Healthy Pediatric Subjects Research Articles

Pulmonary arterial banding in mice may be a suitable model for studies on ventricular mechanics in pediatric pulmonary arterial hypertension

BackgroundThe role of interventricular mechanics in pediatric pulmonary arterial hypertension (PAH) and its relation to right ventricular (RV) dysfunction has been largely overlooked. Here, we characterize the impact of maintained pressure overload in the RV–pulmonary artery (PA) axis on myocardial strain and left ventricular (LV) mechanics in pediatric PAH patients in comparison to a preclinical PA-banding (PAB) mouse model. We hypothesize that the PAB mouse model mimics important aspects of interventricular mechanics of pediatric PAH and may be beneficial as a surrogate model for some longitudinal and interventional studies not possible in children.MethodsBalanced steady-state free precession (bSSFP) cardiovascular magnetic resonance (CMR) images of 18 PAH and 17 healthy (control) pediatric subjects were retrospectively analyzed using CMR feature-tracking (FT) software to compute measurements of myocardial strain. Furthermore, myocardial tagged-CMR images were also analyzed for each subject using harmonic phase flow analysis to derive LV torsion rate. Within 48 h of CMR, PAH patients underwent right heart catheterization (RHC) for measurement of PA/RV pressures, and to compute RV end-systolic elastance (RV_Ees, a measure of load-independent contractility). Surgical PAB was performed on mice to induce RV pressure overload and myocardial remodeling. bSSFP-CMR, tagged CMR, and intra-cardiac catheterization were performed on 12 PAB and 9 control mice (Sham) 7 weeks after surgery with identical post-processing as in the aforementioned patient studies. RV_Ees was assessed via the single beat method.ResultsLV torsion rate was significantly reduced under hypertensive conditions in both PAB mice (p = 0.004) and pediatric PAH patients (p < 0.001). This decrease in LV torsion rate correlated significantly with a decrease in RV_Ees in PAB (r = 0.91, p = 0.05) and PAH subjects (r = 0.51, p = 0.04). In order to compare combined metrics of LV torsion rate and strain parameters principal component analysis (PCA) was used. PCA revealed grouping of PAH patients with PAB mice and control subjects with Sham mice. Similar to LV torsion rate, LV global peak circumferential, radial, and longitudinal strain were significantly (p < 0.05) reduced under hypertensive conditions in both PAB mice and children with PAH.ConclusionsThe PAB mouse model resembles PAH-associated myocardial mechanics and may provide a potential model to study mechanisms of RV/LV interdependency.

STANDARDIZATION OF ROUTINE QUANTIFICATION OF POLYUNSATURATED ACIDS IN PEDIATRIC TOTAL PARENTERAL NUTRITION

Plasma and erythrocyte PUFAs are useful in clinical practice to optimize the parenteral nutrition therapy. The aim of this study was the definition of pediatric PUFAs reference ranges to follow-up patients with IICB. We validated a method to quantify, in plasma and erythrocyte membranes, glycerophospholipids PUFAs by gas chromatography coupled with the highly specific Mass spectrometer. The analyzed PUFAs are only those metabolized by liver: no interferences by oral nor parenteral nutrition are expected. Metabolically significative PUFAs were selected for analysis: ARA (ω6), EPA and DHA (ω3) were quantified because they are precursors of important mediators of inflammation, while Mead Acid determination is useful to calculate the ratio ARA (ω6)/ Mead (ω9), a known marker of essential fatty acid deficiency. We quantified these PUFAs in healthy pediatric subjects to build reference ranges. A pilot study was performed to compare PUFAs of two groups of pediatric patients with IICB (group A fed with Clinoleic® and group B with SMOF®) with reference ranges. Pediatric reference ranges of PUFAs were proposed. A good correlation between plasma and erythrocyte results was shown for the ratio ARA/(EPA+DHA), (R2=0.941). PUFAs assessment is highly recommended in plasma rather than in erythrocytes because plasma is less prone to peroxidation artifacts. Our fast method can offer an accurate, specific and easy-to-handle PUFAs analysis and a useful marker of w6/w3 balance in tissues for routine clinical practice. This work could be a step towards standardization of routine determination of PUFAs.

