Percentile Reference Research Articles

LMS-Based Pediatric Reference Values for Parameters of Phosphate Homeostasis in the HARP Cohort.

The assessment of phosphate homeostasis in children is challenging due to the marked changes in laboratory parameters during growth and development, and the lack of adequate reference values. To develop Lambda-Mu-Sigma (LMS)-based continuous pediatric reference percentiles for 7 key laboratory parameters of phosphate homeostasis. This cross-sectional, single-center study, the HAnnover Reference values for Pediatrics (HARP) study, included 455 children aged 0.1-18 years (254 boys) from outpatient hospital clinics and a secondary school program. Main outcome measures were LMS-based continuous reference percentiles for serum phosphate, plasma intact fibroblast growth factor 23 (iFGF23), and its cofactor soluble Klotho (sKlotho), tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR), fractional tubular reabsorption of phosphate (TRP), and urinary calcium/creatinine (Ca/Crea) and phosphate/creatinine (Pi/Crea) ratios. LMS-based percentiles and z-scores were established for 7 key laboratory parameters of phosphate homeostasis, which were all found to be age-dependent. Serum phosphate, TmP/GFR, and sKlotho associated with sex. Serum phosphate, TmP/GFR, and urinary Ca/Crea and Pi/Crea levels were highest in infancy and declined until age 18 years, while phosphate and TmP/GFR values reached adult levels earlier in girls compared to boys. iFGF23 concentrations are highest in infancy and fall to a stable plateau by 4 years of age, while sKlotho peaks during adolescence. This is the first report of LMS-based continuous pediatric reference percentiles for key laboratory parameters of phosphate homeostasis that allow calculation of standardized patient z-scores to facilitate test result interpretation in children and adolescents.

Reference values for body composition in healthy urban Mexican children and adolescents.

Given the increasing incidence of chronic degenerative diseases related to changes in tissues, the availability of diagnostic tools with greater accuracy in the estimation of body composition (BC) has become necessary. Interpreting the BC values of individuals requires reference data obtained from a healthy population with the same ethnicity, to identify individuals at risk for the development of negative health outcomes. Generate reference values (RV) of body composition (BC) for Mexican children and adolescents. This was an urban-population-based cross-sectional study of healthy Mexican children and adolescents. BC estimations by anthropometry, multifrequency bioimpedance analysis (MF-BIA) and dual-energy X-ray absorptiometry (DXA) where used to create sex- and age-specific RV by means of generalized additive models for location, scale and shape (GAMLSS). We assessed 2104 subjects, and after confirming a clinically and metabolically healthy status, we measured 1659 subjects aged 5-20 years, [806 females (49%) and 853 males (51%)] by anthropometry, MF-BIA and DXA to create sex- and age- smoothed reference centiles, lambda (L), mu (M), and sigma (S) values. We also built sex- and age-smoothed graphic curves for each variable of interest. We present valid RV and curves for BC variables estimated by anthropometry, MF-BIA and DXA from clinically and metabolically healthy urban Mexican children and adolescents. These RV are different from those reported for other populations, and therefore, should be used for clinical and research purposes involving urban Mexican children and adolescents.

Jumping Mechanography: Reference Centiles in Childhood and Introduction of the Nerve-Muscle Index to Quantify Motor Efficiency.

Jumping mechanography provides robust motor function indicators among children. The study aim was to develop centiles for the single 2-leg jump (S2LJ) in German children and adolescents and to identify differences in children with obesity. Data were collected in 2004-2021 through the German DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study. All participants (6-18 years, mean age 11.4) performed annually an S2LJ aiming for maximum height on a Ground Reaction Force Platform. LMS (lambda-mu-sigma), including resampling, was used to develop centiles for velocity (vmax), jump height (hmax), relative force (Fmax/BW), relative power (Pmax/mass), impulse asymmetry and a new parameter to describe jump efficiency, the Nerve-Muscle Index (NMI), defined as vmax/(Fmax/BW). Data from 882 children and adolescents were analyzed (3062 measurements, median 3 per individual). In females, Fmax/BW values were higher in younger age but remained constant in adolescence. vmax, hmax and Pmax/mass increased in childhood, reaching a plateau in adolescence. In males, vmax, hmax and Pmax/mass showed a constant increase and the Fmax/BW remained lower. Children with obesity showed lower Fmax/BW, hmax, vmax and the NMI, hence, lower velocity per relative force unit and less efficient jump. The centiles should be used to monitor motor development in childhood. The NMI is a surrogate for motor efficiency.

