Properties of the full random-effect modeling approach with missing covariate data.

During drug development, a key step is the identification of relevant covariates predicting between-subject variations in drug response. The full random effects model (FREM) is one of the full-covariate approaches used to identify relevant covariates in nonlinear mixed effects models. Here we explore the ability of FREM to handle missing (both missing completely at random (MCAR) and missing at random (MAR)) covariate data and compare it to the full fixed-effects model (FFEM) approach, applied either with complete case analysis or mean imputation. A global health dataset (20 421 children) was used to develop a FREM describing the changes of height for age Z-score (HAZ) over time. Simulated datasets (n = 1000) were generated with variable rates of missing (MCAR) covariate data (0%-90%) and different proportions of missing (MAR) data condition on either observed covariates or predicted HAZ. The three methods were used to re-estimate model and compared in terms of bias and precision which showed that FREM had only minor increases in bias and minor loss of precision at increasing percentages of missing (MCAR) covariate data and performed similarly in the MAR scenarios. Conversely, the FFEM approaches either collapsed at ≥ $$ \ge $$ 70% of missing (MCAR) covariate data (FFEM complete case analysis) or had large bias increases and loss of precision (FFEM with mean imputation). Our results suggest that FREM is an appropriate approach to covariate modeling for datasets with missing (MCAR and MAR) covariate data, such as in global health studies.

Effectiveness of locally produced ready-to-use supplementary foods on the prevention of stunting in children aged 6-23 months: a community-based trial from Pakistan.

Undernutrition is a major public health problem in developing countries. Around 40·2 % of children are stunted in Pakistan. This longitudinal study aimed to assess the effectiveness of locally produced ready-to-use supplementary foods in the prevention of stunting by detecting change in of children in intervention v. control arm against the 2006 WHO growth reference. A community-based non-randomised cluster-controlled trial was conducted from January 2018 to December 2020 in the district of Kurram, Khyber Pakhtunkhwa, Pakistan. A total of 80 clusters (each cluster comprising ≈ 250-300 households) were defined in the catchment population of twelve health facilities. Children aged 6-18 months were recruited n 1680. The intervention included a daily ration of 50 g - locally produced ready-to-use-supplementary food (Wawa-Mum). The main outcome of this study was a change in length for age z-score (LAZ) v. WHO growth standards. Comparison between the interventions was by t test and ANOVA. Cox proportional hazard models were used to assess the association between stunting occurrence and the utilisation of locally produced supplement. Out of the total 1680, fifty-one out of the total 1680, 51·1 out of the total 1680 and 51·1 % (n 859) were male. Mean age 13·9 months (sd + 859) were male. Mean age 13·9 months (sd + -4·4). At baseline, 36·9 % (n 618) were stunted. In the intervention group, mean LAZ score significantly increased from -1·13(2·2 sd) at baseline to -0·93(1·8 sd) at 6-month follow-up (P value 0·01) compared with the control group. The incidence rate of stunting in the intervention arm was 1·3 v. 3·4 per person year in the control arm. The control group had a significantly increased likelihood of stunting (Hazard Ratio (HR) 1·7, 95 % CI 1·46, 2·05, P value < 0·001) v. the intervention group. Locally produced ready-to-use supplementary food is an effective intervention for reducing stunting in children below 2 years of age. This can be provided as part of a malnutrition prevention package to overcome the alarming rates of stunting in Pakistan.

Assessment of accuracy of laboratory testing results, relative to peer group consensus values in external quality control, by bivariate z-score analysis: the example of D-Dimer.

