7 days. Survival analysis was done to compare outcome of children with asthma and pneumonia. Cox regression analysis was done to determine factors associated with prolonged hospitalization and mortality.
Results
Overall mortality was 3.6%. The highest case fatality was due to pneumocystis jirovecii pneumonia (2/4) and pulmonary tuberculosis (2/7). None of the children with asthma syndrome died. Children with ‘asthma syndrome’ had a significantly shorter hospital stay compared to those with pneumonia (p<0.001). Factors independently associated with mortality included hypoxemia (HR = 10.7, 95% CI 1.4- 81.1) and severe malnutrition (HR = 5.7, 95% CI 2.1- 15.8). Factors independently associated with prolonged hospitalization among children with asthma syndrome included age less than 12 months (RR = 1.2, 95% CI 1.0-1.4), hypoxemia (RR = 1.4, 95% CI 1.2-1.7), and severe malnutrition (RR = 1.5 95% CI 1.3-1.8). Similar factors were associated with long duration of hospital stay among children with pneumonia.
Conclusion
This study identified a sharp decline in acute respiratory mortality compared to the previous studies in Mulago hospital. This may be related to focus on and treatment of asthma in this study, and will be analysed in a later study. Bacterial pneumonia is still associated with high case fatality. Hypoxemia, severe malnutrition, and being an infant were associated with poor prognosis among children with acute asthma and pneumonia and need to be addressed in the management protocols.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0285-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s12887-014-0285-4
PMCID: PMC4254222  PMID: 25431036
Asthma; Pneumonia; ‘Under-fives’; Duration of hospitalization; Mortality
35.  Cost-effectiveness analysis of a low-cost bubble CPAP device in providing ventilatory support for neonates in Malawi – a preliminary report 
BMC Pediatrics  2014;14(1):288.
Background
A low-cost bubble continuous positive airway pressure (bCPAP) device has been shown to be an excellent clinical alternative to nasal oxygen for the care of neonates with respiratory difficulty. However, the delivery of bCPAP requires more resources than the current routine care using nasal oxygen. We performed an economic evaluation to determine the cost-effectiveness of a low-cost bCPAP device in providing ventilatory support for neonates in Malawi.
Methods
We used patient-level clinical data from a previously published non-randomized controlled study. Economic data were based on the purchase price of supplies and equipment, adjusted for shelf life, as well as hospital cost data from the World Health Organization. Costs and benefits were discounted at 3%. The outcomes were measured in terms of cost, discounted life expectancy, cost/life year gained and net benefits of using bCPAP or nasal oxygen. The incremental cost-effectiveness ratio and incremental net benefits determined the value of one intervention compared to the other. Subgroup analysis on several parameters (birth weight categories, diagnosis of respiratory distress syndrome, and comorbidity of sepsis) was conducted to evaluate the effect of these parameters on the cost-effectiveness.
Results
Nasal oxygen therapy was less costly (US$29.29) than the low-cost bCPAP device ($57.78). Incremental effectiveness associated with bCPAP was 6.78 life years (LYs). In the base case analysis, the incremental cost-effectiveness ratio for bCPAP relative to nasal oxygen therapy was determined to be $4.20 (95% confidence interval, US$2.29–US$16.67) per LY gained. The results were highly sensitive for all tested subgroups, particularly for neonates with birth weight 1– < 1.5 kg, respiratory distress syndrome, or comorbidity of sepsis; these subgroups had a higher probability that bCPAP would be cost effective.
Conclusion
The bCPAP is a highly cost-effective strategy in providing ventilatory support for neonates in Malawi.
doi:10.1186/s12887-014-0288-1
PMCID: PMC4247223  PMID: 25421903
Cost-effectiveness analysis; Neonate; Malawi; Prematurity; Respiratory distress syndrome; Sepsis; Ventilatory support; Bubble continuous positive airway pressure
36.  Serum 25(OH)D concentrations and atopic diseases at age 10: results from the GINIplus and LISAplus birth cohort studies 
BMC Pediatrics  2014;14(1):286.
Background
Vitamin D is well recognized for its role in skeletal health and its involvement in the modulation of the immune system. In the literature, controversial results are reported for atopic diseases. Thus, we investigated the association between vitamin D status and the prevalence of atopic diseases.
