Healthy Pediatric Cohort Research Articles

Pediatric reference values of NT-proBNP and Galectin-3 based on a French cohort

BackgroundIn pediatric cardiology, the fact that some new biomarkers have assay-specific normal values has to be considered for correct clinical decisions. The current study aimed to provide age-adjusted normative values for NT-proBNP and Galectin-3 using the Abbott immunoassay system from a prospective French pediatric cohort sera collection and to validate our data for NT-proBNP on a second retrospective cohort. MethodsWe analyzed 283 consecutive samples for NT-proBNP and 140 samples for Galectin-3 collected from apparently healthy children (0–18 years) with outpatient treatment at our institution (Hôpital Necker-Enfants malades, Paris, France) during 24 months. ResultsFor NT-proBNP and Galectin-3, we establish four age partitions, respectively two (<2 years / >2 years) and establish upper reference values and their 90 % CI for each biomarker (Galectin-3 (ng/mL): 56 [44–70] / 26 [23–29]). We evaluated the diagnostic performance of our upper reference values of NT-proBNP on a retrospective cohort (n = 428) with positive predictive value of 0.92. ConclusionsUsing Abbott immunoassay system, we report age-specific reference values for NT-proBNP and for the first time for Galectin-3 in a healthy French pediatric cohort. These data call for larger cohort studies to define more robustly percentiles and diagnostic performance for NT-proBNP.

Effect of body mass index on exercise capacity following pediatric heart transplantation.

Obesity and impaired exercise tolerance following heart transplantation increase the risk of post-transplant morbidity and mortality. The aim of this study was to evaluate the effect of body mass index on markers of exercise capacity in pediatric heart transplant recipients and compare this effect with a healthy pediatric cohort. A retrospective analysis of cardiopulmonary exercise test data between 2004 and 2022 was performed. All patients exercised on a treadmill using the Bruce protocol. Inclusion criteria included patients aged 6-21 years, history of heart transplantation (transplant cohort) or no cardiac diagnosis (control cohort) at the time of testing, and a maximal effort test. Patients were further stratified within these two cohorts as underweight, normal, overweight, and obese based on body mass index groups. Two-way analyses of variance were performed with diagnosis and body mass index category as the independent variables. A total of 250 exercise tests following heart transplant and 1963 exercise tests of healthy patients were included. Heart transplant patients across all body mass index groups had higher resting heart rate and lower maximal heart rate, heart rate recovery at 1 min, exercise duration, and peak aerobic capacity (VO2peak). Heart transplant patients in the normal and overweight body mass index categories had higher VO2peak and exercise duration when compared to underweight and obese patients. Underweight status and obesity are strongly associated with lower VO2peak and exercise duration in heart transplant patients. Normal and overweight heart transplant patients had the best markers of exercise capacity.

Predictive Validity of the Whole Child Assessment in a Generally Healthy Pediatric Cohort.

Adverse childhood experience (ACE) exposure is associated with increased risk of poor health outcomes. Several tools to identify ACEs during pediatric practice exist, but few include all 10 ACEs from the original ACE study and none have established predictive validity. Assess predictive validity of the ACE score reported during routine pediatric practice using the Whole Child Assessment (WCA). This retrospective cohort study included children ages 3 to 8 years presenting for well-child care at a low-income resident clinic between May 25, 2016 and March 31, 2018, and ages 5 to 8 years presenting for well-child care at a private insurance clinic between November 1, 2017 and March 31, 2018. Patients with chronic health problems were excluded to prevent confounding by preexisting health problems. The charts of children with 0 to 1 ACEs (lower risk) and 2+ ACEs (higher risk) at baseline were reviewed to collect data on health and psychosocial outcomes at follow-up from diagnoses documented in the medical record and parent-reported outcomes on the WCA. Logistic regression models adjusted for age, gender, and clinic were used to analyze differences in outcomes. We hypothesized that children in the higher risk group at baseline would have more health and psychosocial problems at follow-up. The initial cohort (n = 907) had 669 children with 0 to 1 ACEs and 238 children with 2+ ACEs. At follow-up (mean 718 days, range 329-1155 days), children in the higher risk group had statistically significantly higher rates of ADHD/ADD, school failure/learning problem, and other behavioral/mental problems. Parents of these children also reported on the WCA higher rates of children being nervous or afraid, feeling sad or unhappy, having trouble paying attention or staying still, getting angry or into fights, bullying, poor sleep, and healthcare utilization. There were no statistically significant differences in various physical health concerns measured. This study supports the predictive validity of the WCA to identify subpopulations at risk of developing poor mental health and social-emotional outcomes. While more research is needed to facilitate translation into pediatric practice, these results highlight the strong influence of ACEs on mental health outcomes.

