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1.  Scoping review of patient- and family-oriented outcomes and measures for chronic pediatric disease 
BMC Pediatrics  2015;15:7.
Improvements in health care for children with chronic diseases must be informed by research that emphasizes outcomes of importance to patients and families. To support a program of research in the field of rare inborn errors of metabolism (IEM), we conducted a broad scoping review of primary studies that: (i) focused on chronic pediatric diseases similar to IEM in etiology or manifestations and in complexity of management; (ii) reported patient- and/or family-oriented outcomes; and (iii) measured these outcomes using self-administered tools.
We developed a comprehensive review protocol and implemented an electronic search strategy to identify relevant citations in Medline, EMBASE, DARE and Cochrane. Two reviewers applied pre-specified criteria to titles/abstracts using a liberal accelerated approach. Articles eligible for full-text review were screened by two independent reviewers with discrepancies resolved by consensus. One researcher abstracted data on study characteristics, patient- and family-oriented outcomes, and self-administered measures. Data were validated by a second researcher.
4,118 citations were screened with 304 articles included. Across all included reports, the most-represented diseases were diabetes (35%), cerebral palsy (23%) and epilepsy (18%). We identified 43 unique patient- and family-oriented outcomes from among five emergent domains, with mental health outcomes appearing most frequently. The studies reported the use of 405 independent self-administered measures of these outcomes.
Patient- and family-oriented research investigating chronic pediatric diseases emphasizes mental health and appears to be relatively well-developed in the diabetes literature. Future research can build on this foundation while identifying additional outcomes that are priorities for patients and families.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-015-0323-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4334411
Patient-centered outcomes research; Patient-centered care; Outcomes research; Outcome measures; Metabolism; Inborn errors; Assessment; Patient outcomes; Rare diseases; Family-centered care
2.  Paradoxical exacerbation of myoclonic-astatic seizures by levetiracetam in myoclonic astatic epilepsy 
BMC Pediatrics  2015;15(1):6.
Levetiracetam is a broad spectrum antiepileptic drug (AED) with proven efficacy when used as adjunctive therapy against myoclonic seizures. We report two patients suffering from epilepsy with myoclonic-astatic epilepsy (MAE) who experienced a paradoxical worsening of seizures after initiation of treatment with LEV, a finding not previously described.
Case presentation
Patients included were enrolled in an ongoing large prospective study evaluating children and adults with new onset epilepsy in Lebanon conducted at the American University of Beirut Medical Center in association with the Lebanese Chapter of the International League against Epilepsy. Based on an extensive evaluation, these patients were stratified into idiopathic partial, idiopathic generalized, symptomatic partial or symptomatic generalized epilepsies. Whenever possible the electroclinical syndrome was identified according to the ILAE classification of epilepsy syndromes. Patients were subsequently followed up on regular intervals and were assessed for adverse events, and seizure recurrence.
MAE was diagnosed in five (1.6%) out of 307 consecutive children enrolled in this study. LEV was used as adjunctive therapy in four of those children with two experiencing a substantial and dose related worsening in the frequency of their myoclonic and atonic seizures.
LEV should be used with caution in children with MAE and an exacerbation of seizure frequency temporally related to the introduction of LEV should alert the clinician to the possibility of a paradoxical seizure exacerbation.
PMCID: PMC4329645
Epilepsy; Electroclinical syndrome; Doose syndrome; Antiepileptic; Levetiracetam; Myoclonus
3.  Comparisons of foot anthropometry and plantar arch indices between German and Brazilian children 
BMC Pediatrics  2015;15:4.
Nowadays, trades and research have become closely related between different countries and anthropometric data are important for the development in global markets. The appropriate use of anthropometry may improve wellbeing, health, comfort and safety especially for footwear design. For children a proper fit of footwear is very important, not constraining foot growth and allowing a normal development. The aim of this study was to compare the anthropometric characteristics of German and Brazilian children’s feet from 3 to 10 years of age.
We compared five indirect measures of two databases of children's feet. Forefoot, midfoot and rearfoot widths were measured in static footprints and the Chippaux-Smirak and Staheli indices of the longitudinal arch were calculated.
Brazilian children showed a significantly narrower forefoot from 5 to 10 years, wider rearfoot from 3 to 4 years, wider midfoot for 4 year-olds and narrower midfoot for 10 year-old children. Nevertheless, the Chippaux-Smirak and Staheli indices showed no group differences. The only exception was for 4 year-old Brazilian children who showed a higher Chippaux-Smirak index compared to German children (48.4 ± 17.7%; 42.1 ± 13.8%).
Our study revealed anthropometric differences in absolute forefoot and rearfoot widths of German and Brazilian children, but a similar longitudinal arch development. At 4 years of age, Brazilian children present a foot anthropometry similar to the 3 year-olds and develop the plantar longitudinal arch from 4 to 5 years more rapidly when compared to German children.
PMCID: PMC4335661
Longitudinal plantar arch; Body weight and measures; Child; Preschool; Feet
4.  Levels of evidence: a comparison between top medical journals and general pediatric journals 
BMC Pediatrics  2015;15:3.
Given the large number of publications in all fields of practice, it is essential that clinicians focus on the resources that provide the highest level of evidence (LOE). We sought to determine the LOE that exists in the field of pediatrics, present in the general pediatric as well as high impact clinical literature.
