Multiple Component Analysis of Plasma Growth Hormone in Children with Standard and Short Stature

Growth hormone (GH) concentrations (in ng/ml) were determined by radioimmunoassay, in plasma obtained at about 3-hr intervals during a 24-hr sampling span, from 42 boys and 12 girls of short stature (2-4 standard deviations below their peer group mean), and 13 boys and 9 girls of standard stature. Subjects had 11.20 0.37 years of age at the time of study, and were living on a diurnal waking (∼07:30 to ∼22:30), nocturnal resting routine during sampling. Analysis of these data by single and population-mean cosinor methods as well as by analysis of variance revealed circadian and ultradian prominent components characterizing most groups. Accordingly, a multiple component analysis was undertaken for data of each group separately, as well as for all subjects. A comparison of circadian parameters indicates similar characteristics between short and standard children, whether one compares boys [P=0.674, 0.371 and 0.749 for comparison of rhythm adjusted means (M), amplitudes (A) and acrophases (), respectively], girls (P=0.993,0.914 and 0.397), or all children (P=0.859,0.712 and 0.865). Differences are found, however, in circasemidian characteristics as well as in the prominent 8-hr ultradian component documented for the short but not for the standard children. These ultradian components should be taken into consideration in the design and later evaluation of a time-specified treatment of children of short stature.     

Circadian characteristics of plasma cortisol in children with standard and short stature

Cortisol (CT) concentrations (in micrograms/dl) were determined by radioimmunoassay in plasma obtained at about 3-hr intervals during a 24-hr sampling span from 42 boys and 13 girls of short stature (2-4 standard deviations below their peer group mean), and from a reference group of 11 boys and 10 girls with standard stature, before any treatment were administered to the former. Subjects were 11.20 +/- 0.37 years of age at the time of study, and were living on a diurnal waking (approximately 07:30 to approximately 22:30), nocturnal resting routine during sampling, consuming the usual hospital diet. Circadian rhythm parameters were computed separately for each group by the single and population-mean cosinor fits of a 24-hr cosine curve. A comparison of circadian parameters indicates a statistically significant difference in acrophase (phi; P = 0.033) between short and standard children, as well as added differences in rhythm-adjusted mean (M; P = 0.011) and phi (P = 0.035) between boys and girls of short stature. These differences, as well as any other added information from relevant marker rhythms, should be taken into account for the time-specification of therapy before treatment starts in children of short stature.     

Orcadian Variation in Human Stature

Thyroxine (T₄) and triiodothyronine (T₃) plasma concentrations have been determined during 24-hr sampling periods in six mongrels (age 12-36 months), six beagles (age 35-37 months), three labradors (age 3.5 months) and three beagles (age 5 months). The mean T₄ levels of the labradors were significantly lower than the values found for mongrels or older beagles (P < 0.05), whereas T₃ was higher in the 5 month old beagles compared to the mongrels (P < 0.001), young beagles (P < 0.05) or labradors (P < 0.01).

Circadian and ultradian rhythmicities have been evaluated by cosinor and Fourier analysis. Mongrels and older beagles did have a 12-hr rhythmicity in plasma T₄ (P < 0.05), whereas 5 month old beagles had a circadian one (P < 0.01). A 12-hr rhythmicity was also found for T₃ in the older Beagles (P < 0.05). However, Fourier analysis indicated that the daily variation in T₄ and T₃ plasma levels was inadequately mathematically described by single sinusoidal rhythm and that more harmonic components are to be taken into account.

The obtained data during a 24-hr period indicate that T₄ and T₃ concentrations in plasma may vary according to breed, age and sampling hour.     

