Lower Z-scores Research Articles

Association of cord plasma metabolites with birth weight: results from metabolomic and lipidomic studies of discovery and validation cohorts.

Birth weight is a good predictor of fetal intrauterine growth and long-term health. Although several studies have evaluated the relationship between metabolites and birth weight, no prior study has comprehensively investigated the metabolomic and lipidomic and further validated and quantified meaningful metabolites. Firstly, a pseudotargeted metabolomics approach was applied to detect 2418 metabolites in 504 cord blood samples in the discovery set enrolled from the Wuhan Healthy Baby Cohort (HBC), China. Metabolome-wide association scan (MWAS) analysis and pathway enrichment were applied to discover metabolites and metabolic pathways that were significantly associated with birth weight for gestational age (BWGA) z-score. Logistic regression models were used to analyze the association of metabolites in the most significantly associated pathways with small for gestational age (SGA) and low birth weight (LBW). Subsequently, 350 cord blood samples in a validation cohort were subjected to targeted analysis to validate the metabolites screened from the discovery cohort. In the discovery set, 513 metabolites were significantly associated with BWGA z-score (PFDR <0.05), of which 298 KEGG-annotated metabolites were included in the pathway analysis. The primary bile acid biosynthesis pathway was the most relevant metabolic pathway associated with BWGA z-score in our study. Elevated cord plasma primary bile acids were associated with lower BWGA z-score and higher odds of SGA or LBW in the discovery and validation cohorts. In the validation set, a 2-fold increase in taurochenodeoxycholic acid (TCDCA) and taurocholic acid (TCA) was associated with 0.10 (95% CI: 0.00, 0.20) and 0.18 (95 %CI: 0.04, 0.31) decrease in BWGA z-score, respectively, after adjusting for covariates. In addition, a 2-fold increase in cord plasma TCDCA and TCA was associated with an adjusted odds ratio of 1.52 (1.00, 2.30) and 1.77 (1.05, 2.98) for SGA, respectively. The adjusted ORs for a 2-fold increase in TCDCA and TCA concentrations were 2.39 (95% CI 1.00, 5.71) and 3.21 (0.96, 10.74) for LBW, respectively. The results indicate a significant association between primary bile acids and lower BWGA z-score, as well as higher risk of SGA and LBW. Abnormalities of primary bile acid metabolism may play an important role in restricted fetal development. This article is protected by copyright. All rights reserved.

Disrupted hemodynamic response within dorsolateral prefrontal cortex during cognitive tasks among people with multiple sclerosis-related fatigue.

Mental fatigue is an early and enduring symptom in persons with autoimmune disease particularly multiple sclerosis (MS). Neuromodulation has emerged as a potential treatment although optimal cortical targets have yet to be determined. We aimed to examine cortical hemodynamic responses within bilateral dorsolateral prefrontal cortex (dlPFC) and frontopolar areas during single and dual cognitive tasks in persons with MS-related fatigue compared to matched controls. We recruited persons (15 MS and 12 age- and sex-matched controls) who did not have physical or cognitive impairment and were free from depressive symptoms. Functional near infrared spectroscopy (fNIRS) registered hemodynamic responses during the tasks. We calculated oxyhemoglobin peak, time-to-peak, coherence between channels (a potential marker of neurovascular coupling) and functional connectivity (z-score). In MS, dlPFC demonstrated disrupted hemodynamic coherence during both single and dual tasks, as evidenced by non-significant and negative correlations between fNIRS channels. In MS, reduced coherence occurred in left dorsolateral PFC during the single task but occurred bilaterally as the task became more challenging. Functional connectivity was lower during dual compared to single tasks in the right dorsolateral PFC in both groups. Lower z-score was related to greater feelings of fatigue. Peak and time-to-peak hemodynamic response did not differ between groups or tasks. Hemodynamic responses were inconsistent and disrupted in people with MS experiencing mental fatigue, which worsened as the task became more challenging. Our findings point to dlPFC, but not frontopolar areas, as a potential target for neuromodulation to treat cognitive fatigue.