Accelerometer Metrics: Healthy Adult Reference Values, Associations with Cardiorespiratory Fitness, and Clinical Implications.

Accelerometer-assessed physical activity (PA) can be summarized using cut-point-free or population-specific cut-point-based outcomes. We aimed to 1) examine the interrelationship between cut-point-free (intensity gradient (IG) and average acceleration (AvAcc)) and cut-point-based accelerometer metrics, 2) compare the association between cardiorespiratory fitness (CRF) and cut-point-free metrics to that with cut-point-based metrics in healthy adults aged 20 to 89 yr and patients with heart failure, and 3) provide age-, sex-, and CRF-related reference values for healthy adults. In the COmPLETE study, 463 healthy adults and 67 patients with heart failure wore GENEActiv accelerometers on their nondominant wrist and underwent cardiopulmonary exercise testing. Cut-point-free (IG: distribution of intensity of activity across the day; AvAcc: proxy of volume of activity) and traditional (moderate-to-vigorous and vigorous activity) metrics were generated. The "interpretablePA" R-package was developed to translate findings into clinical practice. IG and AvAcc yield complementary information on PA with both IG ( P = 0.009) and AvAcc ( P < 0.001) independently associated with CRF in healthy individuals (adjusted R2 = 73.9%). Only IG was independently associated with CRF in patients with heart failure ( P = 0.043, adjusted R2 = 38.4%). The best cut-point-free and cut-point-based model had similar predictive value for CRF in both cohorts. We produced age- and sex-specific reference values and percentile curves for IG, AvAcc, moderate-to-vigorous PA, and vigorous PA for healthy adults. IG and AvAcc are strongly associated with CRF and thus indirectly with the risk of noncommunicable diseases and mortality, in healthy adults and patients with heart failure. However, unlike cut-point-based metrics, IG and AvAcc are comparable across populations. Our reference values provide a healthy age- and sex-specific comparison that may enhance the translation and utility of cut-point-free metrics in clinical practice.

Reference Values for Videofluoroscopic Measures of Swallowing: An Update.

It is essential that clinicians have evidence-based benchmarks to support accurate diagnosis and clinical decision making. Recent studies report poor reliability for diagnostic judgments and identifying mechanisms of impairment from videofluoroscopy (VFSS). Establishing VFSS reference values for healthy swallowing would help resolve such discrepancies. Steele et al. (2019) released preliminary reference data for quantitative VFSS measures in healthy adults aged < 60 years. Here, we extend that work to provide reference percentiles for VFSS measures across a larger age span. Data for 16 VFSS parameters were collected from 78 healthy adults aged 21-82 years (39 male). Participants swallowed three comfortable sips each of thin, slightly, mildly, moderately, and extremely thick barium (20% w/v). VFSS recordings were analyzed in duplicate by trained raters, blind to participant and task, using the Analysis of Swallowing Physiology: Events, Kinematics and Timing (ASPEKT) Method. Reference percentiles (p2.5, 5, 25, 50, 75, 95, and 97.5) were determined as per Clinical and Laboratory Standards Institute EP28-A3c guidelines. We present VFSS reference percentile tables, by consistency, for (a) timing parameters (swallow reaction time; the hyoid burst-to-upper esophageal sphincter (UES)-opening interval; UES opening duration; time-to-laryngeal vestibule closure (LVC); and LVC duration) and (b) anatomically scaled pixel-based measures of maximum UES diameter, pharyngeal area at maximum pharyngeal constriction and rest, residue (vallecular, pyriform, other pharyngeal locations, total), and hyoid kinematics (X, Y, XY coordinates of peak position; speed). Clinical decision limits are proposed to demarcate atypical values of potential clinical concern. These updated reference percentiles and proposed clinical decision limits are intended to support interpretation and reliability for VFSS assessment data. https://doi.org/10.23641/asha.24043041.