血清Ghrelin、p21 waf/cip1以及IGF-1与儿童特发性矮小症相关性分析

摘要 目的：研究特发性矮小症（ISS）儿童血清生长激素释放肽（Ghrelin）、p21 waf/cip1以及胰岛素生长因子-1（IGF-1）水平及其临床意义。方法：选择2017年1月到2020年12月在我院接受治疗的特发性矮小症儿童60例（ISS组）,选择同期体检健康儿童60例作为对照（对照组）,比较两组儿童一般资料,检测并比较两组儿童血清Ghrelin、p21 waf/cip1以及IGF-1水平。分析ISS儿童血清Ghrelin、p21 waf/cip1以及IGF-1水平与生长指标的相关性,同时分析治疗对其影响。结果：（1）ISS组患儿性别、年龄和体质指数与对照组比较无显著差异（P>0.05）,但身高、体重以及生长速度显著低于对照组儿童（P<0.05）;（2）ISS组患儿血清Ghrelin和p21 waf/cip1均显著高于对照组,而血清IGF-1显著低于对照组（P<0.05）;（3）ISS组患儿血清Ghrelin和p21 waf/cip1均与身高、体重和生长速度呈负相关,而血清IGF-1与身高、体重和生长速度呈正相关（P<0.05）;（4）治疗显著提高ISS组患儿身高、体重、生长速度以及血清IGF-1水平,而显著降低ISS组患儿血清Ghrelin和p21 waf/cip1水平（P<0.05）。结论：Ghrelin、p21 waf/cip1和IGF-1在特发性矮小症患儿血清中表达异常,共同调控儿童生长发育,是评价儿童生长发育的良好指标。     

Genetic variations at the human growth hormone receptor (GHR) gene locus are associated with idiopathic short stature

GH plays an essential role in the growing child by binding to the growth hormone receptor (GHR) on target cells and regulating multiple growth promoting and metabolic effects. Mutations in the GHR gene coding regions result in GH insensitivity (dwarfism) due to a dysfunctional receptor protein. However, children with idiopathic short stature (ISS) show growth impairment without GH or GHR defects. We hypothesized that decreased expression of the GHR gene may be involved. To test this, we investigated whether common genetic variants (microsatellites, SNPs) in regulatory regions of the GHR gene region were associated with the ISS phenotype. Genotyping of a GT‐repeat microsatellite in the GHR 5′UTR in a Montreal ISS cohort (n = 37 ISS, n = 105 controls) revealed that the incidence of the long/short (L/S) genotype was 3.3× higher in ISS children than controls (P = 0.04, OR = 3.85). In an Italian replication cohort (n = 143 ISS, n = 282 controls), the medium/short (M/S) genotype was 1.9× more frequent in the male ISS than controls (P = 0.017, OR = 2.26). In both ISS cohorts, logistic regression analysis of 27 SNPs showed an association of ISS with rs4292454, while haplotype analysis revealed specific risk haplotypes in the 3′ haploblocks. In contrast, there were no differences in GT genotype frequencies in a cohort of short stature (SS) adults versus controls (CARTaGENE: n = 168 SS, n = 207 controls) and the risk haplotype in the SS cohort was located in the most 5′ haploblock. These data suggest that the variants identified are potentially genetic markers specifically associated with the ISS phenotype.     

Ethnic Differences in Subcutaneous Adiposity and Waist Girth in Children and Adolescents

The purpose of this study was to examine ethnic differences in adiposity as measured by sum of skinfolds (SKF) and waist circumference (WC) in children and adolescents, after statistical adjustment for the BMI and age. A cross sectional sample of 3,218 (55% white, 49% male) children and adolescents aged 5–18 years who participated in the Bogalusa Heart Study (1992–1994) were included in these analyses. Sex‐specific ANOVAs, adjusted for BMI and age, for each 2‐year age group compared measures of adiposity (SKF and WC) between ethnic groups. No significant differences in the proportions of children and adolescents who were overweight and obese by ethnicity or sex were found. Mean SKF in normal weight (P < 0.0001) and overweight (P < 0.0001) categories was higher for white than black children of both sexes. Across most age categories, white boys and girls had significantly higher SKF than black boys and girls, respectively (P ≤ 0.05). Across most age categories, white boys had significantly higher WC than black boys (P ≤ 0.05) with no difference in the girls, when adjusted for BMI and age. Measures of adiposity in childhood and adolescence were significantly higher in white children compared to black children, when adjusted for BMI and age. Throughout childhood and adolescence, white boys and girls had higher SKF and white boys had higher WC. Differences in adiposity between ethnic groups should be considered in disease risk assessment and stratification as they are observed even for a given BMI level.     

