Anastrozole monotherapy further improves near-adult height after the initial combined treatment with leuprorelin and anastrozole in early-maturing girls with compromised growth prediction: results from the second phase of the GAIL study.

Background: The first phase of the GAIL study ("Girls treated with an Aromatase Inhibitor and Leuprorelin," ISRCTN11469487) has shown that the combination of anastrozole and leuprorelin for 24 months is safe and effective in improving the predicted adult height (PAH) in girls with early puberty and compromised growth prediction by +1.21 standard deviation score (SDS; +7.51 cm) compared to inhibition of puberty alone, +0.31 SDS (+1.92 cm). Objectives and hypotheses: In the second phase of the GAIL study, we assessed the adult height (AH)/near-adult height (NAH) at the end of the first phase and, in addition, the efficacy of anastrozole monotherapy thereafter in further improving NAH. Methods: We measured the AH (age 16.5 years)/NAH [bone age (BA), 15 years] of the 40 girls included, divided into two matched groups: group A (20 girls on anastrozole + leuprorelin) and group B (20 girls on leuprorelin alone). Group A was further randomized into two subgroups: A1 and A2. Group A1 (n = 10), after completion of the combined therapy, received anastrozole 1 mg/day as monotherapy until BA 14 years, with a 6-month follow-up. Group A2 (n = 10) and group B (n = 20), who received only the combined treatment and leuprorelin alone, respectively, were recalled for evaluation of AH/NAH. Results: AH or NAH exceeded the PAH at the completion of the 2-year initial phase of the GAIL study in all groups, but the results were statistically significant only in group A1: NAH-PAH group A1, +3.85 cm (+0.62 SDS, p = 0.01); group A2, +1.6 cm (+0.26 SDS, p = 0.26); and group B, +1.7 cm (+0.3 SDS, p = 0.08). The gain in group A1 was significantly greater than that in group A2 (p = 0.04) and in group B (p = 0.03). Anastrozole was determined to be safe even as monotherapy in Group A1. Conclusions: In early-maturing girls with compromised growth potential, the combined treatment with leuprorelin and anastrozole for 2 years or until the age of 11 years resulted in a total gain in height of +9.7 cm when continuing anastrozole monotherapy until the attainment of NAH, as opposed to +7.4 cm if they do not continue with the anastrozole monotherapy and +3.6 cm when treated with leuprorelin alone. Thus, the combined intervention ends at the shortest distance from the target height if continued with anastrozole monotherapy until BA 14 years.

Plasma-Induced Changes in the Metabolome Following Vistula Tart Cherry Consumption.

Evidence suggests that tart cherry (TC) supplementation has beneficial effects on health indices and recovery following strenuous exercise. However, little is known about the mechanisms and how TC might modulate the human metabolome. The aim of this study was to evaluate the influence of an acute high- and low-dose of Vistula TC supplementation on the metabolomic profile in humans. In a randomised, double-blind, placebo controlled, cross-over design, 12 healthy participants (nine male and three female; mean ± SD age, stature, and mass were 29 ± 7 years old, 1.75 ± 0.1 m, and 77.3 ± 10.5 kg, respectively) visited the laboratory on three separate occasions (high dose; HI, low dose; LO, or placebo), separated by at least seven days. After an overnight fast, a baseline venous blood sample was taken, followed by consumption of a standardised breakfast and dose conditions (HI, LO, or placebo). Subsequent blood draws were taken 1, 2, 3, 5, and 8 h post consumption. Following sample preparation, an untargeted metabolomics approach was adopted, and the extracts analysed by LCMS/MS. When all time points were collated, a principal component analysis showed a significant difference between the conditions (p < 0.05), such that the placebo trial had homogeneity, and HI showed greater heterogeneity. In a sub-group analysis, cyanidine-3-O-glucoside (C3G), cyanidine-3-O-rutinoside (C3R), and vanillic acid (VA) were detected in plasma and showed significant differences (p < 0.05) following acute consumption of Vistula TC, compared to the placebo group. These results provide evidence that phenolics are bioavailable in plasma and induce shifts in the metabolome following acute Vistula TC consumption. These data could be used to inform future intervention studies where changes in physiological outcomes could be influenced by metabolomic shifts following acute supplementation.