Associations of long-term exposure to air pollution and noise with body composition in children and adults: Results from the LEAD general population study

BackgroundWhile long-term air pollution and noise exposure has been linked to increasing cardiometabolic disease risk, potential effects on body composition remains unclear. This study aimed to investigate the associations of long-term air pollution, noise and body composition. MethodsWe used repeated data from the LEAD (Lung, hEart, sociAl, boDy) study conducted in Vienna, Austria. Body mass index (BMI; kg/m2), fat mass index (FMI; z-score), and lean mass index (LMI; z-score) were measured using dual-energy x-ray absorptiometry at the first (t0; 2011-ongoing) and second (t1; 2017-ongoing) examinations. Annual particulate matter (PM10) and nitrogen dioxide (NO2) concentrations were estimated with the GRAMM/GRAL model (2015–2021). Day-evening-night (Lden) and night-time (Lnight) noise levels from transportation were modeled for 2017 following the European Union Directive 2002/49/EC. Exposures were assigned to residential addresses. We performed analyses separately in children/adolescents and adults, using linear mixed-effects models with random participant intercepts and linear regression models for cross-sectional and longitudinal associations, respectively. Models were adjusted for co-exposure, lifestyle and sociodemographics. ResultsA total of 19,202 observations (nt0 = 12,717, nt1 = 6,485) from participants aged 6–86 years (mean age at t0 = 41.0 years; 52.9 % female; mean PM10 = 21 µg/m3; mean follow-up time = 4.1 years) were analyzed. Among children and adolescents (age ≤ 18 years at first visit), higher PM10exposure was cross-sectionally associated with higher FMI z-scores (0.09 [95 % Confidence Interval (CI): 0.03, 0.16]) and lower LMI z-scores (−0.05 [95 % CI: −0.10, −0.002]) per 1.8 µg/m3. Adults showed similar trends in cross-sectional associations as children, though not reaching statistical significance. We observed no associations for noise exposures. Longitudinal analyses on body composition changes over time yielded positive associations for PM10, but not for other exposures. ConclusionAir pollution exposure, mainly PM10, was cross-sectionally and longitudinally associated with body composition in children/adolescents and adults. Railway/road-traffic noise exposures showed no associations in both cross-sectional and longitudinal analyses.

Exploring height outcomes with adjuvant aromatase inhibition in growth hormone-deficient male survivors of childhood cancer.

Aromatase inhibitors (AI) may improve height in short stature conditions; however, the effect in childhood cancer survivors (CCS) is unknown. We assessed final adult height (FAH) in CCS treated with AI and GH compared with those treated with GH alone. Retrospective cohort study of GH-deficient male CCS treated between 2007 and 2023. FAH was noted as the height at the fusion of growth plates or 18 years of age. Multivariable linear regression was used to examine treatment association with FAH, adjusting for other risk factors. Ninety-two patients were included; 70 were treated with GH and 22 with combination AI/GH. The mean age at GH initiation did not differ between groups. The mean age at AI initiation was 13.7±1.9 years. A greater proportion of patients in the AI/GH group were treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (p<.01). Multivariable linear regression demonstrated no significant treatment association with FAH Z-score (β=0.04, 95% CI: -0.9 to 0.9). History of spinal radiation (β=-0.93, 95% CI: -1.7 to -0.2), lower starting height Z-score (β=-0.8, 95% CI: -1.2 to -0.4), and greater difference between bone age and chronological age (β=-0.3, 95% CI: -0.5 to -0.07) were associated with lower FAH Z-score. Adjuvant AI was not associated with increased FAH in male CCS compared with GH monotherapy. Future work is needed to determine the optimal adjunctive treatment to maximize FAH for this population.

