Whole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height.

The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare ( < 0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal-regulatory, intergenic-regulatory and deep-intronic annotation. We observed 29 independent variants associated with height at P < 6 × 10 - 10 after conditioning on previously reported variants, with effect sizes ranging from -7cm to +4.7 cm. We also identified and replicated non-coding aggregate-based associations proximal to HMGA1 containing variants associated with a 5 cm taller height and of highly-conserved variants in MIR497HG on chromosome 17. We have developed an approach for identifying non-coding rare variants in regulatory regions with large effects from whole-genome sequencing data associated with complex traits.

On network deconvolution for undirected graphs.

Network deconvolution (ND) is a method to reconstruct a direct-effect network describing direct (or conditional) effects (or associations) between any two nodes from a given network depicting total (or marginal) effects (or associations). Its key idea is that, in a directed graph, a total effect can be decomposed into the sum of a direct and an indirect effects, with the latter further decomposed as the sum of various products of direct effects. This yields a simple closed-form solution for the direct-effect network, facilitating its important applications to distinguish direct and indirect effects. Despite its application to undirected graphs, it is not well known why the method works, leaving it with skepticism. We first clarify the implicit linear model assumption underlying ND, then derive a surprisingly simple result on the equivalence between ND and use of precision matrices, offering insightful justification and interpretation for the application of ND to undirected graphs. We also establish a formal result to characterize the effect of scaling a total-effect graph. Finally, leveraging large-scale genome-wide association study data, we show a novel application of ND to contrast marginal versus conditional genetic correlations between body height and risk of coronary artery disease; the results align with an inferred causal directed graph using ND. We conclude that ND is a promising approach with its easy and wide applicability to both directed and undirected graphs.

Anthropometric indices growth references (length, Weight and Head Circumferences) of children aged 0-24 months in North-East of Iran by GAMLSS.

BACKGROUND: Growth references play a crucial role in the screening, evaluation, and surveillance of children, aiding in the early identification of the requirement for diverse growth-promoting interventions. Variations in human growth across distinct ethnic cohorts arise from genetic disparities, lifestyle variances, nutritional diversity, and diverse social and environmental contexts. Consequently, the selection of growth references markedly influences the prevalence of developmental disorders and nutritional imbalances in children. The study aims to assess the growth percentile of children in the north-east of Iran and establish population-specific reference charts for length, weight, and head circumference spanning from birth to 24 months. METHODS: This cross-sectional population-based research conducted in the north-east of Iran, from 2016 to 2023. The Data extracted from the electronic health records of Mashhad University of Medical Sciences. All apparently healthy children aged from birth to 24 months who were measured at least once by health staff at the ages of birth,1,2,4,6,7,9,12,15,18,24 months were included. The target population of the study were 479,089 children (96.21%), encompassing 233,565 girls (48.75%) and 245,524 boys (51.25%). Gender-specific percentile curves for length, weight, and head circumference concerning age, as well as weight concerning length, were derived using the GAMLSS approach. RESULTS: From the anthropometric information of 479,089 children (245,524 boys and 233,565 girls), growth charts were constructed. In comparison to the standard WHO chart, Iranian neonates displayed lower weight across all percentiles during the first month after birth, exhibited decreased head circumference at the 3rd percentile, and boys showed reduced length across all percentiles. After this age, Iranian children demonstrated increased weight, length, and head circumference. CONCLUSIONS: This research introduces the inaugural large-scale endeavor for indigenous reference charts. Through the noted distinctions from the international reference, the utilization of this novel resource offers the potential to enhance the surveillance of children's growth within the area. Moreover, by accurately assessing growth anomalies such as underweight, stunting, and wasting, it expands the domain of impactful policies in this sphere. Simultaneously, it enables the exploration of the secular trend of children's growth in the forthcoming years.

The Effect of Height on Adverse Short-Term Outcomes After Lower-Extremity Bypass Surgery in Patients with Diabetes Mellitus.

