3B.01: Performance of targeted screening for the identification of hypertension in children

OBJECTIVE: As universal screening of hypertension performs poorly in childhood, targeted screening to children at higher risk of hypertension has been proposed. Our goal was to assess the performance of combined parental history of hypertension and overweight/obesity to identify children with hypertension. We estimated the sensitivity, specificity, negative and positive predictive values of overweight/obesity and parental history of hypertension for the identification of hypertension in children. DESIGN AND METHOD: We analyzed data from a school-based cross-sectional study including 5207 children aged 10 to 14 years from all public 6th grade classes in the canton of Vaud, Switzerland. Blood pressure was measured with a clinically validated oscillometric automated device over up to three visits separated by one week. Children had hypertension if they had sustained elevated blood pressure over the three visits. Parents were interviewed about their history of hypertension. RESULTS: The prevalence of hypertension was 2.2%. 14% of children were overweight or obese and 20% had a positive history of hypertension in either or both parents. 30% of children had either or both conditions. After accounting for several potential confounding factors, parental history of hypertension (odds ratio (OR): 2.6; 95% confidence interval (CI): 1.8-4.0), overweight excluding obesity (OR: 2.5; 95% CI: 1.5-4.2) and obesity (OR: 10.1; 95% CI: 6.0-17.0) were associated with hypertension in children. Considered in isolation, the sensitivity and positive predictive values of parental history of hypertension (respectively 41% and 5%) or overweight/obesity (respectively 43% and 7%) were relatively low. Nevertheless, considered together, the sensitivity of targeted screening in children with either overweight/obesity or paternal history of hypertension was higher (65%) but the positive predictive value remained low (5%). The negative predictive value was systematically high. CONCLUSIONS: Restricting screening of hypertension to children with either overweight/obesity or with hypertensive parents would substantially limit the proportion of children to screen (30%) and allow the identification of a relatively large proportion (65%) of hypertensive cases. That could be a valuable alternative to universal screening.

Improvement of allocentric spatial memory resolution in children from 2 to 4 years of age

Allocentric spatial memory, the memory for locations coded in relation to objects comprising our environment, is a fundamental component of episodic memory and is dependent on the integrity of the hippocampal formation in adulthood. Previous research from different laboratories reported that basic allocentric spatial memory abilities are reliably observed in children after 2 years of age. Based on work performed in monkeys and rats, we had proposed that the functional maturation of direct entorhinal cortex projections to the CA1 field of the hippocampus might underlie the emergence of basic allocentric spatial memory. We also proposed that the protracted development of the dentate gyrus and its projections to the CA3 field of the hippocampus might underlie the development of high-resolution allocentric spatial memory capacities, based on the essential contribution of these structures to the process known as pattern separation. Here, we present an experiment designed to assess the development of spatial pattern separation capacities and its impact on allocentric spatial memory performance in children from 18 to 48 months of age. We found that: (1) allocentric spatial memory performance improved with age, (2) as compared to younger children, a greater number of children older than 36 months advanced to the final stage requiring the highest degree of spatial resolution, and (3) children that failed at different stages exhibited difficulties in discriminating locations that required higher spatial resolution abilities. These results are consistent with the hypothesis that improvements in human spatial memory performance might be linked to improvements in pattern separation capacities.

Clinical Application of Prognostic Gene Expression Signature in Fusion Gene-Negative Rhabdomyosarcoma: A Report from the Children's Oncology Group.

