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1.  Conceptualizing childhood health problems using survey data: a comparison of key indicators 
BMC Pediatrics  2007;7:40.
Background
Many definitions are being used to conceptualize child health problems. With survey data, commonly used indicators for identifying children with health problems have included chronic condition checklists, measures of activity limitations, elevated service use, and health utility thresholds. This study compares these different indicators in terms of the prevalence rates elicited, and in terms of how the subgroups identified differ.
Methods
Secondary data analyses used data from the National Longitudinal Survey of Children and Youth, which surveyed a nationally representative sample of Canadian children (n = 13,790). Descriptive analyses compared healthy children to those with health problems, as classified by any of the key indicators. Additional analyses examined differences between subgroups of children captured by a single indicator and those described as having health problems by multiple indicators.
Results
This study demonstrates that children captured by any of the indicators had poorer health than healthy children, despite the fact that over half the sample (52.2%) was characterized as having a health problem by at least one indicator. Rates of child ill health differed by indicator; 5.6% had an activity limitation, 9.2% exhibited a severe health difficulty, 31.7% reported a chronic condition, and 36.6% had elevated service use. Further, the four key indicators captured different types of children. Indicator groupings differed on child and socio-demographic factors. Compared to children identified by more than one indicator, those identified only by the severe health difficulty indicator displayed more cognitive problems (p < 0.0001), those identified only by the chronic condition checklist had a greater likelihood of reporting allergies or asthma (p < 0.0001), and those identified as having elevated service use only were more affluent (p = 0.01) and showed better overall health (p < 0.0001). Children identified by only a single indicator were less likely to have serious health problems than those identified by two or more indicators.
Conclusion
We provide information useful to researchers when selecting indicators from survey data to identify children with health problems. Researchers and policy makers need to be aware of the impact of such definitions on prevalence rates as well as on the composition of children classified as being in poor health.
doi:10.1186/1471-2431-7-40
PMCID: PMC2248574  PMID: 18053253
2.  Cerebral palsy in a total population of 4–11 year olds in southern Sweden. Prevalence and distribution according to different CP classification systems 
BMC Pediatrics  2007;7:41.
Background
The aim of this study was to investigate the prevalence of cerebral palsy (CP) as well as to characterize the CP population, its participation in a secondary prevention programme (CPUP) and to validate the CPUP database.
Methods
The study population was born 1990–1997 and resident in Skåne/Blekinge on Jan 1st 2002. Multiple sources were used. Irrespective of earlier diagnoses, neuropaediatrician and other professional medical records were evaluated for all children at the child habilitation units. The CPUP database and diagnosis registers at hospital departments were searched for children with CP or psychomotor retardation, whose records were then evaluated. To enhance early prevention, CP/probable CP was searched for also in children below four years of age born 1998–2001.
Results
The prevalence of CP was 2.4/1,000 (95% CI 2.1–2.6) in children 4–11 years of age born in Sweden, excluding post-neonatally acquired CP. Children born abroad had a higher prevalence of CP with more severe functional limitations. In the total population, the prevalence of CP was 2.7/1,000 (95% CI 2.4–3.0) and 48% were GMFCS-level I (the mildest limitation of gross motor function).
One third of the children with CP, who were born or had moved into the area after a previous study in 1998, were not in the CPUP database. The subtype classification in the CPUP database was adjusted in the case of every fifth child aged 4–7 years not previously reviewed.
Conclusion
The prevalence of CP and the subtype distribution did not differ from that reported in other studies, although the proportion of mild CP tended to be higher.
The availability of a second opinion about the classification of CP/CP subtypes is necessary in order to keep a CP register valid, as well as an active search for undiagnosed CP among children with other impairments.
doi:10.1186/1471-2431-7-41
PMCID: PMC2248184  PMID: 18053264
3.  Breastfeeding and childhood asthma: a six-year population-based cohort study 
BMC Pediatrics  2007;7:39.
Background
The question of the protective effect of breastfeeding on development of asthma has raised substantial interest, but the scientific evidence of the optimal duration of breastfeeding is controversial.
Methods
The authors elaborated the optimal duration of breastfeeding with respect to the risk of asthma primarily, and secondarily to the risk of persistent wheezing, cough and phlegm in school age in a population-based cohort study with the baseline in 1991 and follow-up in 1997. The study population comprised 1984 children aged 7 to 14 years at the end of the follow-up (follow-up rate 77). Information on breastfeeding was based on the baseline survey and information on the health outcomes at the follow-up.
Results
There was a U-shaped relation between breastfeeding and the outcomes with the lowest risk with breastfeeding from four to nine months for asthma and seven to nine months for persistent wheezing, cough and phlegm.
Conclusion
Our results suggest a U shape relation between duration of breastfeeding and risk of asthma with an optimal duration of 4 to 6 months. A true concave relation would explain the inconsistent results from the previous studies.
doi:10.1186/1471-2431-7-39
PMCID: PMC2228279  PMID: 18045471
4.  Homocysteine levels in preterm infants: is there an association with intraventricular hemorrhage? a prospective cohort study 
BMC Pediatrics  2007;7:38.
Background
The purpose of this study was to characterize total homocysteine (tHcy) levels at birth in preterm and term infants and identify associations with intraventricular hemorrhage (IVH) and other neonatal outcomes such as mortality, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and thrombocytopenia.
Methods
123 infants < 32 weeks gestation admitted to our Level III nursery were enrolled. A group of 25 term infants were enrolled for comparison. Two blood spots collected on filter paper with admission blood drawing were analyzed by a high performance liquid chromatography (HPLC) method. Statistical analysis included ANOVA, Spearman's Rank Order Correlation and Mann-Whitney U test.