BACKGROUND: We evaluated adverse short-term outcomes after open lower-extremity bypass surgery in patients with diabetes mellitus with a comparison performed based on patient height. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was analyzed to select patients with Current Procedural Terminology codes 35533, 35540, 35556, 35558, 35565, 35566, 35570, and 35571 and with the diagnosis of diabetes mellitus. This resulted in 83 patients 60 inches or less in height, 1,084 between 60 and 72 inches, and 211 patients 72 inches and taller. RESULTS: No differences were observed among groups with respect to the development of a superficial surgical site infection (9.6% versus 6.4% versus 5.7%; P = .458), deep incisional infection (1.2% versus 1.4% versus 2.8%; P = .289), sepsis (2.4% versus 2.0% versus 2.8%; P = .751), unplanned reoperation (19.3% versus 15.6% versus 21.8%; P = .071), or unplanned hospital readmission (19.3% versus 14.8% versus 17.1%; P = .573). A significant difference was observed among groups in the development of a wound disruption (4.8% versus 1.3% versus 4.7%; P = .001). A multivariate regression analysis was performed of the wound disruption outcome with the variables of age, sex, race, ethnicity, height, weight, current smoker, and open wound/wound infection. Race (P = .025) and weight (P = .003) were found to be independently associated with wound disruption, but height was not (P = .701). CONCLUSIONS: The results of this investigation demonstrate no significant differences in short-term adverse outcomes after lower-extremity bypass surgery based on patient height.

Associations of bioelectrical impedance and anthropometric variables among populations and within the full spectrum of malnutrition.

OBJECTIVES: The aim of this study was to evaluate body composition variability assessed by bioimpedance in relation to nutritional status assessed by anthropometry in children and adolescents living in countries characterized by contrasting nutritional conditions. METHODS: The sample was comprised of 8614 children (4245 males; 4369 females), aged 3 to 19 years, from Nepal (477 children), Uganda (488 children and adolescents), UK (297 children and adolescents) and US (7352 children and adolescents). Height-for-age (HAZ) and body mass index-for-age (BAZ) z-scores were calculated according to WHO growth references. Specific bioelectrical impedance vector analysis (BIVA) was used to evaluate body composition variability. In each population sample, the relationship of HAZ and BAZ with bioelectrical outcomes was analysed by confidence ellipses and cubic spline regression, controlling for sex and age. RESULTS: The participants from Uganda and Nepal were more affected by undernutrition, and those from the US and UK by obesity. In all groups, phase angle and specific vector length were weakly associated with HAZ, with null or opposite relationships in the different samples, whereas they were positively associated with BAZ. The stronger association was between vector length, indicative of the relative content of fat mass, and BAZ in the UK and US samples. Confidence ellipses showed that the relationships are more strongly related to phase angle in Nepalese and Ugandan samples. CONCLUSIONS: Bioelectrical values were more strongly associated with BAZ than HAZ values in all population samples. Variability was more related to markers of muscle mass in Ugandan and Nepalese samples and to indicators of fat mass in UK and US samples. Specific BIVA can give information on the variability of body composition in malnourished individuals.

Awareness-Raising Activities to Identify Children with Short Stature.

BACKGROUND: Although short stature is sometimes treatable in children, family members do not always realize that their children have short stature. To develop better educational materials for identifying short stature, we conducted a questionnaire survey on children with short stature. Using the results of the survey, we revised educational activities regarding short stature. METHODS: To assess the effectiveness of the revised activities, we examined changes in the numbers of consultations before and after the changes to the educational activities, the height of children examined after such changes, the test implementation rate, and the test results. RESULTS: After the start of direct promotion for school nursing staff in 2015, the number of outpatients with short stature who visited the hospital significantly increased (16.1/year before 2014 vs. 68.8/year after 2015; p = 0.02). The number of patients hospitalized for a growth hormone secretion stimulation test also significantly increased, from 9.3/year before 2014 to 47.0/year after 2015 (p = 0.02). However, 35% of families did not want to subject their child to a growth hormone stimulating test, even if their child was extremely short. CONCLUSIONS: Our revised educational activities for short stature among school nursing staff, school physicians, and nurses at health centers were more effective than conventional activities consisting of public relations magazines and lectures for the general public. It is important to provide proper explanations to enable a better understanding of hormone therapy.

Tanner's target height formula underestimates final adult height in Korean adolescents and young adults: reassessment of target height based on the Korean National Health and Nutrition Examination Survey 2010-2019.