Reference centile curves for muscle volume and strength of lower-limb muscles of typically developing children aged 0.5-18 years

Reference centile curves for muscle volume and strength of lower-limb muscles of typically developing children aged 0.5-18 years

Birth Weight Reference Percentiles by Gestational Age for Turkish Twin Neonates

Birth Weight Reference Percentiles by Gestational Age for Turkish Twin Neonates

Centile reference curves of the ultrasound-based characteristics of the rectus femoris muscle composition in children at 4-11 years old.

Quantitative diagnostic ultrasound has been proposed as a way to characterize muscle structure, but there is a lack of normative data for children. This study aims to establish age-specific normal ranges for echo-intensity (EI), cross-sectional area (CSA), muscular thickness (MT), and subcutaneous adipose thickness (SAT) values of the rectus femoris muscle in typically developing children. The study recruited 497 children (288 boys and 209 girls) aged 4-10.9 years (mean age 7.39 years), and muscle parameters were measured using 2D B-mode ultrasound. Percentile values and reference curves were calculated using the Lambda, Mu, and Sigma method (LMS). The results showed small variation between measurements for boys compared to girls, with the most significant difference in EI, CSA, and MT values. EI decreased with age, with the most pronounced curve in boys. SAT increased in both sexes, with a slightly higher increase in girls after the age of 9.0 years. This study provides the first age-specific reference norms for the rectus femoris muscle architecture in children, and further research is needed to validate these curves and determine their clinical utility.

Serum neurofilament light chain reference database for individual application in paediatric care: a retrospective modelling and validation study

Neurological conditions represent an important driver of paediatric disability burden worldwide. Measurement of serum neurofilament light chain (sNfL) concentrations, a specific marker of neuroaxonal injury, has the potential to contribute to the management of children with such conditions. In this context, the European Medicines Agency recently declared age-adjusted reference values for sNfL a top research priority. We aimed to establish an age-adjusted sNfL reference range database in a population of healthy children and adolescents, and to validate this database in paediatric patients with neurological conditions to affirm its clinical applicability. To generate a paediatric sNfL reference dataset, sNfL values were measured in a population of healthy children and adolescents (aged 0-22 years) from two large cohorts in Europe (the Coronavirus Antibodies in Kids from Bavaria study, Germany) and North America (a US Network of Paediatric Multiple Sclerosis Centers paediatric case-control cohort). Children with active or previous COVID-19 infection or SARS-CoV-2 antibody positivity at the time of sampling, or a history of primary systemic or neurological conditions were excluded. Linear models were used to restrospectively study the effect of age and weight on sNfL concentrations. We modelled the distribution of sNfL concentrations as a function of age-related physiological changes to derive reference percentile and Z score values via a generalised additive model for location, scale, and shape. The clinical utility of the new reference dataset was assessed in children and adolescents (aged 1-19 years) with neurological diseases (epilepsy, traumatic brain injury, bacterial CNS infections, paediatric-onset multiple sclerosis, and myelin oligodendrocyte glycoprotein antibody-associated disease) from the paediatric neuroimmunology clinic at the University of California San Francisco (San Francisco, CA, USA) and the Children's Hospital of the University of Regensburg (Regensburg, Germany). Samples from 2667 healthy children and adolescents (1336 [50·1%] girls and 1331 [49·9%] boys; median age 8·0 years [IQR 4·0-12·0]) were used to generate the reference database covering neonatal age to adolescence (target age range 0-20 years). In the healthy population, sNfL concentrations decreased with age by an estimated 6·8% per year until age 10·3 years (estimated multiplicative effect per 1 year increase 0·93 [95% CI 0·93-0·94], p<0·0001) and was mostly stable thereafter up to age 22 years (1·00 [0·52-1·94], p>0·99). Independent of age, the magnitude of the effect of weight on sNfL concentrations was marginal. Samples from 220 children with neurological conditions (134 [60·9%] girls and 86 [39·1%] boys; median age 14·7 years [IQR 10·8-16·5]) were used to validate the clinical utility of the reference Z scores. In this population, age-adjusted sNfL Z scores were higher than in the reference population of healthy children and adolescents (p<0·0001) with higher effect size metrics (Cohen's d=1·56) compared with the application of raw sNfL concentrations (d=1·28). The established normative sNfL values in children and adolescents provide a foundation for the clinical application of sNfL in the paediatric population. Compared with absolute sNfL values, the use of sNfL Z score was associated with higher effect size metrics and allowed for more accurate estimation of the extent of ongoing neuroaxonal damage in individual patients. Swiss National Science Foundation, US National Institutes of Health, and the National Multiple Sclerosis Society.