[Management of transition growth hormone deficiency]. / è¿‡æ¸¡æœŸç”Ÿé•¿æ¿€ç´ ç¼ºä¹ç—‡çš„ç®¡ç†.

With an increasing understanding of growth hormone deficiency, there has been a growing emphasis on the management of transition growth hormone deficiency (TGHD) in clinical practice. The inadequate diagnosis and treatment of TGHD have been a major clinical concern, leading to the development of relevant guidelines and consensus internationally. This article summarizes the evaluation, diagnosis, treatment, and clinical challenges of TGHD based on these guidelines, consensus, and existing clinical studies, aiming to optimize and further improve the clinical diagnosis, treatment, and management of TGHD.

Growth in height and its association with overweight and obesity in Mexican children: an evaluation based on a nationally representative sample (ENSANUT 2018).

The present study aimed to estimate the height growth curve for Mexican boys and girls based on their body mass index (BMI) status (normal and overweight/obese) and to develop a height Lambda, Mu, and Sigma (LMS) growth reference for Mexican children aged 2 to 18 years. Methods: Chronological age and height records (7,097 boys and 6,167 girls) were obtained from the Mexican National Survey of Health and Nutrition database. Height growth curves were fitted using the Preece-Baines 1 (PB1) model and the LMS method. Results: Age at peak height velocity (APHV) was 12.4 and 12.7 years for overweight-obese and normal-weight boys, respectively, and was 9.6 and 10.4 years for overweight-obese and normal-weight girls, respectively. Growth velocity was higher at the age of take-off (TO) in overweight-obese children than in normal-weight children (5.2 cm/year vs. 5 cm/year in boys and 6.1 cm/year vs. 5.6 cm/year in girls); nevertheless, the growth velocity at APHV was higher for normal-weight children than for overweight-obese children (7.4 cm/year vs. 6.6 cm/year in boys and 6.8 cm/year vs. 6.6 cm/year in girls, respectively). Distance curves developed in the present study and by the World Health Organization (WHO) using LMS showed similar values for L and S parameters and a higher M value compared with the WHO reference values. Conclusion: This study concluded that overweight-obese children had earlier APHV and lower PHV than normal-weight children. Furthermore, Mexican children and adolescents were shorter than the WHO growth reference by age and sex.

Race and geography impact validity of maximum allowable standing height equations for para-athletes.

World Athletics use maximum allowable standing height (MASH) equations for para-athletes with bilateral lower extremity amputations to estimate stature and limit prosthesis length since longer prostheses can provide running performance advantages. The equations were developed using a white Spanish population; however, validation for other races and geographical groups is limited. This study aimed to determine the validity of the MASH equations for Black and white Americans and whether bias errors between calculated and measured stature were similar between these populations. Sitting height, thigh length, upper arm length, forearm length, and arm span of 1899 male and 1127 female Black and white Americans from the Anthropometric Survey of US Army Personnel database were input into the 6 sex-specific MASH equations to enable comparisons of calculated and measured statures within and between Black and white groups. Two of 12 MASH equations validly calculated stature for Black Americans and 3 of 12 equations were valid for white Americans. Bias errors indicated greater underestimation or lesser overestimation of calculated statures in 10 equations for Black compared to white Americans and in 2 equations for white compared to Black Americans. This study illustrates that race and geography impact the validity of MASH equations.

Effect of pre-season and in-season training on anthropometric variables, somatotype, body composition and body proportion in elite basketball players.