OBJECTIVES: The aim of this study is to develop a practical method for bivariate z-score analysis which can be applied to the survey of an external quality assessment programme. METHODS: To develop the bivariate z-score analysis, the results of four surveys of the international D-Dimer external quality assessment programme of 2022 of the ECAT Foundation were used. The proposed methodology starts by identifying the bivariate outliers, using a Supervised Sequential Hotelling T2 control chart. The outlying data are removed, and all the remaining data are used to provide robust estimates of the parameters of the assumed underlying bivariate normal distribution. Based on these estimates two nested homocentric ellipses are drawn, corresponding to confidence levels of 95 and 99.7 %. The bivariate z-score plot described provides the laboratory with an indication of both systematic and random deviations from zero z-score values. The bivariate z-score analysis was examined within survey 2022-D4 across the three most frequently used methods. RESULTS: The number of z-score pairs included varied between 830 and 857 and the number of bivariate outliers varied between 20 and 28. The correlation between the z-score pairs varied between 0.431 and 0.647. The correlation between the z-score pairs for the three most frequently used varied between 0.208 and 0.636. CONCLUSIONS: The use of the bivariate z-score analysis is of major importance when multiple samples are distributed around in the same survey and dependency of the results is likely. Important lessons can be drawn from the shape of the ellipse with respect to random and systematic deviations, while individual laboratories have been informed about their position in the state-of-the-art distribution and whether they have to deal with systematic and/or random deviations.

A multi-platform normalization method for meta-analysis of gene expression data.

Transcriptomic profiling is a mainstay of translational cancer research and is often used to identify cancer subtypes, stratify responders vs. non-responders patients, predict survival, and identify potential targets for therapeutic intervention. Analysis of gene expression data gathered by RNA sequencing (RNA-seq) and microarray is generally the first step in identifying and characterizing cancer-associated molecular determinants. The methodological advancements and reduced costs associated with transcriptomic profiling have increased the number of publicly available gene expression profiles for cancer subtypes. Data integration from multiple datasets is routinely done to increase the number of samples, improve statistical power, and provide better insight into the heterogeneity of the biological determinant. However, utilizing raw data from multiple platforms, species, and sources introduces systematic variations due to noise, batch effects, and biases. As such, the integrated data is mathematically adjusted through normalization, which allows direct comparison of expression measures among studies while minimizing technical and systemic variations. This study applied meta-analysis to multiple independent Affymetrix microarray and Illumina RNA-seq datasets available through the Gene Expression Omnibus (GEO) and The Cancer Gene Atlas (TCGA). We have previously identified a tripartite motif containing 37 (TRIM37), a breast cancer oncogene, that drives tumorigenesis and metastasis in triple-negative breast cancer. In this article, we adapted and assessed the validity of Stouffer's z-score normalization method to interrogate TRIM37 expression across different cancer types using multiple large-scale datasets.

Trajectory of body mass index and obesity in children with Crohn's disease compared to healthy children.

BACKGROUND: There is increasing recognition that children with Crohn's Disease (CD) can develop obesity. METHODS: Using the RISK Study, an inception cohort of pediatric CD participants, and Bone Mineral Density in Childhood Study (BMDCS), a longitudinal cohort of healthy children, multivariable linear mixed effects, generalized linear mixed effects, and logistic regression models were used to evaluate factors associated with change in body mass index z-score (BMIZ), obesity, and excessive weight gain, respectively. RESULTS: 1029 CD participants (625 exposed to antitumor necrosis factor (anti-TNF) therapy) and 1880 healthy children were included. Change in BMIZ was higher in CD exposed to anti-TNF as compared to CD unexposed to anti-TNF and the healthy reference group. Sex, age, baseline BMIZ, C-reactive protein, anti-TNF, and steroids were associated with changes in BMIZ in CD. CD exposed (odds ratio [OR] 4.81, confidence interval [CI] 4.00-5.78) and unexposed (OR 3.14, CI 2.62-3.76) had a greater likelihood of becoming obese versus the healthy reference group. While the prevalence of obesity was higher at baseline in the healthy reference group (21.3%) versus CD participants (8.5% exposed vs. 11.1% unexposed), rates of obesity were similar by the end of follow-up (21.4% healthy vs. 20.3% exposed vs. 22.5% unexposed). Anti-TNF therapy was an independent risk factor for the development of obesity and excessive weight gain in CD participants. CONCLUSIONS: Patients with CD have dynamic changes in BMIZ over time, and while for most, this is restorative, for some, this can lead to obesity and excessive weight gain. It is important to understand the factors that may lead to these changes, including anti-TNF therapy. Counseling of patients and early lifestyle intervention may be necessary.

Music therapy and weight gain in preterm infants: Secondary analysis of the randomized controlled LongSTEP trial.