Results
The median tHcy was 2.75 μmol/L with an interquartile range of 1.34 – 4.96 μmol/L. There was no difference between preterm and term tHcy (median 2.76, IQR 1.25 – 4.8 μmol/L vs median 2.54, IQR 1.55 – 7.85 μmol/L, p = 0.07). There was no statistically significant difference in tHcy in 31 preterm infants with IVH compared to infants without IVH (median 1.96, IQR 1.09 – 4.35 μmol/L vs median 2.96, IQR 1.51 – 4.84 μmol/L, p = 0.43). There was also no statistically significant difference in tHcy in 7 infants with periventricular leukomalacia (PVL) compared to infants without PVL (median 1.55, IQR 0.25 – 3.45 μmol/L vs median 2.85, IQR 1.34 – 4.82 μmol/L, p = 0.07). Male infants had lower tHcy compared to female; prenatal steroids were associated with a higher tHcy.
Conclusion
In our population of preterm infants, there is no association between IVH and tHcy. Male gender, prenatal steroids and preeclampsia were associated with differences in tHcy levels.
doi:10.1186/1471-2431-7-38
PMCID: PMC2219989  PMID: 18045460
5.  The importance of physician knowledge of autism spectrum disorder: results of a parent survey 
BMC Pediatrics  2007;7:37.
Background
Early diagnosis and referral to treatment prior to age 3–5 years improves the prognosis of children with Autism Spectrum Disorder (ASD). However, ASD is often not diagnosed until age 3–4 years, and medical providers may lack training to offer caregivers evidence-based treatment recommendations. This study tested hypotheses that 1) children with ASD would be diagnosed between ages 3–4 years (replicating prior work), 2) caregivers would receive little information beyond the diagnosis from their medical providers, and 3) caregivers would turn to other sources, outside of their local health care professionals, to learn more about ASD.
Methods
146 ASD caregivers responded to an online survey that consisted of questions about demographics, the diagnostic process, sources of information/support, and the need and availability of local services for ASDs. Hypotheses were tested using descriptives, regression analyses, analyses of variance, and chi-squared.
Results
The average age of diagnosis was 4 years, 10 months and the mode was 3 years. While approximately 40% of professionals gave additional information about ASD after diagnosis and 15–34% gave advice on medical/educational programs, only 6% referred to an autism specialist and 18% gave no further information. The diagnosis of Autism was made at earlier ages than Asperger's Disorder or PDD-NOS. Developmental pediatricians (relative to psychiatrists/primary care physicians, neurologists, and psychologists) were associated with the lowest age of diagnosis and were most likely to distribute additional information. Caregivers most often reported turning to the media (i.e., internet, books, videos), conferences, and other parents to learn more about ASD.
Conclusion
The average age of ASD diagnosis (4 years, 10 months) was later than optimal if children are to receive the most benefit from early intervention. Most professionals gave caregivers further information about ASDs, especially developmental pediatricians, but a sizeable minority did not. This may reflect a lack of training in the wide range of behaviors that occur across the autism spectrum. Parents turned to outside sources to learn more about ASD. We recommend that all physicians receive specialized training about ASDs to improve upon early screening and diagnosis, and then advise caregivers about empirically-supported services.
doi:10.1186/1471-2431-7-37
PMCID: PMC2235850  PMID: 18021459
6.  The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study 
BMC Pediatrics  2007;7:36.
Background
Recently, hyperbaric oxygen therapy (HBOT) has increased in popularity as a treatment for autism. Numerous studies document oxidative stress and inflammation in individuals with autism; both of these conditions have demonstrated improvement with HBOT, along with enhancement of neurological function and cognitive performance. In this study, children with autism were treated with HBOT at atmospheric pressures and oxygen concentrations in current use for this condition. Changes in markers of oxidative stress and inflammation were measured. The children were evaluated to determine clinical effects and safety.
Methods
Eighteen children with autism, ages 3–16 years, underwent 40 hyperbaric sessions of 45 minutes duration each at either 1.5 atmospheres (atm) and 100% oxygen, or at 1.3 atm and 24% oxygen. Measurements of C-reactive protein (CRP) and markers of oxidative stress, including plasma oxidized glutathione (GSSG), were assessed by fasting blood draws collected before and after the 40 treatments. Changes in clinical symptoms, as rated by parents, were also assessed. The children were closely monitored for potential adverse effects.
Results
At the endpoint of 40 hyperbaric sessions, neither group demonstrated statistically significant changes in mean plasma GSSG levels, indicating intracellular oxidative stress appears unaffected by either regimen. A trend towards improvement in mean CRP was present in both groups; the largest improvements were observed in children with initially higher elevations in CRP. When all 18 children were pooled, a significant improvement in CRP was found (p = 0.021). Pre- and post-parental observations indicated statistically significant improvements in both groups, including motivation, speech, and cognitive awareness (p < 0.05). No major adverse events were observed.
Conclusion
In this prospective pilot study of children with autism, HBOT at a maximum pressure of 1.5 atm with up to 100% oxygen was safe and well tolerated. HBOT did not appreciably worsen oxidative stress and significantly decreased inflammation as measured by CRP levels. Parental observations support anecdotal accounts of improvement in several domains of autism. However, since this was an open-label study, definitive statements regarding the efficacy of HBOT for the treatment of individuals with autism must await results from double-blind, controlled trials.
Trial Registration
clinicaltrials.gov NCT00324909
doi:10.1186/1471-2431-7-36
PMCID: PMC2244616  PMID: 18005455
7.  Young patients', parents', and survivors' communication preferences in paediatric oncology: Results of online focus groups 
BMC Pediatrics  2007;7:35.
Background
Guidelines in paediatric oncology encourage health care providers to share relevant information with young patients and parents to enable their active participation in decision making. It is not clear to what extent this mirrors patients' and parents' preferences. This study investigated communication preferences of childhood cancer patients, parents, and survivors of childhood cancer.
Methods
Communication preferences were examined by means of online focus groups. Seven patients (aged 8–17), 11 parents, and 18 survivors (aged 8–17 at diagnosis) participated. Recruitment took place by consecutive inclusion in two Dutch university oncological wards. Questions concerned preferences regarding interpersonal relationships, information exchange and participation in decision making.