The aims of the study were: 1) to evaluate the changes in anthropometric variables, body composition, somatotype and body proportions of elite basketball players throughout the pre-season period; 2) to evaluate the changes in anthropometric variables, body composition, somatotype and body proportions of elite basketball players throughout the in-season period; and 3) to observe if the age and position influenced the variables analyzed. A total of 17 players belonging to the men's ACB league team competing in the Euroleague (age = 23.42 ± 5.28 years-old) participated in the study. The players underwent an anthropometric measurement before and after the pre-season, as well as four evaluations throughout the in-season. Anthropometric indices, somatotype components according to Heath and Carter, and adiposity were calculated. The results show that during the pre-season, body mass, BMI, sum of 6 and 8 skinfolds, waist/hip ratio, adipose tissue (kg), adipose tissue percentage, and endomorphy decreased, while ectomorphy increased. However, no significant changes were found in the variables analyzed throughout the season; except for endomorphy, which increased along the in-season. Playing position and age did not have a significant influence on the changes in the anthropometric variables throughout the pre-season and the in-season. In conclusion, while changes in the anthropometric variables in the pre-season were observed, these remained the same during the in-season.

Association between body stature with ocular biometrics and refraction among Chinese preschoolers.

PURPOSE: To evaluate the association of body stature with ocular biometrics and refraction in preschool children. METHODS: A cross-sectional, school-based study was conducted in Shenzhen, China. Preschool children aged 3 to 6 from 10 randomly-selected kindergartens were recruited. Ocular biometric parameters, including axial length (AL), anterior chamber depth (ACD), vitreous chamber depth (VCD), corneal radius curvature (CR), axial length to corneal radius ratio (AL-to-CR ratio) and lens thickness (LT) were measured using non-contact partial-coherence laser interferometry. Cycloplegic refractions were obtained by a desktop autorefractor. Body height and weight were measured using standard procedures. The association between body stature and ocular biometrics were analyzed with univariable and multivariable regression model. RESULTS: A total of 373 preschoolers were included. AL, ACD, VCD, CR, and AL-to-CR ratio, were positively associated with height and weight (p < 0.05), whereas LT was negatively associated with height and weight (p < 0.01). No association was observed between stature and central cornea thickness and refraction. After adjusted for age and gender in a multivariable regression model, AL had positive associations with height (p < 0.01) and weight (p < 0.01). However, refraction had no significant association with stature parameters. CONCLUSION: Taller and heavier preschoolers had eyes with longer AL, deeper vitreous chamber, and flatter cornea. The significant associations between body stature and ocular biometric parameters reveal the driving influence of body development on the growth of eyeballs in preschoolers.

Biological Identification of Skulls in Indonesian and Thai Populations: Ancestry Estimation, Sex Determination, Stature Estimation, and Age Estimation / Identificación Biológica de Cráneos en Poblaciones de Indonesia y Tailandia: Estimación de Ascendencia, Determinación del Sexo, Estimación de Estatura y Estimación de Edad

SUMMARY: This review article will present an overview of biological profiles in forensic utilities. The biological profile of the skull in the existing literature can help to identify humans, especially if the condition of the victim found is a result of mutilation or a bomb explosion. When it comes to the precision of identifying skeletal remains, the human skull is frequently cited as being first in the estimation of age and ancestry and second in terms of sex and stature. It can be an alternative to assessing the following biological parameters: sex, age, stature, and ancestry. The implementation of biological profiles in the identification process is very important considering that some cases require the assistance of forensic anthropology. This review article shows the importance of the value of skulls. The method that can be applied is craniometry which can be used to determine sex, age, stature, and estimated ancestry. Different results will occur depending on the completeness of the skull. Therefore, estimation formulas have different accurate results. Discriminant function analysis has been performed on various measurement sets and its discriminant power has been validated by many researchers. Geometric morphometric analysis has become the main tool for shape analysis and many attempts have been made to use it in analyzing skulls. Several methods supported by technology have also been developed. It is hoped that the review article will show significant differences in results between studies in Thailand and Indonesia, even though they are in the same racial group.