Coenzyme Q10 administration has no effect on sICAM-1 and metabolic parameters of pediatrics with type 1 diabetes mellitus.

Background: Endothelial dysfunction (ED) plays a key role in the development and progression of microvascular and macrovascular complications in pediatrics with type 1 diabetes mellitus (T1DM). Coenzyme Q10 (CoQ10) is a nutraceutical with a known anti-inflammatory and anti-oxidant activity. This study was conducted to evaluate the potential effect of CoQ10 on ED and various metabolic parameters. Methods: This prospective randomized open-label pilot study was conducted on 49 T1DM pediatric patients. Seven healthy non-diabetic pediatric subjects who didn't receive treatment were included as a control group. Eligible patients were randomly allocated into either group I (n=25); received 100mg of CoQ10 in addition to standard treatment or group II (n=24); received standard treatment only. The levels of; soluble intracellular adhesion molecule-1 (sICAM-1), glycated hemoglobin (HbA1c), fasting blood glucose (FBG), lipid profile, serum creatinine and liver function tests were assessed for both groups at baseline and after 3 months of treatment. Results: At baseline, compared to an age-matched healthy control group sICAM-1 levels were significantly elevated in group II diabetic patients (276.5 (231.6-320.66) vs 221.8 (177.9-267.1ng/ml), p=0.042. After 3 months of treatment no significant difference was observed in sICAM-1, HbA1c, FBG, lipid profile, serum creatinine and liver function tests between the two study groups. A positive correlation was found between sICAM-1 and HbA1c throughout the study (r=0.308, p=0.0054). Conclusion: Administration of CoQ10 for 3 months in T1DM pediatric patients was well tolerated but had no favorable effect on ED or metabolic parameters.

Brain-derived neurotrophic factor levels in pediatric sickle cell disease.

Children with sickle cell disease (SCD) have an increased risk of neurological complications, particularly stroke and silent cerebral infarction (SCI). Brain-derived neurotrophic factor (BDNF) is a nerve growth factor associated with neuronal survival, synaptic plasticity, elevated transcranial Doppler (TCD) velocities and increased risk of stroke in patients with SCD. The objective of this study was to analyze plasma BDNF protein levels in children with SCD participating in the Silent Cerebral Infarct Transfusion Multi-Center Clinical Trial (SIT Trial), comparing plasma samples of children with SCD and SCI to plasma samples from children with SCD without SCI, as well as healthy pediatric control participants. Entry, exit, and longitudinal blood samples were collected from 190 SIT Trial participants with SCD and healthy pediatric controls over time. BDNF levels were measured by enzyme-linked immunosorbent assay. Sample collection was not optimized for measurements of BDNF, but factors affecting BDNF levels were accounted for in analyses. BDNF levels were significantly higher in children with SCD in comparison to healthy pediatric control subjects. BDNF levels significantly increased over time in SCD participants. BDNF levels did not show any significant associations with the presence or absence of SCI or new/progressive SCI/stroke or TCD velocities. Plasma BDNF levels are elevated and increase over time in children with SCD. Additional studies with more longitudinal samples are needed to address the reasons for those increased levels.

Blood Flow Dynamics at the Pulmonary Artery Bifurcation

Knowledge of physiologic hemodynamics is a fundamental requirement to establish pathological findings. However, little is known about the normal flow fields in the pulmonary arteries, especially for children. The purpose of this study is to characterize flow patterns in the pulmonary artery bifurcation of healthy pediatric subjects using direct numerical simulations. A realistic geometry is obtained via statistical shape modeling, by averaging five subject-specific digital models extracted from cardiovascular magnetic resonance datasets of healthy volunteers. Boundary conditions are assigned to mimic physiological conditions at rest, corresponding to a peak Reynolds number equal to 3400 and a Womersley number equal to 15. Results show that the normal bifurcation is highly hemodynamically efficient, as measured by an energy dissipation index. The curvature of the pulmonary arteries is sufficiently small to prevent flow separation along the inner walls, and no signs of a turbulent-like state are found. In line with previous imaging studies, a helical structure protruding into the right pulmonary artery is detected, and its formation mechanism is elucidated in the paper. These findings might help to identify abnormal flow features in patients with altered anatomic and physiologic states, particularly those with repaired congenital heart disease.