OBJECTIVE: Estimating children's target height (TH) plays an important role in diagnosing, evaluating and treating many paediatric endocrinological diseases. However, in many countries, employing Tanner's formula to predict children's final adult height (FAH) is considered misleading. Therefore, this study aimed to re-evaluate the validity of Tanner's formula for predicting the TH of Korean adolescents and young adults and develop a new formula suitable for Korean children. DESIGN/SETTING: Data were derived from the Korean National Health and Nutrition Examination Survey 2010-2019. PATIENTS: A total of 2586 participants (1266 men, 1320 women) were included, excluding participants for whom Tanner's formula could not be calculated because of missing parental height data. MAIN OUTCOME MEASURES: Tanner-based TH was compared with the FAH. RESULTS: The difference between Tanner-based TH and FAH was 4.86±0.178 cm for men and 4.81±0.150 cm for women. Sex-specific univariable and multivariable analyses were conducted to determine variables influencing positive height gap (greater than estimated TH). Both men and women with higher education levels were more likely to exhibit a positive height gap. Those with a history of chronic illness were less likely to exhibit a positive height gap, particularly in women. Using a new formula derived using linear regression analysis, the sum of parental heights explained 27.6% and 30.6% of the variance in sons' and daughters' heights, respectively. CONCLUSIONS: Tanner's formula for calculating TH tended to underestimate FAH; hence, our new formula may offer a better alternative for estimating TH and evaluating growth in Korean children and adolescents.

Nonlinear relationship between the triglyceride-glucose index and alanine aminotransferase in children with short stature.

Metabolic dysfunction associated fatty liver disease (MAFLD) is a common cause of liver disease in children and adolescents. The relationship between insulin resistance (IR) and MAFLD in children with short stature remains largely unknown. The present study was to investigate the relationship between the triglyceride-glucose (TyG) index and alanine aminotransferase (ALT) levels in children with short stature. A total of 1754 children with short stature were enrolled. Anthropometric, biochemical and hormonal indexes were collected through physical measurement examinations and laboratory tests. A nonlinear association was found between the TyG index and ALT. The inflection point of the curve was at a TyG index of 8.24. In multivariate piecewise linear regression, only when the TyG index was greater than 8.24 was there a significant positive association between the TyG index and ALT (ß 5.75, 95% CI 3.30, 8.19; P < 0.001). However, when the TyG index was less than 8.24, there was no significant association between the TyG index and ALT (ß -0.57, 95% CI -1.84, 0.71; P = 0.382). This study demonstrated a nonlinear relationship between TyG index and ALT in children with short stature. This finding suggests that a high TyG index is associated with elevated ALT in children with short stature.

The influence of sex, age, and body height on the pulmonary vascular permeability index - a prospective observational study.

The pulmonary vascular permeability index (PVPI) is a quotient of the extravascular lung water (EVLW) and the pulmonary blood volume (PBV). In acute respiratory distress syndrome (ARDS), the alveolar-capillary membrane integrity is disrupted. The result is a disproportionate increase of EVLW compared to the PBV and, hence, an increase in PVPI. Thus, PVPI has repetitively been discussed to extend the definition of ARDS. Besides sex, the influence of other anthropometric variables on PVPI has not been studied so far. However, since it is known that EVLW depends on body height and sex, we hypothesize that PVPI depends on anthropometric variables as well. This prospective single-center observational study included 1533 TPTD measurements of 251 non-critically ill patients (50.6% men) undergoing elective neuro-, thoracic, or abdominal surgery at the Munich Clinic Bogenhausen of the Technical University of Munich. Multivariate regressions were used to measure the influence of sex, age, and body height on PVPI. In all patients, PVPI was significantly higher in women (P < 0.001), with 34.4% having a PVPI > 2 compared to 15.9% of men. Mean PVPI significantly decreased with height (P < 0.001) and age (P < 0.001). Multivariate regressions allowed the calculation of mean reference surfaces. The 95th percentile surface for PVPI was > 3 for small and young women and well above 2 for all but tall and elderly men. In patients who underwent (lung reduction) thoracic surgery, the PVPI before and after surgery did not differ significantly (P = 0.531), and post-surgical PVPI did not correlate with the amount of lung resected (P = 0.536). Hence, we conclude that PVPI may be independent of the extent of lung volume reduction. However, PVPI is heavily dependent on sex, age, and body height. Anthropometric variables thus have a significant impact on the likelihood of misclassified abnormal PVPI. This warrants further studies since an increased PVPI, e.g. in the context of an ARDS, may be overlooked if anthropometric variables are not considered. We suggest reference surfaces based on the 95th-percentile corrected for sex, age, and height as a novel approach to normalize PVPI.