Este artículo presenta una descripción general de los perfiles biológicos en las utilidades forenses. El perfil biológico del cráneo en la literatura existente puede ayudar a identificar a los humanos, especialmente si la condición en la que se encuentra la víctima es el resultado de una mutilación o la explosión de una bomba. Cuando se trata de la precisión en la identificación de restos óseos, el cráneo humano se cita con frecuencia como el primero en la estimación de edad y ascendencia y el segundo en términos de sexo y estatura. Puede ser una alternativa para evaluar los siguientes parámetros biológicos: sexo, edad, estatura y ascendencia. La implementación de perfiles biológicos en el proceso de identificación es importante considerando que algunos casos requieren la asistencia de la antropología forense. Este artículo de revisión muestra la importancia del valor de las cnezas óseas. El método que se puede aplicar es la craneometría para determinar el sexo, la edad, la estatura y la ascendencia estimada. Se pueden obtener diferentes resultados dependiendo de la integridad del cráneo. Por lo tanto, las fórmulas de estimación tienen resultados precisos diferentes. Se ha realizado un análisis de función discriminante en varios conjuntos de medidas y muchos investigadores han validado su poder discriminante. El análisis a través de la morfometría geométrica se ha convertido en la principal herramienta para el análisis de formas y se ha utilizado frecuentemente en el análisis de cráneos. También se han desarrollado varios métodos apoyados en la tecnología. Se espera que este trabajo muestre diferencias significativas en los resultados entre los estudios realizados en Tailandia e Indonesia, aunque pertenezcan al mismo grupo racial.

Changes in Height and Body Weight Within a Time Period of 35 Years in Males of the Same Age / Cambios en la Altura y el Peso Corporal en un Período de 35 Años en Hombres de la Misma Edad

SUMMARY: Height and body weight measurements are among the most important anthropometric variables when assessing a population's growth, development and body composition. This study aimed to evaluate the height and body weight variability of male entities aged 17-18 years within 35 years. This goal was realized by comparing the height and body weight of the population of the same gender and age in three different time studies. The descriptive statistical parameters and T-test for independent groups show systematic and significant differences in measured variables between three measurements in different timelines. Both in body height and body weight, from measurement to measurement, significant systematic and statistically significant differences (p<0.01) have been identified (1985: BH= 172.8cm, BW= 61.7kg; 2004: BH=176.8 cm, BW=66.9 kg; 2019: BH=178.5 cm, BW=72 kg). The results of this study prove that the change in the socio-economic status of a population over a period time of 35 years can significantly affect the growth and development of children/adolescents.

Las medidas de altura y peso corporal se encuentran entre las variables antropométricas más importantes a la hora de evaluar el crecimiento, el desarrollo y la composición corporal de una población. Este estudio tuvo como objetivo evaluar la variabilidad de la altura y el peso corporal de entidades masculinas de 17 a 18 años dentro de 35 años. Este objetivo se logró comparando la altura y el peso corporal de la población del mismo sexo y edad en tres estudios temporales diferentes. Los parámetros estadísticos descriptivos y la prueba T para grupos independientes muestran diferencias sistemáticas y significativas en las variables medidas entre tres mediciones en diferentes líneas de tiempo. Tanto en la altura como en el peso corporal, de medición en medición, se han identificado diferencias significativas sistemáticas y estadísticamente significativas (p<0,01) (1985: BH= 172,8 cm, BW= 61,7 kg; 2004: BH=176,8 cm, BW=66,9 kg; 2019: BH=178,5 cm, BW=72 kg). Los resultados de este estudio demuestran que el cambio en el estatus socioeconómico de una población durante un período de 35 años puede afectar significativamente el crecimiento y desarrollo de niños/ adolescentes.

[Quality of anthropometric data of children under 5 years in the Brazilian National Food and Nutrition Surveillance System, 2008-2020]. / Qualidade de dados antropométricos de crianças menores de 5 anos no Sistema de Vigilância Alimentar e Nutricional, 2008-2020.