Methods
Serum 25-hydroxy-vitamin D (25(OH)D) concentrations were measured in a sample of 2815 10-years old children from two German birth cohort studies. Self-reported physician-diagnosed eczema, hay fever or allergic rhinitis, and asthma were used as outcome variables as well as specific IgE positivity against common allergens. We applied logistic regression models, deriving adjusted odds ratio estimates (aOR) and 95% confidence intervals (CI).
Results
For asthma and hay fever or allergic rhinitis, no associations existed with serum 25(OH)D concentrations. We observed a significant positive relationship between serum 25(OH)D levels and eczema at age 10 (aOR = 1.09, CI = 1.01-1.17, per 10 nmol/l increase in serum 25(OH)D levels) and for the lifetime prevalence of eczema (aOR = 1.05, CI = 1.01-1.09). Specific IgE positivity for food allergens (aOR = 1.07, CI = 1.02-1.11) and aeroallergens (aOR = 1.05, CI = 1.01-1.08) at age 10, as well as lifetime prevalence, was significantly related to the vitamin D status.
Conclusion
In this study we found no indication that higher blood 25(OH)D levels are associated with decreased risk for any of the atopic outcomes in children. However, we observed a positive association of serum 25(OH)D concentrations with eczema and detectable specific IgE. Due to the given limitations of our study, the clinical relevance of these findings needs further clarification.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0286-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s12887-014-0286-3
PMCID: PMC4251945  PMID: 25421846
Asthma; Atopic diseases; Eczema; Allergic rhinitis; Birth cohort; Hay fever; Sensitization; Vitamin D
37.  Improved insulin sensitivity and body composition, irrespective of macronutrient intake, after a 12 month intervention in adolescents with pre-diabetes; RESIST a randomised control trial 
BMC Pediatrics  2014;14(1):289.
Background
A higher protein to carbohydrate ratio in the diet may potentiate weight loss, improve body composition and cardiometabolic risk, including glucose homeostasis in adults. The aim of this randomised control trial was to determine the efficacy of two structured lifestyle interventions, differing in dietary macronutrient content, on insulin sensitivity and body composition in adolescents. We hypothesised that a moderate-carbohydrate (40-45% of energy), increased-protein (25-30%) diet would be more effective than a high-carbohydrate diet (55-60%), moderate-protein (15%) diet in improving outcomes in obese, insulin resistant adolescents.
Methods
Obese 10–17 year olds with either pre-diabetes and/or clinical features of insulin resistance were recruited at two hospitals in Sydney, Australia. At baseline adolescents were prescribed metformin and randomised to one of two energy restricted diets. The intervention included regular contact with the dietician and a supervised physical activity program. Outcomes included insulin sensitivity index measured by an oral glucose tolerance test and body composition measured by dual-energy x-ray absorptiometry at 12 months.
Results
Of the 111 adolescents recruited, 85 (77%) completed the intervention. BMI expressed as a percentage of the 95th percentile decreased by 6.8% [95% CI: −8.8 to −4.9], ISI increased by 0.2 [95% CI: 0.06 to 0.39] and percent body fat decreased by 2.4% [95% CI: −3.4 to −1.3]. There were no significant differences in outcomes between diet groups at any time.
Conclusion
When treated with metformin and an exercise program, a structured, reduced energy diet, which is either high-carbohydrate or moderate-carbohydrate with increased-protein, can achieve clinically significant improvements in obese adolescents at risk of type 2 diabetes.
Trial registration
Australian New Zealand Clinical Trail Registry ACTRN12608000416392. Registered 25 August 2008.
doi:10.1186/s12887-014-0289-0
PMCID: PMC4252020  PMID: 25422027
Insulin sensitivity; Body composition; Macronutrient intake; Adolescents; Pre-diabetes
38.  Ambient air pollution and birth defects in Haikou city, Hainan province 
BMC Pediatrics  2014;14(1):283.
Background
Evidence shows exposure to ambient air pollution during pregnancy was associated with an increased risk of adverse birth outcomes, such as preterm birth, low birth weight and intrauterine growth retardation, but the results for birth defects have been inconsistent.
Methods
The data on birth defects was collected from the Birth Defects Monitoring Network of Haikou city. Air pollution data for PM10, SO2 and NO2 were obtained from Haikou Environmental Monitoring Center. Logistic regression analysis was used to evaluate these associations.