Clinical pediatric literature, published between April 2011 and March 2012 inclusive in high-impact clinical journals (HICJ) (New England Journal of Medicine, Journal of the American Medical Association, & The Lancet) and the highest-impact general pediatric journals (GPJ) (Pediatrics, Journal of Pediatrics, & Archives of Pediatrics & Adolescent Medicine), was assessed. In addition to the LOE, articles were evaluated on criteria including subspecialty within pediatrics, number of authors, number of centers, and other parameters. Eligible level I randomized control trials were appraised using the Consolidated Standards of Reporting Trials (CONSORT) guidelines.
Of 6511 articles screened, 804 met inclusion criteria (68 in HICJ and 736 in GPJ). On average, LOE in pediatrics-focused articles within The Lancet were significantly higher than all GPJ (p < 0.05). Average CONSORT scores were significantly higher in HICJ vs. GPJ (15.2 vs. 13.6, respectively, p < 0.001).
LOE and quality of randomized control trials within the pediatric field is highest within HICJ, however, only represent a small proportion of data published. Following CONSORT criteria, and promoting studies of high LOE may allow authors and readers to turn to journals and articles of greater clinical impact.
PMCID: PMC4336754
Evidence-based medicine; Data quality; Journal impact factor
5.  Association of dual-task walking performance and leg muscle quality in healthy children 
BMC Pediatrics  2015;15(1):2.
Previous literature mainly introduced cognitive functions to explain performance decrements in dual-task walking, i.e., changes in dual-task locomotion are attributed to limited cognitive information processing capacities. In this study, we enlarge existing literature and investigate whether leg muscular capacity plays an additional role in children’s dual-task walking performance.
To this end, we had prepubescent children (mean age: 8.7 ± 0.5 years, age range: 7–9 years) walk in single task (ST) and while concurrently conducting an arithmetic subtraction task (DT). Additionally, leg lean tissue mass was assessed.
Findings show that both, boys and girls, significantly decrease their gait velocity (f = 0.73), stride length (f = 0.62) and cadence (f = 0.68) and increase the variability thereof (f = 0.20-0.63) during DT compared to ST. Furthermore, stepwise regressions indicate that leg lean tissue mass is closely associated with step time and the variability thereof during DT (R2 = 0.44, p = 0.009). These associations between gait measures and leg lean tissue mass could not be observed for ST (R2 = 0.17, p = 0.19).
We were able to show a potential link between leg muscular capacities and DT walking performance in children. We interpret these findings as evidence that higher leg muscle mass in children may mitigate the impact of a cognitive interference task on DT walking performance by inducing enhanced gait stability.
PMCID: PMC4325950  PMID: 25652949
Gait; Cognitive interference; Body composition; Muscle mass; Children
6.  Association between sudden infant death syndrome and diphtheria-tetanus-pertussis immunisation: an ecological study 
BMC Pediatrics  2015;15(1):1.
Sudden infant death syndrome (SIDS) continues to be one of the main causes of infant mortality in the United States. The objective of this study was to analyse the association between diphtheria-tetanus-pertussis (DTP) immunisation and SIDS over time.
The Centers for Disease Control and Prevention provided the number of cases of SIDS and live births per year (1968–2009), allowing the calculation of SIDS mortality rates. Immunisation coverage was based on (1) the United States Immunization Survey (1968–1985), (2) the National Health Interview Survey (1991–1993), and (3) the National Immunization Survey (1994–2009). We used sleep position data from the National Infant Sleep Position Survey. To determine the time points at which significant changes occurred and to estimate the annual percentage change in mortality rates, we performed joinpoint regression analyses. We fitted a Poisson regression model to determine the association between SIDS mortality rates and DTP immunisation coverage (1975–2009).
SIDS mortality rates increased significantly from 1968 to 1971 (+27% annually), from 1971 to 1974 (+47%), and from 1974 to 1979 (+3%). They decreased from 1979 to 1991 (−1%) and from 1991 to 2001 (−8%). After 2001, mortality rates remained constant. DTP immunisation coverage was inversely associated with SIDS mortality rates. We observed an incidence rate ratio of 0.92 (95% confidence interval: 0.87 to 0.97) per 10% increase in DTP immunisation coverage after adjusting for infant sleep position.
Increased DTP immunisation coverage is associated with decreased SIDS mortality. Current recommendations on timely DTP immunisation should be emphasised to prevent not only specific infectious diseases but also potentially SIDS.
PMCID: PMC4326294  PMID: 25626628
Sudden infant death syndrome; Diphtheria-tetanus-pertussis immunisation; Time trends
7.  Dietary intake in 6-year-old children from southern Poland: part 2 – vitamin and mineral intakes 
BMC Pediatrics  2014;14(1):310.
Studies on vitamin and mineral intakes in children are very important: firstly because of the high prevalence of diet-related diseases and secondly because of the widespread consumption of highly processed foods which are characterised by high energy content and low density of essential nutrients. Therefore, the purpose of this study was to analyse vitamin and mineral intakes in 6-year-old children from southern Poland.
Vitamin and mineral intakes were estimated from a three-day food record in 120 children, 64 girls and 56 boys, aged 6 years. Nutrient densities were estimated as amounts per 1000 kcal (4185 kJ) of energy intake. Statistical analysis was carried out by means of the IBM SPSS Statistics computer programme, version 19. The studied population was divided according to gender.
Intakes of folic acid (μg/1000 kcal) and vitamin C (mg, mg/1000 kcal) were significantly higher in girls. Nutrient densities for all vitamins were higher in girls, however, these results did not reach statistical significance. Intake of vitamin D was lower than EAR in all of the studied children. Intakes of sodium (mg) and zinc (mg) were significantly higher in boys. Intakes of the remaining minerals were higher in boys, however, these findings did not reach statistical significance. Nutrient densities for all minerals, except for sodium, zinc and manganese, were higher in girls. All of the studied children had sodium intakes above UL.