#1458 Adverse muscle composition predicts all-cause mortality in CKD

Abstract Background and Aims Sarcopenia is common in CKD and associates with morbidity and mortality. A rapid and standardized MRI (Magnetic Resonance Imaging) scan protocol allows an accurate muscle composition analysis by quantification of skeletal muscle volume and muscle fat infiltration (MFI). The combined observation of low muscle volume and high muscle fat infiltration, i.e. adverse muscle composition (AMC), is a prevalent muscle composition phenotype within CKD and associates to poor function, high prevalence of comorbidity, and an increased risk for coronary heart disease (CHD). It has also been shown that AMC is an independent predictor of all-cause mortality in patients with non-alcoholic fatty liver disease and in general population. In this study we aimed to investigate muscle composition as predictor of all-cause mortality within participants with CKD in the UK Biobank imaging study (UKB). Method This is a prospective study including UKB participants with CKD defined as having an eGFR cystatin C &amp;lt; 60 ml/min/1, 73 m2. A control group was created by matching each participant with CKD for sex, age, and BMI to four participants with normal eGFR. Cystatin C was analyzed based on blood samples at time of study enrolment 7-9 years prior to the MRI. Fat-tissue free thigh muscle volume and MFI were quantified using a rapid neck-to-knee water and fat separated MRI protocol and automated image analysis (AMRA® Researcher). For each participant, a personalized muscle volume z-score (sex- and body size-specific) was calculated and combined with MFI to divide the participants into four muscle composition phenotype groups; 1) normal muscle composition, 2) only low muscle volume, 3) only high MFI and 4) AMC, using previously published thresholds based on the whole UKB cohort. The thresholds were the 25th percentile (&amp;lt; -0.68 SD) for muscle volume z-score and the 75th percentile (men &amp;gt;7.69%; women &amp;gt;8.82%) for MFI. The mortality data were obtained through the UKB´s linkage to national death registries. All-cause mortality was investigated using Kaplan-Meier curves and Cox regression. Models within participants with CKD were crude and subsequently adjusted for sex, age, BMI, low hand grip strength (&amp;lt;16/27 kg for females/males), physical activity, smoking, alcohol, and previous diagnosis of cancer, prevalent CHD and type 2 diabetes, all assessed at the time of imaging. Results Conclusion AMC, determined by standardized MRI, was a strong predictor of all-cause mortality in CKD. The study results indicate that CKD patients with poor muscle health, identified as having both low muscle volume z-score and high MFI, have a significantly higher mortality risk. This vulnerable group would potentially benefit from targeted interventions and is also of specific interest when evaluating new treatments for CKD.

Relationship between urinary sodium excretion and bone mineral density in pediatrics: population-based study from KNHANES V 2010-2011.

Osteoporosis poses a growing public health challenge worldwide. While calcium and vitamin D may influence bone mineral density (BMD), the effect of sodium (Na) intake, particularly in pediatrics, remains unexplored. This study aimed to evaluate the relationship between urinary Na excretion and BMD in a Korean pediatric population. A total of 2,018 participants (1,084 males and 934 females) aged 10-18 years were included from the data obtained from Korea National Health and Nutrition Examination Survey V (2010-2011). Daily Na intake was about 4,560 mg and 3,600 mg in boys and girls, respectively. The mean intake of Na per day was positively correlated with the increment of urine Na/Cr ratio quartile (p<0.001). The BMD z-score [lumbar spine (LS), femur neck (FN), and whole body except head (WB)] in the group with high Na/Cr ratio (4th quartile, 4Q) was significantly less than in those with low Na/Cr ratio (1st quartile, 1Q) (p<0.001). Moreover, the LS (p=0.028), FN (p=0.002) and WB (p=0.056) in the 4Q group showed 2.0 times, 2.8 times, and 1.9 times greater risk of low BMD z-scores than in the 1Q group, even after adjusting for other confounding factors, such as age, sex, BMI, vitamin D, moderate activity, and household incomes. Our findings suggest a strong negative association between urine Na excretion and BMD among Korean children and adolescents. The results underscore the importance of public health interventions targeting Na intake. Further longitudinal studies are recommended toclarify the long-term effects of Na on bone health in younger populations.

Independent and joint effects of neighborhood-level environmental and socioeconomic exposures on body mass index in early childhood: The environmental influences on child health outcomes (ECHO) cohort

Past studies support the hypothesis that the prenatal period influences childhood growth. However, few studies explore the joint effects of exposures that occur simultaneously during pregnancy. To explore the feasibility of using mixtures methods with neighborhood-level environmental exposures, we assessed the effects of multiple prenatal exposures on body mass index (BMI) from birth to age 24 months. We used data from two cohorts: Healthy Start (n = 977) and Maternal and Developmental Risks from Environmental and Social Stressors (MADRES; n = 303). BMI was measured at delivery and 6, 12, and 24 months and standardized as z-scores. We included variables for air pollutants, built and natural environments, food access, and neighborhood socioeconomic status (SES). We used two complementary statistical approaches: single-exposure linear regression and quantile-based g-computation. Models were fit separately for each cohort and time point and were adjusted for relevant covariates. Single-exposure models identified negative associations between NO2 and distance to parks and positive associations between low neighborhood SES and BMI z-scores for Healthy Start participants; for MADRES participants, we observed negative associations between O3 and distance to parks and BMI z-scores. G-computations models produced comparable results for each cohort: higher exposures were generally associated with lower BMI, although results were not significant. Results from the g-computation models, which do not require a priori knowledge of the direction of associations, indicated that the direction of associations between mixture components and BMI varied by cohort and time point. Our study highlights challenges in assessing mixtures effects at the neighborhood level and in harmonizing exposure data across cohorts. For example, geospatial data of neighborhood-level exposures may not fully capture the qualities that might influence health behavior. Studies aiming to harmonize geospatial data from different geographical regions should consider contextual factors when operationalizing exposure variables.