OBJECTIVES: This study assessed the association between MT and weight gain among preterm infants hospitalized in Neonatal Intensive Care Units. METHODS: Data collected during the international, randomized, Longitudinal Study of Music Therapy's Effectiveness for Premature Infants and their Caregivers (LongSTEP) study were compared between the MT group and the standard care (SC) group. Weights were recorded at birth, enrollment, and discharge. Weight percentiles, Z-scores, weight gain velocity, and extrauterine growth restriction (EUGR) were calculated. RESULTS: Among 201 preterm infants included, no significant differences in weight parameters (weight, weight percentiles, weight Z-scores; all p ≥ 0.23) were found between the MT group (n = 104) and the SC (n = 97) group at birth, enrollment, or discharge. No statistical differences in EUGR represented by change in Z-scores from birth to discharge were recorded between MT and SC (0.8 vs. 0.7). Among perinatal parameters, younger gestational age (p = 0.005) and male sex (p = 0.012) were associated with increased risk of EUGR at discharge. Antenatal steroid treatment, systemic infection, bronchopulmonary dysplasia, neurological morbidities, retinopathy of prematurity, necrotizing enterocolitis, parental factors (amount of skin-to-skin care, bonding, anxiety, and depression questionnaire scores), and type of enteral nutrition did not significantly influence weight gain parameters (all p > 0.05). CONCLUSIONS: In the LongSTEP study, MT for preterm infants and families was not associated with better weight parameters compared to the SC group. The degree of prematurity remains the main risk factor for unfavorable weight parameters.

EfficientNet-deep quantum neural network-based economic denial of sustainability attack detection to enhance network security in cloud.

Cloud computing (CC) is a future revolution in the Information technology (IT) and Communication field. Security and internet connectivity are the common major factors to slow down the proliferation of CC. Recently, a new kind of denial of service (DDoS) attacks, known as Economic Denial of Sustainability (EDoS) attack, has been emerging. Though EDoS attacks are smaller at a moment, it can be expected to develop in nearer prospective in tandem with progression in the cloud usage. Here, EfficientNet-B3-Attn-2 fused Deep Quantum Neural Network (EfficientNet-DQNN) is presented for EDoS detection. Initially, cloud is simulated and thereafter, considered input log file is fed to perform data pre-processing. Z-Score Normalization ;(ZSN) is employed to carry out pre-processing of data. Afterwards, feature fusion (FF) is accomplished based on Deep Neural Network (DNN) with Kulczynski similarity. Then, data augmentation (DA) is executed by oversampling based upon Synthetic Minority Over-sampling Technique (SMOTE). At last, attack detection is conducted utilizing EfficientNet-DQNN. Furthermore, EfficientNet-DQNN is formed by incorporation of EfficientNet-B3-Attn-2 with DQNN. In addition, EfficientNet-DQNN attained 89.8% of F1-score, 90.4% of accuracy, 91.1% of precision and 91.2% of recall using BOT-IOT dataset at K-Fold is 9.

Shared Genetic Influences Between Loss-of-Control Eating and Body Mass Index in Adolescent Twins.

OBJECTIVE: Pediatric loss-of-control (LOC) eating is associated with high BMI and predicts binge-eating disorder and obesity onset with age. Research on the etiology of this common comorbidity has not explored the potential for shared genetic risk. This study examined genetic and environmental influences on LOC eating and its shared influence with BMI. METHOD: Participants were 499 monozygotic and 398 same-sex dizygotic twins (age = 17.38 years ± 0.67, BMIz = 0.03 ± 1.03, 54% female) from the Colorado Center for Antisocial Drug Dependence Study. LOC eating was assessed dichotomously. Self-reported height and weight were converted to BMIz. Univariate and bivariate twin models estimated genetic and environmental influences on LOC eating and BMIz. RESULTS: More girls (21%) than boys (9%, p < 0.001) reported LOC eating. The phenotypic correlation with BMIz was 0.03 in girls and 0.18 in boys. Due to the nonsignificant phenotypic correlation in girls, bivariate twin models were fit in boys only. Across all models, the best-fitting model included genetic and unique environmental effects. Genetic factors accounted for 0.51 (95% CI: 0.23, 0.73) of the variance of LOC eating in girls and 0.54 (0.18, 0.90) in boys. The genetic correlation between LOC eating and BMIz in boys was 0.45 (0.15, 0.75). DISCUSSION: Findings indicate moderate heritability of LOC eating in adolescence, while emphasizing the role of unique environmental factors. In boys, LOC eating and BMIz share a proportion of their genetic influences.