Inadequate intakes of vitamin D, calcium and potassium in the studied 6-year-olds along with excessive sodium intake are the risk factors for developing osteoporosis and hypertension. To prevent these diseases in the studied children, educational programmes for both preschool staff and parents should be worked out and implemented.
PMCID: PMC4297393  PMID: 25539749
Children; Dietary intake; Vitamins; Minerals; Nutrition; Diet
8.  Child mental health in Jordanian orphanages: effect of placement change on behavior and caregiving 
BMC Pediatrics  2014;14(1):1173.
To assess the mental health and behavioral problems of children in institutional placements in Jordan to inform understanding of current needs, and to explore the effects of placement change on functioning and staff perceptions of goodness-of-fit.
An assessment was completed of 134 children between 1.5–12 years-of-age residing in Jordanian orphanages. The Child Behavior Checklist was used to assess prevalence rates of problems across externalizing and internalizing behavior and DSM-IV oriented subscales. Also included was caregiver perceived goodness-of-fit with each child, caregiving behavior, and two placement change-clock variables; an adjustment clock measuring time since last move, and an anticipation clock measuring time to next move.
28% were in the clinical range for the internalizing domain on the CBCL, and 22% for the externalizing domain. The children also exhibited high levels of clinical range social problems, affective disorder, pervasive developmental disorder, and conduct problems. Internalizing problems were found to decrease with time in placement as children adjust to a prior move, whereas externalizing problems increased as the time to their next age-triggered move drew closer, highlighting the anticipatory effects of change. Both behavioral problems and the change clocks were predictive of staff perceptions of goodness-of-fit with the children under their care.
These findings add to the evidence demonstrating the negative effects of orphanage rearing, and highlight the importance of the association between behavioral problems and child-caregiver relationship pathways including the timing of placement disruptions and staff perceptions of goodness-of-fit.
PMCID: PMC4278229  PMID: 25528351
Orphanage; Institutional care; Mental health; Behavioral problems; Internalizing; Externalizing; Goodness-of-fit; Placement change; Placement disruption
9.  “You can’t just jump on a bike and go”: a qualitative study exploring parents’ perceptions of physical activity in children with type 1 diabetes 
BMC Pediatrics  2014;14(1):313.
Parents of children with Type 1 Diabetes Mellitus (T1DM) have an important role in supporting diabetes management behaviours and helping to maintain their child’s healthy lifestyle. Physical activity has known benefits for children with T1DM [Diabet Med 31: 1163-1173], but children with chronic health conditions typically have low levels of physical activity. Research is needed to build an understanding of the experience of physical activity for children with T1DM. The purpose of this study was to understand parents’ perceptions of what influences physical activity for children with T1DM and to inform the practice of those working with children who have T1DM.
Data were collected through semi-structured interviews with 20 parents (18 mothers, 2 fathers) who had a child aged 7 – 13 years with T1DM in the UK. Interviews were recorded, transcribed verbatim and data were analysed using thematic analysis [Qual Res Psychol 3: 77-101, 2006]).
Factors believed to influence participation in physical activity are presented as 7 major themes and 15 subthemes. Themes that emerged included the conflict between planning and spontaneous activity, struggles to control blood glucose, recognition of the importance of physical activity, the determination of parents, children relying on their parents to manage physical activity, the importance of a good support system and individual factors about the children that influence physical activity participation.
This study highlights that parents serve as gate-keepers for children’s physical activity. The findings provide insight into the need for T1DM knowledge and competence in personnel involved in the supervision of children’s physical activities. Healthcare providers should collaborate with families to ensure understanding of how to manage physical activity. The findings sensitise professionals to the issues confronted by children with T1DM and their parents, as well as the methods used by children and their families to overcome obstacles to physical activity. The implications for further research, clinical practice, and physical activity promotion with children with T1DM are discussed.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0313-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4297408  PMID: 25526774
Children; Type 1 diabetes; Physical activity; Parent perceptions; Qualitative; Thematic analysis
10.  Immunization interventions to interrupt hepatitis B virus mother-to-child transmission: a meta-analysis of randomized controlled trials 
BMC Pediatrics  2014;14(1):307.
This study aimed to determine the clinical efficacy of various immune interventions on mother-to-child transmission (MTCT) of hepatitis B virus (HBV).
We retrieved different immune strategies on how to prevent MTCT reported in the literature from Chinese and English electronic databases from the viewpoint of intrauterine and extrauterine prevention. Relative risk (RR) and 95% confidence interval (CI) methods were used.
Twenty-five articles on intrauterine prevention and 16 on extrauterine prevention were included in the analysis. Intrauterine prevention could reduce infants’ HBV infection rate (RR = 0.36, 95% CI: 0.28-0.45) and increase their anti-hepatitis B surface–positive rate (RR = 2.42, 95% CI: 1.46-4.01) at birth. Compared with passive immunization, passive-active immunization could reduce infants’ HBV infection rate (RR = 0.66, 95% CI: 0.52-0.84) at birth, even at more than 12 months of age (RR = 0.54, 95% CI: 0.42-0.69). Subgroup analysis demonstrated similar results except for pregnant women who were hepatitis B surface antigen–positive. Funnel plots and Egger’s tests showed publication bias mainly in intrauterine prevention not in extrauterine one.
