Statistical models for pediatric endocrinology

Background: Modelling references for biomarkers as reference curves enables calculation of patient z-scores that are adjusted for both gender and covariance with age during childhood.Aim: To establish biomarker reference curves using the ‘LMS’ method previously employed for conventional growth charts.Design, Setting and Participants: Cross-sectional study of healthy Norwegian girls (n=647) and boys (n=465) in ages 6 to 16 years were recruited in the Bergen Growth Study (2016). Blood samples were analyzed using state-of-the-art instruments.Results: Reference curves for several biomarkers were established in the ‘LMS’ framework and provided here for clinical implementation. Conclusion: The ‘LMS’ reference framework is already used to create conventional growth charts and may also be applied in clinical biochemistry.

Spirometric reference equations for Cameroonians aged 4 to 89 years derived using lambda, mu, sigma (LMS) method

Background Spirometric reference values are well known in several ethnic groups but the normative spirometric values of blacks living in Africa have been less studied. The purpose of this study is to establish normative spirometric equations from a representative population of Cameroonian children and adults and compare these equations with those developed by the Global Lung Initiative (GLI) and in Nigerians. Methods Spirometric data from healthy Cameroonians aged 4–89 years randomly collected between 2014 and 2018 were used to derive reference equations using generalized additive model for location (mu), shape (lambda) and scale (sigma). Results A total of 625 children and adolescents (290 males and 335 females) and 1152 adults (552 males and 600 females) were included in the study. The prediction equation for spirometric index was written as: M = Exp[a0 + a1*ln (Height) + a2*ln (Age) + Mspline, Mspline was age related spline contribution]. Applying the GLI standards for African Americans resulted in overall values greater than those found in our study for forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC). These values were very close in children and adolescents while the values obtained with the GLI equations for African Americans were significantly higher in adults. FEV1/FVC ratio in our study was similar for adult males but lower in adult females (88% vs 85%, difference = + 3.5%) when applying Nigerian standards. Conclusions FEV1 and FVC of the Cameroonian infant and adolescent population are very close to those of black Americans. However, FEV1 and FVC of Cameroonian adults are significantly lower than those of black American adults. These equations should allow a more suitable interpretation of spirometry in the Cameroonian population.

Establishment of Reference Intervals For Serum Liver Function Tests Among Healthy Elderly Population In Northeast China: A Retrospective Study

Background: Liver function changes with age, however, there are few studies that are specific for the elderly. This study is aimed to establish reference intervals (RIs) of serum liver function tests among healthy elderly population aged between 60-89 in northeast China.Methods: Subjects were colleted from laboratory information system (LIS) in the First Hospital of Jilin University. The following parameters were collected: aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), total protein (TP) albumin (ALB), total bilirubin (TBIL), and direct bilirubin (DBIL). Tukey method was used to eliminate outliers. The Harris and Boyd method and Mann-Whitney U-test were performed to evaluate significant differences between subgroups of sex and age. The lambda-mu-sigma (LMS) method was used to analyze the dynamic changes of analytes. RIs were established by the non-parametric method.Results: A total of 23597 healthy individuals, including 20048 subjects (18-59 years old) and 3549 subjects (60-89 years old) were enrolled in the study. AST, ALT, TP and ALB required no sex partition. Except for AST, ALP and TBIL, ALT, GGT, TP, ALB and DBIL required different levels of age partitions. Serum ALT and ALB levels decreased with age, ALB showed apparent decreases throughout the aging process. DBIL showed an increase trend over time. This study showed different results compared with RIs in other studies.Conclusions: The RIs for liver function tests among healthy elderly population were different from those of other young individuals. There were apparent sex or age differences in the RIs of liver function for the elderly. Therefore, it is necessary to establish sex- and age-specific RIs of serum liver function tests among elderly population.