Determinants of bone mass accrual in transgender and gender diverse youth undergoing pubertal suppression therapy.

INTRODUCTION/BACKGROUND: Gender-affirming care for gender diverse and transgender (GDTG) youth includes puberty suppression with gonadotropin-releasing hormone agonists (GnRHa). Puberty is a critical period of bone mass accrual, and pubertal suppression may impact bone health. Previous studies have shown a decrease in areal bone mineral density (aBMD) Z-score while on puberty suppression. However, the rate of bone mass accrual and its determinants during GnRHa therapy are not known. METHODOLOGY: This is a retrospective chart review of GDTG youth with aBMD assessment within six months of starting GnRHa monotherapy at Cincinnati Children's Hospital Medical Center between 01/2011 and 12/2022. In individuals with follow-up aBMD assessment, we calculated their aBMD velocity and generated Z-scores using reference data from the Bone Mineral Density in Childhood Study. The determinants of baseline height-adjusted aBMD and aBMD velocity Z-scores were assessed with multiple linear regression models. RESULTS: Thirty-six participants (36% assigned female at birth (AFAB), mean age at first aBMD assessment 12 ± 1.1 years) had baseline height-adjusted aBMD Z-score of -0.053 ± 0.79. Among 16 participants with follow-up aBMD assessment, the mean aBMD velocity Z-score was -0.42 ± 1.13 (-0.27 ± 0.79 in AFAB vs -0.52 ± 1.32 in assigned male at birth, p = 0.965). Baseline aBMD Z-scores significantly correlated with age at the first aBMD assessment (adjusted R2 0.124, p = 0.02) with combined modeling including age at first aBMD assessment and BMI Z-score being most significant (adjusted R2 0.21, p = 0.008). Only BMI Z-scores were positively associated with the aBMD-velocity Z-scores (adjusted R2 0.255, p = 0.046). CONCLUSIONS: GDTG youth undergoing GnRHa therapy appeared to have below-average aBMD velocity Z-scores. A lower BMI Z-score was a determinant of lower baseline height-adjusted aBMD and aBMD velocity Z-scores. Building on previous studies, our study highlights aBMD velocity as a novel technique for bone health surveillance in GDTG youth.

Mid-upper arm circumference only protocol in Pakistan: missed opportunities for children suffering from severe acute malnutrition? A mixed-methods observational study.

OBJECTIVE: We investigated the missed treatment opportunities affecting programmes using mid-upper arm circumference (MUAC) as the sole anthropometric criterion for identification and monitoring of children suffering from severe acute malnutrition (SAM). DESIGN: Alongside MUAC, we assessed weight-for-height Z-score (WHZ) in children screened and treated according to the national MUAC only protocol in Pakistan. Besides, we collected parents' perceptions regarding the treatment received by their children through qualitative interviews. SETTING: Data were collected from October to December 2021 in Tando Allah Yar District, Sindh. SUBJECTS: All children screened in the health facilities (n 8818) and all those discharged as recovered (n 686), throughout the district, contributed to the study. All children screened in the community in the catchment areas of five selected health facilities also contributed (n 8459). Parents of forty-one children randomly selected from these same facilities participated in the interviews. RESULTS: Overall, 80·3 % of the SAM cases identified during community screening and 64·1 % of those identified in the health facilities presented a 'WHZ-only' diagnosis. These figures reached 93·9 % and 84·5 %, respectively, in children aged over 24 months. Among children treated for SAM and discharged as recovered, 25·3 % were still severely wasted according to WHZ. While parents positively appraised the treatment received by their children, they also recommended to extend eligibility to other malnourished children in their neighbourhood. CONCLUSION: In this context, using MUAC as the sole anthropometric criterion for treatment decisions (referral, admission and discharge) resulted in a large number of missed opportunities for children in need of timely and adequate care.

Assessment of aortic dilatation in Chinese children and adolescents with Turner syndrome: a single center experience.