The lifestyle for brain health index, the cluster of differentiation 33 (CD33) gene, and cognitive function among rural Chinese older adults: A population-based study

BackgroundWe sought to examine the associations of the Lifestyle for Brain Health (LIBRA) index with cognitive function among rural Chinese older adults and to explore the potential role of cluster of differentiation 33 gene (CD33) in the associations. MethodsThis population-based cross-sectional study included 4914 dementia-free participants (age ≥60 years; 56.43 % women) in the 2018 baseline examination of MIND-China. The LIBRA index was generated from 11 factors. We used a neuropsychological test battery to assess episodic memory, verbal fluency, attention, executive function, and global cognition. The CD33(rs3865444) polymorphism was detected using multiple-polymerase chain reaction amplification. Data were analyzed using the general linear regression models. ResultsA higher LIBRA index was associated with multivariable-adjusted β-coefficient (95 %CI) of -0.011(-0.020- -0.001) for global cognitive z-score, -0.020(-0.033- -0.006) for episodic memory, and -0.016(-0.029- -0.004) for verbal fluency. The CD33(rs3865444) was associated with a lower global cognitive z-score in the additive (CA vs. CC: β-coefficient=0.042; 95 %CI=0.008–0.077), the dominant (CA+AA vs. CC: 0.040; 0.007–0.073), and the over-dominant (CA vs. CC+AA: 0.043; 0.009–0.077) models. Similar results were obtained for verbal fluency and attention. The CD33 gene showed statistical interactions with LIBRA index on cognitive function (Pinteraction<0.05) such that a higher LIBRA index was significantly associated with lower z-scores of global cognition and attention only among CD33 CC carriers (P < 0.05). ConclusionsThis population-based study reveals for the first time that a higher LIBRA index is associated with worse cognitive performance in rural Chinese older adults and that CD33 gene could modify the association.

30-sit-to-stand power is a better tool than isometric knee extensor strength to detect motor impairment in people with haemophilic arthropathy.

Regular assessment of motor impairments is crucial in people with haemophilic arthropathy (PwHA). This study aimed to determine if there are differences in 30-secondssit-to-stand (30-STS) power and maximal voluntary isometric contraction (MVIC) of the knee extensors between PwHA and healthy control group (CG). The secondary aims were to investigate the correlation between 30-STS power and MVIC of knee extensors with clinical characteristics and to assess their effectiveness in identifying motor impairment in PwHA. A cross-sectional study was conducted by collecting data from PwHA (n=17) and a sedentary CG (n=15). MVIC (torque) and 30-STS power were normalised to body mass. Correlation analysis and simple linear regression adjusted for age were used to assess the association between tests and clinical variables. Using z-scores derived from the mean and standard deviation of the CG, we compared the MVIC and the 30-STS power in PwHA. PwHA showed lower MVIC and 30-STS power compared to CG (p<.001; large effect size d>.8). Lower 30-STS power was associated with greater joint impairment and greater fear of movement, whereas MVIC showed no association with clinical variables. 30-STS power showed a lower z-score compared to MVIC (p<.001). In addition, 30-STS power detected 47% of PwHA with motor impairment compared to 0% for MVIC (p=.002). Our results suggest that 30-STS power may be more effective than knee extensors MVIC in detecting motor impairment in PwHA. Consequently, lower limb skeletal muscle power, rather than maximum knee extensor strength, appears to be more affected in PwHA.

Coffee consumption might be associated with lower potential risk and severity of metabolic syndrome: national health and nutrition examination survey 2003-2018.

Metabolic syndrome (MetS) is a clinical syndrome characterized by multiple metabolic disorders and is a serious global health problem. The coffee effect, acting as one of the most prevalent beverages on metabolic syndrome, is debatable. We included patients from the National Health and Nutrition Examination Survey 2003-2018 and used a comprehensive evaluation called the MetS z-score to assess the severity of metabolic syndrome. The relationship between coffee, decaffeinated coffee, tea, and MetS z-scores was explored using a weighted linear regression. We also divided the participants into metabolic and non-metabolic syndrome groups according to the NCEP/ATP III criteria for the subgroup analysis. A total of 14,504 participants were included in this study. The results demonstrated that drinking more than three cups of coffee daily was significantly linked to lower MetS z-scores (p < 0.001). Daily coffee consumption was also associated with lower BMI (p = 0.02), systolic blood pressure (p < 0.001), Homeostatic Model Assessment for Insulin Resistance (p < 0.001), and triglycerides (p < 0.001), while it was positively correlated with HDL-C (p = 0.001). Participants who consumed more than three cups of coffee daily had a lower MetS z-score in the MetS (p < 0.001) and non-MetS (p = 0.04) groups. This research indicates that coffee consumption is linked to MetS severity. However, decaffeinated coffee and tea intake were unrelated to MetS severity.