The planning, monitoring, and evaluation of food and nutrition actions depend on reliable estimates based on adequate anthropometric data. The study aimed to analyze the quality of anthropometric data of children aged under 5 years in the Brazilian National Food and Nutrition Surveillance System (SISVAN) from 2008 to 2020. The sample comprised 23,453,620 children aged under 5 years. Initially, we evaluated the distribution of missing values and values outside the spectrum of the instrument, and calculated the digit preference index for weight and height. The nutritional indexes height for age (HAZ), weight for age (WAZ), and body mass index for age (BAZ) were calculated according to the World Health Organization 2006 child growth standards. Then, we identified the biologically implausible values (BIV) and calculated the standard deviation (SD) of the nutritional indexes. For each municipality, we calculated the mean and SD of HAZ and WAZ; and plotted the SD values as a function of the mean. In all Federative Units, the digit preference index reached a minimum value of 80 for height and 20 for weight. For the three nutritional indexes, there was a reduction in the frequency of BIV in the 2008-2020 period. Even after the exclusion of BIV, we identified high variability for the three nutritional indexes. The indicators evaluated showed low quality of measurement, especially in the North and Northeast regions. Our results indicate insufficient quality of anthropometric data in children aged under 5 years, and reinforce the need to invest in actions to improve the collection and recording of anthropometric information.

O planejamento, o monitoramento e a avaliação das ações de alimentação e nutrição dependem de estimativas confiáveis realizadas a partir de dados antropométricos de qualidade adequada. O objetivo deste estudo foi analisar a qualidade de dados antropométricos de crianças menores de 5 anos no Sistema de Vigilância Alimentar e Nutricional (SISVAN) no período de 2008 a 2020. A amostra compreendeu 23.453.620 crianças menores de 5 anos. Inicialmente, avaliamos a distribuição de valores faltantes e de valores fora do espectro do equipamento e calculamos o índice de preferência de dígito para peso e altura. Os índices nutricionais altura para idade (A-I), peso para idade (P-I) e índice de massa corporal para idade (IMC-I) foram calculados com a utilização do padrão de crescimento da Organização Mundial da Saúde, de 2006. Em seguida, sinalizamos os valores biologicamente implausíveis (VBI) e calculamos o desvio padrão (DP) dos índices nutricionais. Para cada município, calculamos a média e o DP de A-I e P-I e plotamos os valores de DP em função da média. Em todas as Unidades Federativas, o índice de preferência de dígito alcançou valor mínimo de 80 para altura e 20 para peso. Para os três índices nutricionais, houve redução da frequência de VBI no período de 2008 a 2020. Mesmo após a exclusão dos VBI, identificamos elevada variabilidade para os três índices nutricionais. Os indicadores avaliados demonstraram baixa qualidade da mensuração principalmente nas regiões Norte e Nordeste. Nossos resultados indicam qualidade insuficiente dos dados antropométricos em crianças menores de 5 anos e reforçam a necessidade de investimento em ações para o aprimoramento da coleta e do registro das informações antropométricas.

La planificación, monitoreo y evaluación de acciones de alimentación y nutrición dependen de estimaciones confiables realizadas a partir de datos antropométricos de calidad adecuada. El objetivo del estudio fue analizar la calidad de datos antropométricos de niños menores de 5 años en el Sistema de Vigilancia Alimentaria y Nutricional (SISVAN) entre los años 2008 y 2020. La muestra se compuso de 23.453.620 niños menores de 5 años. Al principio, evaluamos la distribución de valores faltantes y de valores fueras del espectro del equipo, y calculamos el índice de preferencia de dígito para peso y altura. Los índices nutricionales altura para edad (A-E), peso para edad (P-E) e índice de masa corporal para edad (IMC-E) se calcularon utilizando el patrón de crecimiento de la Organización Mundial de la Salud de 2006. Luego, indicamos los valores biológicamente inverosímiles (VBI) y calculamos la desviación estándar (DE) de los índices nutricionales. Para cada municipio, calculamos la media y la DE de A-E y P-E; y representamos los valores de DE en función de la media. En todas las Unidades Federativas, el índice de preferencia de dígito alcanzó el valor mínimo de 80 para altura y 20 para peso. Para los tres índices nutricionales, hubo una disminución de la frecuencia de VBI entre los años de 2008 y 2020. Incluso tras excluir los VBI, identificamos una alta variabilidad para los tres índices nutricionales. Los indicadores evaluados demostraron una baja calidad de medición, sobre todo en las regiones Norte y Nordeste. Nuestros resultados indican una calidad insuficiente de datos antropométricos en niños menores de 5 años y fortalecen la necesidad de inversión en acciones para mejorar la recolección y registro de las informaciones antropométricas.