The long-term protective effect of pregnant women injected with hepatitis B immunoglobulin during pregnancy should be further validated by large-scale randomized trials. Newborns of pregnant women who carried HBV should undergo a passive-active immunization strategy.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0307-2) contains supplementary material, which is available to authorized users.
PMCID: PMC4297423  PMID: 25526664
Hepatitis B immunoglobulin; Hepatitis B virus; Meta-analysis; Mother-to-child transmission
11.  Growth and safety evaluation of infant formulae containing oligosaccharides derived from bovine milk: a randomized, double-blind, noninferiority trial 
BMC Pediatrics  2014;14(1):306.
A limited number of nondigestible oligosaccharides are available for use in infant formula. This study evaluated growth and safety in infants fed formula supplemented with a mixture of bovine milk-derived oligosaccharides (BMOS). This mixture, which was generated from whey permeate, contains galactooligosaccharides and other oligosaccharides from bovine milk, such as 3′- and 6′-sialyllactose. We hypothesized that growth in infants fed BMOS-supplemented formula would be noninferior to that in infants fed standard formula.
Healthy term infants ≤14 days old were randomly assigned to standard formula (control; n = 84); standard formula with BMOS (IF-BMOS; n = 99); or standard formula with BMOS and probiotics (Bifidobacterium longum, Lactobacillus rhamnosus) (IF-BMOS + Pro; n = 98). A breastfed reference group was also enrolled (n = 30). The primary outcome was mean weight gain/day from enrollment to age 4 months (noninferiority margin: −3.0 g/day).
189 (67.3%) formula-fed infants were included in the primary analysis. Mean differences in weight gain between the control and IF-BMOS and IF-BMOS + Pro groups were <1 g/day, with 97.5% confidence intervals above −3.0 g/day, indicating noninferior weight gain in the BMOS formula groups. Compared with control, infants in the BMOS groups had more frequent (p < 0.0001) and less hard (p = 0.0003) stools. No significant differences were observed between the control and BMOS groups in caregivers’ reports of flatulence, vomiting, spitting up, crying, fussing, and colic. When based on clinical evaluation by the investigator, the incidence of colic was higher (p = 0.01) in IF-BMOS than in control; the incidence of investigator-diagnosed colic was not significantly different in control and IF-BMOS + Pro (p = 0.15). Stool bifidobacteria and lactobacilli counts were higher with IF-BMOS + Pro compared with control (p < 0.05), whereas Clostridia counts were lower (p < 0.05) in both BMOS groups compared with control.
Infant formula containing BMOS either with or without probiotics provides adequate nutrition for normal growth in healthy term infants. Further studies are needed to fully explore the digestive tolerance of BMOS formula.
Trial registration NCT01886898. Registered 24 June 2013.
PMCID: PMC4297447  PMID: 25527244
Infant formula; Bovine milk-derived oligosaccharides; Infant nutrition; Healthy infants
12.  An epidemiological evaluation of pediatric long bone fractures — a retrospective cohort study of 2716 patients from two Swiss tertiary pediatric hospitals 
BMC Pediatrics  2014;14(1):314.
Children and adolescents are at high risk of sustaining fractures during growth. Therefore, epidemiological assessment is crucial for fracture prevention. The AO Comprehensive Injury Automatic Classifier (AO COIAC) was used to evaluate epidemiological data of pediatric long bone fractures in a large cohort.
Data from children and adolescents with long bone fractures sustained between 2009 and 2011, treated at either of two tertiary pediatric surgery hospitals in Switzerland, were retrospectively collected. Fractures were classified according to the AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF).
Age, sex, BMI, injury and treatment data were recorded. Children were classified into four age classes and five BMI classes were applied. Seven major accident categories were established. Study parameters were tabulated using standard descriptive statistics. The relationship of categorical variables was tested using the chi-square test. The Children’s BMI was compared to WHO reference data and Swiss population data.
For a total of 2716 patients (60% boys), 2807 accidents with 2840 long bone fractures (59% radius/ulna; 21% humerus; 15% tibia/fibula; 5% femur) were documented. Children’s mean age (SD) was 8.2 (4.0) years (6% infants; 26% preschool children; 40% school children; 28% adolescents). Adolescent boys sustained more fractures than girls (p < 0.001). The leading cause of fractures was falls (27%), followed by accidents occurring during leisure activities (25%), at home (14%), on playgrounds (11%), and traffic (11%) and school accidents (8%). There was boy predominance for all accident types except for playground and at home accidents. The distribution of accident types differed according to age classes (p < 0.001). Twenty-six percent of patients were classed as overweight or obese — higher than data published by the WHO for the corresponding ages — with a higher proportion of overweight and obese boys than in the Swiss population (p < 0.0001).
Overall, differences in the fracture distribution were sex and age related. Overweight and obese patients seemed to be at increased risk of sustaining fractures. Our data give valuable input into future development of prevention strategies. The AO PCCF proved to be useful in epidemiological reporting and analysis of pediatric long bone fractures.
PMCID: PMC4302599  PMID: 25528249
Pediatric; Long bone fracture; Classification; Epidemiology; AO COIAC
13.  Severe persistent unremitting dermatitis, chronic diarrhea and hypoalbuminemia in a child; Hartnup disease in setting of celiac disease 
BMC Pediatrics  2014;14(1):311.
Celiac disease (CD) is a complex autoimmune disorder that can lead to an inflammatory small intestinal villous atrophy and malabsorption.
Hartnup disease is an autosomal recessive disorder caused by increased urinary excretion of neutral amino acids. Co-occurrence of Hartnup disease and CD is extremely rare with only a single case reported.