Associations between prenatal metal and metalloid mixtures in teeth and reductions in childhood lung function

BackgroundMetal(oid)s have been cross-sectionally associated with lung function outcomes in childhood but there is limited data on their combined effects starting in utero. Child sex may further modify these effects. ObjectiveExamine associations between in utero and early life exposure to metals assessed via novel dentine biomarkers and childhood lung function and explore effect modification by child sex. MethodsAnalyses included 291 children enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a longitudinal birth cohort study in Mexico City. Weekly dentine levels of arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), manganese (Mn), nickel (Ni), and lead (Pb) were measured from 15 weeks pre-birth to 15 weeks post birth in deciduous children's teeth. Lung function was tested at ages 8–14 years and then modeled as age, height and sex adjusted z-scores. Associations were modeled using lagged weighted quantile sum (LWQS) regression to evaluate the potential for a time-varying mixture effect adjusting for maternal age and education at enrollment and exposure to environmental tobacco smoke in pregnancy. Models were also stratified by sex. ResultsWe identified a window of susceptibility at 12–15 weeks pre-birth in which the metal mixture was associated with lower FVC z-scores in children aged 8–14 years. Cd and Mn were the largest contributors to the mixture effect (70 %). There was also some evidence of effect modification by sex, in which the mean weights and weighted correlations over the identified window was more evident in males when compared to females. In the male stratum, Cd, Mn and additionally Pb also dominated the mixture association. ConclusionsPrenatal metal(oid) exposure was associated with lower lung function in childhood. These findings underscore the need to consider both mixtures and windows of susceptibility to fully elucidate effects of prenatal metal(oid) exposure on childhood lung function.

THE PREVALENCE AND RISK FACTORS FOR ARTERIAL HYPERTENSION IN CHILDREN WITH IDIOPATHIC NEPHROTIC SYNDROME

Objective: Arterial hypertension (AH) is claimed to be an uncommon finding in children with idiopathic nephrotic syndrome (INS). The study aimed to analyze blood pressure, prevalence, and risk factors of AH in children with INS. Design and method: In 153 children with INS (9.32±3.84 years, 100 boys), we evaluated systolic and diastolic blood pressure (mm Hg, Z-scores), age at onset of the disease, anthropometric data, response to steroids, results of kidney biopsy, number of INS relapses, and medications. Results: The mean age at disease onset was 4.39±2.38 years; 67 patients had steroid-sensitive nephrotic syndrome (SSNS), 12 frequently relapsing nephrotic syndrome (FRNS), 58 steroid-dependent nephrotic syndrome (SDNS), and 16 steroid-resistant nephrotic syndrome (SRNS). Kidney biopsy was performed in 26: 5 – minimal change disease, 11 – mesangial proliferation, 10 – focal and segmental glomerulosclerosis. AH at disease onset was found in 10 (6.5%) patients in the following 11 (7.2%) after corticosteroid initiation. The observation period was 4.93±3.80 years, and AH was found in 31 (20.3%) – in 3 (4.5%) patients with SSNS, 2 (16.7%) with FRNS, 20 (34.5%) with SDNS, and 6 (37.5%) with SRNS. Patients with AH had lower height Z-score (-0.46±1.20 vs. 0.18±1.15, p=0.006), higher BMI Z-score (1.15±1.10 vs. 0.41±1.09, p&lt;0.001), number of INS relapses (8.32±6.78 vs. 4.41±3.82, p&lt;0.001), and current prednisone dose (0.49±0.67 vs. 0.18±0.29 [mg/kg/24h], p&lt;0.001). Systolic blood pressure Z-score at the end of observation correlated with age (r=-0.192, p=0.017), BMI Z-score (r=0.368, p&lt;0.001), and present prednisone dose [mg/kg/24h] (r=0.186, p=0.021), diastolic blood pressure Z-score with BMI Z-score (r=0.231, p=0.004), and number of INS relapses (r=0.163, p=0.044). In Cox Proportional Hazard presence of SDNS and SRNS were the only predictors of AH (SDNS: HR=4.80, 95CI(1.30-17.75), SRNS: HR=4.77, 95CI(1.06-21.53)). Conclusions: 1. Approximately one-third of patients with SDNS and SRNS develop arterial hypertension in the course of the disease. 2. Steroid dependence and steroid resistance are the strongest predictors of AH in children with INS. Other determinants of blood pressure elevation in this group of patients are high BMI and a high number of relapses.