Soluble Isoform of Suppression of Tumorigenicity 2 (ST2) Biomarker in a Large Cohort of Healthy Pediatric Population: Determination of Reference Intervals.

Introduction: Only little data exists on ST2 reference intervals in healthy pediatric populations despite the high importance of this biomarker in adults with heart failure. The aim of the study was to assess the reference intervals of ST2 in a wide healthy pediatric cohort. Methods: We evaluated the serum concentrations of ST2 biomarker in 415 healthy pediatric subjects referred to our analysis laboratory. Subjects were categorized according to age (i.e., 0–6 (n = 79), 7–11 (n = 142) and 12–18 years (n = 191)) and sex. They were not suffering from any cardiac disorders, metabolic disorders, lung diseases, autoimmune disorders or malignancies. A written consent was obtained for each individual. No duplicate patients were included in the analysis and the presence of outliers was investigated. Reference intervals (Mean and central 95% confidence intervals) were determined. Results: Three outliers have been identified and removed from the analysis (60.0, 64.0 and 150.2 ng/mL). A total of 412 subjects were therefore included. The mean value for the whole population was 15.8 ng/mL (2.4–36.4 ng/mL). Males present a significantly higher mean concentration compared to females (17.2 versus 14.4 ng/mL, p = 0.001). A significant trend toward higher ST2 values with age was also observed, but for males only (r = 0.43, p < 0.0001). If considering age partitions, only males of 12–18 years (mean = 21.7 ng/mL) had significantly higher ST2 values compared to the other groups (ranging from 11.9 for males 0–6 years to 15.2 for females 12–18 years; p < 0.0001). Conclusions: We described age and sex-specific reference intervals for ST2 in a large healthy pediatric population. We found that ST2 values differ between sexes if considering all participants. A significant increase in ST2 with age was also observed, but only for males of 12–18 years.

Anti-mullerian hormone (AMH) reference values in the CALIPER cohort of healthy community children and adolescents

The assessment of anti-mullerian hormone (AMH) pre- and post-gonadotoxic treatment helps define reproductive potential in young female adults facing cancer treatment. Normative childhood AMH levels are not well defined. Our objective was to help establish accurate pediatric reference intervals (RIs) for which AMH can be used to assess AMH in pediatric/adolescent survivors.Healthy female volunteers aged 6–<19 years were recruited from the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort. 300 serum samples were analyzed for AMH using an automated assay. Basic demographics and menstrual cycle data on the subjects were recorded at time of sample collection. Serum AMH distribution and RIs (2.5th and 97.5th percentiles) were established in four age groups.One recommended RI (0.98–7.84 ng/mL) was established for females aged 6–<19 years after outlier removal. Females 6–<9 years demonstrated significantly lower mean AMH concentration than did females 9–<12 years (Mean ± SD: 3.18 ± 1.62 and 4.16 ± 2.55 ng/mL, respectively), who in turn demonstrated significantly higher AMH concentrations than those aged 12–<15 years (Mean ± SD: 3.75 ± 1.61 ng/mL). Statistical differences are unlikely to be clinically meaningful. Menstrual status and ethnicity did not significantly impact AMH concentrations (p = 0.787 and p = 0.0965, respectively).This is the largest series of its kind using a contemporary, automated, single-batched AMH assay in a healthy pediatric female cohort. In conjunction with future data points and longitudinal data, the RI established may be a useful adjunct to reproductive health counselling delivered to pediatric cancer patients requiring fertility damaging therapies.