Case presentation
We report a 3-year girl with chronic diarrhea, Hypoalbuminemia and exfoliative erythema. She was diagnosed with celiac disease, which did not improve on gluten free diet. Hartnup disease was suspected and was confirmed by neutral aminoaciduria. Niacin was started and followed by dramatic improvement.
Presence of Celiac and Hartnup disease in single individual is very rare. Complete nutritional assessment of refractory celiac patient can reveal underlying nutritional deficiency.
PMCID: PMC4308912  PMID: 25526748
14.  Perinatal factors associated with early neonatal deaths in very low birth weight preterm infants in Northeast Brazil 
BMC Pediatrics  2014;14(1):312.
In Brazil, the prevalence of prematurity has increased in recent years and it is a major cause of death in the neonatal period. Therefore, this study aims at assessing perinatal factors associated with early neonatal deaths in very low birth weight preterm infants born in a region of Brazil with low Human Development Index.
Prospective cohort study of inborns with gestational age 230/7-316/7 weeks and birthweight 500-1499 g without malformations in 19 public reference hospitals of the state capitals of Brazil’s Northeast Region. Perinatal variables associated with early neonatal death were determined by Cox regression analysis.
Among 627 neonates, 179 (29%) died with 0–6 days after birth. Early death was associated to: absence of antenatal steroids (HR 1.59; 95% CI 1.11-2.27), multiple gestation (1.95; 1.28-3.00), male sex (2.01; 1.40-2.86), 5th minute Apgar <7 (2.93; 2.03-4.21), birthweight <1000 g (2.58; 1.70-3.88), gestational age <28 weeks (2.07; 1.42-3.02), use of surfactant (1.65; 1.04-2.59), and non-use of a pain scale (1.89; 1.24-2.89).
Biological variables and factors related to the quality of perinatal care were associated with the high chance of early death of preterm infants born in reference hospitals of Northeast Brazil.
PMCID: PMC4308919  PMID: 25528150
Premature newborn infant; Very low weight newborn infant; Neonatal mortality; Early neonatal mortality; Neonatal ICU
15.  Improved nutrient intake following implementation of the consensus standardised parenteral nutrition formulations in preterm neonates – a before-after intervention study 
BMC Pediatrics  2014;14(1):309.
New standardised parenteral nutrition (SPN) formulations were implemented in July 2011 in many neonatal intensive care units in New South Wales following consensus group recommendations. The aim was to evaluate the efficacy and safety profile of new consensus formulations in preterm infants born less than 32 weeks.
A before-after intervention study conducted at a tertiary neonatal intensive care unit. Data from the post-consensus cohort (2011 to 2012) were prospectively collected and compared retrospectively with a pre-consensus cohort of neonates (2010).
Post-consensus group commenced parenteral nutrition (PN) significantly earlier (6 v 11 hours of age, p 0.005). In comparison to the pre-consensus cohort, there was a higher protein intake from day 1 (1.34 v 0.49 g/kg, p 0.000) to day 7 (3.55 v 2.35 g/kg, p 0.000), higher caloric intake from day 1 (30 v 26 kcal/kg, p 0.004) to day 3 (64 v 62 kcal/kg, p 0.026), and less daily fluid intake from day 3 (105.8 v 113.8 mL/kg, p 0.011) to day 7 (148.8 v 156.2 mL/kg, p 0.025), and reduced duration of lipid therapy (253 v 475 hr, p 0.011). This group also had a significantly greater weight gain in the first 4 weeks (285 v 220 g, p 0.003).
New consensus SPN solutions provided better protein intake in the first 7 days and were associated with greater weight gain in the first 4 weeks. However, protein intake on day 1 was below the consensus goal of 2 g/kg/day.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0309-0) contains supplementary material, which is available to authorized users.
PMCID: PMC4275977  PMID: 25514973
Parenteral nutrition; Newborn; Standardised formulation
16.  Renal thromboembolism during treatment with recombinant activated factor VII (rFVIIa) in a child with hemophilia B with factor IX inhibitors 
BMC Pediatrics  2014;14(1):315.
Serious thromboembolic events connected with rFVIIa therapy in hemophilia patients are rare. Only three cases are reported in children, all of them with hemophilia A.
Case presentation
We present unique case of patient with hemophilia B and high titer inhibitors to coagulation FIX, who developed severe renal damage due to thromboembolic event during rFVIIa therapy, associated with unsuspected renovascular anomalies.
Caution is necessary if hematuria B requires administration of rFVIIa. US color doppler renal imaging before and after drug administration should be sufficient as an early warning.
PMCID: PMC4279815  PMID: 25515020
17.  Sleep and breathing in premature infants at 6 months post-natal age 
BMC Pediatrics  2014;14(1):303.
Poor sleep contributes to the developmental problems seen in preterm infants. We evaluated sleep problems in preterm infants 6 months of post-gestational age using the subjective Brief Infant Sleep Questionnaire (BISQ) and objective sleep tests. We also compared the sleep of premature infants with that of full-term infants.
The study included 68 6-month-old full-term healthy infants and 191 premature infants born at <37 weeks gestation. All parents completed the BISQ-Chinese version and sleep diaries. At the same time, all premature infants were submitted to one night of polysomnography (PSG) in the sleep laboratory and also were set up with an actigraph kept for 7 days. Statistical analyses were performed using correlation coefficients and the t-test with SPSS version 18 to compare questionnaire responses with other subjective and objective measures of sleep.