The effect of benzylpenicillin prohylaxis after birth on length and weight of syphilis-exposed infants in eastern China.

BACKGROUND: We conducted this study to assess the impact of an intervention to interrupt mother-to-child transmission on the height and weight of syphilis-exposed infants after receiving penicillin prophylaxis after birth and to provide a scientific basis for further elimination of mother-to-child transmission. METHODS: We recruited 419 infants born to syphilis-infected mothers from 2015 to 2020 in Changzhou, and performed 1:1 matching to infants born to syphilis-free mothers during the same period. All infants were followed up to 18 months of age. We collected height and weight data and compared them. RESULTS: At 18 months of age, the height and weight of the syphilis-exposed infants were almost greater than the WHO reference standards. However, when compared with local unexposed infants, there were almost no differences. The boys born to mothers who received two courses of treatment had longer body lengths at 18 months of age than did those born to mothers who did not receive two courses of treatment, and the girls born to mothers who did not receive treatment had lower body weights at 3 months of age than did both treated groups. CONCLUSION: The growth trajectory of infants without congenital syphilis born to syphilis-infected mothers is virtually indistinguishable from that of the general local population. Syphilis-exposed newborns can receive preventive treatment as a public health intervention.

Defining childhood hypertension: is it too complicated? An evaluation of the potential impact of different approaches in an Australian paediatric population.

OBJECTIVES: Current American Academy of Pediatrics (AAP) and European Society of Hypertension (ESH) thresholds defining hypertension in children use blood pressure (BP) normalised to age, sex and height. However, scare data exists regarding the relative importance of these variables to accurately model the 95th quantile of BP. We hypothesised that height alone may fit the population data equally well compared to more complex definitions. We also compare the potential impact of various thresholds for defining hypertension in an Australian population. METHODS: Longitudinal data from the Raine Study were used, with 2248 participants contributing 7479 valid BP values across the 3/5/10/14/17-year study visits. BP was measured after 5 min rest, ≥3 times at each visit, using a Dinamap device. Quantile regression was used to predict the 95th percentile of BP, with nonlinear modelling of covariates through restricted cubic spline terms. RESULTS: At a single visit, 6-16% of young children exceeded the ESH threshold and 12-23% the AAP threshold. The transition to fixed thresholds (≥13 years AAP, ≥16 years ESH), increased the number of males (AAP only) and reduced the number of females considered hypertensive. A quantile regression model constructed with Raine Study data using height-only as the explanatory variable better predicted BP than the respective model using age-only (or a combination of the two). CONCLUSIONS: There may be large differences in the prevalence of hypertension according to AAP and ESH criteria, with a marked sex-discrepancy emerging from the point of fixed threshold application in adolescence. It may not be necessary to normalise BP by both age and height, the latter being a better predictor of childhood BP. Simpler methods may be preferable in clinical practice but require validation against clinical outcomes.

Establishing age- and sex-specific anthropometric growth references standards for South Punjab adolescents utilizing the LMS method: findings from the Pakistani population.