Results
Participants expressed detailed and multi-faceted views regarding their needs and preferences in communication in paediatric oncology. They agreed on the importance of several interpersonal and informational aspects of communication, such as honesty, support, and the need to be fully informed. Participants generally preferred a collaborative role in medical decision making. Differences in views were found regarding the desirability of the patient's presence during consultations. Patients differed in their satisfaction with their parents' role as managers of the communication.
Conclusion
Young patients' preferences mainly concur with current guidelines of providing them with medical information and enabling their participation in medical decision making. Still, some variation in preferences was found, which faces health care providers with the task of balancing between the sometimes conflicting preferences of young cancer patients and their parents.
doi:10.1186/1471-2431-7-35
PMCID: PMC2206018  PMID: 17996108
8.  Intimate partner violence and infant morbidity: evidence of an association from a population-based study in eastern Uganda in 2003 
BMC Pediatrics  2007;7:34.
Background
Although recent studies suggest that there is an association between intimate partner violence and child mortality, the underlying mechanisms are still unknown. It is against this background that as a secondary objective, we set out to explore whether an association exists between intimate partner violence and illness in infants.
Methods
We conducted a population based household survey in Mbale, eastern Uganda in 2003. Participants were 457 women (with 457 infants) who consented to participate in the study. We measured socio-demographics of women and occurrence of intimate partner violence. We measured socio-demographics, immunization, nutritional status, and illness in the previous two weeks of the children.
Results
The mean age of the women was 25 years (SD 5.7) while the mean age of the infants was 6 months (SD 3.5). The prevalence of lifetime intimate partner violence was 54% (95% CI 48%–60%). During the previous two weeks, 50% (95% CI 50%–54%) of the children had illness (fever, diarrhoea, cough and fast breathing). Lifetime intimate partner violence was associated with infant illness (OR 1.8, 95% CI 1.2–2.8) and diarrhoea (OR 2.0, 95% CI 1.2–3.4).
Conclusion
Our findings suggest that infant illnesses (fever, diarrhoea, cough and fast breathing) are associated with intimate partner violence, and provide insights into previous reports that have shown an association between intimate partner violence and child mortality, suggesting possible underlying mechanisms. Our findings also highlight the importance of intimate partner violence on the health of children, and the need for further research in this area.
doi:10.1186/1471-2431-7-34
PMCID: PMC2186330  PMID: 17988374
9.  A family-based education program for obesity: a three-year study 
BMC Pediatrics  2007;7:33.
Background
The epidemic of obesity is increasing in all countries. However, the number of controlled studies focusing on childhood obesity, with a long follow-up is still limited. Even though Behavioral Therapy shows some efficacy, it requires a prolonged teamwork that is not always available in public health settings. In addition, Behavioral Therapy is not always accepted. We describe a new intensive and sustainable family-based, Therapeutic Education program for childhood obesity.
Methods
Controlled clinical study: a family-based Therapeutic Education program without dietetic prescription involving overweight and obese children/adolescents, without evident psychological troubles, and their families. The program consisted of three clinical and therapeutic education sessions, carried out by a single physician. Further sessions were carried out every six months in the first year and then every year.
Study population: 190 overweight children, 85 treated with a therapeutic education program (45 males and 40 females, mean age of 10.43 ± 3) with an average BMI% of 154.72 ± 19.6% and 105 matched children, treated with traditional dietary approach.
Children's Body Mass Index (BMI) % and BMI Standard Deviation Score measured at baseline and after a three year-follow-up, were compared. Statistical tests: ANOVA-RM (repeated measures) controlled for distribution by Kolmogorov-Smirnov, Bartlett's test or correspondent non-parametric procedures, X2 tests or Fisher's exact test and simple linear regression.
Results
After a follow-up of 2.7 ± 1.1 years, 72.9% of the children who followed the Therapeutic Education Program obtained a BMI% reduction, compared to 42.8% of children who followed the traditional dietary treatment. Weight reduction was good in moderately obese children and in the severely obese. In addition, a smaller proportion of children treated with therapeutic education had negative results (BMI increase of >10%) compared to those treated with dietary approach (11.8% vs. 25.7%); finally, periodic phone calls reduced the drop-out rate in the therapeutic education group.
Conclusion
These results indicate the efficacy and sustainability of the Therapeutic Education program, that was completely carried out by a single pediatrician; in addition, it met with an elevated participant acceptance, suggesting a convenient therapeutic solution for skilled pediatricians and selected obese children, when Behavioral Therapy is not available or teamwork is poor.
doi:10.1186/1471-2431-7-33
PMCID: PMC2194673  PMID: 17953755
10.  A qualitative assessment of factors influencing acceptance of a new rotavirus vaccine among health care providers and consumers 
BMC Pediatrics  2007;7:32.
Background
In 2006, a new rotavirus vaccine (RotaTeq) was licensed in the US and recommended for routine immunization of all US infants. Because a previously licensed vaccine (Rotashield) was withdrawn from the US for safety concerns, identifying barriers to uptake of RotaTeq will help develop strategies to broaden vaccine coverage.
Methods
We explored beliefs and attitudes of parents (n = 57) and providers (n = 10) towards rotavirus disease and vaccines through a qualitative assessment using focus groups and in-depth interviews.
Results
All physicians were familiar with safety concerns about rotavirus vaccines, but felt reassured by RotaTeq's safety profile. When asked about likelihood of using RotaTeq on a scale of one to seven (1 = "absolutely not;" 7 = "absolutely yes") the mean score was 5 (range = 3–6). Physicians expressed a high likelihood of adopting RotaTeq, particularly if recommended by their professional organizations and expressed specific interest in post-marketing safety data. Similarly, consumers found the RotaTeq safety profile to be favorable and would rely on their physician's recommendation for vaccination. However, when asked to rank likelihood of having their child vaccinated against rotavirus (1 = "definitely not get;" 7 = "definitely get"), 29% ranked 1 or 2, 36% 3 or 4, and 35% 5 to 7.