The sleep problems indicated in the subjective questionnaire for the premature infants, particularly: “the nocturnal sleep duration, number of night awakenings, daytime sleep duration, duration of time with mouth breathing, and loud-noisy breathing” had significant correlations with sleep diaries, actigraphy and PSG results. The BISQ showed that duration of infant’s sleeping on one side, nocturnal sleep duration, being held to fall asleep, number of nighttime awakenings, daytime sleep duration, subjective consideration of sleep problems, loud-noisy breathing, and duration spent crying during the night were significantly different between the premature infants and the term infants. PSG confirmed the presence of a very high percentage (80.6%) of premature infants with AHI > 1 event/hour as indicated by the questionnaire.
Premature infants have more sleep problems than full-term infants, including the known risk of abnormal breathing during sleep, which has been well demonstrated already with the BISQ-Chinese (CBISQ).
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0303-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4272529  PMID: 25510740
Sleep questionnaire; Sleep-disordered breathing; Prematurity; Full-term infant
18.  Early life determinants of low IQ at age 6 in children from the 2004 Pelotas Birth Cohort: a predictive approach 
BMC Pediatrics  2014;14(1):308.
Childhood intelligence is an important determinant of health outcomes in adulthood. The first years of life are critical to child development. This study aimed to identify early life (perinatal and during the first year of life) predictors of low cognitive performance at age 6.
A birth cohort study started in the city of Pelotas, southern Brazil, in 2004 and children were followed from birth to age six. Information on a broad set of biological and social predictors was collected. Cognitive ability—the study outcome—was assessed using the Wechsler Intelligence Scale for Children (WISC). IQ scores were standardized into z-scores and low IQ defined as z < −1. We applied bootstrapping methods for internal validation with a multivariate logistic regression model and carried out external validation using a second study from the 1993 Pelotas Birth Cohort.
The proportion of children with IQ z-score < −1 was 16.9% (95% CI 15.6–18.1). The final model included the following early life variables: child’s gender; parents’ skin color; number of siblings; father’s and mother’s employment status; household income; maternal education; number of persons per room; duration of breastfeeding; height-for-age deficit; head circumference-for-age deficit; parental smoking during pregnancy; and maternal perception of the child’s health status. The area under the ROC curve for our final model was 0.8, with sensitivity of 72% and specificity of 74%. Similar results were found when testing external validation by using data from the 1993 Pelotas Birth Cohort.
The study results suggest that a child’s and her/his family’s social conditions are strong predictors of cognitive ability in childhood. Interventions for promoting a healthy early childhood development are needed targeting children at risk of low IQ so that they can reach their full cognitive potential.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0308-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4272809  PMID: 25510879
Child development; Birth cohort; Intelligence; Cognition; Social determinants of health; Brazil
19.  Primary Care Triple P for parents of NICU graduates with behavioral problems: a randomized, clinical trial using observations of parent–child interaction 
BMC Pediatrics  2014;14(1):305.
Preterm-born or asphyxiated term-born children show more emotional and behavioral problems at preschool age than term-born children without a medical condition. It is uncertain whether parenting intervention programs aimed at the general population, are effective in this specific group. In earlier findings from the present trial, Primary Care Triple P was not effective in reducing parent-reported child behavioral problems. However, parenting programs claim to positively change child behavior through enhancement of the parent–child interaction. Therefore, we investigated whether Primary Care Triple P is effective in improving the quality of parent–child interaction and increasing the application of trained parenting skills in parents of preterm-born or asphyxiated term-born preschoolers with behavioral problems.
For this pragmatic, open randomized clinical trial, participants were recruited from a cohort of infants admitted to the neonatal intensive care units of two Dutch hospitals. Children aged 2–5 years, with a gestational age <32 weeks and/or birth weight <1500 g and children with a gestational age 37–42 weeks and perinatal asphyxia were included. After screening for a t-score ≥60 on the Child Behavior Checklist, children were randomly assigned to Primary Care Triple P (n = 34) or a wait-list control group (n = 33). Trial outcomes were the quality of parent–child interaction and the application of trained parenting skills, both scored from structured observation tasks.
There was no effect of the intervention on either of the observational outcome measures at the 6-month trial endpoint.
Primary Care Triple P, is not effective in improving the quality of parent–child interaction nor does it increase the application of trained parenting skills in parents of preterm-born or asphyxiated term-born children with behavioral problems. Further research should focus on personalized care for these parents, with an emphasis on psychological support to reduce stress and promote self-regulation.
Trial registration
Netherlands National Trial Register NTR2179. Registered 26 January 2010.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0305-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4273431  PMID: 25495747
Primary Care Triple P; Parenting intervention; Preterm birth; Perinatal asphyxia; RCT; Parent–child interaction; Positive parenting skills
20.  The etiologies of non-CF bronchiectasis in childhood: a systematic review of 989 subjects 
BMC Pediatrics  2014;14(1):4.
While cystic fibrosis (CF) is the most common cause of bronchiectasis in childhood, non-CF bronchiectasis is associated with a wide variety of disorders. The objective of this study was to determine the relative prevalence and specific etiologies on non-CF bronchiectasis in childhood.
EMBASE, Medline, OVID Cochrane Reviews, Directory of Open Access Journals, Open Science Directory, EPSCO information services, and OAlster were searched electronically and the bibliographies of selected studies were searched manually. The search was conducted independently by 2 authors. Study Selection: (1) any clinical trial, observational study or cross-sectional case series of 10 or more patients with a description of the conditions associated with bronchiectasis; (2) subjects aged 21 years or younger; (3) cystic fibrosis was excluded and; (4) the diagnosis was confirmed by computed tomography of the chest. Data Extraction: Patient number, age range, inclusion criteria, diagnostic criteria, patient source, and categorical and specific etiology.