环境因素对儿童特发性矮身材影响的临床研究

目的：探讨环境因素对儿童特发性矮身材的影响。方法：采用病例对照的研究方法,对100例特发性矮身材患者组和100例正常对照儿童组分别进行体格测量,问卷调查家庭基本情况、出生史、饮食习惯、生活方式、生长速率、家庭生活条件、经济状况、父母文化程度等环境因素资料进行Logistic回归分析。结果：家族矮小史、母亲文化程度、家庭经济状况、偏食、运动时间、留守儿童影响特发性矮身材的发生。结论：因素与儿童特发性矮身材有关,为特发性矮身材儿童早期干预提供临床依据。     

Physical activity levels of normal-weight and overweight girls and boys during primary school recess

Objective: This study aimed to compare moderate‐to‐vigorous physical activity (MVPA) and vigorous physical activity (VPA) in normal‐weight and overweight boys and girls during school recess. Research Methods and Procedures: Four hundred twenty children, age 6 to 10 years, were randomly selected from 25 schools in England. Three hundred seventy‐seven children completed the study. BMI was calculated from height and weight measurements, and heart rate reserve thresholds of 50% and 75% reflected children's engagement in MVPA and VPA, respectively. Results: There was a significant main effect for sex and a significant interaction between BMI category and sex for the percent of recess time spent in MVPA and VPA. Normal‐weight girls were the least active group, compared with overweight boys and girls who were equally active. Fifty‐one boys and 24 girls of normal weight achieved the 40% threshold; of these, 30 boys and 10 girls exceeded 50% of recess time in MVPA. Eighteen overweight boys and 22 overweight girls exceeded the 40% threshold, whereas 8 boys and 8 girls exceeded the 50% threshold. Discussion: Overweight boys were significantly less active than their normal‐weight male counterparts; this difference did not hold true for girls. Even though nearly double the number of normal‐weight children achieved the 40% of MVPA during recess compared with overweight children, physical activity promotion in school playgrounds needs to be targeted not only at overweight but at other health parameters, as 40 overweight children met the 40% MVPA target proposed for recess.     

Increased oxidative stress in children with attention deficit hyperactivity disorder

Objectives: The purpose of this study was to investigate oxidative stress in children with attention deficit hyperactivity disorder (ADHD).

Methods: Total oxidant status (TOS), total antioxidant status (TAS), paraxonase-1 (PON-1) and arylesterase (ARE) activity were measured in 76 children (44 boys, 32 girls) diagnosed with ADHD according to the DSM-IV and 78 healthy children (46 boys, 32 girls).

Results: Age and sex were similar between the groups (P?>?0.05). TOS and the oxidative stress index (OSI) were higher in the patient group than the control group (P?<?0.001). PON-1 (P?=?0.002), ARE (P?=?0.010) activity and TAS (P?<?0.001) were lower in the patient group than the control group.

Discussion: We found decreased PON-1, ARE activity and TAS, and increased TOS and OSI in children with ADHD. Our study showed that there is significantly increased oxidative stress in children with ADHD.     

Application of Body Mass Index According to Height-Age in Short and Tall Children

Background

In children with either delayed or accelerated growth, expressing the body mass index (BMI) to chronological age might lead to invalid body composition estimates. Reference to height-age has been suggested for such populations; however its validity has not been demonstrated.