Effect of treatment with growth hormone on body composition and metabolic profile of short children born small for gestational age.

OBJECTIVE: To assess the effect of recombinant growth hormone (rGH) on body composition and metabolic profile of prepubertal short children born small for gestational age (SGA) before and after 18 months of treatment. METHODS: It is a clinical, non-randomized, and paired study. Children born SGA, with birth weight and/or length <-2 standard deviations (SD) for gestational age and sex, prepubertal, born at full term, of both genders, with the indication for treatment with rGH were included. The intervention was performed with biosynthetic rGH at doses ranging from 0.03 to 0.05 mg/kg/day, administered subcutaneously, once a day at bedtime. Total lean mass (LM) and total fat mass (FM) were carried out using dual-energy X-ray absorptiometry (DXA), and the metabolic profile was assessed for insulin, glycemia, IGF-1 levels and lipid profile. RESULTS: Twelve patients (nine girls, 8.17±2.39 y) were evaluated; three patients dropped out of the study. There was an increase of LM adjusted for length (LMI) (p=0.008), LMI standard deviation score (SDS) adjusted for age and sex (p=0.007), and total LM (p<0.001). The percentage of body fat (BF%) and abdominal fat (AF) remained unaltered in relation to the beginning of treatment. Among the metabolic variables, blood glucose remained within normal levels, and there was a reduction in the number of participants with altered cholesterol (p=0.023). CONCLUSIONS: The effect of rGH treatment was higher on LM than in FM, with increased LM adjusted for length and standardized for age and sex. Glycemia remained within the normal limits, and there was a decreased number of children with total cholesterol above the recommended levels.

Identifying biologically implausible values in big longitudinal data: an example applied to child growth data from the Brazilian food and nutrition surveillance system.

BACKGROUND: Several strategies for identifying biologically implausible values in longitudinal anthropometric data have recently been proposed, but the suitability of these strategies for large population datasets needs to be better understood. This study evaluated the impact of removing population outliers and the additional value of identifying and removing longitudinal outliers on the trajectories of length/height and weight and on the prevalence of child growth indicators in a large longitudinal dataset of child growth data. METHODS: Length/height and weight measurements of children aged 0 to 59 months from the Brazilian Food and Nutrition Surveillance System were analyzed. Population outliers were identified using z-scores from the World Health Organization (WHO) growth charts. After identifying and removing population outliers, residuals from linear mixed-effects models were used to flag longitudinal outliers. The following cutoffs for residuals were tested to flag those: -3/+3, -4/+4, -5/+5, -6/+6. The selected child growth indicators included length/height-for-age z-scores and weight-for-age z-scores, classified according to the WHO charts. RESULTS: The dataset included 50,154,738 records from 10,775,496 children. Boys and girls had 5.74% and 5.31% of length/height and 5.19% and 4.74% of weight values flagged as population outliers, respectively. After removing those, the percentage of longitudinal outliers varied from 0.02% (<-6/>+6) to 1.47% (<-3/>+3) for length/height and from 0.07 to 1.44% for weight in boys. In girls, the percentage of longitudinal outliers varied from 0.01 to 1.50% for length/height and from 0.08 to 1.45% for weight. The initial removal of population outliers played the most substantial role in the growth trajectories as it was the first step in the cleaning process, while the additional removal of longitudinal outliers had lower influence on those, regardless of the cutoff adopted. The prevalence of the selected indicators were also affected by both population and longitudinal (to a lesser extent) outliers. CONCLUSIONS: Although both population and longitudinal outliers can detect biologically implausible values in child growth data, removing population outliers seemed more relevant in this large administrative dataset, especially in calculating summary statistics. However, both types of outliers need to be identified and removed for the proper evaluation of trajectories.