Conclusion
Our qualitative assessment provides complementary data to recent quantitative surveys and suggests that physicians and parents are likely to adopt the newly licensed rotavirus vaccine. Increasing parental awareness of the rotavirus disease burden and providing physicians with timely post-marketing surveillance data will be integral to a successful vaccination program.
doi:10.1186/1471-2431-7-32
PMCID: PMC2203981  PMID: 17945010
11.  Focus on Function – a randomized controlled trial comparing two rehabilitation interventions for young children with cerebral palsy 
BMC Pediatrics  2007;7:31.
Background
Children with cerebral palsy receive a variety of long-term physical and occupational therapy interventions to facilitate development and to enhance functional independence in movement, self-care, play, school activities and leisure. Considerable human and financial resources are directed at the "intervention" of the problems of cerebral palsy, although the available evidence supporting current interventions is inconclusive. A considerable degree of uncertainty remains about the appropriate therapeutic approaches to manage the habilitation of children with cerebral palsy. The primary objective of this project is to conduct a multi-site randomized clinical trial to evaluate the efficacy of a task/context-focused approach compared to a child-focused remediation approach in improving performance of functional tasks and mobility, increasing participation in everyday activities, and improving quality of life in children 12 months to 5 years of age who have cerebral palsy.
Method/Design
A multi-centred randomized controlled trial research design will be used. Children will be recruited from a representative sample of children attending publicly-funded regional children's rehabilitation centers serving children with disabilities in Ontario and Alberta in Canada. Target sample size is 220 children with cerebral palsy aged 12 months to 5 years at recruitment date. Therapists are randomly assigned to deliver either a context-focused approach or a child-focused approach. Children follow their therapist into their treatment arm. Outcomes will be evaluated at baseline, after 6 months of treatment and at a 3-month follow-up period. Outcomes represent the components of the International Classification of Functioning, Disability and Health, including body function and structure (range of motion), activities (performance of functional tasks, motor function), participation (involvement in formal and informal activities), and environment (parent perceptions of care, parental empowerment).
Discussion
This paper presents the background information, design and protocol for a randomized controlled trial comparing a task/context-focused approach to a child-focused remediation approach in improving functional outcomes for young children with cerebral palsy.
Trial registration
[clinical trial registration #: NCT00469872]
doi:10.1186/1471-2431-7-31
PMCID: PMC2131748  PMID: 17900362
12.  A systematic review of cooling for neuroprotection in neonates with hypoxic ischemic encephalopathy – are we there yet? 
BMC Pediatrics  2007;7:30.
Background
The objective of this study was to systematically review randomized trials assessing therapeutic hypothermia as a treatment for term neonates with hypoxic ischemic encephalopathy.
Methods
The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL databases, reference lists of identified studies, and proceedings of the Pediatric Academic Societies were searched in July 2006. Randomized trials assessing the effect of therapeutic hypothermia by either selective head cooling or whole body cooling in term neonates were eligible for inclusion in the meta-analysis. The primary outcome was death or neurodevelopmental disability at ≥ 18 months.
Results
Five trials involving 552 neonates were included in the analysis. Cooling techniques and the definition and severity of neurodevelopmental disability differed between studies. Overall, there is evidence of a significant effect of therapeutic hypothermia on the primary composite outcome of death or disability (RR: 0.78, 95% CI: 0.66, 0.92, NNT: 8, 95% CI: 5, 20) as well as on the single outcomes of mortality (RR: 0.75, 95% CI: 0.59, 0.96) and neurodevelopmental disability at 18 to 22 months (RR: 0.72, 95% CI: 0.53, 0.98). Adverse effects include benign sinus bradycardia (RR: 7.42, 95% CI: 2.52, 21.87) and thrombocytopenia (RR: 1.47, 95% CI: 1.07, 2.03, NNH: 8) without deleterious consequences.
Conclusion
In general, therapeutic hypothermia seems to have a beneficial effect on the outcome of term neonates with moderate to severe hypoxic ischemic encephalopathy. Despite the methodological differences between trials, wide confidence intervals, and the lack of follow-up data beyond the second year of life, the consistency of the results is encouraging. Further research is necessary to minimize the uncertainty regarding efficacy and safety of any specific technique of cooling for any specific population.
doi:10.1186/1471-2431-7-30
PMCID: PMC2031882  PMID: 17784966
13.  A randomised controlled trial of early insulin therapy in very low birth weight infants, "NIRTURE" (neonatal insulin replacement therapy in Europe) 
BMC Pediatrics  2007;7:29.
Background
Studies in adult intensive care have highlighted the importance of insulin and improved glucose control on survival, with 32% reduction in mortality, 22% reduction in intensive care stay and halving of the incidence of bacteraemia. Very low birth weight infants requiring intensive care also have relative insulin deficiency often leading to hyperglycaemia during the first week of life. The physiological influences on insulin secretion and sensitivity, and the potential importance of glucose control at this time are not well established. However there is increasing evidence that the early postnatal period is critical for pancreatic development. At this time a complex set of signals appears to influence pancreatic development and β cell survival. This has implications both in terms of acute glucose control but also relative insulin deficiency is likely to play a role in poor postnatal growth, which has been associated with later motor and cognitive impairment, and fewer β cells are linked to risk of type 2 diabetes later in life.
Methods
A multi-centre, randomised controlled trial of early insulin replacement in very low birth weight babies (VLBW, birth weight < 1500 g). 500 infants will be recruited from 10 centres in the UK and Europe. Babies will be randomised to receive a continuous insulin infusion (0.05 units/kg/h) or to receive standard neonatal care from the first day of life and for the next 7 days. If blood glucose (BG) levels fall infants will receive 20% dextrose titrated to maintain normoglycaemia (4–8 mmol/l). If BG is consistently above 10 mmol/l babies will receive standard treatment with additional insulin infusion. The primary end point will be mortality on or before expected date of delivery, secondary end points will be markers of morbidity and include episodes of sepsis, severity of retinopathy, chronic lung disease and growth.