Untargeted metabolomic profiling identifies disease-specific signatures in food allergy and asthma

Food allergy (FA) affects an increasing proportion of children for reasons that remain obscure. Novel disease biomarkers and curative treatment options are strongly needed. We sought to apply untargeted metabolomic profiling to identify pathogenic mechanisms and candidate disease biomarkers in patients with FA. Mass spectrometry-based untargeted metabolomic profiling was performed on serum samples of children with either FA alone, asthma alone, or both FA and asthma, as well as healthy pediatric control subjects. In this pilot study patients with FA exhibited a disease-specific metabolomic signature compared with both control subjects and asthmatic patients. In particular, FA was uniquely associated with a marked decrease in sphingolipid levels, as well as levels of a number of other lipid metabolites, in the face of normal frequencies of circulating natural killer T cells. Specific comparison of patients with FA and asthmatic patients revealed differences in the microbiota-sensitive aromatic amino acid and secondary bile acid metabolism. Children with both FA and asthma exhibited a metabolomic profile that aligned with that of FA alone but not asthma. Among children with FA, the history of severe systemic reactions and the presence of multiple FAs were associated with changes in levels of tryptophan metabolites, eicosanoids, plasmalogens, and fatty acids. Children with FA have a disease-specific metabolomic profile that is informative of disease mechanisms and severity and that dominates in the presence of asthma. Lower levels of sphingolipids and ceramides and other metabolomic alterations observed in children with FA might reflect the interplay between an altered microbiota and immune cell subsets in the gut.

P.273Serum neurofilament light chain in type 1 spinal muscular atrophy: 30 months data from first part of a branaplam phase II study

Results from patients with neurodegenerative diseases have shown that neurofilament light chain (NfL) is a sensitive, blood-based marker that can identify patients, aid in prediction of long-term outcomes, and be used to assess effects of treatment. At present, little is known about NfL levels in the blood of patients with spinal muscular atrophy (SMA). The present study assesses the relevance of serum NfL as a potential biomarker for SMA Type I disease activity and therapy response. Baseline serum NfL levels were determined in 12 patients with SMA Type I (2.2-7.6 months of age) who were enrolled in a first-in-human study of branaplam (LMI070 × 2201- NCT02268552; EudraCT number 2014-002053-19, part 1), an oral small-molecule RNA splicing modulator. Consecutive samples were collected at the end of a respective 13-week treatment cycle period when available. The range of pre-treatment NfL levels in Type I patients was 177-983 pg/mL and did not overlap with the range measured from healthy pediatric subjects with 1-4 years of age (1.7-22.9 pg/mL, n=21). There was also an inverse correlation between pre-treatment NfL levels and CHOP INTEND scores, a measure of motor skills. NfL levels decreased within the first 13-week treatment period under branaplam and reached the range of 1-4 year old healthy subjects after 26 weeks. NfL levels after at least 30 months of treatment will be presented. These results suggest that pre-treatment serum NfL levels differentiate patients with SMA Type I from healthy subjects and may be correlated with CHOP INTEND scores. Measurement of serum NfL may also be considered as a biomarker for SMA therapy response. These conclusions are limited by the small number of samples evaluated and the lack of data from healthy pediatric infants within the first year of age. The dynamic course of blood NfL levels in SMA patients requires further study.

Heart Rate Variability and Gastric Electrical Response to a Cold Pressor Task in Youth with Functional Dyspepsia.