Methods

Anthropometric data of healthy children were obtained from the German KiGGS survey. We selected three samples with different height distributions representing short stature (mean height SDS: -1.6), normal stature (height SDS: 0), and tall stature (height SDS: +1.6), and compared BMI-for-age and BMI-for-height-age between these samples across the paediatric age range. Differences between samples were tested using Kruskal-Wallis one-way analysis of variance and permutation tests.

Results

At a given age, BMI was distributed towards lower values in short, and towards higher values in tall subjects as compared to a population with average height distribution. Expressing BMI to height-age eliminated these differences in boys with a short stature from 4 years to 14 years of age, in tall boys from 4 to 16 years, in short girls aged 2-10 years or tall girls aged 2-17 years.

Conclusion

From late infancy to adolescent age, BMI distribution co-varies with height distribution and referencing to height-age appears appropriate within this age period. However, caution is needed when data about pubertal status are absent.     

Exome sequencing reveals genetic architecture in patients with isolated or syndromic short stature

Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations. Although the diagnostic utility of clinical genetic testing in short stature has been implicated, the genetic architecture and the utility of genomic studies such as exome sequencing(ES) in a sizable cohort of patients with short stature have not been investigated systematically. In this study, we recruited 561 individuals with short stature from two centers in China during a 4-year period. We performed ES for all patients and available parents. All patients were retrospectively divided into two groups: an isolated short stature group(group I, n = 257) and an apparently syndromic short stature group(group II, n = 304). Causal variants were identified in 135 of 561(24.1%) patients. In group I, 29 of 257(11.3%) of the patients were solved by variants in 24 genes. In group II, 106 of 304(34.9%) patients were solved by variants in 57 genes. Genes involved in fundamental cellularprocess played an important role in the genetic architecture of syndromic short stature. Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature.     

Exercise performance and magnetic resonance imaging-determined thigh muscle volume in children

This study examined the relationships between thigh muscle volume (TMV) and aerobic and anaerobic performance in children. A total of 32 children, 16 boys and 16 girls, aged 9.9 (0.3) years completed a treadmill running test to exhaustion for the determination of peak oxygen uptake (peak V˙O₂) and a Wingate Anaerobic Test (WAnT) for the determination of peak power (PP) and mean power (MP). The volume of the right thigh muscle was determined using magnetic resonance imaging. TMV was not significantly different in boys and girls [2.39 (0.29) l vs 2.18 (0.38) l, P > 0.05]. Peak V˙O₂ and MP were significantly higher in boys than girls (P < 0.01) whether expressed in absolute, mass-related or allometrically scaled terms. Absolute PP was not significantly different in boys and girls but mass-related and allometrically scaled values were higher in boys (P < 0.01). TMV was correlated with absolute peak V˙O₂, PP and MP in both sexes (r = 0.52–0.89, P < 0.01). In boys, mass-related PP was correlated with TMV (r =0.53, P < 0.01), and in girls mass-related peak V˙O₂ was correlated with TMV (r = −0.61, P < 0.01). However, in neither sex were allometrically scaled peak V˙O₂, PP or MP correlated with TMV (P > 0.05). There were no significant differences between boys and girls in terms of peak V˙O₂, PP or MP when expressed in a ratio to TMV or allometrically scaled TMV. In conclusion, this study has demonstrated that, when body size is appropriately accounted for using allometric scaling, TMV is unrelated to indices of aerobic and anaerobic power in 10-year-old children. Furthermore, there appear to be no qualitative differences in the muscle function of boys and girls in respect of aerobic and anaerobic function. Accepted: 4 February 1997     

Physical growth and nutritional status of Tsimane' Amerindian children of lowland Bolivia

This study examines patterns of growth and nutritional status of indigenous Tsimane' children under 9 years of age (n = 199 boys and 210 girls), based on a cross-sectional sample from 58 villages from the Beni Deparment of lowland Bolivia. Compared with US children, Tsimane' children are quite short, with linear growth tracking at or below the US 5th centile in both sexes. The prevalence of low height-for-age ("stunting;" HA Z-scores 相似文献   