Living in a Neighborhood With Limited Access to Broadband Internet Is Associated With Adverse Pregnancy Outcomes [ID 2683563

INTRODUCTION: The internet is an essential tool for ensuring health care access and delivery. We aimed to estimate the association between living in an area with limited broadband internet access and specific adverse pregnancy outcomes. METHODS: We performed an electronic health record-based retrospective cohort study of pregnant people who delivered at a referral medical center between September 1, 2019, and June 1, 2022. Primary outcomes were preterm birth, low birth weight (less than 2,500 g) and birth weight z-score for gestational age. Neighborhood internet access was defined as the proportion of residents with internet access in the pregnant person’s census tract of residence, based on the 2020 American Community Survey estimate and determined by geocoding. We used multivariable logistic or linear regression analysis to estimate the independent effect of internet access and computed adjusted odds ratios (aOR) or mean differences with 95% CIs for a 5-unit increase in the proportion with internet access for a given census tract. RESULTS: Among 5,190 pregnant people included, 885 (17.1%) had a preterm birth, 728 (14.0%) delivered a low-birth weight neonate, and 515 (9.9%) had a small-for-gestational age neonate. After adjusting for relevant confounders, increasing internet access was associated with reduced odds of preterm birth (aOR 0.97; 95% CI, 0.93–1.00; P=.048), reduced odds of low birth weight (aOR 0.95; 95% CI, 0.91–0.98), and increasing birth weight z-score (Beta 0.02; 95% CI, 0.01–0.03). CONCLUSION: Living in neighborhoods with better broadband internet coverage was associated with reduced odds of preterm birth, decreased odds of delivering a low-birth weight neonate, and increasing birth weight.

Visual impairment and cognitive performance: A nationwide study of 1.4 million adolescents.

Previous research highlights the adverse effects of visual impairment (VI) on academic achievement in children, yet its impact on cognitive performance among adolescents and young adults remains under-studied. Therefore, this investigation aimed to analyse this association in a nationwide sample of Israeli adolescents. A retrospective population-based cross-sectional study was conducted among 1,410,616 Israeli-born adolescents aged 16-19 years, who were assessed before mandatory military service between 1993 and 2017. The definition of VI was based on best-corrected visual acuity (BCVA) measurements using a standard Snellen chart. Adolescents with BCVA worse than 6/9 in either or both eyes were classified as having unilateral or bilateral VI, respectively. Cognitive performance was measured using the General Intelligence Score (GIS), based on a validated four-domain test. Relationships were analysed using regression models yielding adjusted odds ratios (ORs) for low (<-1 standard deviation [SD]) and high (≥1 SD) cognitive Z-scores. Of 1,410,616 adolescents (56.1% men), 13,773 (1.0%) had unilateral and 3980 (0.3%) had bilateral VI. Unilateral VI was associated with adjusted ORs for low and high cognitive Z-scores of 1.24 (1.19-1.30) and 0.84 (0.80-0.89), respectively. ORs were accentuated for bilateral VI, reaching 1.62 (1.50-1.75) and 0.81 (0.74-0.90) for low and high cognitive Z-scores, respectively. Cognitive performance subscores mirrored these results, with the visual-spatial functioning subtest demonstrating the greatest effect size. These associations persisted in sub-analyses restricted to adolescents with amblyopia-related VI, mild VI and unimpaired health status. Visual impairment, including mild and unilateral cases, is associated with reduced cognitive performance scores assessed in late adolescence. Further research is required to gain a comprehensive understanding of the dynamics underlying this relationship.

Growth in children with nephrotic syndrome: a post hoc analysis of the NEPTUNE study.

Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression. Anthropometric measurements in children < 18years enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were collected. The longitudinal association of medication exposure and nephrotic syndrome characteristics with height z-score and growth velocity was determined using adjusted Generalized Estimating Equation regression and linear regression. A total of 318 children (57.2% males) with a baseline age of 7.64 ± 5.04years were analyzed. The cumulative steroid dose was 216.4 (IQR 61.5, 652.7) mg/kg (N = 233). Overall, height z-scores were not significantly different at the last follow-up compared to baseline (- 0.13 ± 1.21 vs. - 0.23 ± 1.71, p = 0.21). In models adjusted for age, sex, and eGFR, greater cumulative steroid exposure (β - 7.5 × 10-6, CI - 1.2 × 10-5, - 3 × 10-6, p = 0.001) and incident cases of NS (vs. prevalent) (β - 1.1, CI - 2.22, - 0.11, p = 0.03) were significantly associated with lower height z-scores over time. Rituximab exposure was associated with higher height z-scores (β 0.16, CI 0.04, 0.29, p = 0.01) over time. Steroid dose was associated with lower height z-score, while rituximab use was associated with higher height z-score.

Continuous epileptiform discharges are associated with worse neurodevelopmental findings in a congenital Zika syndrome prospective cohort

PurposeThis study aimed to identify continuous epileptiform discharges (CEDs) on electroencephalograms (EEG) and to determine their clinical significance in children with congenital Zika syndrome (CZS). MethodsThis prospective cohort study included 75 children diagnosed with CZS born from March 2015 and followed up until September 2018 (age up to 36 months). EEG was performed to detect CEDs up to 24 months old. Data on obstetric, demographic, and clinical signs; cranial computed tomography (CT); ophthalmology examination; anti-seizure medication; growth; and motor development were collected. Fisher's exact test was used to verify the associations between categorical variables, and the T- test was used to compare the mean z-scores of anthropometric measurements between the groups with and without CED. ResultsCEDs were identified in 41 (54.67 %) children. The mean age of CEDs identification was 12.24 ± 6.86 months. Bilateral CEDs were shown in 62.89 % of EEGs. CEDs were associated with severe congenital microcephaly, defined by z-score >3 standard deviation of head circumference (HC) below the mean for sex and age (p = 0.025), and worse outcomes, including first seizure before 6 months (p = 0.004), drug-resistant epilepsy (p < 0.001), chorioretinal scarring or mottling (p = 0.002), and severe CT findings (p = 0.002). The CED group had lower mean z-scores of HC up to 24 months of age. ConclusionThis is the first description of the prevalence and significance of CEDs that also remains during wakefulness in patients with CZS. New investigations may suggest that it is more appropriate to classify the EEG not as a CED, but as a periodic pattern. Anyway, CEDs may be a marker of neurological severity in children with CSZ.

Comparison of the performance of NIPT and NIPT-plus for fetal chromosomal aneuploidy and high Z-score increases the positive predictive value.

To evaluate non-invasive prenatal testing (NIPT) and expanded non-invasive prenatal testing (NIPT-plus) for detecting aneuploidies at different sequencing depths and assess Z-score accuracy in predicting trisomies 21, 18, 13, 45X, and 47XXX. Pregnancies with positive NIPT or NIPT-plus results detected at the prenatal diagnosis center of Nanfang Hospital were included in this retrospective study, between January 2017 and December 2022. Invasive prenatal diagnostic results were collected. Logistic regression analyses were used to study the relationship between Z-score and positive predictive value (PPV). Optimal cut-off values were obtained based on receiver operating characteristic analysis, and PPVs were calculated in different groups. We evaluated 1348 pregnant women with positive results, including 930 reported by NIPT and 418 reported by NIPT-plus. NIPT reported significantly more rare chromosomal aneuploidies (RCAs), and NIPT-plus had a significantly higher PPV for trisomy 21 (T21). Logistic regression analyses showed a significant association (P < 0.001) between Z-score and PPVs for T21 and trisomy 18 (T18). A linear relationship was observed between fetal fraction (FF) and Z-values in the true positive cases of T21 and T18.The high Z-score group had significantly higher PPVs than the low Z-score group for T21, T18, trisomy 13, and 47XXX, but not for 45X. The Z-score is helpful in assessing NIPT or NIPT-plus results. Therefore, we suggest including the Z-score and FF in the results. By combining the Z-score, FF, and maternal age, clinicians can interpret NIPT results more accurately and improve personal counsel to reduce patients' anxiety.