While stress has been implicated in functional dyspepsia (FD), the mechanisms by which stress results in symptoms are not well defined. The aim of the current study was to assess gastric myoelectric and autonomic changes in response to a physical stressor in youth with FD. In a group of healthy controls and pediatric FD subjects, we recorded ECG and EGG signals 30min before and 60min after, a cold pressor task (CPT). Gastric EGG and heart rate variability (HRV) parameters were calculated in pre- and post-CPT stages and in short intervals. The pre-CPT percent tachygastria was higher in FD subjects as compared to controls. However, CPT did not induce any EGG changes in either controls or FD subjects and the two groups did not differ from each other post-CPT. The CPT resulted in an increase in HRV and standard deviation of NN intervals in controls; there was no change in any HRV parameter in FD subjects. Acute physical stress does not appear to induce gastric electrical abnormalities in youth with FD. Youth with FD appear to lack the normal flexible autonomic response to a physical stressor.

Partially Wireless Pulse Oximetry Reduces Loss of Signal Integrity due to Motion in Children.

Continuous pulse oximetry monitoring is routine in many pediatric inpatient units, generating hundreds of alarms per patient per day, up to 90% of which are false (nonactionable). We hypothesized that continuously monitoring pulse oximetry with a partially wireless monitor without physical connection to a wall unit (wireless pox) will decrease episodes of loss of signal integrity (LOSI) generated by motion artifact in healthy pediatric subjects completing age-appropriate activities compared with a traditional wall-connected pulse oximeter (control pox), thereby reducing false alarms. Thirty-six healthy children, aged 1 to 17 years, were continuously monitored simultaneously with a wireless pox and a control pox while performing increasing levels of activity for 20 minutes. Continuous pulse oximetry data were recorded in 2 second intervals. Data were analyzed for LOSI. The Wilcoxon signed rank test was then used to compare the control pox to the wireless pox. The wireless pox had fewer mean number of alarms due to LOSI (control 7.86, wireless 4.17, P = .0031) and fewer mean episodes of LOSI not leading to alarms (control 9.94, wireless 6.92, P = .0006). The control pox had a longer percent time in alarm state related to LOSI in all age groups. This prospective observational study found that the wireless pox has decreased number and duration of events of LOSI compared with the control pox in healthy children. Implementation of partially wireless pulse oximetry in pediatric inpatient units may decrease episodes of LOSI and false alarms from motion artifact.

Safety and Immunogenicity Study of QIVc in Healthy Pediatric Subjects

Safety and Immunogenicity Study of QIVc in Healthy Pediatric Subjects

Stepwise approach of development of dermo-cosmetic products in healthy and atopic dermatitis paediatric population: safety evaluation, clinical development and postmarket surveillance.

Background/objectivesPaediatric skin, considered sensitive, and infant skin, more susceptible to percutaneous toxicity, require specially formulated cosmetic products. As recently shown, early use of emollients in infants “at risk” of developing atopic dermatitis has shown controversial results in reducing the incidence of atopic dermatitis. Development of dermo‐cosmetic products for this specific population should especially ensure tolerance and safety. In absence of good clinical practice guideline, we propose here a stepwise approach for the development of paediatric cosmetic skincare products.MethodsOur stepwise methodology for cosmetics aimed at paediatrics, starts with in vitro assessment of product's ingredients safety, followed by preclinical and clinical evaluations of the final product, including sequentially: (1) Repeated Open Application Test (ROAT), (2) Human Repeated Insult Patch Test (HRIPT), (3) In‐use dermatological and ophthalmological tolerance studies (sequentially in 3a: healthy adults, 3b: healthy paediatric subjects and finally 3c: paediatric patients). We also describe the integrated cosmetovigilance–toxicological surveillance during the clinical development phase and postmarketing.ResultsAs illustrated with one dermo‐cosmetic product intended to be used as a preventative/maintenance treatment for atopic dermatitis in paediatric population, we show that using this stepwise methodology to test a product reduces potential risks of irritation and contact dermatitis in this sensitive population.ConclusionStandardized ethical stepwise development approach is needed to ensure the commercialization of safe and well‐tolerated dermo‐cosmetics for paediatrics. The approach described here could potentially serve as guidance for evaluation of new paediatric cosmetic products.

Normal values of native T1 and T2 relaxation times on 3T cardiac MR in a healthy pediatric population aged 9-18 years.