Background: The physical health of adolescents is crucial for the prosperity and sustainable development of a nation. Developing specific growth standards is essential for prioritizing the wellbeing of the youth of Pakistan. This study aimed to establish normative standards for height, weight, and body mass index (BMI) among 12- to 16-year-olds in South Punjab, facilitating accurate health assessments and tailored interventions. Method: This study utilized a cross-sectional design and stratified random sampling to select 2,970 adolescents (49.73% boys and 50.26% girls) aged 12-16 years from South Punjab, Pakistan. Anthropometric measurements, including height, weight, and BMI, were collected. The data were stratified by age and sex, and smoothed percentile curves were computed using the LMS method, which incorporates the L (γ-lambda), M (µ-mu), and S (δ-sigma) parameters. The results were compared to international references to provide a comprehensive analysis. Results: The results highlight sex-specific trends in anthropometric indicators among adolescents. Boys exhibited higher mean values in height (160.50 ± 11.50 cm), weight (45.02 ± 9.78 kg), and BMI (17.30 ± 2.41) than girls (158.57 ± 9.34 cm, 41.00 ± 7.89 kg, and 16.29 ± 2.82, respectively). Growth patterns indicate boys grow faster in height and weight between ages 12 and 14, whereas girls show slower annual increases. Comparative analysis with international standards reveals that boys' height and weight were generally lower than international medians (P50th), whereas girls' height was comparable or higher. BMI values for both sexes were lower than international norms, reflecting unique regional growth patterns. Conclusion: This research establishes updated age- and sex-specific normative reference standards for adolescents in South Punjab, Pakistan. The study revealed that Pakistani adolescent boys exhibit higher mean values in height, weight, and BMI than girls, with faster growth rates between ages 12 and 14. Compared to international standards, Pakistani adolescents show lower BMI values, highlighting unique regional growth patterns. These standards have practical applications in screening, monitoring, and health strategy planning, contributing to efforts to promote a healthier future for the population. Future studies are recommended to utilize these local growth references for health surveillance and treatment in the local population.

[Clinical characteristics and management status of Turner syndrome in 1 089 children].

Objective: To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China. Methods: As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed. Results: Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 µg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years. Conclusions: The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.

Should a single growth standard be used to judge the nutritional status of children under age 5 years globally? No.

Universal growth standards for under-five children, given the worldwide variation in healthy growth and several determinants of anthropometry, are imprecise measures of nutritional status, particularly when used cross-sectionally. In constructing the global-use WHO growth standard, linear growth differences between contributing sites and pooled mean were >0.2 SD in 37% of observations. Systematic reviews confirm even greater variability, notably amplified for weight-for-age and head-circumference-for-age metrics. Unsurprisingly, developed nations had higher, and LMICs lower, growth dimensions. Contextual growth references predict neonatal morbidities, pathological short stature, macrocephaly, cardiometabolic risk factors, and adult noncommunicable diseases better than the WHO standards. Child body composition also varies contextually, with greater adiposity despite comparable weights in South Asian populations. Thus, contextual references, though not the perfect solution, are better suited for everyday practice and nutrition policy. Growth standards should only be used as a screening for clinical judgments aided by precise biomarkers.

Higher peak height velocity in early maturing girls depends on insulin rather than fat mass or IGF-I.

OBJECTIVE: Age at pubertal onset has decreased over the recent decades. Early maturing girls have longer puberty duration, and higher peak height velocity (PHV) than late maturing girls. To what extent this is generated by increased insulin-like growth factor-I (IGF-I), fat mass, or fasting insulin levels is currently unknown. DESIGN, SETTING, PARTICIPANTS: A population-based study-part of the COPENHAGEN puberty study-longitudinal part. Eighty-one girls evaluated biannually for a median of 10 (2-15) visits for a total of 815 evaluations. METHODS: Pubertal staging, anthropometric measures, PHV, skin fold thickness (SFT), and IGF-I and fasting insulin levels were measured. RESULTS: Early maturing girls achieved similar final height compared to late maturing girls (166.1 vs 167.1 cm, P = .36). Early pubertal onset was associated with significantly greater PHV (8.7 vs 7.4 cm/year, P < .001) and a longer puberty duration (age at onset of breast development to age at PHV [1.8 vs 1.1 years, P < .001]) compared with late maturation. After correcting for age at pubertal onset, neither body mass index, SFT, nor IGF-I levels differed between early vs late maturing girls. By contrast, fasting insulin levels were significantly higher in early compared with late maturing girls 1.5, 2.0, and 3.0 years after pubertal onset (all P = .039). CONCLUSION: Growth velocity was higher and more prolonged in early compared with late maturing girls and associated with higher insulin levels. Thus, the higher insulin levels may compensate for the shorter total growth period by intensifying the pubertal growth period. CLINICAL TRIAL REGISTRATION NUMBER: NCT01411527.