Effects of breastfeeding on trajectories of body fat and BMI throughout childhood

Objective: To investigate the effect of breastfeeding in healthy boys and girls on their trajectories of percent body fat (%BF) and BMI standard deviation scores (BMI–SDS) throughout childhood. Methods and Procedures: Analyses of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study included data from 219 male and 215 female term participants, born between 1984 and 1999, with repeated anthropometric measurements between 0.5 and 7 years and prospective data on duration of breastfeeding. Results: Among boys with an overweight mother (OW‐M), analyses adjusted for potential confounders revealed that not or shortly breastfed (≤17 weeks) boys did not experience the age‐dependent decrease in %BF seen in all children with normal weight mothers (NW‐Ms). In contrast, boys fully breastfed for >17 weeks were protected against the adverse effect of maternal overweight (effect of long breastfeeding vs. no/short breastfeeding among boys with OW‐Ms: 0.46%/year; s.e. 0.18; P = 0.01). There was also a suggestion of an interaction between maternal overweight and breastfeeding for the BMI–SDS trajectory (0.08 SDS/year; s.e. 0.04; P = 0.07). Among boys with NW‐Ms mothers and the corresponding subgroups of girls, breastfeeding had little effect on the development of %BF or BMI–SDS throughout childhood. Discussion: Our study suggests that breastfeeding could offset a potential programming effect for childhood adiposity among boys with OW‐Ms, to whom advice to breast‐feed should thus be specifically targeted.     

Adult outcome of normal children who are short or underweight at age 7 years.

OBJECTIVES--To evaluate the adult growth outcome (at age 23) of children who are short or underweight at age 7 years in whom no identifiable pathological cause exists for their poor growth. DESIGN--Longitudinal follow up of a birth cohort. SETTING--The national child development study (1958 birth cohort) of Great Britain. SUBJECTS--523 children with a height or a weight below the fifth centile at age 7. Of these, 70 (13.4%) were excluded because they had a longstanding illness that could account for their poor growth. The remaining 453 subjects, who were followed to age 23, provided the base group from which those with additional data, such as parental height, were obtained. RESULTS--55/174 (31.6%) boys who were short at age 7 became short men; 60/211 (28.4%) girls who were short at age 7 became short women. Among boys who were underweight at age 7, 46/160 (28.7%) were still underweight at age 23, while 61/200 (30.5%) girls underweight at age 7 became underweight women. Having short parents did not increase the probability of being small as an adult. Children with delayed puberty were as likely to remain small as those in whom puberty was not delayed. CONCLUSIONS--One in three normal children who was short or underweight at age 7 became a short or underweight adult. This informs the management of short children and may be valuable when prolonged growth hormone treatment for short stature is being considered.     

38年来济南、青岛儿童少年生长的长期变化

本文分析了济南、青岛1962—2000年7—18岁儿童少年生长发育的长期变化趋势。38年间,济南市7—18岁男女生身高平均增长15 48cm(男)、12 09cm(女),体重平均增长15 76kg(男)、10 01kg(女),胸围平均增长7 88cm(男)、4 10cm(女);青岛市7—18岁男女生身高平均增长17 12cm(男)、13 19cm(女),体重平均增长16 98kg(男)、10 46kg(女),胸围平均增长6 72cm(男)、3 05cm(女)。青岛市男女生身高的增长幅度显著大于济南。     