Simplified digital balance assessment in typically developing school children

BackgroundPostural balance can be considered a conjoined parameter of gross motor performance. It is acquired in early childhood and honed until adolescence, but may also be influenced by various conditions. A simplified clinical assessment of balance and posture could be helpful in monitoring motor development or therapy particularly in pediatric patients. While analogue scales are considered unprecise and lab-based force-plate posturography lacks accessibility, we propose a novel kinematic balance assessment based on markerless 3D sensor technology. Research questionCan balance and posture be assessed by tracking kinematic data using a single 3D motion tracking camera and are the results representative of normal motor development in a healthy pediatric cohort? MethodsA proprietary algorithm was developed and tested that uses skeletal data from the Microsoft Kinect™ V2 3D motion capture camera to calculate and track the center of mass in real time during a set of balance tasks. The algorithm tracks the distance of the COM traveled over time to calculate a balance score (COM speed). For this study, 432 school children aged 4−18 years performed 5 balance tasks and the resulting balance scores were analyzed and correlated with demographic data. ResultsPreliminary experiments demonstrated that the system was able to reliably detect differences in COM speed during different balance tasks. The method showed moderate correlation with age and sex. Athletic activity positively correlated with balance skill in the age group < 8 years, but not in older children. Body mass appeared not to be correlated with balance ability. SignificanceThis study demonstrates that markerless 3D motion analysis can be used for the clinical assessment of coordination and balance and could potentially be used to monitor gross motor performance at the point-of-care.

Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort.

Cardiac troponin (cTn) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are increasingly used clinically to evaluate and prognosticate acute myocardial infarction and heart failure, respectively. Pediatric reference intervals and cut-offs have not been established for Roche's Elecsys Troponin T hs (high sensitive) assay. Although pediatric reference intervals exist for NT-proBNP, cut-off values do not exist. In this study, we report reference intervals and 99th percentile cut-offs in a large, healthy Canadian pediatric population using the CALIPER cohort. Blood samples from 484 healthy children and adolescents between 0 and <19 years old were recruited from hospital outpatient clinics and community settings. Serum samples were analyzed using Roche's Cobas e411 and evaluated for high-sensitivity cTnT (hs-cTnT) and NT-proBNP concentrations. 95% reference intervals and 99th percentile cut-off values were established. Three hs-cTnT age partitions were established (0 to <6 months, 6 months to <1 year, and 1 to <19 years) with highest concentrations observed in children under 1 year. Two NT-proBNP age partitions were established (0 to <1 year, and 1 to <19 years), also with higher concentrations in infants under 1 year of age. For each of these age partitions, the 99th percentile cut-off, 95% reference interval, and proportion of detectable concentrations were determined. This is the first study to examine hs-cTnT and NT-proBNP reference values together in a healthy pediatric cohort without other clinical indications. We present 99th percentile cut-offs, which will allow clinicians to appropriately evaluate cardiovascular disease in children and adolescents.

Adenosine deaminase 2 activity negatively correlates with age during childhood

BackgroundHuman adenosine deaminase 2 (ADA2) is an extracellular enzyme that negatively regulates adenosine-mediated cell signaling by converting adenosine to inosine. Altered ADA2 enzyme activity has been associated with some viral infections and rheumatic diseases. The potential utility of ADA2 as a biomarker is, however, limited by the absence of established ranges of ADA2 concentration and enzyme activity in the healthy population. It is known that ADA2 enzyme activity is lower in adults, but when (and why) this decline happens is not known. The purpose of this study was to establish normative ranges of ADA2 enzyme activity and protein concentration in the healthy pediatric population.MethodsWe modified a commercially available ADA2 enzyme activity assay to enable higher throughput analysis of fresh, frozen and hemolyzed blood samples. With this assay and ADA2 protein immunoblotting, we analyzed ADA2 enzyme activity and protein concentration in blood plasma from a cohort of children and adolescents (n = 94) aged 5 months to 18 years. One-way ANOVA with subsequent Tukey multiple comparison test was used to analyze group differences. Reference intervals were generated using the central 95% of the population (2–97.5 percentiles).ResultsADA2 enzyme activity was consistent in fresh, frozen, and hemolyzed sera and plasma as measured by our modified assay. Analysis of plasma samples from the healthy pediatric cohort revealed that ADA2 enzyme activity is significantly lower in older children than in younger children (p < 0.0001). In contrast, there was no significant correlation between ADA2 protein concentration and either age or ADA2 enzyme activity.ConclusionWe observed that ADA2 enzyme activity, but not ADA2 protein concentration, negatively correlates with age in a cohort of children and adolescents. Our findings stress the importance of appropriate age-matched controls for assessing ADA2 enzyme activity in the clinical setting.