Trial Registration
Current Controlled Trials ISRCTN78428828. EUDRACT Number 2004-002170-34
doi:10.1186/1471-2431-7-29
PMCID: PMC1994677  PMID: 17692117
14.  Influenza vaccination coverage: findings from immunization information systems 
BMC Pediatrics  2007;7:28.
Background
Beginning with the 2004–05 influenza season, the Advisory Committee on Immunization Practices (ACIP) strengthened their existing encouragement that children aged 6–23 months receive influenza vaccination by creating a formal recommendation.
Methods
Well-functioning sentinel project immunization information systems (IIS) in Arizona (AIIS) and Michigan (MIIS) were used to calculate vaccination coverage among children aged 6–23 months during the 2004–05 influenza season. We calculated 2 measures of vaccination coverage: a) receipt of 1 or more doses of influenza vaccine September 2004-March 2005 and b) receipt of 2 or more doses (ie, fully vaccinated). We compared the dose administration distribution among children needing 1 and 2 doses and by provider type. Coverage by age and timeliness of vaccine doses entered into the IIS were also analyzed.
Results
Influenza vaccination coverage levels among children were 30% and 27% in AIIS and MIIS, respectively, for receipt of 1 or more doses; 13% and 11% of children, respectively, were fully vaccinated. Peaks in dose administration among children needing 1 and 2 doses were similar. There were differences in vaccine administration between public and private providers. Coverage was higher among younger children and over 75% of all influenza vaccine doses were entered into the IIS within 30 days after receipt of vaccine.
Conclusion
Though almost 1/3 of children received 1 or more doses of vaccine in 2 IIS sentinel projects during the first season of the new recommendation, emphasis needs to be placed on increasing the proportion of children fully vaccinated. IIS data can be used for timely monitoring of vaccination coverage assessments.
doi:10.1186/1471-2431-7-28
PMCID: PMC1940249  PMID: 17662126
15.  A randomized controlled trial of sucrose and/or pacifier as analgesia for infants receiving venipuncture in a pediatric emergency department 
BMC Pediatrics  2007;7:27.
Background
Although sucrose has been accepted as an effective analgesic agent for procedural pain in neonates, previous studies are largely in the NICU population using the procedure of heel lance. This is the first report of the effect of sucrose, pacifier or the combination thereof for the procedural pain of venipuncture in infants in the pediatric emergency department population.
Methods
The study design was a double (sucrose) and single blind (pacifier), placebo-controlled randomized trial – factorial design carried out in a pediatric emergency department. The study population was infants, aged 0 – 6 months. Eighty-four patients were randomly assigned to one of four groups: a) sucrose b) sucrose & pacifier c) control d) control & pacifier. Each child received 2 ml of either 44% sucrose or sterile water, by mouth. The primary outcome measure: FLACC pain scale score change from baseline. Secondary outcome measures: crying time and heart rate change from baseline.
Results
Sucrose did not significantly reduce the FLACC score, crying time or heart rate. However sub-group analysis revealed that sucrose had a much greater effect in the younger groups. Pacifier use reduced FLACC score (not statistically significant), crying times (statistically significant) but not heart rate. Subgroup analysis revealed a mean crying time difference of 76.52 seconds (p < 0.0171) (0–1 month) and 123.9 seconds (p < 0.0029) (1–3 month). For subgroup age > 3 months pacifier did not have any significant effect on crying time. Age adjusted regression analysis revealed that both sucrose and pacifier had significant effects on crying time. Crying time increased with both increasing age and increasing gestational age.
Conclusion
Pacifiers are inexpensive, effective analgesics and are easy to use in the PED for venipuncture in infants aged 0–3 months. The benefits of sucrose alone as an analgesic require further investigation in the older infant, but sucrose does appear to provide additional benefit when used with a pacifier in this age group.
Trial registration
Current Controlled Trials ISRCTN15819627
doi:10.1186/1471-2431-7-27
PMCID: PMC1950500  PMID: 17640375
16.  Community health and medical provision: impact on neonates (the CHAMPION trial) 
BMC Pediatrics  2007;7:26.
Background
The trial aims to evaluate whether neonatal mortality can be reduced through systemic changes to the provision and promotion of healthcare. Neonatal mortality rates in India are high compared to other low income countries, and there is a wide variation of rates across regions. There is evidence that relatively inexpensive interventions may be able to prevent up to 75% of these deaths. One area with a particularly high rate is Mahabubnagar District in Andhra Pradesh, where neonatal mortality is estimated to be in the region of 4–9%. The area suffers from a vicious cycle of both poor supply of and small demand for health care services. The trial will assess whether a package of interventions to facilitate systemic changes to the provision and promotion of healthcare may be able to substantially reduce neonatal mortality in this area and be cost-effective. If successful, the trial is designed so that it should be possible to substantially scale up the project in regions with similarly high neonatal mortality throughout Andhra Pradesh and elsewhere.
Methods/Design
This trial will be a cluster-randomised controlled trial involving 464 villages in Mahabubnagar District. The package of interventions will first be introduced in half of the villages with the others serving as controls. The trial will run for a period of three years. The intervention in the trial has two key elements: a community health promotion campaign and a system to contract out healthcare to non-public institutions. The health promotion campaign will include a health education campaign, participatory discussion groups, training of village health workers and midwives, and improved coordination of antenatal services. The intervention group will also have subsidised access to pregnancy-related healthcare services at non-public lth centres (NPHCs).
The primary outcome of the trial will be neonatal mortality. Secondary outcomes will include age at and cause of neonatal death, neonatal morbidity, maternal mortality and morbidity, health service usage, costs and several process and knowledge outcomes.