BACKGROUND: Patients with Turner syndrome (TS) face an increased risk of developing aortic dilatation (AD), but diagnosing AD in children presents greater complexity compared to adults. This study aimed to investigate the application of various assessment indicators of AD in Chinese children and adolescents with TS. METHODS: This study included TS patients admitted to Shenzhen Children's Hospital from 2017 to 2022. Cardiovascular lesions were diagnosed by experienced radiologists. Patients without structural heart disease were divided into different body surface area groups, then the Chinese TS population Z-score (CHTSZ-score) of the ascending aorta was calculated and compared with other indicators such as aortic size index (ASI), ratio of the ascending to descending aortic diameter (A/D ratio), and TSZ-score (Quezada's method). RESULTS: A total of 115 TS patients were included, with an average age of 10.0 ± 3.7 years. The incidences of the three most serious cardiovascular complications were 9.6% (AD), 10.4% (coarctation of the aorta, CoA), and 7.0% (bicuspid aortic valve, BAV), respectively. The proportion of developing AD in TS patients aged ≥ 10 years was higher than that in those < 10 years old (16.6% vs. 1.8%, P = 0.009), and the proportion of patients with CoA or BAV who additionally exhibited AD was higher than those without these conditions (31.6% vs. 5.2%, P < 0.001). The ASI, A/D ratio, TSZ-score, and CHTSZ-score of the 11 patients with AD were 2.27 ± 0.40 cm/m2, 1.90 ± 0.37, 1.28 ± 1.08, and 3.07 ± 2.20, respectively. Among the AD patients, only 3 cases had a TSZ-score ≥ 2, and 2 cases had a TSZ-score ≥ 1. However, based on the assessment using the CHTSZ-score, 6 patients scored ≥ 2, and 5 patients scored ≥ 1. In contrast, the TSZ-score generally underestimated the aortic Z-scores in Chinese children with TS compared to the CHTSZ-score. CONCLUSIONS: The applicability of ASI and A/D ratio to children with TS is questionable, and racial differences can affect the assessment of TSZ-score in the Chinese population. Therefore, establishing the CHTSZ-score specifically tailored for Chinese children and adolescents is of paramount importance.

Newly Developed Sex-Specific Z Score Model for Coronary Artery Diameter in a Pediatric Population.

BACKGROUND: This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice. METHODS: This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit. RESULTS: Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula. CONCLUSION: A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.

Computed Tomography Measurement of the Aorta in Midaortic Syndrome in Children and Adolescents and Their Clinical Manifestations and Outcomes.

Midaortic syndrome (MAS) presents challenges in diagnosis due to the absence of well-defined diagnostic criteria in pediatric patients. This retrospective study aimed to aid in the diagnosis of MAS by employing computed tomography (CT) to measure the z-score of the aorta as well as to identify and understand its clinical features. CT images, echocardiography findings, and medical records of 17 patients diagnosed with MAS between 1997 and 2023 were reviewed, and z-scores were calculated. Aortic size on follow-up CT, blood pressure, and left ventricular function and hypertrophy at the last follow-up were analyzed, and possible prognostic factors were examined. Except for one patient, all individuals exhibited a z-score below - 2 at the level corresponding to stenosis. Left ventricular dysfunction occurred more frequently in patients aged < 5 years (p = 0.024). Patients with idiopathic MAS showed a better prognosis in terms of blood pressure and follow-up aortic size (p = 0.051 and 0.048, respectively). CT-measured aortic z-scores may be useful for the diagnosis and follow-up of MAS.

Impact of calorie intake and weight gain after Norwood procedure on the outcome of stage II palliation.