Proportionate universalism intervention is effective for tackling nutritional social gradient in adolescents: the PRALIMAP-INÈS mixed randomised trial

ObjectiveThis study aimed to investigate the effectiveness of proportionate universalism intervention to reduce the slope of the nutritional social gradient in adolescents. Study designA mixed (experimental and quasi-experimental) multicentre trial. MethodsData from 985 adolescents of the PRALIMAP-INÈS trial (North-eastern France, 2012–2015) were analysed. For this, adolescents were split into five social classes according to the Family Affluence Scale: Highly Less Advantaged (H.L.Ad; n = 33), Less Advantaged (L.Ad; n = 155), Intermediate (Int; n = 404), Advantaged (Ad; n = 324) and Highly Advantaged (H.Ad; n = 69). The overweight care management was a standard care for all and a strengthened one adapted to the social class of adolescents. The main outcome was the 1-year change of the body mass index z-score (BMIz) slope. Other nutritional outcomes were BMI, ΔBMIp95 (BMI minus 95th percentile of the WHO reference), %BMIp95 (percent of 95th percentile of the WHO reference), leisure-time sport, consumption of fruits and vegetables and consumption of sugary foods and drinks. ResultsThe inclusion data confirmed a weight social gradient expressed by a significant BMIz linear regression coefficient (β = −0.09 [−0.14 to −0.04], P < 0.0001). The higher the social class, the lower the BMIz. The 1-year BMIz linear regression coefficient was −0.07 [−0.12 to −0.02], corresponding to a significant weight social gradient reduction of 23.3% (β = 0.021 [0.001 to 0.041]; P = 0.04). Consistent results were found for other nutritional outcomes. ConclusionsPRALIMAP-INÈS shows that proportionate universalism intervention is effective to reduce the adolescents’ nutritional social gradient and suggests that equitable health programmes and policies are a realistic goal.

Estimation of Reference Values for External Genitalia Parameters in North Indian Preterm and Term Male Newborns.

To generate gestation-wise normative data of external genitalia measurements in North Indian term and preterm male newborns. This was a hospital-based cross-sectional observational study. Male neonates born between 28-42 wk of gestation (at 24-72h of life) were consecutively recruited in the study. Newborns with major congenital malformations, chromosomal anomalies, multifetal gestation and birth injuries were excluded. Data on various genital measurements were collected [Stretched penile length (SPL), penile width (PW), upper anogenital distance (AGDu), lower anogenital distance (AGDl) and anogenital ratio (AGR)]. Out of 532 newborns, 208 (39.1%) were preterm. Mean (± SD) SPL and PW were 27.9 ± 3.6mm and 10.6 ± 1.3mm respectively. The mean values for AGDl, AGDu and AGR were 20.13 ± 4.04mm, 39.2 ± 5.59mm, and 0.51 ± 0.07, respectively. SPL less than 21mm in a term male newborn and 17.5mm in preterm should be considered micropenis (<2.5 SD) in our population. Gestation-wise percentile charts for SPL, PW, AGDl, AGDu and AGR were generated. The reference values and percentile charts generated can serve as local normative data for accurate interpretation of genital measurements in North Indian newborns, assessment of ambiguous genitalia and avoiding diagnostic errors.