Variation in body size and weight status among Hindu and Muslim Indian males born in the 1890s through the 1950s.

Hindus and Muslims represent the two largest religions in India, and also differ in nutritional status, health-related habits and standard of living associated with economic disparities. In this context, the present study considered estimated secular changes in body size, proportions, and weight status among Hindu and Muslim Indian men. The data are from anthropological surveys in the 1970s which included measurements of height, weight and sitting height of 43,950 males 18-84 years (birth years 1891-1957). Leg length was estimated; the BMI and sitting height/height ratio were calculated. Heights of men 35 + years were adjusted for estimated height loss with age. Weight status was also classified relative to WHO criteria for the BMI. Anthropometric characteristics of the two groups were compared with MANCOVA with age and geographic region as covariates. Linear regression of height on year of birth was also used to estimate secular change in each group. Heights, weights, and BMIs tended to be, on average, greater among Muslim than Hindu men at most ages, while distributions by weight status between groups were negligible. Sitting height was greater among Muslim men but estimated leg length did not differ between groups; the sitting height/height ratio thus suggested proportionally shorter legs among Muslim men. Results of the regression analyses indicated negligible differences in secular change between groups across the total span of birth years but indicated a decline in adjusted heights of men in both groups born between 1891 through 1930s and little secular change among those born in the 1930s through 1957. The variation in heights, weights and BMIs between Muslim and Hindu men at most ages suggested variation in socio-economic status and dietary habits between the groups, whereas the negligible estimated secular changes in height between groups likely reflected economic, social, and nutritional conditions during the interval of British rule and the transition to independence.

Early life body size and puberty markers as predictors of breast cancer risk later in life: A neural network analysis.

BACKGROUND: The early life factors of birthweight, child weight, height, body mass index (BMI) and pubertal timing are associated with risks of breast cancer. However, the predictive value of these factors in relation to breast cancer is largely unknown. Therefore, using a machine learning approach, we examined whether birthweight, childhood weights, heights, BMIs, and pubertal timing individually and in combination were predictive of breast cancer. METHODS: We used information on birthweight, childhood height and weight, and pubertal timing assessed by the onset of the growth spurt (OGS) from 164,216 girls born 1930-1996 from the Copenhagen School Health Records Register. Of these, 10,002 women were diagnosed with breast cancer during 1977-2019 according to a nationwide breast cancer database. We developed a feed-forward neural network, which was trained and tested on early life body size measures individually and in various combinations. Evaluation metrics were examined to identify the best performing model. RESULTS: The highest area under the receiver operating curve (AUC) was achieved in a model that included birthweight, childhood heights, weights and age at OGS (AUC = 0.600). A model based on childhood heights and weights had a comparable AUC value (AUC = 0.598), whereas a model including only childhood heights had the lowest AUC value (AUC = 0.572). The sensitivity of the models ranged from 0.698 to 0.760 while the precision ranged from 0.071 to 0.076. CONCLUSION: We found that the best performing network was based on birthweight, childhood weights, heights and age at OGS as the input features. Nonetheless, this performance was only slightly better than the model including childhood heights and weights. Further, although the performance of our networks was relatively low, it was similar to those from previous studies including well-established risk factors. As such, our results suggest that childhood body size may add additional value to breast cancer prediction models.

Application of a Web-based Tool for Quantitative Bias Analysis: The Example of Misclassification Due to Self-reported Body Mass Index.

