Demographics of blood pressure and hypertension in children on renal replacement therapy in Europe

Hypertension is a well-known complication in children on renal replacement therapy and an important risk factor for cardiovascular disease in later life. In order to define the prevalence of and risk factors for hypertension among children, we enrolled 3337 pediatric patients from 15 countries in the ESPN/ERA-EDTA Registry of whom 464 were on hemodialysis, 851 on peritoneal dialysis, and 2023 had received a renal allograft. Hypertension was defined as either systolic or diastolic blood pressures in the 95th percentile or greater for age, height, and gender or use of antihypertensive medication. Analyses were adjusted for age, gender, duration, and modality of renal replacement therapy. In 10 countries in which information on the use of antihypertensive medication was available, hypertension was present in over two-thirds of hemodialysis, peritoneal dialysis, or transplant patients. Blood pressure values above the 95th percentile were significantly more prevalent in very young patients (under 3 years) compared to 13- to 17-year olds (odds ratio 2.47), during the first year compared to over 5 years of renal replacement therapy (odds ratio 1.80), and in patients on hemodialysis compared to transplant recipients or those on peritoneal dialysis (odds ratios of 2.48 and 1.59, respectively). Over time, mean blood pressures decreased in both hemodialysis and transplant patients, but not in peritoneal dialysis patients. Hence, our findings highlight the extent of the problem of hypertension in children with end-stage renal disease in Europe.

Nasolabial symmetry and aesthetics in children with complete unilateral cleft lip and palate

The objective of this study was to evaluate the association between nasolabial symmetry and aesthetics in children with complete unilateral cleft lip and palate (CUCLP). Frontal and basal photographs of 60 consecutively treated children with CUCLP (cleft group: 41 boys and 19 girls, mean (SD) age 11 (2) years) and 44 children without clefts (control group: 16 boys and 28 girls, mean (SD) age 11(2) years), were used for evaluation of nasolabial symmetry and aesthetics. Nasal and labial measurements were made to calculate the coefficient of asymmetry (CA). The 5-grade aesthetic index described by Asher-McDade et al. was used to evaluate nasolabial appearance. Correlation and regression analysis were used to identify an association between aesthetics and CA, sex, and the presence of CUCLP. Ten measurements in the cleft, and 2 in the control, group differed significantly between the cleft and non-cleft (or right and left) sides, respectively. The significantly higher values of 9 of 11 CA in the children with CUCLP indicated that they had more asymmetrical nasolabial areas than children without clefts. However, the regression analyses showed that only a few CA were associated with nasolabial aesthetics. In conclusion, nasolabial aesthetics and nasolabial symmetry seem to be only weakly associated in patients with CUCLP.

Clinical characteristics and outcomes in children hospitalised with pandemic influenza A/H1N1/09 virus infection – a nationwide survey by the Pediatric Infectious Diseases Group of Switzerland

OBJECTIVE To describe all patients admitted to children's hospitals in Switzerland with a diagnosis of influenza A/H1N1/09 virus infection during the 2009 influenza pandemic, and to analyse their characteristics, predictors of complications, and outcome. METHODS All patients ≤18-years-old hospitalised in eleven children's hospitals in Switzerland between June 2009 and January 2010 with a positive influenza A/H1N1/09 reverse transcriptase polymerase chain reaction (RT-PCR) from a nasopharyngeal specimen were included. RESULTS There were 326 PCR-confirmed patients of whom 189 (58%) were younger than 5 years of age, and 126 (38.7%) had one or more pre-existing medical condition. Fever (median 39.1 °C) was the most common sign (85.6% of all patients), while feeding problems (p = 0.003) and febrile seizures (p = 0.016) were significantly more frequent in children under 5 years. In 142 (43.6%) patients there was clinical suspicion of a concomitant bacterial infection, which was confirmed in 36 patients (11%). However, severe bacterial infection was observed in 4% of patients. One third (n = 108, 33.1%) of the patients were treated with oseltamivir, 64 (59.3%, or 20% overall) within 48 hours of onset of symptoms. Almost half of the patients (45.1%) received antibiotics for a median of 7 days. Twenty patients (6.1%) required intensive care, mostly for complicated pneumonia (50%) without an underlying medical condition. The median duration of hospitalisation was 2 days (range 0-39) for 304 patients. Two children (<15 months of age with underlying disease) died. CONCLUSIONS Although pandemic influenza A/H1N1/09 virus infection in children is mostly mild, it can be severe, regardless of past history or underlying disease.