Reference blood pressure values obtained using the auscultation method for 2-year-old Japanese children: from the Japan Environment and Children’s Study

BackgroundReference blood pressure (BP) values for Japanese children based on a large number of measurements by auscultation have not yet been established.MethodsThis was a cross-sectional analysis of data from a birth-cohort study. The data from the sub-cohort study conducted for children at the age of 2 years in the Japan Environment and Children’s Study from April 2015 to January 2017 were analyzed. BP was measured via auscultation using an aneroid sphygmomanometer. Each participant was measured in triplicate, and the average value of two consecutive measurements with a difference of less than 5 mmHg was recorded. The reference BP values were estimated using the lambda–mu–sigma (LMS) method and compared with those obtained via the polynomial regression model.ResultsData from 3361 participants were analyzed. Although the difference between the estimated BP values by the LMS and the polynomial regression model was small, the LMS model was more valid based on the results of the fit curve of the observed values and regression models for each model. For 2-year-old children with heights in the 50th percentile, the 50th, 90th, 95th, and 99th percentile reference values of systolic BP (mmHg) for boys were 91, 102, 106, and 112, and that for girls were 90, 101, 103, and 109, respectively, and those of diastolic BP for boys were 52, 62, 65, and 71, and that for girls were 52, 62, 65, and 71, respectively.ConclusionThe reference BP values for 2-year-old Japanese children were determined based on auscultation and were made available.

Interpreting two TSH results from the same patient.

When the patient's mean (setpoint) concentration of an analyte is unknown and the physician tries to judge the clinical condition from the analyte concentration in two separate specimens taken a time apart, we believe that the two values should be judged against a bivariate reference interval derived from clinically healthy and stable individuals, rather than using univariate reference limits and comparing the difference between the values against reference change values (RCVs). In this work we compared the two models, using s-TSH as an example. We simulated two s-TSH measurement values for 100,000 euthyreot subjects, and plotted the second value against the first, along with a markup of the central 50, 60, 70, 80, 90, and 95 % of the bivariate distribution, in addition to the 2.5 and 97.5 percentile univariate reference limits and the 2.5 and 97.5 percentile RCVs. We also estimated the diagnostic accuracy of the combination of the 2.5 and 97.5 univariate percentile reference limits and the 2.5 and 97.5 percentile RCVs against the central 95 % of the bivariate distribution. Graphically, the combination of the 2.5 and 97.5 univariate reference limits and the 2.5 and 97.5 percentile RCVs did not accurately delineate the central 95 % of the bivariate distribution. Numerically, the sensitivity and specificity of the combination were 80.2 and 92.2 %, respectively. The concentrations of s-TSH measured in two samples taken at separate times from a clinically healthy and stable individual cannot be accurately interpreted using the combination of univariate reference limits and RCVs.

Reference Ranges and Development Patterns of Fetal Myocardial Function Using Speckle Tracking Echocardiography in Healthy Fetuses at 17 to 24 Weeks of Gestation.

The purposes of the study were to develop reference ranges and maturation patterns of fetal cardiac function parameters measured by speckle tracking echocardiography (STE) using multiple biometric variables at 17 to 24 weeks' gestation among Thai fetuses and to compare with other previous reports. The four-chamber view of the fetal heart in 79 healthy fetuses was suitably analyzed by STE to establish the best-fit regression model. The 95% reference intervals and Z-score equations of fetal cardiac function parameters were computed. The fractional area change of both ventricles, left ventricular (LV) end-diastolic and end-systolic volumes, LV stroke volume, LV cardiac output (CO), and LV CO per kilogram were all increased according to gestational age (GA) and five fetal biometric measurements. However, the global longitudinal strain, basal-apical length fractional shortening (BAL-FS), BAL annular free wall and septal wall FS, BAL free wall and septal wall annular plane systolic excursions, 24-segment transverse width FS, as well as LV ejection fraction were all independent of GA or other somatic characteristics. There were varying development patterns between fetal right and left ventricles of these cardiac function indices across the gestation period. Our study created Z-score and corresponding centile calculators, 5th and 95th centile reference tables, and corresponding graphs and determined the normal evolution across gestation using multiple somatic growth and age variables between 17 and 24 gestational weeks. These nomograms serve as an essential prerequisite for quantitatively evaluating fetal cardiac contractility and allow for precisely detecting early changes in the fetal heart function. · Most fetal cardiac function measurements were correlated with all the independent variables.. · Fetal ventricular function parameters have their own characteristic maturation changes.. · Racial variability may not occupy an important place for fetal myocardial function during these GA..