BACKGROUND: This study aimed to assess the impact of caloric intake and weight-for-age-Z-score after the Norwood procedure on the outcome of bidirectional cavopulmonary shunt. METHODS: A total of 153 neonates who underwent the Norwood procedure between 2012 and 2020 were surveyed. Postoperative daily caloric intake and weight-for-age-Z-score up to five months were calculated, and their impact on outcome after bidirectional cavopulmonary shunt was analysed. RESULTS: Median age and weight at the Norwood procedure were 9 days and 3.2 kg, respectively. Modified Blalock-Taussig shunt was used in 95 patients and right ventricle to pulmonary artery conduit in 58. Postoperatively, total caloric intake gradually increased, whereas weight-for-age-Z-score constantly decreased. Early and inter-stage mortality before stage II correlated with low caloric intake. Older age (p = 0.023) at Norwood, lower weight (p < 0.001) at Norwood, and longer intubation (p = 0.004) were correlated with low weight-for-age-Z-score (< -3.0) at 2 months of age. Patients with weight-for-age-Z-score < -3.0 at 2 months of age had lower survival after stage II compared to those with weight-for-age-Z-score of -3.0 or more (85.3 versus 92.9% at 3 years after stage II, p = 0.017). There was no difference between inter-stage weight gain and survival after bidirectional cavopulmonary shunt between the shunt types. CONCLUSION: Weight-for-age-Z-score decreased continuously throughout the first 5 months after the Norwood procedure. Age and weight at Norwood and intubation time were associated with weight gain. Inter-stage low weight gain (Z-score < -3) was a risk for survival after stage II.

The effect of Lactobacillus reuteri on pulmonary function test and growth of cystic fibrosis patients.

INTRODUCTION: Cystic fibrosis (CF) patients frequently experience gut microbiota dysbiosis. Probiotic supplementation is a potential therapeutic approach to modify gut microbiota and improve CF management through the gut-lung axis. The aim of this study was to investigate the effect of Lactobacillus reuteri supplementation on pulmonary function test, respiratory symptoms and growth in CF patients. METHODS: A randomized, placebo-controlled clinical trial was carried out on 40 children with CF aged from 6 to 20 years. Participants were designated to receive either L. reuteri or placebo daily for 4 months. Pulmonary function tests, weight, height and body mass index (BMI) z-scores were measured pre and post treatment. RESULTS: The median baseline BMI of the patients was 16.28 kg m-2. A significant change in the probiotic group's BMI z-score after the study period was observed (P = 0.034) but not for weight and height z-scores (P > 0.05). After treatment, Pseudomonas aeruginosa grew in sputum cultures of seven in the placebo and one patient in the intervention group (P = 0.03) while at baseline it grew in the sputum of four patients in each group. There was no significant difference in forced expiratory volume in the first second, forced expiratory flow at 25-75% or forced vital capacity change between the two groups after the treatment period (P > 0.05). Additionally, no significant differences were found in pulmonary exacerbations, hospitalization frequencies or COVID-19 infection between the two groups during the study (P > 0.05). CONCLUSION: The results suggest that L. reuteri supplementation may impact the growth of severely malnourished CF patients. Furthermore, it may be concluded that this strain might reduce P. aeruginosa in the sputum culture of CF patients. © 2024 Society of Chemical Industry.

[Effect of gestational weight gain on growth trajectory in children aged 0 to 3 years].

OBJECTIVE: To describe the growth trajectory of body mass index for age Z score(BAZ) in children aged 0 to 3 years and to explore the association between gestational weight gain and BAZ growth trajectory. METHODS: Based on a prospective cohort study, we recruited pregnant women in their early pregnancy into this study from 2013 to 2017 in Taicang of Jiangsu Province, tracked their weight changes until they gave birth, and calculated and evaluated their gestational weight gain(GWG) as appropriate, inadequate or excessive GWG based on Chinese GWG standard. Children's height/length and weight were measured at birth, 1, 3, 6, 8, 12, 18, 24, 30 and 36 months of age, and their BAZ scores were calculated. Group-based trajectory modeling(GBTM) was used for fitting BAZ trajectories. Multilevel Logistic regression was used to analyze the association between the level of GWG and BAZ growth trajectories. RESULTS: There were 1864 mother-child pairs in the study, and three groups of BAZ trajectories were fitted including slow growth trajectory(34.07%), appropriate growth trajectory(48.23%), and fast growth trajectory(17.70%). In univariate analysis, compared with children whose mothers had appropriate GWG, the children whose mothers had inadequate GWG were more likely in the group of slow growth trajectory(OR = 1.95, 95%CI 1.28-2.96), and the children whose mothers had excessive GWG were more likely in the group of fast growth trajectory(OR = 1.57, 95% CI 1.19-2.07). After adjusting for maternal pre-pregnancy body mass index(BMI) and parity, and the child's gender and birth weight, the children whose mothers gained in adequate GWG were more likely in the group of slow growth trajectory(OR = 1.84, 95%CI 1.19-2.84), while the association between excessive GWG and fast growth trajectory was not statistically significant(OR = 1.26, 95%CI 0.94-1.68). CONCLUSION: The BAZ trajectories of children aged 0-3 years can be categorized into slow, appropriate, and fast growth groups, and children's slow growth was associated with maternal inadequate GWG.