Discussion
The trial will be run by independent research and service delivery arms and supervised by a trial steering committee. A data monitoring committee will be put in place to monitor the trial and recommend stopping/continuation according to a Peto-Haybittle rule. The primary publication for the trial will follow CONSORT guidelines for cluster randomised controlled trials. Criteria for authorship of all papers, presentations and reports resulting from the study will conform to ICMJE standards.
Trial Registration
Current Controlled Trials ISRCTN24104646
doi:10.1186/1471-2431-7-26
PMCID: PMC2031883  PMID: 17625023
17.  Incidence rates of progressive childhood encephalopathy in Oslo, Norway: a population based study 
BMC Pediatrics  2007;7:25.
Background
Progressive encephalopathy (PE) in children is a heterogeneous group of diseases mainly composed of metabolic diseases, but it consists also of neurodegenerative disorders where neither metabolic nor other causes are found. We wanted to estimate the incidence rate and aetiology of PE, as well as the age of onset of the disease.
Methods
We included PE cases born between 1985 and 2003, living in Oslo, and registered the number presenting annually between 1985 and 2004. Person-years at risk between 0 and 15 years were based on the number of live births during the observation period which was divided into four 5-year intervals. We calculated incidence rates according to age at onset which was classified as neonatal (0–4 weeks), infantile (1–12 months), late infantile (1–5 years), and juvenile (6–12 years).
Results
We found 84 PE cases representing 28 diagnoses among 1,305,997 person years, giving an incidence rate of 6.43 per 100,000 person years. The age-specific incidence rates per 100,000 were: 79.89 (<1 year), 8.64 (1–2 years), 1.90 (2–5 years), and 0.65 (>5 years). 66% (55/84) of the cases were metabolic, 32% (27/54) were neurodegenerative, and 2% (2/84) had HIV encephalopathy. 71% (60/84) of the cases presented at < 1 year, 24% (20/84) were late infantile presentations, and 5% (4/84) were juvenile presentations. Neonatal onset was more common in the metabolic (46%) (25/55) compared to the neurodegenerative group (7%) (2/27). 20% (17/84) of all cases were classified as unspecified neurodegenerative disease.
Conclusion
The overall incidence rate of PE was 6.43 per 100,000 person years. There was a strong reduction in incidence rates with increasing age. Two-thirds of the cases were metabolic, of which almost half presented in the neonatal period.
doi:10.1186/1471-2431-7-25
PMCID: PMC1914055  PMID: 17597517
18.  Leukocyte counts in urine reflect the risk of concomitant sepsis in bacteriuric infants: A retrospective cohort study 
BMC Pediatrics  2007;7:24.
Background
When urine infections are missed in febrile young infants with normal urinalysis, clinicians may worry about the risk – hitherto unverified – of concomitant invasion of blood and cerebrospinal fluid by uropathogens. In this study, we determine the extent of this risk.
Methods
In a retrospective cohort study of febrile 0–89 day old infants evaluated for sepsis in an urban academic pediatric emergency department (1993–1999), we estimated rates of bacteriuric sepsis (urinary tract infections complicated by sepsis) after stratifying infants by urine leukocyte counts higher, or lower than 10 cells/hpf. We compared the global accuracy of leukocytes in urine, leukocytes in peripheral blood, body temperature, and age for predicting bacteruric sepsis. The global accuracy of each test was estimated by calculating the area under its receiver operating characteristic curve (AUC). Chi-square and Fisher exact tests compared count data. Medians for data not normally distributed were compared by the Kruskal-Wallis test.
Results
Two thousand two hundred forty-nine young infants had a normal screening dipstick. None of these developed bacteremia or meningitis despite positive urine culture in 41 (1.8%). Of 1516 additional urine specimens sent for formal urinalysis, 1279 had 0–9 leukocytes/hpf. Urine pathogens were isolated less commonly (6% vs. 76%) and at lower concentrations in infants with few, compared to many urine leukocytes. Urine leukocytes (AUC: 0.94) were the most accurate predictors of bacteruric sepsis. Infants with urinary leukocytes < 10 cells/hpf were significantly less likely (0%; CI:0–0.3%) than those with higher leukocyte counts (5%; CI:2.6–8.7%) to have urinary tract infections complicated by bacteremia (N = 11) or bacterial meningitis (N = 1) – relative risk, 0 (CI:0–0.06) [RR, 0 (CI: 0–0.02), when including infants with negative dipstick]. Bands in peripheral blood had modest value for detecting bacteriuric sepsis (AUC: 0.78). Cases of sepsis without concomitant bacteriuria were comparatively rare (0.8%) and equally common in febrile young infants with low and high concentrations of urine leukocytes.
Conclusion
In young infants evaluated for fever, leukocytes in urine reflect the likelihood of bacteriuric sepsis. Infants with urinary tract infections missed because of few leukocytes in urine are at relatively low risk of invasive bacterial sepsis by pathogens isolated from urine.
doi:10.1186/1471-2431-7-24
PMCID: PMC1906775  PMID: 17567901
19.  Phono-spectrographic analysis of heart murmur in children 
BMC Pediatrics  2007;7:23.
Background
More than 90% of heart murmurs in children are innocent. Frequently the skills of the first examiner are not adequate to differentiate between innocent and pathological murmurs. Our goal was to evaluate the value of a simple and low-cost phonocardiographic recording and analysis system in determining the characteristic features of heart murmurs in children and in distinguishing innocent systolic murmurs from pathological.
Methods
The system consisting of an electronic stethoscope and a multimedia laptop computer was used for the recording, monitoring and analysis of auscultation findings. The recorded sounds were examined graphically and numerically using combined phono-spectrograms. The data consisted of heart sound recordings from 807 pediatric patients, including 88 normal cases without any murmur, 447 innocent murmurs and 272 pathological murmurs. The phono-spectrographic features of heart murmurs were examined visually and numerically. From this database, 50 innocent vibratory murmurs, 25 innocent ejection murmurs and 50 easily confusable, mildly pathological systolic murmurs were selected to test whether quantitative phono-spectrographic analysis could be used as an accurate screening tool for systolic heart murmurs in children.