Troponin in acute chest pain to risk stratify and guide effective use of computed tomography coronary angiography (TARGET-CTCA): a randomised controlled trial

BackgroundThe majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death.MethodsTARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. After myocardial infarction and clear alternative diagnoses have been ruled out, participants with intermediate cardiac troponin concentrations (5 ng/L to 99th centile upper reference limit) will be randomised 1:1 to outpatient CTCA plus standard of care or standard of care alone. The primary endpoint is myocardial infarction or cardiac death. Secondary endpoints include clinical, patient-centred, process and cost-effectiveness. Recruitment of 2270 patients will give 90% power with a two-sided P value of 0.05 to detect a 40% relative risk reduction in the primary endpoint. Follow-up will continue until 97 primary outcome events have been accrued in the standard care arm with an estimated median follow-up of 36 months.DiscussionThis randomised controlled trial will determine whether high-sensitivity cardiac troponin-guided CTCA can improve outcomes and reduce subsequent major adverse cardiac events in patients presenting to the emergency department who do not have myocardial infarction.Trial registrationClinicalTrials.gov Identifier: NCT03952351. Registered on May 16, 2019.

HIGH PREVALENCE OF NEW HYPERTENSION AND EARLY VASCULAR AGING: A REPORT FROM MAY MEASUREMENT MONTH 2019 SCREENING PROGRAMME IN BULGARIA

Objective: Hypertension remains a major public health issue with inadequate control worldwide. The May Measurement Month (MMM) initiative by the International Society of Hypertension was implemented in Bulgaria in 2019 aiming to raise hypertension awareness and control. Increased arterial stiffness may indicate high cardiovascular risk, but little is known about its prevalence at the population level. Design and method: Adult volunteers (&gt;18 years) were recruited through opportunistic screening in 21 of 28 administrative areas in the country. Information on medical history and triplicate sitting blood pressure (BP) measurements were obtained using validated automated upperarm devices. Aortic pulse wave velocity (aoPWV) was estimated, using age, systolic BP, and waveform characteristics. Using age-specific percentiles from a nonhypertensive group, we defined healthy (HVA) and early (EVA) vascular aging. Results: A total of 3678 participants were analyzed [mean age 58.8±16.5 years, men 37.2%, 71.2% had BP measurement in the last 12 months]. Mean BP was 135/82 mm Hg. In all, 45.4% of participants had elevated BPs (&gt;140/90 mm Hg), 58.3% out of 1910 participants with known hypertension, and 31.4% out of 1768 participants without known hypertension. In all, 4,67% of participants had aoPWV below 10th reference percentile (HVA), with a negligible proportion above 50 years. In total, 40.5% were above the 90th reference percentile (EVA), with proportions rising from one-quarter in youngest partcipants bellow 50 to one-half in oldest participants. In participants with EVA, BP was elevated during the measurement in 82.6%. Among participants without established HTN, according to European guidelines in 18.4 % BP was elevated, when measured during the campaign. The lowest proportion of newly diagnosed hypertension was found in HVA group – 4.8% and the highest 30% in EVA group. Figure 1 gives information for blood pressure measured according to quintiles of vascular aging groups. Conclusions: The prevalence of hypertension in Bulgaria is high, with considerable potential for improving awareness, treatment, and control. The high prevalence of early vascular aging and higher incidence of newly diagnosed hypertension in this group of patient at early age is alarming.