Predictive values of Mallampati score, tonsillar size, and BMI z-score in the presence and severity of obstructive sleep apnea in pediatric population.

Background/aim: Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder in children. Determination of risk factors for the development of OSA is essential for early diagnosis and treatment of the disease and decreases the risk of negative consequences. This study aimed to investigate the predictive values of Mallampati score, tonsillar size, and BMI z-score in the presence and severity of OSA in children. Materials and methods: This prospective cross-sectional study included 114 children with OSA symptoms. All children were assessed by BMI z-score, Mallampati score, and tonsillar size and underwent overnight polysomnography. They were consecutively selected and assigned to 4 groups as follows: Group 1 included normal-weight with a low Mallampati score; Group 2 involved normal-weight with a high Mallampati score; Group 3 included obese with a low Mallampati score; and Group 4 involved obese with a high Mallampati score. Results: Of the 114 included children, 58 were female and 56 were male, with a mean age of 13.1 ± 2.9 years. OSA frequency and apnea-hypopnea index were significantly higher in group 4 compared with other groups (p = 0.003 and p < 0.0001, respectively), whereas average and minimum spO2 were significantly lower (for both, p = 0.001). Mallampati score and BMI z-score were found to be significant for predicting OSA (odds ratio = 4.147, 95% CI: 1.440-11.944; p = 0.008 and odds ratio = 1.760, 95% CI: 1.039-2.980; p = 0.035, respectively). Among OSA patients, the Mallampati score, tonsillar size, and BMI z-score were found to be significant for predicting OSA severity (odds ratio = 4.520, 95% CI: 1.332-15.335, p = 0.015, odds ratio = 9.177, 95% CI: 2.513-33.514, p = 0.001, and odds ratio = 2.820, 95% CI: 1.444-5.508; p = 0.002, respectively). Conclusion: The coexistence of the Mallampati score and BMI z-score significantly increases the presence of OSA in children. Mallampati score, tonsillar size, and BMI z-score are promising parameters for predicting OSA severity.

Longitudinal Relationship Between Anemia and Statural Growth Impairment in Children and Adolescents With Nonglomerular CKD: Findings From the Chronic Kidney Disease in Children (CKiD) Study.

RATIONALE & OBJECTIVE: Anemia and statural growth impairment are both prevalent in children with nonglomerular chronic kidney disease (CKD) and are associated with poor quality of life and increased morbidity and mortality. However, to date no longitudinal studies have demonstrated a relationship between anemia and statural growth in this population. STUDY DESIGN: The CKD in Children (CKiD) study is a multicenter prospective cohort study with over 15 years of follow-up observation. SETTING & PARTICIPANTS: CKiD participants younger than 22 years with nonglomerular CKD who had not reached final adult height. EXPOSURE: Age-, sex-, and race-specific hemoglobin z score. OUTCOME: Age- and sex-specific height z score. ANALYTICAL APPROACH: The relationship between hemoglobin and height was quantified using (1) multivariable repeated measures paired person-visit analysis, and (2) multivariable repeated measures linear mixed model analysis. Both models were adjusted for age, sex, body mass index, estimated glomerular filtration rate, acidosis, and medication use. RESULTS: Overall, 67% of the 510 participants studied had declining hemoglobin z score trajectories over the follow-up period, which included 1,763 person-visits. Compared with average hemoglobin z scores of≥0, average hemoglobin z scores of less than -1.0 were independently associated with significant growth impairment at the subsequent study visit, with height z score decline ranging from 0.24 to 0.35. Importantly, in 50% of cases hemoglobin z scores of less than -1.0 corresponded to hemoglobin values higher than those used as cutoffs defining anemia in the KDIGO clinical practice guideline for anemia in CKD. When stratified by age, the magnitude of the association peaked in participants aged 9 years. In line with paired-visit analyses, our mixed model analysis demonstrated that in participants with baseline hemoglobin z score less than -1.0, a hemoglobin z score decline over the follow-up period was associated with a statistically significant concurrent decrease in height z score. LIMITATIONS: Limited ability to infer causality. CONCLUSIONS: Hemoglobin decline is associated with growth impairment over time in children with mild to moderate nonglomerular CKD, even before hemoglobin levels reach the cutoffs that are currently used to define anemia in this population.