FOUR-SITE SKINFOLDS THICKNESS PERCENTILES of SCHOOLCHILDREN and ADOLESCENTS in TURKEY

Objective: The primary purpose of this study was to establish Turkish smoothed centile charts and LMS tables for four-site skinfold thickness based on a population-based sample and secondary purpose was to elaborate a reference for the percentage of body fat. Design: A cross-sectional and descriptive study was conducted between January and May 2017. Triceps, biceps and subscapular, suprailiac skinfold thickness were measured using Holtain skinfold caliper. Age and gender specific percentile values were determined with the LMS method, and body fat percentage was calculated using the Westrate and Deurenberg equation. Setting: Afyonkarahisar province in Turkey. Participants: This study was conducted on 4565, 6-18 years old students. Results: The triceps, biceps, and subscapular skinfolds of the girls were higher than the boys. From the age of seven, the sum of four skinfold thicknesses of the girls was more than those of the boys. This difference became more evident after the age of 12. Although fat percentages of girls showed a fluctuating change, it decreased with the age in boys. Westrate and Deurenberg equation fat percentages of girls until adolescence were lower than boys, but increased after 12 years of age and exceeded that of boys. Conclusions: This study has provided sex and age specific reference values for skinfold thickness, and has shown that obesity in girls is higher than in boys in schoolchildren in Afyonkarahisar. This study has also shown that skinfold thickness measurements are a valuable tool for screening obesity in children.

Physical fitness percentiles of Polish children aged 4–7 years

The purpose of this study was to report sex- and age-specific physical fitness level in Polish children aged 4 to 7. 11.709 children participated in the study, including 5.684 girls and 6.025 boys aged 4 to 7 who attended kindergarten institutions throughout Poland. Physical fitness was assessed using four tests developed by Sekita including shuttle run 4 × 5 m with moving the block, standing long jump, throwing 1 kg medicine ball with two hands above the head and 20 m run. Percentile charts were developed separately for males and females using the LMS method. Boys showed higher physical fitness values than girls. In addition, an increase in the level of physical fitness was observed along with the age of the subjects. The developed reference values by age and sex in the field of physical fitness can be used for diagnostic purposes and assessing the level of physical fitness of preschool children. In addition, they can be helpful for healthcare professionals, parents and teachers to develop children’s motor activation programs and monitor their physical fitness.

Folate and Cobalamin Serum Levels in Healthy Children and Adolescents and Their Association with Age, Sex, BMI and Socioeconomic Status

This study proposes age- and sex-specific percentiles for serum cobalamin and folate, and analyzes the effects of sex, age, body mass index (BMI), and socioeconomic status (SES) on cobalamin and folate concentrations in healthy children and adolescents. In total, 4478 serum samples provided by healthy participants (2 months–18.0 years) in the LIFE (Leipzig Research Centre for Civilization Diseases) Child population-based cohort study between 2011 and 2015 were analyzed by electrochemiluminescence immunoassay (ECLIA). Continuous age-and sex-related percentiles (2.5th, 10th, 50th, 90th, 97.5th) were estimated, applying Cole’s LMS method. In both sexes, folate concentrations decreased continuously with age, whereas cobalamin concentration peaked between three and seven years of age and declined thereafter. Female sex was associated with higher concentrations of both vitamins in 13- to 18-year-olds and with higher folate levels in one- to five-year-olds. BMI was inversely correlated with concentrations of both vitamins, whilst SES positively affected folate but not cobalamin concentrations. To conclude, in the assessment of cobalamin and folate status, the age- and sex-dependent dynamic of the respective serum concentrations must be considered. While BMI is a determinant of both vitamin concentrations, SES is only associated with folate concentrations.

Application of Quantile Regression to Examine Changes in the Distribution of Stunting of Indian Children Aged 0-36 Months Using Four Rounds of NFHS Data.

Background: In India, it has been observed that the prevalence of stunting among under-five children decreased, but the prevalence is still alarmingly high. In previous studies, traditional (linear and logistic) regression analyses were used, and these analyses were limited to encapsulated cross-distribution variations. Our study's objective was to examine how the different determinants are heterogenous in various percentiles. Methods: This article examined the change in the stunting distribution of children and examined the relationships between the key covariate's trends and patterns in stunting among children aged <3 years over a period of 24 years. Four successive rounds of the National Family Health Survey data 1992-93, 1998-99, 2005-06, and 2015-16 were used for analysis. The final study included 206579 children aged <3 years (N= 106136 male, 100443 female). To explain and analyze differences in the stunting distribution, the lambda-mu-sigma (LMS) method was used. Trends in stunting distribution over time were analysed using separate sex-stratified quantile regression (QR). The selected socioeconomic, demographic and other predictors considered for this analysis. Results: The quantile regressions have clearly indicated that mothers who have higher than primary level education were beneficial to decrease child malnutrition at the lower end of the distribution. The age, birth order, mother's body-mass-index (BMI) and wealth, among others, were some more determining factors for HAZ. Results of selected quantile regression estimated at 5th, 10th, 25th, 50th, 75th, 90th, and 95th quantiles. The wealth index was a highly negative association with lower quantiles compared to upper quantiles in stunting However, in the age classification, as the age increases, there was a negative association in the upper quantiles of stunting. Small size at birth was having a negative association in all the quantiles of stunting. Conclusions: The outcome of various covariates working differently across the stunting distribution was suggested by quantile regression. The major discrepancies in different aspects were underlined by socioeconomic and demographic aspects of India. The heterogeneity of this effect was shown using quantile regression.