MULT: An allometric body mass index (ABMI) reference to assess nutritional status of multiethnic children and adolescents.

OBJECTIVES: To develop an allometric body mass index (ABMI) reference that adjusts the weight in relation to height, taking into account the changes during development (MULT ABMI reference), and to compare it with international BMI references. METHODS: The MULT ABMI reference was constructed through the LMS method, calculated with 65 644 ABMI observations of 17 447 subjects aged 5-22 years, from the United Kingdom, Ethiopia, India, Peru, Vietnam, Portugal, and Brazil. The M, S, and L curves of the MULT ABMI reference were compared with the curves of the MULT, World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), International Obesity Task Force (IOTF), and Dutch Growth Study (DUTCH). RESULTS: The greater differences in the M curve between MULT ABMI and WHO, CDC, IOTF, DUTCH, and MULT BMI references were around puberty (138 to 150 months for boys; 114 to 132 for girls). MULT ABMI presented S values similar to IOTF and DUTCH BMI references for boys 60 to 114 months and then became higher, approaching the MULT BMI S values from 198 to 240 months. For girls the MULT ABMI S values were close to the IOTF, CDC, and DUTCH from 60 to 110 months, and then became higher, approaching the MULT BMI S values until 240 months. CONCLUSION: MULT ABMI presented an advantage in comparison to the existing BMI references because it takes into account the growth changes during puberty and is a new option to assess the nutritional status of multiethnic populations.

Mendelian randomization analysis reveals causal association of anthropometric measures on sepsis risk and mortality.

The objective of this study was to explore the potential causalities of fat mass, nonfat mass and height (henceforth, 'anthropometric measures') with sepsis risk and mortality. We conducted the Mendelian randomization (MR) investigation using genome-wide association study (GWAS) summary statistics of anthropometric measures, sepsis, and sepsis mortality. The GWAS summary data from the UK Biobank was used. Firstly, MR analysis was performed to estimate the causal effect of anthropometric measures on the risk of sepsis. The inverse-variance weighted (IVW) method was utilized as the primary analytical approach, together with weighted median-based method. Cochrane's Q test and MR-Egger intercept test were performed to assess heterogeneity and pleiotropy, respectively. Finally, we performed a series of sensitivity analyses to enhance the precision and veracity of our findings. The IVW method showed that genetically predicted weight-related measures were suggestively linked to an increased risk of sepsis. However, height displayed no causal association with sepsis risk and mortality. Furthermore, weight-related measures also displayed significant MR association with the sepsis mortality, except body nonfat mass and right leg nonfat mass. However, MVMR analysis indicated the observed effects for weight-related measures in the univariable MR analyses are more likely a bias caused by the interrelationship between anthropometric measures. According to the MR-Egger intercept assessment, our MR examination was not influenced by horizontal pleiotropy (all p>0.05). Moreover, the reliability of the estimated causal association was confirmed by the sensitivity analyses. In conclusion, these findings provided vital new knowledge on the role of anthropometric-related measures in the sepsis etiology.

Body roundness index and the risk of hypertension: a prospective cohort study in Southwest China.

BACKGROUND: Body roundness index (BRI) is an anthropometric measure related to obesity, combining waist circumference (WC) and height to more accurately reflect body fat. This study aims to investigate the relationship between BRI and the risk of hypertension using data from a prospective cohort study in Southwest China. METHODS: Data for the study were derived from Guizhou Population Health Cohort Study (GPHCS), established in 2010. A total of 9,280 participants (aged 18 to 95 years, mean 41.53 ± 14.15 years) from 48 townships across 12 districts/counties were surveyed at baseline through multistage stratified random cluster sampling. Cox proportional risk models were employed to analyze the association between BRI and the risk of hypertension, estimating hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for confounding factors. The relationship between BRI and the onset time of hypertension was analyzed using the time failure acceleration model. RESULTS: Over a median follow-up period of 6.64 years, 1,157 participants were diagnosed with hypertension. After adjusting for confounding variables, each unit increase in BRI was associated with a 17% increase in hypertension risk (HR = 1.17, 95% CI: 1.11, 1.24, P for trend < 0.001). Compared to participants in the first quartile (Q1) of BRI, the risk of hypertension for those in the third quartile (Q3) and fourth quartile (Q4) was 1.31 (95% CI: 1.10, 1.56) and 1.53 (95% CI: 1.28, 1.84), respectively. Each unit increase in BRI advanced the onset of hypertension by 0.26 years (95% CI: 0.16, 0.35). CONCLUSION: This study indicates that BRI has a positive association with hypertension and can accelerate the onset of hypertension in the Chinese population. It is suggested that reducing BRI by controlling abdominal fat may be one of the effective measure to prevent hypertension.