Reference standards for follicular density in ovarian cortex from birth to sexual maturity.

RESEARCH QUESTION: Are age-normalized reference values for human ovarian cortical follicular density adequate for tissue quality control in fertility preservation? DESIGN: Published quantitative data on the number of follicles in samples without known ovarian pathology were converted into cortical densities to create reference values. Next, a sample cohort of 126 girls (age 1-24 years, mean ± SD 11 ± 6) with cancer, severe haematological disease or Turner syndrome were used to calculate Z-scores for cortical follicular density based on the reference values. RESULTS: No difference was observed between Z-scores in samples from untreated patients (0.3 ± 3.5, n = 30) and patients treated with (0.5 ± 2.9, n = 48) and without (0.1 ± 1.3, n = 6) alkylating chemotherapy. Z-scores were not correlated with increasing cumulative exposure to cytostatics. Nevertheless, Z-scores in young treated patients (0-2 years -2.1 ± 3.1, n = 10, P = 0.04) were significantly lower than Z-scores in older treated patients (11-19 years, 2 ± 1.9, n = 15). Samples from patients with Turner syndrome differed significantly from samples from untreated patients (-5.2 ± 5.1, n = 24, P = 0.003), and a Z-score of -1.7 was identified as a cut-off showing good diagnostic value for identification of patients with Turner syndrome with reduced ovarian reserve. When this cut-off was applied to other patients, analysis showed that those with indications for reduced ovarian reserve (n = 15) were significantly younger (5.9 ± 4.2 versus 10.7 ± 5.9 years, P = 0.004) and, when untreated, more often had non-malignant haematologic diseases compared with those with normal ovarian reserve (n = 24, 100% versus 19%, P = 0.009). CONCLUSION: Z-scores allow the estimation of genetic- and treatment-related effects on follicular density in cortical tissue from young patients stored for fertility preservation. Understanding the quality of cryopreserved tissue facilitates its use during patient counselling. More research is needed regarding the cytostatic effects found in this study.

Performance of serum neurofilament light chain in a wide spectrum of clinical courses of amyotrophic lateral sclerosis-a cross-sectional multicenter study.

BACKGROUND AND PURPOSE: The objective was to assess the performance of serum neurofilament light chain (sNfL) in amyotrophic lateral sclerosis (ALS) in a wide range of disease courses, in terms of progression, duration and tracheostomy invasive ventilation (TIV). METHODS: A prospective cross-sectional study at 12 ALS centers in Germany was performed. sNfL concentrations were age adjusted using sNfL Z scores expressing the number of standard deviations from the mean of a control reference database and correlated to ALS duration and ALS progression rate (ALS-PR), defined by the decline of the ALS Functional Rating Scale. RESULTS: In the total ALS cohort (n = 1378) the sNfL Z score was elevated (3.04; 2.46-3.43; 99.88th percentile). There was a strong correlation of sNfL Z score with ALS-PR (p < 0.001). In patients with long (5-10 years, n = 167) or very long ALS duration (>10 years, n = 94) the sNfL Z score was significantly lower compared to the typical ALS duration of <5 years (n = 1059) (p < 0.001). Furthermore, in patients with TIV, decreasing sNfL Z scores were found in correlation with TIV duration and ALS-PR (p = 0.002; p < 0.001). CONCLUSIONS: The finding of moderate sNfL elevation in patients with long ALS duration underlined the favorable prognosis of low sNfL. The strong correlation of sNfL Z score with ALS-PR strengthened its value as progression marker in clinical management and research. The lowering of sNfL in correlation with long TIV duration could reflect a reduction either in disease activity or in the neuroaxonal substrate of biomarker formation during the protracted course of ALS.