Pupillometry measures of autonomic nervous system regulation with advancing age in a healthy pediatric cohort

To determine if variables of the pupillary light response mature with age and sex in a healthy pediatric cohort and the utility of pupillometry in assessment among pediatric participants. After 1 min in a dark room to establish baseline, pupillometry was performed on 323 healthy, pediatric participants (646 eyes; 2-21years; 175 females). Variables included initial pupil diameter, pupil diameter after light stimulus, percent pupillary constriction, latency to onset of constriction, average constriction velocity, maximum constriction velocity, average dilation velocity, and time from light stimulus to 75% of the initial pupil diameter. Data analyses employed ANOVAs and non-linear regressions. Analyses of age group differences revealed that participants 12-21years old had a larger initial pupil diameter and pupil diameter after light stimulus, with males aged 12-18 years demonstrating a larger pupil diameter than all younger participants (ps < 0.05). Participants 12-18years old had a slower maximum constriction velocity than participants 6-11yearsold, with no sex differences (ps < 0.05). Furthermore, males aged 12-18yearsold had a smaller percent constriction than males 6-11years old(ps < 0.05). Regressions revealed that percent constriction and dilation velocity seemed to mature linearly, initial pupil diameter and ending pupil diameter matured quadratically, and the constriction velocity terms matured cubically. Results revealed maturation of the pupillary light response by age and sex in healthy pediatric participants. Given the value of the pupillary light response as a biomarker, the results provide normative benchmarks for comparison in health and disease, including opiate-exposed and concussion patients.

P422Evaluation of semi-automated threshold-based CMR post-processing of ventricular size and function in a large healthy pediatric cohort

P422Evaluation of semi-automated threshold-based CMR post-processing of ventricular size and function in a large healthy pediatric cohort

Homocysteine Metabolism in Children and Adolescents: Influence of Age on Plasma Biomarkers and Correspondent Genotype Interactions.

Background: Imbalance of homocysteine (Hcy) metabolism links with several pathologies; nevertheless, it is poorly characterized in pediatric populations. This study investigated the impact of age on plasma concentrations of Hcy and relevant biomarkers along with correspondent genotype interactions. Methods: A healthy pediatric cohort aged 9 (n = 195) and 17 (n = 128) years old (yo) was studied. Immunoassays and GC-MS-SIM-mode quantified plasma levels of Hcy and biomarkers. PCR-RFLP or quantitative-PCR assays assessed common variations in related genes. Results: Age impacted on levels of Hcy and metabolic markers: older children presented with the lowest folates and total-cobalamin (tCbl), while with the highest Hcy concentrations, whereas methylmalonic acid (MMA) and holotranscobalamin (Holo-TC) levels remained similar in 9-yo and 17-yo children. The relationships between B-vitamins and metabolic markers were also dependent on age. Only in the older children, MMA correlated with tCbl and Holo-TC, and MMA levels were markedly higher in the 17-yo subjects presenting with the lowest quartiles of Holo-TC concentrations. Lastly, age also impacted on the correlations between genotype and biomarkers. In the 17-yo group, however not in the 9-yo children, tHcy differed between MTHFR 677 genotypes, with subjects who had the MTHFR 677TT genotype displaying the highest tHcy concentrations. Conclusions: Age impacts on the Hcy metabolism dynamics in a pediatric population.