The High Prevalence of Overweight and Obesity in Mexican Children

Objective: To establish the prevalence of overweight and obesity in Mexican children 10 to 17 years of age according to the percentiles from both the Centers of Disease Control and Prevention (CDC) and the International Obesity Task Force (IOTF). Research Methods and Procedures: Heights and weights were measured in children from nationally representative, randomly chosen households in the Mexican National Health Survey 2000. The study population consisted of 7862 boys and 8947 girls, 10 to 17 years of age. Measurements used were the percentage of children in the corresponding BMI categories for overweight and obesity specified by the CDC and the IOTF BMI percentiles. Results: The children were short, with mean Z scores for height by age varying from ? 0.62 ± 1.26 to ?1.12 ± 1.06 in boys and from ?0.45 ± 1.25 to ?1.19 ± 1.12 in girls. CDC‐based overweight prevalences varied by age from 10.8% to 16.1% in boys and 14.3% to 19.1% in girls, with obesity prevalences from 9.2% to 14.7% in boys and 6.8% to 10.6% in girls; these prevalences did not relate to stunting. IOTF‐based excess weight prevalences were similar, with higher overweight rates (boys, 15.4% to 18.8%; girls, 18.4% to 22.3%) but lower obesity rates (boys, 6.1% to 9%; girls, 5.9% to 8.2%). Discussion: Mexican children have one‐half the overweight/obesity prevalences of U.S. Mexican‐American children; however, there are higher rates in Northern Mexico, which is closer to the U.S. These escalating rates of excess weight demand new prevention, as well as management, policies.     

长治市幼儿园4—5岁儿童四季生长情况

作者对山西省长治市幼儿园1980和1981年出生的216名儿童(男125、女91),在1985年四季生长的情况进行了测量和统计分析。结果表明,男童年均身高增长6.12厘米,体重增长2.49公斤;女童年均身高增长5.65厘米,体重增长2.35公斤。各季身高和体重增长值经F检验,季节差异均非常显著(p<0.01)。一年内最佳生长季节为秋季,同其它三季比较,经Dunnett检验,只有春季男女儿童身高增长和冬季女童体重增长与秋季相比,差异不显著(P<0.05)。其余各季增长同秋季比较,差异均非常显著(P<0.01)。     

Reformulation of BMI and Percent Body Fat to Remove the Height Bias in 8‐year‐olds

BMI and percent body fat (%BF) are both related to height (Ht) in prepubertal children, so may misrepresent childhood adiposity, especially in tall or short children. We sought to construct replacement functions for BMI and %BF that are independent of Ht. Fat mass (FM) was measured using dual‐energy X‐ray absorptiometry, together with Ht and body mass (BM) in 746 healthy boys and girls aged 8 years (0.34 s.d.). Relationships between BM, FM, and Ht were measured and values of p and q derived such that the functions BM. Ht^?p and FM.BM^?q were unrelated to Ht. BM was not directly proportional to Ht², BMI being significantly related to Ht in both boys and girls (P < 0.001). BM was proportional to Ht³, BM. Ht^?3 being independent of Ht. Similarly, FM was not directly proportional to BM and %BF was significantly related to Ht (P < 0.001). While FM was proportional to BM², FM.BM^?1.5 was the function found to be independent of Ht. Using the 85th and 95th percentiles as the cutoffs for overweight and obesity respectively, 6.4% of the boys and 6.8% of the girls were classified differently by BMI and the Ht independent measure BM. Ht^?3. Similarly, 10.1% boys and 13.7% girls were classified differently by %BF and the Ht independent measure FM.BM^?1.5. We propose that improved diagnostic accuracy of body composition in 8‐year‐olds is provided by the BM function (BMF, BM. Ht^?3) and FM function (FMF, FM.BM^?1.5) replacing BMI and %BF, which both overestimate the adiposity of taller children and underestimate it in shorter children.     

Reported versus measured adult statures

Reported and measured statures were obtained for 100 husband-wife pairs. In addition, wives were asked to specify whether their husbands were tall, medium, or short. Correlations between reported and measured statures are high (0.84–0.97) and wives tend to overestimate their own measured stature by about 1 cm, and that of their husbands by about 1.3 cm. Wives correctly classify their husbands as tall, medium, or short in about 70% of the cases, using terciles of the stature distribution of American men as the standard. Reported statures may be useful proxies for measured statures for certain purposes. In the absence of measured or reported statures, a wife's categorization of her husband as tall, medium, or short may be satisfactory for some group studies.