Native myocardial T1 and T2 relaxation times are diagnostic tools used in clinical practice for adult and pediatric populations. Use of a mapping technique requires accurate knowledge of normal ranges in healthy patients, which is lacking in pediatric populations. To establish normal values for native T1 and T2 mapping in healthy pediatric subjects of different ages and sex. Prospective. Thirty-eight healthy children (9-18 years; mean age 14.0 ± 2.7). Cardiac MR with a 3T scanner. T1 and T2 mapping using MyoMaps software. T1 and T2 relaxation times were calculated from a 0.7-1.0 cm2 region of interest placed at the mid-ventricular short-axis slice in the interventricular septum by two observers. Inter- and intraobserver variability was assessed. The Student's t-test or the Mann-Whitney test for unpaired samples was applied to compare one continuous variable between two category groups. One-way analysis of variance (ANOVA) or a Kruskal-Wallis test was applied to compare one continuous variable between three category groups. Correlation between two continuous variables was assessed with a Pearson or Spearman test. The mean native T1 relaxation time was 1223 ± 29 msec and T2 relaxation time was 43 ± 4.5 msec. There was no correlation between T1 /T2 values and age or body surface area (for T1 P = 0.94 and 0.90 and for T2 P = 0.19 and 0.64, respectively). There was weak correlation between T1 values and body mass index (BMI) (r = 0.448, P = 0.005). T2 values were significantly higher in females compared with males (44.6 ± 4.2 vs. 40.4 ± 3.8 msec, P = 0.002). We found a significant rise of T2 relaxation time in the pubertal period (age 13-15 years) comparing to prepubertal (age 9-12 years). Inter- and intraobserver agreement of T1 (r = 0.93; r = 0.99) and T2 (r = 0.96; r = 0.95) were high. We report normal values of native T1 and T2 relaxation times obtained with Myomaps software for 3T cardiac MR in a healthy pediatric population. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:912-918.

Janus kinase 1/2 inhibition for the treatment of autoinflammation associated with heterozygous TNFAIP3 mutation

Janus kinase 1/2 inhibition for the treatment of autoinflammation associated with heterozygous TNFAIP3 mutation

Paediatric brain tissue properties measured with magnetic resonance elastography.

The aim of this study is to characterise the stiffness of white and grey matter in paediatric subjects using magnetic resonance elastography (MRE) and to determine whether these properties change throughout normal development. MRE was performed using a clinical 3T MRI scanner at three frequencies (30, 40 and 60Hz) on 36 healthy paediatric subjects aged between 7 and 18years (19 F) and 11 adults aged 23-44years (6 F). Anatomical and diffusion tensor imaging was also collected. The stiffness quantified as the magnitude of the complex shear modulus (G*), fractional anisotropy (FA), mean diffusivity (MD) and volume of white and grey matter were calculated. One-way analysis of variance and Tukey's multiple comparison tests were used to compare data in age groups separated into children (7-12years), adolescents (13-18years) and adults (18+ years), and Spearman's correlations were performed for paediatric data. White and grey matter stiffness for each frequency and their frequency dependence was found to be very similar in paediatric and adult subjects (p > 0.05 all variables). No significant correlations were found when comparing G* with age, FA, MD or volume. Adult G*, FA, MD and volume values were within range of others reported in the literature. Paediatric white and grey matter stiffness values are similar to those of adults. We conclude that clinically, adult values can be used as a baseline measure in paediatric brain MRE.

Validation of an ambient measurement system (AMS) for physical activities in a paediatric population

Ambient measurement systems (AMSs) can enable continuous assessment of functional performance at home, increasing the availability of data for monitoring of neuromuscular disease. An AMS passively measures movement whenever someone is in range of the sensor, without the need for any wearable sensors. The current study evaluates the performance of an AMS for three metrics associated with functional assessments in Duchenne muscular dystrophy (DMD): ambulation speed, rise-to-stand speed and arm-raise speed. Healthy paediatric subjects performed a series of functional tasks and were graded by both a human rater and an AMS. Linear mixed-effect models were fit to calculate agreement between the two measurement methods. For all activities, the AMS and human rater supplied similar measurements of average speed, with correlation coefficients of 0.76–0.92 and systematic differences ranging in magnitude from 0 to 0.48 m per second. The largest systematic difference was for the 10-m run, which was likely due to human rater reaction time. Systematic differences in arm-raise measurements were due to incomplete execution of movements by test participants. These results are consistent with previous studies comparing automated and manual measurements of movement. This study demonstrates that an AMS device is able to measure ambulation speed, rise-to-stand speed and arm-raise speed in a paediatric population in a controlled setting without the need for complicated installation, calibration or worn sensors.