From 491 studies identified, 12 studies encompassing 989 children with non-CF bronchiectasis were selected. Sixty-three percent of the subjects had an underlying disorder. Infectious (17%), primary immunodeficiency (16%), aspiration (10%), ciliary dyskinesia (9%), congenital malformation (3%), and secondary immunodeficiency (3%) were the most common disease categories; 999 etiologies were identified. Severe pneumonia of bacterial or viral etiology and B cell defects were the most common disorders identified.
The majority of children with non-CF bronchiectasis have an underlying disorder. A focused history and laboratory investigated is recommended.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0299-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4275950
Non-CF bronchiectasis; Children; Etiology
21.  Natural history of conjugated bilirubin trajectory in neonates following parenteral nutrition cessation 
BMC Pediatrics  2014;14(1):2.
There is little published data regarding the rate of bilirubin clearance in newborns following total parenteral nutrition (TPN) cessation, particularly in the neonatal intensive care unit (NICU) population without intestinal failure.
The primary aim of this retrospective chart review was to determine the duration and severity of bilirubin elevation in neonates without intestinal failure. Secondary aims were to determine factors that would influence the duration and severity of this biochemical elevation. The authors conducted a retrospective chart review of all infants receiving TPN for ≥ 21 days and with elevated conjugated bilirubin (CB) ≥3 mg/dL upon TPN cessation in a tertiary care NICU from January 1, 2008 to December 1, 2010. Patients with known causes of liver disease or without laboratory values at least four weeks after PN cessation were excluded. Time to maximum conjugated bilirubin (maxCB) post TPN cessation and normalization were the primary outcomes. Secondary factors including number/timing of sepsis events, ethnicity, and ursodiol use were also evaluated.
Forty three infants met inclusion criteria. The majority of patients had increased CB post TPN cessation (“up” group; 27/43, 63%) with maxCB reached 13 days (SD ± 10.3) after TPN cessation. The majority of the cohort achieved normalization of the bilirubin prior to discharge (28/43, 65%). There was no difference in rate of normalization (p = 0.342) between the “up” group (59%) and the group of patients whose bilirubin trended downward following PN cessation (“down” group, 75%). There were no differences between the two groups with respect to gestational age at birth, birth weight, number of sepsis events, gram negative sepsis events, or intestinal resection. Only 30% of Hispanic patients had increased CB post TPN cessation compared to the majority (71%) of non-Hispanic patients. The maxCB of those that had complete normalization was significantly lower value than the maxCB of those that did not normalize (p = 0.016).
Nearly two-thirds of infants experience a rise in serum bilirubin following PN cessation that can last for weeks, but cholestasis generally improves with time in the majority of infants.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0298-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4275980
Neonatal cholestasis; Parenteral nutrition
22.  Clinical evaluation of viral acute respiratory tract infections in children presenting to the emergency department of a tertiary referral hospital in the Netherlands 
BMC Pediatrics  2014;14(1):1.
The relative incidence and clinical impact of individual respiratory viruses remains unclear among children presenting to the hospital emergency department with acute respiratory tract infection (ARTI).
During two winter periods, respiratory virus real-time multiplex PCR results were evaluated from children (< 18 years) presenting to the emergency department of a tertiary referral hospital with ARTI that had been sampled within 48 hours of hospital presentation. In an attempt to identify virus-specific distinguishing clinical features, single virus infections were correlated with presenting signs and symptoms, clinical findings and outcomes using multivariate logistic regression.
In total, 274 children with ARTI were evaluated and most were aged < 3 years (236/274, 86%). PCR detected respiratory viruses in 224/274 (81.8%) children and included 162 (59%) single and 62 (23%) mixed virus infections. Respiratory syncytial virus (RSV) and human rhinovirus (HRV) single virus infections were common among children aged < 3 years, but proportional differences compared to older children were only significant for RSV (95% CI 1.3–15). Clinical differentiation between viral ARTIs was not possible due to common shared presenting signs and symptoms and the high frequency of mixed viral infections. We observed virus-associated outcome differences among children aged < 3 years. Oxygen treatment was associated with RSV (OR 3.6) and inversely correlated with FLU (OR 0.05). Treatment with steroids (OR 3.4) or bronchodilators (OR 3.4) was associated with HRV. Severe respiratory complications were associated with HRV (OR 3.5) and inversely correlated with RSV (OR 0.24).
Respiratory viruses are frequently detected in young children presenting to the hospital emergency department with ARTI and require PCR diagnosis since presenting signs and symptoms are not discriminant for a type of virus. RSV and HRV bear a high burden of morbidity in the pediatric clinical setting.
PMCID: PMC4276012
Acute respiratory tract infection; Pediatric emergency department; Respiratory virus; Signs and symptoms; Clinical outcome
23.  Parents’ experiences of communication with neonatal intensive-care unit staff: an interview study 
BMC Pediatrics  2014;14(1):3.
An infant’s admission to a neonatal intensive-care unit (NICU) inevitably causes the parents emotional stress. Communication between parents and NICU staff is an essential part of the support offered to the parents and can reduce their emotional stress. The aim of this study was to describe parents’ experiences of communication with NICU staff.
A hermeneutic lifeworld interview study was performed with 18 families whose children were treated in the level III NICU at a university hospital in Sweden. The interviews were analysed to gain an interpretation of the phenomenon of how parents in the NICU experienced their communication with the staff, in order to find new ways to understand their experience.