L-DOPA Test in the Diagnosis of Childhood Short Stature: Evaluation of Growth Hormone Peaks Over Time.

INTRODUCTION: In childhood, growth hormone (GH) deficiency (GHD) diagnosis is based on auxological assessment and biochemical provocative tests, whose reliability remains disputed. Recently, several papers have been published on standardising the duration of some tests. The aim of our study was to analyse the possible length reduction of the L-DOPA provocative test. METHODS: We retrospectively investigated the response of GH to L-DOPA in 256 children, analysing 267 tests (some patients were retested over time for the persistence of severe auxopathy). We studied the same data considering GH peak threshold both at 8 ng/mL (Italian GHD cut-off) and at 10 ng/mL (international cut-off). Based on stimulation tests, patients were divided into two groups: GHD and no-GHD short children. We described the results in the whole population and then clustering for gender and pubertal stage. We termed as index the test stopped at 90 min. RESULTS: The GH peak after L-DOPA mostly occurred at 60 min. The sensitivity of the index test was the highest, while the specificity was slightly higher using the 8 ng/mL threshold (specificity = 0.68; 95% CI 0.60-0.76) then using the 10 ng/mL threshold (specificity = 0.56; 95% CI 0.47-0.65) at 90 min. The two ROC curves showed moderate performance of the test at 90 min. While the negative predictive value was 100% in both tests, the positive predictive value was slightly better with 10 ng/mL cut-off. Considering the two groups established by GHD definition and placing a GH threshold at 10 ng/mL, stopping L-DOPA test time at 90 min would have changed the test result and subsequentially patient's classification in 3/267 of the analysed tests (1.1%), while with the Italian GH threshold value at 8 ng/mL in 7/267 of the tests (2.6%). CONCLUSIONS: Our research shows that omitting 120-min time reduces L-DOPA test specificity, especially with GHD cut-off at 10 ng/mL.

Multi-scaling allometry in human development, mammalian morphology, and tree growth.

Various animal and plant species exhibit allometric relationships among their respective traits, wherein one trait undergoes expansion as a power-law function of another due to constraints acting on growth processes. For instance, the acknowledged consensus posits that tree height scales with the two-thirds power of stem diameter. In the context of human development, it is posited that body weight scales with the second power of height. This prevalent allometric relationship derives its nomenclature from fitting two variables linearly within a logarithmic framework, thus giving rise to the term "power-law relationship." Here, we challenge the conventional assumption that a singular power-law equation adequately encapsulates the allometric relationship between any two traits. We strategically leverage quantile regression analysis to demonstrate that the scaling exponent characterizing this power-law relationship is contingent upon the centile within these traits' distributions. This observation fundamentally underscores the proposition that individuals occupying disparate segments of the distribution may employ distinct growth strategies, as indicated by distinct power-law exponents. We introduce the innovative concept of "multi-scale allometry" to encapsulate this newfound insight. Through a comprehensive reevaluation of (i) the height-weight relationship within a cohort comprising 7, 863, 520 Japanese children aged 5-17 years for which the age, sex, height, and weight were recorded as part of a national study, (ii) the stem-diameter-height and crown-radius-height relationships within an expansive sample of 498, 838 georeferenced and taxonomically standardized records of individual trees spanning diverse geographical locations, and (iii) the brain-size-body-size relationship within an extensive dataset encompassing 1, 552 mammalian species, we resolutely substantiate the viability of multi-scale allometric analysis. This empirical substantiation advocates a paradigm shift from uni-scaling to multi-scaling allometric modeling, thereby affording greater prominence to the inherent growth processes that underlie the morphological diversity evident throughout the living world.