Results
The risk of birth defects was related to PM10 levels (adjusted OR = 1.039; 95% CI = 1.016-1.063) and SO2 levels (adjusted OR = 0.843; 95% CI = 0.733-0.969) for the second month of pregnancy. In the third month of pregnancy, the risk of birth defects was also related to PM10 levels (adjusted OR = 1.066; 95% CI = 1.043-1.090) and SO2 levels (adjusted OR = 0.740; 95% CI = 0.645-0.850).
Conclusion
The study provides evidence that exposure to PM10 and SO2 during the second and third month of pregnancy may associated with the risk of birth defects.
doi:10.1186/s12887-014-0283-6
PMCID: PMC4254194  PMID: 25416166
Air pollution; Birth defects; PM10; SO2; NO2
39.  [No title available] 
PMCID: PMC4289257  PMID: 25399544
40.  Late-onset volvulus without malrotation in extremely preterm infants - a case–control-study 
BMC Pediatrics  2014;14(1):287.
Background
Volvulus without malrotation in preterm infants is a rare but potentially life-threatening event of unknown aetiology. Confusion with necrotising enterocolitis may delay surgical intervention thereby aggravating morbidity and mortality.
We aimed at elucidating potential risk factors for, and characteristic clinical signs of, volvulus without malrotation in preterm infants.
Methods
Retrospective, single-centre case–control study (2007–2011). For every index patient, five infants of similar gestational age, birth weight and birth year were evaluated. Additionally, all 9 cases of necrotising enterocolitis occurring during the above period were evaluated. Data are presented as median (interquartile range).
Results
Five extremely premature infants suffering from volvulus without malrotation were identified (gestational age at birth 24.4 (23.6-25.5) weeks, birth weight 480 (370–530) g). All were small for gestational age and female; three out of five died. Volvulus occurred several weeks after birth, whereas necrotising enterocolitis occurred significantly earlier. Beyond that, no striking differences in clinical or laboratory presentation of volvulus without malrotation and necrotising enterocolitis were found. Infants with volvulus had significantly more frequent manipulations with rectal tubes for flatulence, but there were no differences in the frequency of enemas, abdominal massage or defecation. In infants with volvulus, nasal high-frequency oscillation was used more frequently for respiratory support, and PEEP-level tended to be higher.
Conclusions
In extremely premature infants volvulus without malrotation represents a life-threatening event that occurs typically several weeks after birth with an acute abdomen and seems to affect predominantly girls. Infants requiring intensive non-invasive respiratory support might be at highest risk.
doi:10.1186/s12887-014-0287-2
PMCID: PMC4233038  PMID: 25388806
Intestinal volvulus; Acute abdomen; Newborn; Infant premature; Necrotising enterocolitis
41.  Association between coenzyme Q10 and glucose transporter (GLUT1) deficiency 
BMC Pediatrics  2014;14(1):284.
Background
It has been demonstrated that glucose transporter (GLUT1) deficiency in a mouse model causes a diminished cerebral lipid synthesis. This deficient lipid biosynthesis could contribute to secondary CoQ deficiency. We report here, for the first time an association between GLUT1 and coenzyme Q10 deficiency in a pediatric patient.
Case presentation
We report a 15 year-old girl with truncal ataxia, nystagmus, dysarthria and myoclonic epilepsy as the main clinical features. Blood lactate and alanine values were increased, and coenzyme Q10 was deficient both in muscle and fibroblasts. Coenzyme Q10 supplementation was initiated, improving ataxia and nystagmus. Since dysarthria and myoclonic epilepsy persisted, a lumbar puncture was performed at 12 years of age disclosing diminished cerebrospinal glucose concentrations. Diagnosis of GLUT1 deficiency was confirmed by the presence of a de novo heterozygous variant (c.18+2T>G) in the SLC2A1 gene. No mutations were found in coenzyme Q10 biosynthesis related genes. A ketogenic diet was initiated with an excellent clinical outcome. Functional studies in fibroblasts supported the potential pathogenicity of coenzyme Q10 deficiency in GLUT1 mutant cells when compared with controls.
Conclusion
Our results suggest that coenzyme Q10 deficiency might be a new factor in the pathogenesis of G1D, although this deficiency needs to be confirmed in a larger group of G1D patients as well as in animal models. Although ketogenic diet seems to correct the clinical consequences of CoQ deficiency, adjuvant treatment with CoQ could be trialled in this condition if our findings are confirmed in further G1D patients.
doi:10.1186/s12887-014-0284-5
PMCID: PMC4228097  PMID: 25381171
Glucose transporter type I deficiency; SLC2A1 gene; Coenzyme Q10; Ataxia; Ketogenic diet
42.  Exclusive breastfeeding among women taking HAART for PMTCT of HIV-1 in the Kisumu Breastfeeding Study 
BMC Pediatrics  2014;14(1):280.