Longitudinal brain atrophy rates in presymptomatic genetic frontotemporal dementia

AbstractBackgroundIn light of upcoming clinical trials for genetic frontotemporal dementia (FTD), it is important to identify at what age brain atrophy rates start to accelerate and deviate from normal aging effects to find the optimal starting point for treatment. We aimed to investigate longitudinal brain atrophy rates in the presymptomatic stage of genetic FTD, using normative brain volumetry software.Method34 GRN, eight MAPT, and 14 C9orf72 presymptomatic mutation carriers underwent longitudinal volumetric T1‐weighted MRI of the brain with a one‐ to two‐year interval (mean number of scans = 3.5, SD = 1.6). Images were automatically analyzed with Quantib® ND which consisted of volume measurements (CSF and grey + white matter) of lobes (left, right, and combined), cerebellum, and hippocampus. All volumes were compared to reference centile curves based on a large population‐derived sample of non‐demented individuals (n = 4951). Mixed‐effects models were fitted to analyze atrophy rates of the different gene groups as a function of age, and were corrected for sex, head coil, and scanner software version.ResultAtrophy rates of the total brain, frontal lobe, and temporal lobe differed between gene groups (all p&lt;0.002). GRN mutation carriers declined faster than the reference centile curves for all brain areas, though relative volumes remained between 5th and 75th percentile between the ages of 45 – 70. In MAPT mutation carriers, frontal lobe volume was already at the 5th percentile at age 45, and showed further decline between the ages 50‐60. Temporal lobe volume started in the 50th percentile at age 45, but showed fastest decline over time compared to other brain structures. Frontal, temporal, parietal and cerebellar volume already started below the 5th percentile compared to the reference centile curves at age 45 for C9orf72 mutation carriers, but there was minimal decline over time until the age of 60.ConclusionWe provide evidence for longitudinal brain atrophy in the presymptomatic stage of genetic FTD. The affected brain areas and the age after which atrophy rates start to accelerate and diverge from normal aging slopes differed between gene groups. These results highlight the value of normative volumetry software for disease‐tracking and staging biomarkers in genetic FTD.

Pediatric reference values of alkaline phosphatase: Analysis from a German population-based cohort and influence of anthropometric and blood parameters

BackgroundDue to different growth and metabolic processes, reference values of alkaline phosphatase (AP) for children aged 3 month to 18 years are dependent on age and sex. They are not constant and differ from those of adults due to the growth processes taking place. Accordingly, reference levels of AP continuous across these ages were generated for boys and girls based on of a large German health- and population-based study, LIFE Child. We considered AP at different growth and Tanner stages and additionally its association with other anthropometric parameters. The association between AP and BMI was of particulary great interest due to controversial literature on this topic. The role of AP in liver metabolism was investigated by examining ALAT, ASAT, and GGT. Methods3976 healthy children (12,093 visits) were included from the LIFE Child study from 2011 to 2020. The subjects´ age ranged from 3 months to 18 years. Serum samples from 3704 subjects (10,272 cases, 1952 boys and 1753 girls) were analysed for AP after applying specific exclusion criteria. After calculating of reference percentiles, associations between AP and height-SDS, growth velocity, BMI-SDS, Tanner stage and the liver enzymes ALAT, ASAT and GGT were examined via linear regression models. ResultsIn the continuous reference levels, AP showed a first peak during the first year of life, followed by a plateau at a lower level until the start of puberty. In girls, AP increased beginning at the age 8, with a peak around 11 years, in boys beginning at the age 9, with a peak around age 13. Afterwards, AP values decreased continuously until age 18. In Tanner stages 1 and 2, AP levels did not differ between the two sexes. We found a strong positive association between AP-SDS and BMI-SDS. We also observed a significantly positive association between AP-SDS and height-SDS, which was stronger in boys than in girls. We found different intensities in the associations of AP with growth velocity depending on age group and sex. Furthermore, we found a significantly positive association between ALAT and AP in girls but not in boys, whereas ASAT-SDS and GGT-SDS were significantly positively associated with AP-SDS in both sexes. ConclusionSex and age, but also BMI may act as confounding factors for AP reference ranges. Our data confirm the remarkable association between AP and growth velocity (or height-SDS, respectively) during infancy and puberty. In addition, we were able to specify the associations between AP and ALAT, ASAT, and GGT and their differences in both sexes. These relations should be considered when evaluating liver and bone metabolism markers, especially in infancy.