In vivo ankle joint kinematics from dynamic magnetic resonance imaging using a registration-based framework

In this paper, we propose a method for non-invasively measuring three-dimensional in vivo kinematics of the ankle joint from a dynamic MRI acquisition of a single range-of-motion cycle. The proposed approach relies on an intensity-based registration method to estimate motion from multi-plane dynamic MRI data. Our approach recovers not only the movement of the skeleton, but also the possibly non-rigid temporal deformation of the joint. First, the rigid motion of each ankle bone is estimated. Second, a four-dimensional (3D+time) high-resolution dynamic MRI sequence is estimated through the use of the log-euclidean framework for the computation of temporal dense deformation fields. This approach has been then applied and evaluated on in vivo dynamic MRI data acquired for a pilot study on six healthy pediatric cohort in order to establish in vivo normative joint biomechanics. Results demonstrate the robustness of the proposed pipeline and very promising high resolution visualization of the ankle joint.

Principal component and correlation analysis of biochemical and endocrine markers in a healthy pediatric population (CALIPER)

BackgroundReference intervals (i.e. normative ranges) established from a healthy reference population are essential to accurately interpret disease biomarkers. Biomarker concentration may partially depend on associations with other biomarkers due to various physiological and pathophysiological processes. In this study, a robust correlation analysis was performed to identify physiological biomarker associations in the healthy pediatric CALIPER cohort. MethodsPopulation reference values for 35 biochemical and 20 fertility/endocrine markers were analyzed for correlations in all subjects, male adolescents, female adolescents, and young children. Associations between biomarkers were assessed by Spearman's rank correlation and a multivariate analysis technique, principal component analysis (PCA). ResultsOf 197, 90, 59, and 32 significant correlations between biochemical markers in all subjects, male adolescents, female adolescents, and children, respectively, 23, 19, 16, and 9 were moderately strong (r > 0.5 or r < −0.5). Of 98, 24, 33, and 16 significant correlations between fertility/endocrine markers in all subjects, male adolescents, female adolescents, and children, respectively, 17, 8, 11, and 5 were moderately strong. Results were agreeable between Spearman's rank method and PCA. In some cases, biomarker correlations differed between sexes. ConclusionsUsing PCA, this study provides for the first time an extensive analysis of circulating biomarker associations in a healthy pediatric cohort. These data can inform future studies of potential confounding factors or particular variables that should be considered in test result interpretation for specific diseases.

Assessment of brain-derived neurotrophic factor and osteopontin in a healthy pediatric population.

Biomarkers are routinely used for noninvasive identification or monitoring of disease processes in clinical practice, as well as surrogate end points for drug development. There is a significant lack of data regarding biomarkers in children. An understanding of biomarker levels in a healthy pediatric cohort is essential as more studies begin to apply noninvasive biomarkers to pediatric populations. Brain-derived neurotrophic factor (BDNF) functions in neuronal survival and plasticity and is associated with exercise capacity and inflammatory disease processes. Osteopontin (OPN) plays a regulatory role in inflammation and may be a clinically useful biomarker of cardiovascular disease processes, ventricular remodeling, and skeletal muscle regeneration. This study describes our initial experience with a cohort of healthy pediatric patients and seeks to provide normal values of BDNF and OPN with correlation to age, gender, and cardiovascular and fitness measures. Serum BDNF and plasma OPN were measured using enzyme-linked immunosorbent assay in 33 healthy pediatric subjects. Subjects underwent complete cardiac evaluation, including echocardiography, exercise stress testing, and health risk assessment. The 5th–95th percentile was 5.63–37.86 ng/ml for serum BDNF and 4.9–164.9 ng/ml for plasma OPN. Plasma OPN correlated with number of days of exercise per week (r = 0.46, p = 0.008). No other correlations were significant. This study provides the initial data on serum BDNF and plasma OPN in children and begins to explore the relationships of BDNF and OPN to cardiovascular health and fitness in the pediatric population.