PURPOSE: Pediatric rhabdomyosarcoma (RMS) has two common histologic subtypes: embryonal (ERMS) and alveolar (ARMS). PAX-FOXO1 fusion gene status is a more reliable prognostic marker than alveolar histology, whereas fusion gene-negative (FN) ARMS patients are clinically similar to ERMS patients. A five-gene expression signature (MG5) previously identified two diverse risk groups within the fusion gene-negative RMS (FN-RMS) patients, but this has not been independently validated. The goal of this study was to test whether expression of the MG5 metagene, measured using a technical platform that can be applied to routine pathology material, would correlate with outcome in a new cohort of patients with FN-RMS. EXPERIMENTAL DESIGN: Cases were taken from the Children's Oncology Group (COG) D9803 study of children with intermediate-risk RMS, and gene expression profiling for the MG5 genes was performed using the nCounter assay. The MG5 score was correlated with clinical and pathologic characteristics as well as overall and event-free survival. RESULTS: MG5 standardized score showed no significant association with any of the available clinicopathologic variables. The MG5 signature score showed a significant correlation with overall (N = 57; HR, 7.3; 95% CI, 1.9-27.0; P = 0.003) and failure-free survival (N = 57; HR, 6.1; 95% CI, 1.9-19.7; P = 0.002). CONCLUSIONS: This represents the first, validated molecular prognostic signature for children with FN-RMS who otherwise have intermediate-risk disease. The capacity to measure the expression of a small number of genes in routine pathology material and apply a simple mathematical formula to calculate the MG5 metagene score provides a clear path toward better risk stratification in future prospective clinical trials. Clin Cancer Res; 21(20); 4733-9. ©2015 AACR.

Antibody levels against GLURP R2, MSP1 block 2 hybrid and AS202.11 and the risk of malaria in children living in hyperendemic (Burkina Faso) and hypo-endemic (Ghana) areas.

Differences in parasite transmission intensity influence the process of acquisition of host immunity to Plasmodium falciparum malaria and ultimately, the rate of malaria related morbidity and mortality. Potential vaccines being designed to complement current intervention efforts therefore need to be evaluated against different malaria endemicity backgrounds. The associations between antibody responses to the chimeric merozoite surface protein 1 block 2 hybrid (MSP1 hybrid), glutamate-rich protein region 2 (GLURP R2) and the peptide AS202.11, and the risk of malaria were assessed in children living in malaria hyperendemic (Burkina Faso, n = 354) and hypo-endemic (Ghana, n = 209) areas. Using the same reagent lots and standardized protocols for both study sites, immunoglobulin (Ig) M, IgG and IgG sub-class levels to each antigen were measured by ELISA in plasma from the children (aged 6-72 months). Associations between antibody levels and risk of malaria were assessed using Cox regression models adjusting for covariates. There was a significant association between GLURP R2 IgG3 and reduced risk of malaria after adjusting age of children in both the Burkinabe (hazard ratio 0.82; 95 % CI 0.74-0.91, p < 0.0001) and the Ghanaian (HR 0.48; 95 % CI 0.25-0.91, p = 0.02) cohorts. MSP1 hybrid IgM was associated (HR 0.85; 95 % CI 0.73-0.98, p = 0.02) with reduced risk of malaria in Burkina Faso cohort while IgG against AS202.11 in the Ghanaian children was associated with increased risk of malaria (HR 1.29; 95 % CI 1.01-1.65, p = 0.04). These findings support further development of GLURP R2 and MSP1 block 2 hybrid, perhaps as a fusion vaccine antigen targeting malaria blood stage that can be deployed in areas of varying transmission intensity.

Psychomotor Development of 18-Months Children With Orofacial Clefts

Objective - To describe the global and language development of children with cleft palate or cleft lip and palate at the age of 18 months, and to evaluate whether the type of cleft has an impact on psychomotor development. Study Design - Prospective cohort study. Settings - Tertiary care hospital Patients - All children born between December 2002 and November 2009 with an orofacial cleft, operated and seen at the developmental unit (UD) of the same hospital at the age of 18 months. Outcome Measures - Developmental quotients of the Griffiths Mental Development Scale and the French Communicative Development Inventory (IFDC) were used to assess the overall and language development of the children. Statistics- The population characteristics were described with means for continuous variables, and frequencies for binary or categorical variables. Chi-squared and regression analysis were used to analyse the results. Results - 69 children with clefts were examined at the age of 18 months with the IFDC and the Griffith test. The results showed that there was no significant difference in the test results of language development and global psychomotor development between the children with different types of clefts, and all were within the normal range. Conclusion - Psychomotor development is not affected by orofacial clefts, and there is no difference between children with cleft palate or cleft lip and palate.