BACKGROUND: We describe the use of Apisensr, a web-based application that can be used to implement quantitative bias analysis for misclassification, selection bias, and unmeasured confounding. We apply Apisensr using an example of exposure misclassification bias due to use of self-reported body mass index (BMI) to define obesity status in an analysis of the relationship between obesity and diabetes. METHODS: We used publicly available data from the National Health and Nutrition Examination Survey. The analysis consisted of: (1) estimating bias parameter values (sensitivity, specificity, negative predictive value, and positive predictive value) for self-reported obesity by sex, age, and race-ethnicity compared to obesity defined by measured BMI, and (2) using Apisensr to adjust for exposure misclassification. RESULTS: The discrepancy between self-reported and measured obesity varied by demographic group (sensitivity range: 75%-89%; specificity range: 91%-99%). Using Apisensr for quantitative bias analysis, there was a clear pattern in the results: the relationship between obesity and diabetes was underestimated using self-report in all age, sex, and race-ethnicity categories compared to measured obesity. For example, in non-Hispanic White men aged 40-59 years, prevalence odds ratios for diabetes were 3.06 (95% confidence inerval = 1.78, 5.30) using self-reported BMI and 4.11 (95% confidence interval = 2.56, 6.75) after bias analysis adjusting for misclassification. CONCLUSION: Apisensr is an easy-to-use, web-based Shiny app designed to facilitate quantitative bias analysis. Our results also provide estimates of bias parameter values that can be used by other researchers interested in examining obesity defined by self-reported BMI.

Association of height, foot length, and pubertal development in children aged 3-18: a cross-sectional survey in China.

Objective: This study aimed to analyze the growth patterns of height and foot length (FL) among Chinese children aged 3-18 and examine their associations with puberty development. Methods: A cross-sectional survey was conducted in September 2022 in Beijing. Data were collected through questionnaires and on-site physical examinations. The growth patterns and velocity of height and FL in different age groups were described, and their associations with puberty development were analyzed. Results: From an age perspective, the peak FL growth occurred between 9 and 11 years (boys were 11 years and girls were 9 years), while the peak height growth occurred at 11 ~ 13 years for boys and 9 ~ 11 years for girls. Additionally, boys and girls reached 99.0% of their final FL at the ages of 14 and 13, respectively, while they reached 99.0% of their final height at the ages of 16 and 15, respectively. From the perspective of Tanner stage, the age of peak FL growth in boys coincided with the age of the G2 stage, while in girls it occurred slightly earlier than the mean age of the B2 stage. The peak height growth for both boys and girls occurred between Tanner stages 2 and 3. Conclusion: Boys and girls reach their peak FL growth at 11 and 9 years old, respectively, which were both 2 years earlier than their peak height growth. The peak FL growth occurred around the onset of puberty, while the peak height growth occurred between Tanner stages 2 and 3.

Prediction of body mass index and skeletal maturity for early menarche risk at menarche onset: a cross-sectional study of Chinese girls.

BACKGROUND: This study aimed to assess the predictive value of body mass index (BMI) and skeletal maturity for the occurrence of early menarche in Chinese girls. METHODS: A cross-sectional analysis was conducted on 785 girls aged 8.1-14.6 years who visited our hospital within 3 months of menarche onset. Early menarche was defined as menarche age (MA) <10 years. Skeletal maturity was classified based on the difference between bone age (BA) and chronological age (CA), termed BA-CA; advanced BA was defined as BA-CA>2 years. RESULTS: The average MA was 10.7 (SD: 1.1) years, with a prevalence of early menarche of 23.3%. BA exhibited relative stability compared with MA, with an average of 12.8 (SD: 0.5) years at menarche onset. At menarche onset, the average height, weight and BMI were 149.1 (SD: 5.1) cm, 43.3 (SD: 7.2) kg and 19.4 (SD: 2.8) kg/m², respectively. Logistic regression analyses indicated that every 1-year increment in BA-CA was independently associated with a 18.90-fold higher risk of early menarche (95% CI 11.77 to 30.32), respectively, and remained statistically significant even after adjusting for height or mid-parental height. Furthermore, the prediction of BA-CA for early menarche demonstrated a dose-dependent pattern across BMI categories, with the greatest risk observed in normal-weight girls, the lowest risk in obese girls and an intermediate risk in overweight girls at the same degree of BA advancement. CONCLUSIONS: Our findings provide evidence supporting the significant contributions of BMI and skeletal maturity in predicting early menarche among Chinese girls at menarche onset. Additionally, the results suggest a dose-dependent relationship between skeletal maturity and BMI categories, with normal-weight girls displaying a higher risk of early menarche compared to overweight and obese girls with the same degree of BA advancement.