Identifying Critical Design Parameters for Improved Body Temperature Measurements: A Clinical Study Comparing Transient and Predicted Temperature Measurements

Readily available store brand, or “home,” thermometers are used countless times in the home and clinic as a first diagnostic measure of body temperature. Measurement inaccuracies may lead to unnecessary medical visits or medication (false positives), or, potentially worse, lack of intervention when a person is truly sick (false negatives). A critical first step in the design process is to determine the shortcomings of the existing designs. For this project, we evaluated the accuracy of three currently available store brand thermometers in a pediatric population. The accuracies of the thermometers were assessed by comparing their body temperature predictions to those measured by a specially designed and calibrated and fast-responding reference thermometer. The reference thermometer was placed at the measurement site simultaneously with the store brand thermometer and recorded the temperature at the measurement site continuously. More than 300 healthy or sick pediatric subjects were enrolled in this study. Temperatures were measured at both the oral and axillary (under the arm) sites. The store brand thermometer measurements characteristically deviated from the reference thermometer temperature after 120 s, and the deviations did not follow a consistent pattern. The Brand C thermometers had the greatest deviations of up to 3.7 °F (2.1 °C), while the Brand A thermometers had the lowest deviations; however, they still deviated by up to 1.9 °F (1.1 °C). The data showed that the tested store brand thermometers had lower accuracy than the ±0.2 °F (0.1 °C) indicated in their Instructions for Use. Our recorded reference (transient) data showed that there was a wide variation in the transient temperature profiles. The store brand thermometers tested stated in their documentation that they are able to predict a body temperature based on transient temperature values over the first 5–10 s of measurements, implying that they use an embedded algorithm to extrapolate to the steady-state temperature. Significant deviations from the maximum temperature after time t = 4.6t0.63 illustrated that the transient temperature profiles may not be represented by an exponential function with a single time constant, t0.63. The accuracy of those embedded algorithms was not confirmed by our study, since the predicted body temperatures do not capture the large variations observed over the initial 10 s of the measurements. A thermometer with an error of several degrees Fahrenheit may result in a false positive or negative diagnosis of fever in children. The transient temperature measurements from our clinical study represent unique and critical data for helping to design the next generation of readily available, highly accurate, home thermometers.

Prevalence of Arnold nerve reflex in subjects with and without chronic cough: Relevance to Cough Hypersensitivity Syndrome

IntroductionCough is induced by stimulation of structures innervated by the vagus nerve, including the upper and lower airways and distal esophagus. The Arnold nerve reflex describes cough resulting from stimulation of the external auditory canal, which is innervated by the auricular branch of the vagus. We have recently reported the increased prevalence of this reflex in adults, but not children, with chronic cough, relative to healthy adult and pediatric subjects. The prevalence of the Arnold nerve reflex in patients with pulmonary disease but without chronic cough has not been investigated previously. MethodsThree hundred adults and 100 children with chronic cough, 50 adults with stable pulmonary disease but without chronic cough, as well as 100 adult and 100 pediatric volunteers, underwent evaluation consisting of stimulation of the external auditory canal of each ear with a cotton-tipped applicator. Cough occurring within 10 s of stimulation was considered induced by the intervention. ResultsArnold's nerve reflex was present in 23.3% of adults and 3% of children with chronic cough. The prevalence of the reflex was 2% among healthy adults and children. In adults with chronic cough, Arnold's nerve reflex was observed more commonly in women (29.3%) than men (10.5%), and was unilateral in the majority of patients (88.6%). In patients with respiratory disease but without chronic cough, Arnold nerve reflex was present in 2%. ConclusionsThe greater than 11-fold prevalence of the Arnold nerve reflex in adults with chronic cough compared with healthy volunteers and adults with respiratory disease but without chronic cough, supports the concept of the Cough Hypersensitivity Syndrome (CHS), in which vagal hypersensitivity is proposed to underlie chronic refractory cough. The absence of increased prevalence among children with chronic cough suggests that CHS is an acquired condition, perhaps triggered by viral respiratory infection or other environmental factor.