Blood glucose and prognosis in children with presumed severe malaria: is there a threshold for 'hypoglycaemia'?

OBJECTIVES: Hypoglycaemia (glucose <2.2 mmol/l) is a defining feature of severe malaria, but the significance of other levels of blood glucose has not previously been studied in children with severe malaria. METHODS: A prospective study of 437 consecutive children with presumed severe malaria was conducted in Mali. We defined hypoglycaemia as <2.2 mmol/l, low glycaemia as 2.2-4.4 mmol/l and hyperglycaemia as >8.3 mmol/l. Associations between glycaemia and case fatality were analysed for 418 children using logistic regression models and a receiver operator curve (ROC). RESULTS: There was a significant difference between blood glucose levels in children who died (median 4.6 mmol/l) and survivors (median 7.6 mmol/l, P < 0.001). Case fatality declined from 61.5% of the hypoglycaemic children to 46.2% of those with low glycaemia, 13.4% of those with normal glycaemia and 7.6% of those with hyperglycaemia (P < 0.001). Logistic regression showed an adjusted odds ratio (AOR) of 0.75 (0.64-0.88) for case fatality per 1 mmol/l increase in baseline blood glucose. Compared to a normal blood glucose, hypoglycaemia and low glycaemia both significantly increased the odds of death (AOR 11.87, 2.10-67.00; and 5.21, 1.86-14.63, respectively), whereas hyperglycaemia reduced the odds of death (AOR 0.34, 0.13-0.91). The ROC [area under the curve at 0.753 (95% CI 0.684-0.820)] indicated that glycaemia had a moderate predictive value for death and identified an optimal threshold at glycaemia <6.1 mmol/l, (sensitivity 64.5% and specificity 75.1%). CONCLUSIONS: If there is a threshold of blood glucose which defines a worse prognosis, it is at a higher level than the current definition of 2.2 mmol/l.

Overweight and obesity in children: known facts and new trends

The prevalence of overweight and obesity in children is increasing. A growing number of children are thus suffering from complications of obesity. Contributing factors can be found on an individual level as well as in the familial and social environment of affected children. Currently there is no single evidence-based treatment strategy available. Studies from family practice are scarce. Multimodal, long-term, easily accessible treatments as offered in family practice are promising and likely to be cost-effective. The sustainability of these changes in behavior still needs to be demonstrated.

Dental Caries and Microbiota in Children with Black Stain and Non-discoloured Dental Plaque

Aim: We aimed to assess caries experience and microbiota in systemically healthy children with black stain (BS) and non-discoloured plaque. Methods: Forty-six children with BS and 47 counterparts with non-discoloured plaque aged 7.9 ± 1.3 years were clinically examined. Dental caries was scored using WHO criteria. Samples of BS and non-discoloured dental plaque were collected from tooth surfaces. The DNA of the samples was extracted and real-time PCR was performed to determine the total number of bacteria and the species Streptococcus mutans, S. sobrinus, Lactobacillus sp., Actinomyces naeslundii, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum. Results: Children with BS had lower DMFT (p = 0.013), lower DT values (p = 0.005) and a tendency to lower caries prevalence (p = 0.061) than children with non-discoloured plaque. Plaque samples of the BS group contained higher numbers of A. naeslundii (p = 0.005) and lower numbers of F. nucleatum (p = 0.001) and Lactobacillus sp. (p = 0.001) compared to the non-discoloured plaque samples of the control group. Comparing the children with BS and non-discoloured plaque, higher counts for A. naeslundii (p = 0.013) were observed in caries-free children with BS while in caries-affected children with BS, lower counts of F. nucleatum (p = 0.007) were found. Counts of Lactobacillus sp. were higher in non-discoloured plaque samples than in BS of caries-free and caries-affected children. Conclusion: Results suggest that the different microbial composition of BS might be associated with the lower caries experience in affected subjects. The role of black-pigmented bacteria associated with periodontitis needs further studies. © 2013 S. Karger AG, Basel.