Pilot study analyzing automated ECG screening of hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is one of the leading causes of sudden cardiac death in athletes. However, preparticipation ECG screening has often been criticized for failing to meet cost-effectiveness thresholds, in part because of high false-positive rates and the cost of ECG screening itself. The purpose of this study was to assess the testing characteristics of an automated ECG algorithm designed to screen for HCM in a multi-institutional pediatric cohort. ECGs from patients with HCM aged 12 to 20 years from 3 pediatric institutions were screened for ECG criteria for HCM using a previously described automated computer algorithm developed specifically for HCM ECG screening. The results were compared to a known healthy pediatric cohort. The studies then were read by trained electrophysiologists using standard ECG criteria and compared to the results of automated screening. One hundred twenty-eight ECGs from unique patients with phenotypic HCM were obtained and compared with 256 studies from healthy control patients matched in 2:1 fashion. When presented with the ECGs, the non-voltage-based algorithm resulted in 81.2% sensitivity and 90.7% specificity. A trained electrophysiologist read the same data according to the Seattle Criteria, with 71% sensitivity with 95.7% specificity. The sensitivity of screening as well as the components of the ECG screening itself varied by institution. This pilot study demonstrates a potential for automated ECG screening algorithms to detect HCM with testing characteristics similar to that of a trained electrophysiologist. In addition, there appear to be differences in ECG characteristics between patient populations, which may account for the difficulties in universal screening.

Lower Plasma Soluble Transferrin Receptor Range in Healthy Indian Pediatric Cohort as Compared to Asian and Western Data.

Soluble serum transferrin receptor is derived from erythroid transferrin receptor expressed on surface of developing erythroid cells. It can be detected in blood using sensitive ELISA methodology and blood levels reflect physiological iron dependent erythropoiesis state in bone marrow. Normal adult levels vary from 2 to 5mg/l. However, pediatric studies are few and describe normal ranges to the tune of 1.0-3.0mg/l, which are relatively lower than that of adults. In present study 40 healthy children (2-12years) were evaluated to establish normal soluble transferrin receptor range. The mean transferrin receptor levels were 0.39mg/l with a range of 0.17-2.1mg/l. The levels were low as compared to mean levels described in other studies from West and our country (4.39 and 2.0mg/l respectively). Since, no internationally standard method for reporting and testing for transferrin receptor levels are yet available, hence it is imperative to establish normal control ranges in different population cohorts, especially in pediatric age group, to better interpret their levels in diagnostic context.

Systolic and Diastolic Myocardial Response to Exercise in a Healthy Pediatric Cohort

The aims of the present study were to evaluate the feasibility and reproducibility of color Doppler tissue imaging (DTI) and two-dimensional speckle-tracking echocardiography during semisupine cycle ergometricstress echocardiography and to establish normal myocardial systolic and diastolic left ventricular (LV) and right ventricular (RV) response to exercise in children. This was a single-center prospective study of 62 healthy children (35 girls). The median age was 14years (range, 8-19years). A stepwise semisupine cycle ergometric protocol was used. Color DTI peak systolic (s') and peak diastolic (e') velocities and myocardial acceleration during isovolumic contraction were measured in the LV lateral wall, RV free wall, and septum. Early mitral inflow Doppler (E) was measured from the apical four-chamber view, and the ratio of diastolic filling to tissue early diastolicvelocity (E/e') was calculated. LV and RV longitudinal strain were measured from four-chamber apical views. LV circumferential strain was derived from the parasternal short-axis view at the midventricular level. The relationship of each parameter with increasing heart rate was evaluated at each stage of exercise. During exercise color DTI, velocities were obtained in 96% of subjects, with isovolumic contraction having the lowest feasibility among DTI measurements (89%). Strain analysis was measurable in 87% of subjects, with LV longitudinal strain measured in 98% of the subjects compared with 93% for circumferential strain. RV longitudinal strain had the lowest feasibility (70%). A linear relationship was observed between heart rate and color DTI velocities, E, E/e', and myocardial longitudinal and circumferential strain. The relationship between isovolumic contraction and heart rate was exponential. This study provides reference values for systolic and diastolic reserve during exercise in healthy children as measured by color DTI and two-dimensional speckle-tracking echocardiography. These data allow the evaluation of myocardial response in pediatric cardiac disease.

Is Motor Performance in 5.5-Year-Old Children Associated with the Presence of Generalized Joint Hypermobility?