NEW REFERENCE PARAMETERS FOR BODY MASS INDEX IN CHILDREN AGED SIX TO TEN YEARS

ABSTRACT Objective: To determine new body mass index (BMI) reference values to classify the nutritional status of children aged six to ten years old from the city of Montes Claros (state of Minas Gerais), Southeast Brazil. Methods: The sample consisted of 3,863 individuals from both genders. Body mass and height were measured to determine the BMI. We adopted the Lambda, Mu, and Sigma (LMS) method to obtain the cut-off points. After that, each stratum curve was smoothed using quartic polynomials by gender. Average interpolation was used to determine the biannual distribution values. We calculated the 3rd, 85th, and 95th centiles to classify underweight, overweight, and obesity, respectively, according to gender and age. Results: After tabulating the LMS parameters at biannual intervals by gender, we plotted a graphic with seven centiles of BMI distribution and calculated the new BMI parameters for children aged 6-10 years old from the city of Montes Claros. The cut-off values for underweight, overweight, and obesity classification were, respectively, 17.5, 25 and 30 kg/m2. Conclusions: For the studied children, the use of traditional BMI references may result in the overestimation of underweight and underestimation of overweight and obesity. Studies should be carried out with periodic updates, respecting the characteristics of each location in order to use BMI reference values to classify the nutritional status of children and adolescents.

Birthweight by gestational age reference centile charts for Greek neonates

ABSTRACTObjectiveThe development of population based, sex-specific, birthweight for gestational age (GA) first-time reference centile charts for liveborn singletons in Greece.DesignSecondary analysis of national birth registry dataParticipantsData of birthweight by GA of all 633201 singleton live births in Greece between 2011 and 2017 were collected from the Hellenic Statistical Authority (ELSTAT).Main outcome measuresAfter excluding implausible birthweights, we estimated gender specific birthweight centiles for every gestational week from 22nd to 40th+ using the Lambda-Mu-Sigma (LMS) method via the GAMLSS package in R. Small (10th centile) and large-for GA (90th centile) cut-offs in certain gestational weeks were compared to previously published charts.ResultsMore than 90% of the 621043 neonates were born at term (>37 weeks of GA). The mean birthweight for boys and girls at 40+ weeks of GA were 3473 grams and 3327 grams respectively. Most neonates were born at 38 weeks of GA with a mean birth-weight of 3097 (97655 girls) and 3237 (104722 boys) grams. The proposed national centiles identified more or less deviant percentages of small and large for GA neonates in comparison to other (inter)national centiles.ConclusionsThe new centile charts provide important information on the contemporary distribution of birthweight for gestational age in Greece. They may assist physicians to classify high-risk neonates at birth based on national population data. Accurate identification of those in need of special care will help to prevent possible adverse sequelae in the perinatal period and beyond.

Age- and Sex-Specific Pediatric Reference Intervals of Serum Electrolytes in Jilin Province of China Using the A Priori Approach

Objectives The purpose of this study was to establish age- and sex-specific pediatric reference intervals of serum potassium (K), sodium (Na), chlorine (Cl), calcium (Ca), magnesium (Mg), and phosphorus (P) using a direct sampling technique. Methods In accordance with the a priori approach, healthy individuals (n = 6,466, aged 1 month to &lt;18 years) were enrolled from five regions in Jilin Province, China, and all analytes were performed in the center laboratory. Reference intervals were divided according to the regression tree and Harris and Boyd’s method, and then they were calculated by the nonparametric rank method. The dynamic changes of reference intervals were evaluated by the lambda-mu-sigma (LMS) method. Results Reference intervals of serum Na and Ca were divided into three age-specific partitions. The concentrations of K, Cl, and Mg remained stable with age. However, only dramatic sex-specific changes of P were shown in those 11 to less than 13 years old and 13 to less than 15 years old, with an earlier peak time in females than in males. The correlation between Na and Cl was the strongest among all serum electrolytes (r = 0.31). Conclusions Serum electrolyte reference intervals for children and adolescents were established by regression tree, z test, and the LMS method, which provide a more accurate interpretation for diagnosis and prognosis evaluation of clinical pediatric diseases.