Asthma and obesity in children: current evidence and potential systems biology approaches.

Both obesity and asthma are highly prevalent, complex diseases modified by multiple factors. Genetic, developmental, lung mechanical, immunological and behavioural factors have all been suggested as playing a causal role between the two entities; however, their complex mechanistic interactions are still poorly understood and evidence of causality in children remains scant. Equally lacking is evidence of effective treatment strategies, despite the fact that imbalances at vulnerable phases in childhood can impact long-term health. This review is targeted at both clinicians frequently faced with the dilemma of how to investigate and treat the obese asthmatic child and researchers interested in the topic. Highlighting the breadth of the spectrum of factors involved, this review collates evidence regarding the investigation and treatment of asthma in obese children, particularly in comparison with current approaches in 'difficult-to-treat' childhood asthma. Finally, the authors propose hypotheses for future research from a systems-based perspective.

Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration

Background: With expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa. Methods: Pooled analysis of routine individual data from children who initiated ART in 7 South African treatment programs with 6-monthly viral load and CD4 monitoring produced Kaplan-Meier estimates of probability of virologic failure (2 consecutive unsuppressed viral loads with the second being >1000 copies/mL, after ≥24 weeks of therapy) and switch to second-line. Cox-proportional hazards models stratified by program were used to determine predictors of these outcomes. Results: The 3-year probability of virologic failure among 5485 children was 19.3% (95% confidence interval: 17.6 to 21.1). Use of nevirapine or ritonavir alone in the initial regimen (compared with efavirenz) and exposure to prevention of mother to child transmission regimens were independently associated with failure [adjusted hazard ratios (95% confidence interval): 1.77 (1.11 to 2.83), 2.39 (1.57 to 3.64) and 1.40 (1.02 to 1.92), respectively]. Among 252 children with ≥1 year follow-up after failure, 38% were switched to second-line. Median (interquartile range) months between failure and switch was 5.7 (2.9-11.0). Conclusions: Triple ART based on nevirapine or ritonavir as a single protease inhibitor seems to be associated with a higher risk of virologic failure. A low proportion of virologically failing children were switched.

Genetic variations in IL28B and allergic disease in children

Environmental changes affecting the relationship between the developing immune system and microbial exposure have been implicated in the epidemic rise of allergic disease in developed countries. While early developmental differences in T cell function are well-recognised, there is now emerging evidence that this is related to developmental differences in innate immune function. In this study we sought to examine if differences associated with innate immunity contribute to the altered immune programming recognised in allergic children. Here, we describe for the first time, the association of carriage of the T allele of the tagging single nucleotide polymorphism rs12979860 3 kb upstream of IL28B, encoding the potent innate immune modulator type III interferon lambda (IFN-λ3), and allergy in children (p = 0.004; OR 4.56). Strikingly, the association between rs12979860 genotype and allergic disease is enhanced in girls. Furthermore, carriage of the T allele at rs12979860 correlates with differences in the pro-inflammatory profile during the first five years of life suggesting this contributes to the key differences in subsequent innate immune development in children who develop allergic disease. In the context of rising rates of disease, these immunologic differences already present at birth imply very early interaction between genetic predisposition and prenatal environmental influences.

First-day step-down to oral outpatient treatment versus continued standard treatment in children with cancer and low-risk fever in neutropenia. A randomized controlled trial within the multicenter SPOG 2003 FN study

The standard treatment of fever in chemotherapy-induced neutropenia (FN) includes emergency hospitalization and empirical intravenous antimicrobial therapy. This study determined if first-day step-down to oral outpatient treatment is not inferior to continued standard regarding safety and efficacy in children with low-risk FN.

Cotrimoxazole prophylactic treatment prevents malaria in children in sub-Saharan Africa: systematic review and meta-analysis

OBJECTIVES Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa. METHODS We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses. RESULTS Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire. CONCLUSIONS Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children.