Cardiovascular magnetic resonance derived biventricular strain in healthy adolescents: reference values and comparison between myocardial tagging and feature-tracking

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Instituto de Salud Carlos III (ISCIII) European Regional Development Fun/European Social Fund (A way to make Europe/Investing in your future). Background Strain measurements have demonstrated to be earlier and more sensitive markers of contractile dysfunction than ejection fraction (EF) alone. Myocardial tagging (MT) is considered the reference standard for CMR strain measurements, but its clinical application is limited because acquisition and analysis are laborious and time consuming. Feature-tracking (FT) CMR allows strain quantification using steady-state in free-precession (SSFP) sequence, which is obtained in routine CMR protocols, being easily applicable in clinical practice. Literature regarding reference strain values in pediatric populations is scarce and, to the best of our knowledge, there are no studies comparing FT and MT in healthy adolescents. Purpose To provide CMR strain reference values in healthy adolescents and compare FT to MT results. Methods A CMR study was performed in healthy adolescents enrolled in the "Early ImaginG Markers of unhealthy lifestyles in Adolescents" (EnIGMA) project using a 3-Tesla CMR scanner between March and October 2021. The imaging protocol included a cine SSFP to provide images for chamber size and function, including FT; and MT acquisitions using spatial modulation of magnetization (SPAMM) technique. Cine acquisitions included the entire left ventricular (LV) short axis and long-axis 4 chamber (4c)- and 2 chamber (2c)-views, while MT acquisitions included three short axis slices (basal, mid and apical) and long-axis 4c-view. Endo- and epicardial borders were manually contoured in the end-diastolic (ED) phase. A non-rigid, elastic algorithm was used for segmentation and registration for strain quantification. If tracking was suboptimal, the software only allowed adaptations of the contours on the ED image. Longitudinal (LS) and circumferential (CS) strains were obtained for the LV and right ventricle (RV). Results CMR scans were performed in 123 adolescents (64 girls, 52.0%) with a mean age of 16.0 years (standard deviation [SD]=0.4), a mean LVEF of 62.5% (SD=4.1) and a mean RVEF of 56.2% (SD=4.6). Reference percentiles (P) 3, 10, 25, 50, 90 and 97 for strain values by sex are provided in Figure 1. FT-measured LVLS and LVCS were higher in girls than in boys (-19.8 vs -17.8%, p&amp;lt;0.01; and -22.2 vs -21.0%, p&amp;lt;0.01; respectively), and these differences were confirmed with MT analysis. There were no consistent between-sex differences for RVLS and RVCS. Bland-Altman analyses showed reasonable agreement between FT and MT for LVLS, LVCS, RVLS and RVCS (Figure 2 A, B, C and D). Conclusions This study provided CMR derived reference values for left and right ventricle strain in adolescents aged 15 to 18 years. This work suggests that FT is a reasonably valid technique to measure LV and RV strain in this population. This information may be useful for diagnostic and prognostic implications in adolescent patients.

Comparison of frame index reference percentiles in Argentine and European boys and girls.

The frame index (FI), based on measurements of elbow breadth and height, is the body frame size parameter most frequently used in child and adolescent populations to assess skeletal robustness. In 2018, the first FI reference percentiles were elaborated with data of boys and girls aged 0-18 years from different European populations. In Argentina, the FI reference values were published in 2022. The present study aims to compare the Argentine (AR) and European (EU) FI reference percentiles to evaluate possible variation in bone robustness between populations. The values of the 3rd, 50th and 97th percentiles of the AR and EU FI references for boys and girls aged 4-14 years were compared using the Wilcoxon test (p < .05). Percentage differences between means (PDM) were calculated to analyze the magnitude of the differences between both references. The R 3.2.0 program was used to plot the percentile curves. The FI reference values were lower in AR than in EU in both the 3rd and the 50th percentiles, regardless of sex and age. Conversely, the AR reference values of the 97th percentile were higher than the EU values at most ages. The comparison of the AR and EU FI references showed similar age and sex growth patterns. However, differences in percentile values between populations were observed, highlighting the importance of having local references for the evaluation of skeletal robustness.