Results
The phono-spectrograms of the most common innocent and pathological murmurs were presented as examples of the whole data set. Typically, innocent murmurs had lower frequencies (below 200 Hz) and a frequency spectrum with a more harmonic structure than pathological cases. Quantitative analysis revealed no significant differences in the duration of S1 and S2 or loudness of systolic murmurs between the pathological and physiological systolic murmurs. However, the pathological murmurs included both lower and higher frequencies than the physiological ones (p < 0.001 for both low and high frequency limits). If the systolic murmur contained intensive frequency components of over 200 Hz, or its length accounted for over 80 % of the whole systolic duration, it was considered pathological. Using these criteria, 90 % specificity and 91 % sensitivity in screening were achieved.
Conclusion
Phono-spectrographic analysis improves the accuracy of primary heart murmur evaluation and educates inexperienced listener. Using simple quantitative criterias a level of pediatric cardiologist is easily achieved in screening heart murmurs in children.
doi:10.1186/1471-2431-7-23
PMCID: PMC1906774  PMID: 17559690
20.  Computerized acoustic assessment of treatment efficacy of nebulized epinephrine and albuterol in RSV bronchiolitis 
BMC Pediatrics  2007;7:22.
Aim
We evaluated the use of computerized quantification of wheezing and crackles compared to a clinical score in assessing the effect of inhaled albuterol or inhaled epinephrine in infants with RSV bronchiolitis.
Methods
Computerized lung sounds analysis with quantification of wheezing and crackles and a clinical score were used during a double blind, randomized, controlled nebulized treatment pilot study. Infants were randomized to receive a single dose of 1 mgr nebulized l-epinephrine or 2.5 mgr nebulized albuterol. Computerized quantification of wheezing and crackles (PulmoTrack®) and a clinical score were performed prior to, 10 minutes post and 30 minutes post treatment. Results were analyzed with Student's t-test for independent samples, Mann-Whitney U test and Wilcoxon test.
Results
15 children received albuterol, 12 received epinephrine. The groups were identical at baseline. Satisfactory lung sounds recording and analysis was achieved in all subjects. There was no significant change in objective quantification of wheezes and crackles or in the total clinical scores either within the groups or between the groups. There was also no difference in oxygen saturation and respiratory distress.
Conclusion
Computerized lung sound analysis is feasible in young infants with RSV bronchiolitis and provides a non-invasive, quantitative measure of wheezing and crackles in these infants.
Trial registration number: ClinicalTrials.gov NCT00361452
doi:10.1186/1471-2431-7-22
PMCID: PMC1896161  PMID: 17543129
21.  Children with pertussis inform the investigation of other pertussis cases among contacts 
BMC Pediatrics  2007;7:21.
Background
The number of reported pertussis has increased in the last two decades. However, many cases of pertussis may be underreported or not diagnosed. The World Health Organization estimates that pertussis causes 200.000 – 400.000 deaths each year, most deaths are in infants and in developing countries. Infants with pertussis can indicate an undetected source cases in the community.
Methods
At a University Hospital in Brazil individuals that had frequent contacts with a child with confirmed pertussis (the index case) and had recent history of cough were enrolled into the study. Nasopharyngeal swabs were collected from every contact that had cough within the last 21 days. Cases confirmation followed the guidelines of the Center for Disease Control and Prevention – Atlanta, U.S.A.
Results
Pertussis diagnosis was confirmed in 51 children, (considered the index cases). Among the index cases, 72.5% (37/51) were under 6 months of age; culture for Bordetella pertussis was positive in 78.4% (40/51). Pertussis was confirmed in 39% (107/276) of the contacts of 51 index cases. Among these contacts identified as a pertussis case, 40.2% (43/107) were between 6 months and 111/2 years of age and 59.8% (64/107) were older than 111/2 years of age. Pertussis was confirmed by culture in 11.2% (12/107) of them and by epidemiologic linkage in 88.8% (95/107). Each index case allowed identifying two new cases of pertussis.
Conclusion
Public health authorities should consider implementing early recognition of pertussis index cases and searching for pertussis cases among the contacts. Treatment of the cases and prophylaxis of the contacts is fundamental to control outbreaks in the community.
doi:10.1186/1471-2431-7-21
PMCID: PMC1894795  PMID: 17518997
22.  Survival and major neurodevelopmental impairment in extremely low gestational age newborns born 1990–2000: a retrospective cohort study 
BMC Pediatrics  2007;7:20.
Background
It is important to determine if rates of survival and major neurodevelopmental impairment in extremely low gestational age newborns (ELGANs; infants born at 23–27 weeks gestation) are changing over time.
Methods
Study infants were born at 23 to 27 weeks of gestation without congenital anomalies at a tertiary medical center between July 1, 1990 and June 30, 2000, to mothers residing in a thirteen-county region in North Carolina. Outcomes at one year adjusted age were compared for two epochs of birth: epoch 1, July 1, 1990 to June 30, 1995; epoch 2, July 1, 1995 to June 30, 2000. Major neurodevelopmental impairment was defined as cerebral palsy, Bayley Scales of Infant Development Mental Developmental Index more than two standard deviations below the mean, or blindness.
Results
Survival of ELGANs, as a percentage of live births, was 67% [95% confidence interval: (61, 72)] in epoch 1 and 71% (65, 75) in epoch 2. Major neurodevelopmental impairment was present in 20% (15, 27) of survivors in epoch 1 and 14% (10, 20) in epoch 2. When adjusted for gestational age, survival increased [odds ratio 1.5 (1.0, 2.2), p = .03] and major neurodevelopmental impairment decreased [odds ratio 0.54 (0.31, 0.93), p = .02] from epoch 1 to epoch 2.