Background
One of the most effective ways to promote the prevention of mother-to-child transmission (PMTCT) of HIV-1 in resource-limited settings is to encourage HIV-positive mothers to practice exclusive breastfeeding (EBF) for the first 6 months post-partum while they receive antiretroviral therapy (ARV). Although EBF reduces mortality in this context, its practice has been low. We studied the rate of adherence to EBF and assessed associated maternal and infant characteristics using data from a phase II PMTCT clinical trial conducted in Western Kenya which included a counseling intervention to encourage EBF by all participants.
Methods
We analyzed data from the Kisumu Breastfeeding Study (KiBS), conducted between July 2003 and February 2009. This study enrolled a total of 522 HIV-1 infected pregnant women. Data on breastfeeding were available for 480 mother-infant pairs. Infant feeding and general nutrition counseling began at 35 weeks gestation and continued throughout the 6 month post-partum intervention period, following World Health Organization (WHO) infant feeding guidelines. Data on infant feeding were collected during routine clinic visits and home visits using food frequency questionnaires and dietary recall methods. Participants were instructed to exclusively breastfeed until initiation of weaning at 5.5 months post-partum. We used Kaplan-Meier methods to estimate the rates of EBF at 5.25 months post-partum, stratified by maternal and infant characteristics measured at enrollment, delivery, and 2 weeks post-partum.
Results
The estimated EBF rate at 5.25 months post-partum was 80.4%. Only 3% of women introduced other foods (most commonly water with or without glucose, cow’s milk, formula, and fruit) by 2 months; this percentage increased to 5% of women by 4 months. Women who had ≥3 previous births (p < 0.01) and who were not living with the infant’s father (p = 0.04) were more likely to exclusively breastfeed. Mixed feeding was more common for male infants than for female infants (p = 0.04).
Conclusion
Exclusive breastfeeding was common in this clinical trial, which emphasized EBF as a best practice until infants reached 5.5 months of age. Counseling initiated prior to delivery and continued during the post-partum period provided a consistent message reinforcing the benefits of EBF. The findings from this study suggest high adherence to EBF in resource limited settings can be achieved by a comprehensive counseling intervention that encourages EBF.
doi:10.1186/1471-2431-14-280
PMCID: PMC4326202  PMID: 25380718
43.  [No title available] 
PMCID: PMC4289204  PMID: 25373393
44.  [No title available] 
PMCID: PMC4289403  PMID: 25370708
45.  [No title available] 
PMCID: PMC4289197  PMID: 25367591
46.  Cutaneous vasculitis in patients with autoimmune polyendocrine syndrome type 1: report of a case and brief review of the literature 
BMC Pediatrics  2014;14(1):272.
Background
Autoimmune polyendocrine syndrome type 1, also known as autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy, is a rare autosomal recessive disease due to pathogenic variants in the AIRE gene. Classic features of the syndrome are mucocutaneous candidiasis, chronic idiopathic hypoparathyroidism and Addison disease. However, other endocrine and non-endocrine components, may occur with a different prevalence. In addition to ectodermal features, which are quite common features of the disease, APS 1 patients may experience other types of skin alterations, such as vasculitic skin rash. An early diagnosis of APS 1 can be very challenging, due to the high clinical heterogeneity, and a considerable delay may occur between the appearance of symptoms and the diagnosis.
Case presentation
We report on a girl affected by APS 1 who presented with cutaneous vasculitis when she was seven-months old, some years before the onset of the common components of the disease.