To determine the prevalence of generalized joint hypermobility (GJH) in Dutch children aged 5.5 years, and to examine the association between GJH and motor performance and development over time. A prospective cohort of 249 children was recruited. GJH was assessed with the Beighton test at age 5.5 years. Motor performance was evaluated at age 2.0 years using the Bayley Scales of Infant Development, Second Edition and at age 5.5 years using the Movement Assessment Battery for Children-Second Edition (subscore categories: manual dexterity, aiming and catching, and static and dynamic balance). In 249 children, the prevalence of GJH, defined by the Beighton test score, was 34.1% for a score ≥ 4, 22.5% for a score ≥ 5, and 16.5% for a score ≥ 6. No significant association was found between GJH and total motor performance. Manual dexterity in girls (Beighton score ≥ 4) was positively associated with higher level of motor performance (β [SE] = 0.38 [0.17]; P = .028), ranging from +0.04 SD to +0.72 SD, even after correction for covariates. A significant interaction between GJH and body mass index (BMI) growth was found, indicating that the effect of GJH on the rate of development of motor performance declines with increasing BMI growth (β = 0.05 [0.02]; P = .031). In this healthy pediatric cohort, GJH was present in one-third of the sample, and no significant association was found between GJH and total motor performance. The effect of GJH on the rate of development of motor performance appears to decline with increasing BMI growth. Longitudinal prospective studies are recommended to detect influences of GJH on motor performance over time, as well as the influence of body composition and Beighton cutoff points.

Estimating intracranial volume using intracranial area in healthy children and those with childhood status epilepticus.

BackgroundCorrecting volumetric measurements of brain structures for intracranial volume (ICV) is important in comparing volumes across subjects with different ICV. The aim of this study was to investigate whether intracranial area (ICA) reliably predicts actual ICV in a healthy pediatric cohort and in children with convulsive status epilepticus (CSE).MethodsT1-weighted volumetric MRI was performed on 20 healthy children (control group), 10 with CSE with structurally normal MRI (CSE/MR-), and 12 with CSE with structurally abnormal MRI (CSE/MR+). ICA, using a mid-sagittal slice, and the actual ICV were measured.ResultsA high Spearman correlation was found between the ICA and ICV measurements in the control (r = 0.96; P < 0.0001), CSE/MR− (r = 0.93; P = 0.0003), and CSE/MR+ (r = 0.94; P < 0.0001) groups. On comparison of predicted and actual ICV, there was no significant difference in the CSE/MR− group (P = 0.77). However, the comparison between predicted and actual ICV was significantly different in the CSE/MR+ (P = 0.001) group. Our Bland–Altman plot showed that the ICA method consistently overestimated ICV in children in the CSE/MR+ group, especially in those with small ICV or widespread structural abnormalities.ConclusionsAfter further validation, ICA measurement may be a reliable alternative to measuring actual ICV when correcting volume measurements for ICV, even in children with localized MRI abnormalities. Caution should be applied when the method is used in children with small ICV and those with multilobar brain pathology.

Reference Values and Calculation of z-Scores of Echocardiographic Measurements of the Normal Pediatric Right Ventricle

Determination of right ventricular (RV) size and function has gained more interest in recent years in adults and children, especially in patients with congenital heart disease. Data on normal RV size parameters in children are scant. The aim of this study was to investigate growth-related changes in RV internal dimensions in a healthy pediatric cohort and the predictive value of RV parameters in identifying enlarged right ventricles in children with secundum-type atrial septal defects (ASD). A prospective study was conducted in a group of 576 healthy children (aged 1 day to 18 years) and 37 children (aged 1.4 to 17.7 years) with moderate-sized to large ASDs. The effects of age, body length, body weight, and body surface area were determined on the following RV parameters: end-diastolic basal diameter, end-diastolic midcavity diameter, end-diastolic length, end-systolic length, end-diastolic area, and end-systolic area. The predictive value of normal values stratified for age, body weight, body length, and body surface area was tested in children with ASDs. RV end-diastolic basal diameter, end-diastolic midcavity diameter, end-diastolic length, end-systolic length, end-diastolic area, and end-systolic area showed positive correlations with age, body length, body surface area, and body weight. In this population, RV z scores showed high specificity for detecting patients with ASDs, with sensitivity up to 89%, especially in children <8 years of age. In conclusion, the normal ranges of pediatric RV internal dimensions are provided. The z scores of these RV parameters were also calculated. Normal RV z scores might be important predictors in identifying enlarged right ventricles in patients with ASDs.