Conclusion
The probability of survival increased while that of major neurodevelopmental impairment decreased during the 1990's in this regionally based sample of ELGANs.
doi:10.1186/1471-2431-7-20
PMCID: PMC1876228  PMID: 17477872
23.  Aerobic exercise in adolescents with obesity: preliminary evaluation of a modular training program and the modified shuttle test 
BMC Pediatrics  2007;7:19.
Background
Increasing activity levels in adolescents with obesity requires the development of exercise programs that are both attractive to adolescents and easily reproducible. The aim of this study was to develop a modular aerobic training program for adolescents with severe obesity, with a focus on variety, individual targets and acquiring physical skills. We report here the effects on aerobic fitness from a pilot study. Furthermore, we examined the feasibility of the modified shuttle test (MST) as an outcome parameter for aerobic fitness in adolescents with severe obesity.
Methods
Fifteen adolescents from an inpatient body weight management program participated in the aerobic training study (age 14.7 ± 2.1 yrs, body mass index 37.4 ± 3.5). The subjects trained three days per week for 12 weeks, with each session lasting 30–60 minutes. The modular training program consisted of indoor, outdoor and swimming activities. Feasibility of the MST was studied by assessing construct validity, test-retest reliability and sensitivity to change.
Results
Comparing pretraining and end of training period showed large clinically relevant and significant improvements for all aerobic indices: e.g. VO2 peak 17.5%, effect size (ES) 2.4; Wmax 8%, ES 0.8. In addition, a significant improvement was found for the efficiency of the cardiovascular system as assessed by the oxygen pulse (15.8%, ES 1.6).
Construct validity, test-retest reliability and sensitivity to change of the MST were very good. MST was significantly correlated with VO2 peak (r = 0.79) and Wmax (r = 0.84) but not with anthropometric measures. The MST walking distance improved significantly by 32.5%, ES 2.5. The attendance rate at the exercise sessions was excellent.
Conclusion
This modular, varied aerobic training program has clinically relevant effects on aerobic performance in adolescents with severe obesity. The added value of our aerobic training program for body weight management programs for adolescents with severe obesity should be studied with a randomized trial. This study further demonstrated that the MST is a reliable, sensitive and easy to administer outcome measure for aerobic fitness in adolescent body weight management trials.
doi:10.1186/1471-2431-7-19
PMCID: PMC1866229  PMID: 17445257
24.  Mild gestational diabetes in pregnancy and the adipoinsular axis in babies born to mothers in the ACHOIS randomised controlled trial 
BMC Pediatrics  2007;7:18.
Background
Mild gestational diabetes is a common complication of pregnancy, affecting up to 9% of pregnant women. Treatment of mild GDM is known to reduce adverse perinatal outcomes such as macrosomia and associated birth injuries, such as shoulder dystocia, bone fractures and nerve palsies. This study aimed to compare the plasma glucose concentrations and serum insulin, leptin and adiponectin in cord blood of babies of women (a) without gestational diabetes mellitus (GDM), (b) with mild GDM under routine care, or (c) mild GDM with treatment.
Methods
95 women with mild GDM on oral glucose tolerance testing (OGTT) at one tertiary level maternity hospital who had been recruited to the ACHOIS trial at one of the collaborating hospitals and randomised to either Treatment (n = 46) or Routine Care (n = 49) and Control women with a normal OGTT (n = 133) were included in the study. Women with mild GDM (treatment or routine care group) and OGTT normal women received routine pregnancy care. In addition, women with treated mild GDM received dietary advice, blood glucose monitoring and insulin if necessary.
The primary outcome measures were cord blood concentrations of glucose, insulin, adiponectin and leptin.
Results
Cord plasma glucose was higher in women receiving routine care compared with control, but was normalized by treatment for mild GDM (p = 0.01). Cord serum insulin and insulin to glucose ratio were similar between the three groups. Leptin concentration in cord serum was lower in GDM treated women compared with routine care (p = 0.02) and not different to control (p = 0.11). Adiponectin was lower in both mild GDM groups compared with control (Treatment p = 0.02 and Routine Care p = 0.07), while the adiponectin to leptin ratio was lower for women receiving routine care compared with treatment (p = 0.08) and control (p = 0.05).
Conclusion
Treatment of women with mild GDM using diet, blood glucose monitoring and insulin if necessary, influences the altered fetal adipoinsular axis characteristic of mild GDM in pregnancy.
doi:10.1186/1471-2431-7-18
PMCID: PMC1865537  PMID: 17430602
25.  Passive smoking as a risk factor of anemia in young children aged 0–35 months in Jordan 
BMC Pediatrics  2007;7:16.
Background
Passive smoking unfavorably affects pregnancy, child birth and child health. Passive smoking associates with still-birth, premature birth as well as acute respiratory infection, asthma, disorder in red blood cell metabolism in children. This study examined the effects of passive smoking on anemia in young children in Jordan.
Methods
The analysis based on the information from 740 children aged 0–35 months that were tested for hemoglobin levels included in the 2002 Jordan Population and Family Health Survey. This study used multivariate logistic regression method to analyze the effect of passive smoking on anemia in young children in Jordan, controlling for a number of risk factors and confounding factors for anemia.
Results
Results indicated that independent of other risk factors and confounding factors, anemia in young children was strongly positively associated with exposure to passive smoking from both parents (OR= 2.99, p < 0.01). Severely undernourished children were at higher risk of anemia independent of passive smoking and other risk factors (OR= 5.29, p < 0.05). Children age 24–35 months, children born to mothers age 35–49, and children lived in households with a hygienic toilet facility were less likely to suffer from anemia.
Conclusion
Passive smoking from both parents was strongly positively associated with anemia in young children in Jordan independent of other risk factors and confounding factors. The results support the importance of smoking prevention during and after pregnancy that prevent childhood anemia and others morbidities in young children.
doi:10.1186/1471-2431-7-16
PMCID: PMC1854899  PMID: 17425780

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