Conclusion
Clinical picture of APS 1 may be characterized by isolated rare or atypical autoimmune or immune-mediated manifestations, even years before the onset of the classic components of the disease. Among these uncommon features, skin rashes of variable form and duration may occur, most of them being associated with histopathological features of vasculitis. Our case suggests that cutaneous vasculitis may represent a first sign of APS 1. The clinical significance of cutaneous vasculitis in the context of APS 1 is still debated. It may represent a rare, unusual, early component of the disease or a clinical manifestation secondarily related to the typical APS 1 components (i.e. autoimmune thyroid disease), which are frequently associated with rheumatologic-like signs and symptoms. Alternatively, it may be the expression of an independent disease co-occuring with APS 1. In conclusion, our case suggests that children presenting with unexplained vasculitic skin rash should be followed-up in order to early identify APS 1.
doi:10.1186/1471-2431-14-272
PMCID: PMC4286916  PMID: 25361846
APS 1; AIRE; Cutaneous vasculitis; Autoimmunity
47.  Children’s psychological and behavioral responses following pediatric intensive care unit hospitalization: the caring intensively study 
BMC Pediatrics  2014;14(1):276.
Background
Pediatric intensive care unit (PICU) hospitalization places children at increased risk of persistent psychological and behavioral difficulties following discharge. Despite tremendous advances in medical technology and treatment regimes, approximately 25% of children demonstrate negative psychological and behavioral outcomes within the first year post-discharge. It is imperative that a broader array of risk factors and outcome indicators be explored in examining long-term psychological morbidity to identify areas for future health promotion and clinical intervention. This study aims to examine psychological and behavioral responses in children aged 3 to 12 years over a three year period following PICU hospitalization, and compare them to children who have undergone ear, nose and/or throat (ENT) day surgery.
Methods/Design
This mixed-methods prospective cohort study will enrol 220 children aged 3 to 12 years during PICU hospitalization (study group, n = 110) and ENT day surgery hospitalization (comparison group, n = 110). Participants will be recruited from 3 Canadian pediatric hospitals, and followed for 3 years with data collection points at 6 weeks, 6 months, 1 year, 2 years and 3 years post-discharge. Psychological and behavioral characteristics of the child, and parent anxiety and parenting stress, will be assessed prior to hospital discharge, and again at each of the 5 subsequent time points, using standardized measures. Psychological and behavioral response scores for both groups will be compared at each follow-up time point. Multivariate regression analysis will be used to adjust for demographic and clinical variables at baseline. To explore baseline factors predictive of poor psychological and behavioral scores at 3 years among PICU patients, correlation analysis and multivariate linear regression will be used. A subgroup of 40 parents of study group children will be interviewed at years 1 and 3 post-discharge to explore their perceptions of the impact of PICU hospitalization on their children and enhance our understanding of findings generated from standardized measures in the larger cohort study. An interpretive descriptive approach will guide qualitative data collection and analysis.
Discussion
This study aims to generate new information regarding the magnitude and duration of psychological and behavioral disturbances among children admitted to PICUs, potentially leading to remedial or preventive interventions.
doi:10.1186/1471-2431-14-276
PMCID: PMC4286947  PMID: 25344699
Pediatric intensive care; Child outcomes; Longitudinal follow-up; Psychological and behavioral characteristics; Study protocol
48.  Dose of early intervention treatment during children’s first 36 months of life is associated with developmental outcomes: an observational cohort study in three low/low-middle income countries 
BMC Pediatrics  2014;14(1):281.
Background
The positive effects of early developmental intervention (EDI) on early child development have been reported in numerous controlled trials in a variety of countries. An important aspect to determining the efficacy of EDI is the degree to which dosage is linked to outcomes. However, few studies of EDI have conducted such analyses. This observational cohort study examined the association between treatment dose and children’s development when EDI was implemented in three low and low-middle income countries as well as demographic and child health factors associated with treatment dose.
Methods
Infants (78 males, 67 females) born in rural communities in India, Pakistan, and Zambia received a parent-implemented EDI delivered through biweekly home visits by trainers during the first 36 months of life. Outcome was measured at age 36 months with the Mental (MDI) and Psychomotor (PDI) Development Indices of the Bayley Scales of Infant Development-II. Treatment dose was measured by number of home visits completed and parent-reported implementation of assigned developmental stimulation activities between visits. Sociodemographic, prenatal, perinatal, and child health variables were measures as correlates.
Results
Average home visits dose exceeded 91% and mothers engaged the children in activities on average 62.5% of days. Higher home visits dose was significantly associated with higher MDI (mean for dose quintiles 1–2 combined = 97.8, quintiles 3–5 combined = 103.4, p = 0.0017). Higher treatment dose was also generally associated with greater mean PDI, but the relationships were non-linear. Location, sociodemographic, and child health variables were associated with treatment dose.