Do Paralympic athletes suffer from brittle bones? Prevalence and risk factors of low bone mineral density in Paralympic athletes

BackgroundBone health may be a concern in Paralympic athletes, given the presence of multiple risk factors predisposing these athletes to low bone mineral density (BMD). Objective: We aimed to assess the prevalence of low BMD among Paralympic athletes participating in various sport disciplines, and to identify potential risk factors for low BMD. MethodsSeventy Paralympic athletes, of whom 51 % were wheelchair-dependent, were included in this cross-sectional study. BMD of the whole-body, lumbar spine, total hip, and femoral neck were assessed by dual-energy x-ray absorptiometry. Comparisons between groups were conducted by one-way ANOVA, and regression analyses were conducted to identify potential risk factors for low BMD. ResultsThe prevalence of low BMD (Z-score < −1.0) was highest at femoral neck (34 %), followed by total hip (31 %), whole-body (21 %), and lumbar spine (18 %). Wheelchair-dependent athletes had significantly lower BMD Z-scores compared to the non-wheelchair-dependent athletes at whole-body level (−0.5 ± 1.4 vs 0.2 ± 1.3; P = 0.04), total hip (−1.1 ± 1.2 vs 0.0 ± 1.1; P < 0.01), and femoral neck (−1.0 ± 1.3 vs −0.1 ± 1.2; P < 0.01). At the lumbar spine, low BMD was completely absent in wheelchair basketball and tennis players. Regression analyses identified body mass, wheelchair dependence, and type of sport, as the main risk factors for low BMD. ConclusionsIn this cohort of Paralympic athletes, low BMD is mainly present at the hip, and to a lesser extent at the whole-body and lumbar spine. The most prominent risk factors for low BMD in Paralympic athletes are related to mechanical loading patterns, including wheelchair use, the type of sport, and body mass.

Predictors for pathological bone fractures in children undergoing liver transplantation: A retrospective cohort study.

Hepatic osteodystrophy refers to bone disorders associated with chronic liver disease, including children undergoing liver transplantation (LT). The aim of this study was to quantify the prevalence of pathological fractures (PF) in children before and after LT and to identify associated factors for their occurrence. Children aged 0-18 years who underwent LT from 1/2005 to 12/2020 were included in this retrospective study. Data on patient demographics, types and anatomical locations of fracture and biological workups were extracted. Variables were assessed at 3 time points: T - 1 at the moment of listing for LT; T0 at the moment of LT and T + 1 at 1-year post-LT. A total of 105 children (49 [47%] females) were included in this study. Median age at LT was 19 months (range 0-203). Twenty-two patients (21%) experienced 65 PF, 11 children before LT, 10 after LT, and 1 before and after LT. The following variables were observed as associated with PF: At T - 1, low weight and height z-scores, and delayed bone age; at T0, low weight and height z-scores, high total and conjugated bilirubin; at T + 1, persistent low height z-score. Patients in the PF-group were significantly more under calcium supplementation and/or nutritional support at T - 1, T0 and T + 1. More than one in five children needing LT sustain a PF before or after LT. Patients with low weight and height z-scores and delayed bone age are at increased risk for PF. Nutritional support remains important, even if to date it cannot fully counteract the risks of PF.

Reduced lung function during childhood in identical twins with discordant fetal growth: a cohort study

Fetal growth restriction (FGR) can negatively affect lung development, leading to increased respiratory morbidity and reduced lung function later in life. Studies regarding the impact of FGR on lung function in singletons are influenced by genetic, obstetric, and maternal factors. To overcome these confounding factors, we aim to investigate lung function in identical twins with selective FGR (sFGR). Lung function assessments were performed in identical twins with sFGR born in our centre between March 1, 2002, and December 31, 2017, aged between 5 and 17 years. sFGR was defined as birthweight discordance ≥20%. Outcome measures consisted of forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), and transfer factor for carbon monoxide (DLCO) and were compared between the smaller and larger twin. Thirty-nine twin pairs performed spirometry of sufficient quality. Median gestational age at birth was 34.3 (interquartile range (IQR) 32.1-36.0) weeks with median birthweights of 1500 (IQR 1160-1880) grams and 2178 (IQR 1675-2720) grams for the smaller and larger twin, respectively. Smaller twins had significantly lower z-scores for FEV1 (-0.94 versus-0.41, p=0.0015), FVC (-0.56 versus-0.06, p<0.0001) and DLCO (-0.50 versus 0.00, p<0.0001) compared to larger co-twins. Although being genetically identical, sFGR in identical twins is associated with a reduction in static and dynamic lung volume and a reduction in lung diffusion, even when taking the reduced lung volume into account. This indicates that adverse growth conditions in utero negatively affect lung development and function, potentially contributing to an increase in respiratory morbidities later in life. The Dutch Heart Foundation and The Bontius Foundation.