Parents’ experience of communication with the staff during their infant’s stay at the NICU can be described by the main theme ‘being given attention or ignored in their emotional situation’. The main theme derives from three themes; (1) meeting a fellow human being, (2) being included or excluded as a parent and (3) bearing unwanted responsibility.
This study shows that parents experienced communication with the NICU staff as essential to their management of their situation. Attentive communication gives the parents relief in their trying circumstances. In contrast, lack of communication contributes to feelings of loneliness, abandonment and unwanted responsibility, which adds to the burden of an already difficult situation. The level of communication in meetings with staff can have a decisive influence on parents’ experiences of the NICU.
The staff should thus be reminded of their unique position to help parents handle their emotional difficulties. The organization should facilitate opportunities for good communication between parents and staff through training, staffing and the physical health care environment.
PMCID: PMC4276021
Communication; Hermeneutic lifeworld approach; Neonatal intensive care; Parental experience
24.  Perceived stigma by children on antiretroviral treatment in Cambodia 
BMC Pediatrics  2014;14(1):5.
HIV-related stigma diminishes the quality of life of affected patients. Little is known about perceived and enacted stigma of HIV-infected children in resources-limited settings. We documented the prevalence of perceived stigma and associated factors associated among children on antiretroviral therapy (ART) at a referral hospital in Cambodia.
After informed consent, a standardized pre-tested 47-item questionnaire was confidentially administered to consecutive children (7 to 15 years) or their guardians if the child was 18 months to 6 years, during their routine ART visits. The questionnaire explored the sociodemographics of the child and the parents, HIV history, adherence to ART, tolerance of ART and perceived stigma. Associations between perceived stigma and the children’s characteristics were measured by bivariate and multivariate analyses.
Of 183 children, 101 (55.2%) had lost at least one and 45 (24.6%) both parents; 166 (90.7%) went to school. Of 183 children (female: 84, 45.9%, median age 7.0 years, interquartile range: 2.0-9.6), 79 (43.2%) experienced perceived stigma, including rejection by others (26.8%), no invitations to social activities (18.6%) and exclusion from games (14.2%). A total of 43 (23.5%) children were fearful of their disease and 61 (53.9%) of 113 older than 6 years reported knowledge of their HIV status. Of 136 children over five years and eligible for education, 7 (3.8%) could not go to school due to perceived stigma. Incomplete adherence to ART was reported for 17 (9.2%) children. In multivariate analysis, school attendance (odds ratio [OR]: 3.9; 95% confidence interval [CI]: 2.0-7.9) and income of less than one dollar per person per day (OR: 2.2, 95% CI: 1.1-4.5) were associated with perceived stigma. Conversely, receipt of social support (OR: 0.4, 95% CI 0.2-0.9) was associated with lower risk of perceived stigma.
Perceived stigma in pediatric ART patients remains a significant issue in Cambodia. Psychological support and interventions should be developed in hospitals, schools, and underprivileged communities to prevent HIV-related stigma for affected children.
PMCID: PMC4276259
AIDS; Cambodia; Children; Discrimination; Exclusion; HIV; Perceived stigma; School; Stigma; Stigmatization
25.  Abnormal movements associated with oropharyngeal dysfunction in a child with Chiari I malformation 
BMC Pediatrics  2014;14(1):1174.
Chiari I malformations (CM I) are rare hindbrain herniations. Dysphagia and other oropharyngeal dysfunctions may be associated with CM I, but to our knowledge, no clinical presentation similar to ours has ever been reported. The purpose of this communication is to draw attention to a unique and atypical clinical presentation of a child with CM I.
Case presentation
A 7-year-old boy was evaluated for a two month history of atypical movements which would occur in the evening, and last for an hour after eating. These stereotypical movements with the head and chest bending forward and to the left side, accompanied by a grimace, were associated with sensation of breath locking without cyanosis. Pain and dysphagia were absent. The neurological examination was normal. The possibility of Sandifer syndrome posturing occurring with gastroesopageal reflux disease was considered but neither pain nor back hyperextension were associated with the atypical movements. Neither proton pump inhibitors (PPI) nor prokinetic agents improved his symptoms.
Upper endoscopy and esophageal biopsy did not reveal eosinophilic esophagitis nor reflux esophagitis. Ear, throat and nose (ENT) exam was normal. A severe gastroparesis was demonstrated on milk scan study. Two 24 hour oesophageal pH probe studies pointed out severe gastroesophageal reflux (GER). High resolution manometric evaluation of the oesophagus revealed normal sphincter pressures and relaxations with no dysmotility of the esophageal body. Electroencephalography and polysomnography were normal. A brain magnetic resonance imaging (MRI) was performed and revealed a CM I: cerebellar tonsils extending to 12 mm, with syringomyelia (D4-D5).
For a long period of time, the child’s abnormal movements were considered to be nothing but tics and the CM I a fortuitous finding. Since the child remained symptomatic despite medical treatment, it was decided to proceed with surgery. One year after the onset of his symptoms, he underwent posterior fossa decompression with upper cervical laminectomy and expansion duroplasty. Postoperative MRI confirmed adequate decompression. His atypical posture and dyspnea completely resolved after surgery and he remains asymptomatic two years later.
Children may have atypical presentations of CM I. Thus, CM I diagnosis should be considered in unexplained atypical oropharyngeal dysfunctions.
PMCID: PMC4279813  PMID: 25491728
Chiari I malformation; Oropharyngeal dysfunction; Abnormal movements; Gastroesophageal reflux (GER); Gastroesophageal reflux disease (GERD)

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