Conclusions
Receiving a higher dose of EDI during the first 36 months of life is generally associated with better developmental outcomes. The higher benefit appears when receiving ≥91% of biweekly home visits and program activities on ≥67% of days over 3 years. It is important to ensure that EDI is implemented with a sufficiently high dose to achieve desired effect. To this end groups at risk for receiving lower dose can be identified and may require special attention to ensure adequate effect.
doi:10.1186/1471-2431-14-281
PMCID: PMC4288653  PMID: 25344731
Treatment dose; Early developmental intervention; Neurodevelopmental disability; Birth asphyxia; Developing countries
49.  Effect of low birth weight on childhood asthma: a meta-analysis 
BMC Pediatrics  2014;14(1):275.
Background
Low birth weight is strongly correlated with an increased risk of adult diseases. Additionally, low birth weight might be a risk factor for asthma later in life.
Methods
A systematic literature search of the PubMed database from 1966 to November 2013 was conducted. The criteria for inclusion of papers were as follows: case–control or cohort studies; the odds ratio (OR) or risk ratio (RR) estimates with the corresponding 95% confidence intervals (CIs) were presented, or there were sufficient data for calculation; and studies were published in English up to October 2013. Random-effect and fixed-effect meta-analyses, meta-regression, and cumulative meta-analysis were conducted.
Results
Thirteen cohort studies and 1,105,703 subjects were included. The overall pooled RRs (95% CIs) of asthma risk for low birth weight were 1.162 (fixed-effects model, 95% CI, 1.128–1.197) and 1.152 (random-effects model, 95% CI, 1.082–1.222). In stratified analyses, the effect of low birth weight on childhood asthma was strong, particularly in studies conducted in Europe, those with a small sample size, and those published recently. A meta-regression analysis did not find significant determinants.
Conclusions
This meta-analysis shows that low birth weight significantly increases the risk of childhood asthma.
doi:10.1186/1471-2431-14-275
PMCID: PMC4288645  PMID: 25339063
Birth weight; Childhood asthma; Meta-analysis; Systematic review
50.  A randomized controlled trial on a multicomponent intervention for overweight school-aged children – Copenhagen, Denmark 
BMC Pediatrics  2014;14(1):273.
Background
Obesity amongst children is a growing problem worldwide. In contrast to adults, little is known on the effects of controlled weight loss on components of the metabolic syndrome in children. The primary aim of the study was to evaluate the effects of a 20-week exercise and diet guidance intervention on body mass index (BMI) in a group of overweight children. Our hypothesis was an observed reduction in BMI and secondarily in body fat content, insulin insensitivity, and other components of the metabolic syndrome in the intervention group.
Methods
School children from Copenhagen were randomly allocated to an intervention group (n = 19) or a control group (n = 19). Anthropometric assessment, whole body dual-energy X-ray absorptiometry scan, two hours oral glucose tolerance test, steps measured by pedometer, and fitness tests were measured at baseline and at 20 weeks.
Results
Thirty-seven children (30 girls) participated at baseline, aged 8.7 ± 0.9 years with a BMI of 21.8 ± 3.7 kg/m2 (mean ± SD), and 36 children completed the study. The intervention group decreased their BMI (the intervention effect is the difference in change between the groups adjusted for the respective baseline values (DELTA) = -2.0 kg/m2, 95% CI: -2.5; -1.5, P <0.001), total body mass (DELTA = -4.0 kg, 95% CI: -4.9; -3.0, P <0.001), and fat mass (DELTA = -3.3 kg, 95% CI: -4.2; -2.7, P <0.001) compared to the control group after the intervention. The intervention group displayed decreased waist, hip and waist-to-height ratio (WHtR) (all three variables; P <0.001), area under curve for plasma insulin (P <0.05), and increased mean and minimum steps/day (P <0.05 and P <0.01, respectively).
Conclusions
The multicomponent intervention had significant favorable effects on BMI, weight, WHtR, mean and minimum steps/day, and fat mass. In addition, similar beneficial metabolic effects were found in the children as shown in adults, e.g. increase in peripheral insulin sensitivity.
Trial registration
Clinicaltrials.gov Identifier number NCT01660789.
doi:10.1186/1471-2431-14-273
PMCID: PMC4287468  PMID: 25330848
Overweight children; Obesity; Randomized controlled trial; Multicomponent intervention; Physical activity; Diet counseling; Body mass index; Blood glucose; Insulin; Insulin resistance

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