P163 A comparison of the dietary regimen between pediatric patients with Celiac disease and the healthy pediatric subjects

P163 A comparison of the dietary regimen between pediatric patients with Celiac disease and the healthy pediatric subjects

Lack of association between LTF gene polymorphisms and different caries status in primary dentition.

Dental caries is related to cariogenic bacteria, salivary components, oral hygiene and host susceptibility. Lactoferrin is an important antimicrobial glycoprotein in saliva; however, the role of the LTF gene in caries susceptibility is unclear. We investigated the association between LTF polymorphisms and the severity of caries. Our study included 910 healthy paediatric subjects (aged 24-48months) categorised into three groups: 403 with no caries or white-spot lesions; 230 with moderate caries (8≤dmft≤12); and 277 with severe caries (13≤dmft≤20). Information regarding the subjects' oral habits was gathered using questionnaires. The LTF rs1126477 and rs1126478 polymorphism alleles were genotyped by Sanger sequencing. The three groups showed no significant differences in LTF polymorphisms alleles, genotypes or haplotypes distribution. Multifactor dimensionality reduction analysis showed that the interactions between breastfeeding for a duration >24months, night feeding >24months and high frequency of sweet food intake increased the risk of caries (p=0.0014); however, we detected no interaction effect between the LTF polymorphisms and oral habits on caries susceptibility. The LTF rs1126477 and rs1126478 polymorphisms showed no association with the different levels of caries risk in our Chinese paediatric cohort.

Pediatric reference intervals for calculated LDL cholesterol, non-HDL cholesterol, and remnant cholesterol in the healthy CALIPER cohort

ObjectivesIncreased prevalence of pediatric obesity and associated co-morbidities has heightened the concern for cardiovascular disease (CVD) risk later in life. Although the fasting lipid profile is traditionally used to assess CVD risk, the non-fasting lipid profile may simplify lipid testing and better predict CVD risk. Unfortunately, non-fasting lipid reference values are limited, particularly for children. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has recruited thousands of healthy pediatric subjects to develop a pediatric reference interval database. Here, CALIPER reports pediatric reference intervals for non-fasting calculated low-density lipoprotein cholesterol (LDLc), non-high-density lipoprotein cholesterol (non-HDLc) and remnant cholesterol. MethodsNon-fasting serum samples from the CALIPER cohort of community children and adolescents were previously analyzed for HDLc, total cholesterol, and triglycerides. These values were used to calculate LDLc, non-HDLc, and remnant cholesterol and subsequently establish reference intervals with corresponding 90% confidence intervals according to CLSI EP28-A3c guidelines. Reference intervals were also calculated using alternative statistical methods highlighted in recent literature. ResultsAll three lipid parameters required an age partition at 1 year due to wider reference intervals in the first year of life. LDLc and non-HDLc required sex partitioning for subjects 1–<10 years. Non-HDLc upper reference limit was higher than the 2011 National Heart, Lung, and Blood Institute (NHLBII) pediatric recommended cut-offs, suggesting elevated atherogenic lipoproteins in a proportion of apparently healthy pediatric subjects. The LDLc upper reference limit (10–<19 year partition) was the same as the NHLBI cut-off, potentially due to lower calculated LDLc values in the non-fasting state. ConclusionsWith the increased use of non-fasting lipid profiles, age- and sex-specific reference intervals and appropriate clinical decision limits are necessary for pediatric lipid monitoring. Our data supports the notion that appropriate decision limits, rather than reference intervals, should be used to interpret lipid levels in children as there is a high prevalence of hyperlipidemia in the apparently healthy pediatric population.