Lars Gelander

Pubertal growth assessment.

Almost all available sets of height growth reference values are constructed in a cross-sectional manner, except for a few studies in which longitudinal sampling was used. Such reference values are, however, flawed because of considerable individual variation in the timing of puberty, especially among children with early or late pubertal maturation. An additional complicating factor is that the magnitude of the total pubertal growth spurt is significantly larger among those individuals with early pubertal maturation, compared with late maturation. Based on the growth records of 145 healthy Swedish children followed longitudinally, this study introduces a pre-pubertal standard for the assessment of pre-pubertal height for children with late onset of puberty. By plotting the height values of a child in a chart containing pre-pubertal reference values, the onset of the pubertal growth spurt can be identified by a change in the pre-pubertal height standard deviation score values of 0.3 standard deviations or more over a period of 1 year. Once the pubertal onset is established, a highly accurate final height prediction method can be applied to the data, as described in this article, in which height and age at pubertal onset are the only two measures required. The r2 value of the prediction model was over 0.80 for both sexes. Finally, a method for assessing total pubertal height gain is presented. The method adjusts for the timing of puberty and is based on the height and age at pubertal onset, plus the observed final height.

Monthly measurements of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 in healthy prepubertal children : Characterization and relationship with growth : The 1-year growth study

The usefulness of measurements of IGF-I or IGF-binding protein-3 (IGFBP-3) in the clinical management of growth disorders is dependent on the extent of physiologic variation in their concentrations. Our purpose was therefore to investigate the longitudinal intraindividual variation in serum concentration of IGF-I and IGFBP-3 in healthy prepubertal children. Monthly serum samples and auxologic measurements were taken over a period of 1 y from 65 prepubertal children (38 boys, 27 girls; mean age 9.1 y, range 7.8-10.8). Concentrations of IGF-I and IGFBP-3 were measured by RIA. The mean (±SD) serum concentration of IGF-I in the children was 165 ± 42.0 µg/L, with a mean coefficient of variation (CV) of 13.9% around the annual mean serum concentration for each child. The corresponding mean concentration of IGFBP-3 was 3273 ± 604.5 µg/L, and the mean CV for each child was 9.7%. These monthly longitudinal variations in IGF-I and IGFBP-3 were parallel to changes in longitudinal growth. Short-term changes (1 mo) in IGF-I were positively correlated with changes in weight (rs = 0.42, p < 0.0005) and body mass index (rs = 0.45, p < 0.0005), and negatively correlated with minor intercurrent illnesses (-0.32; p < 0.05). Seasonal fluctuations also occurred, with short term changes in IGF-I (1 mo) and IGFBP-3 (3 mo), increasing with increasing outdoor temperatures (rs = 0.30, p < 0.05 and rs = 0.39, p < 0.005, respectively). We conclude, that there are significant changes in both IGF-I and IGFBP-3 that occur in association with growth, and that IGF-I is more sensitive than IGFBP-3 to short-term changes in weight, body mass index, and intercurrent illnesses. Physiologic short-term changes must therefore be taken into consideration when using serum levels of IGF-I or IGFBP-3 in the evaluation of the short or slowly growing child.

Body composition, as assessed by bioelectrical impedance spectroscopy and dual-energy X-ray absorptiometry, in a healthy paediatric population.

The aim of this study was to determine the level of agreement between body composition measurements by dual‐energy X‐ray absorptiometry (DXA), single‐frequency bioelectrical impedance analysis (BIA) and multifrequency bioelectrical impedance spectroscopy (BIS). Fat‐free mass (FFM), body fat mass and body fatness (percentage fat) were measured by DXA, BIA and BIS in 61 healthy children (37M, 24F, aged 10.9–13.9 y). Estimates of FFM, body fat mass and body fatness were highly correlated (r= 0.73–0.96, p > 0.0001) between the different methods. However, a Bland‐Altman comparison showed wide limits of agreement between the methods. The mean differences between methods for FFM ranged from 2.31 ± 7.76 kg to 0.48 ± 7.58 kg. Mean differences for body fat mass ranged from 0.16 ± 5.06 kg to 2.95 ± 5.65 kg and for body fatness from 2.3 ± 7.8% to 0.8 ± 9.3%. Calculations of body composition with BIS were not superior to BIA. However, BIA overestimated fat mass in lean subjects and underestimated fat mass in overweight subjects more than BIS, compared with DXA.

Distinctions between short- and long-term human growth studies.

It is known what the aim is in a complete long‐term growth study; the final height is the outcome measure, although the annual height velocity values provide additional information. Strictly, short‐term growth studies are also defined in terms of minimum length of observation, i.e. one month, as well as the type of measurement errors to be considered. The poor correlation between short‐ and long‐term growth velocity values has led to the conclusion that the short‐term study cannot be interpreted in long‐term perspectives, and vice versa. There is a need to debate the way in which results of short‐term studies should be interpreted. This is especially important when short‐term growth is taken as the outcome measure in a controlled study. Our proposal is that such studies must include information about the growth achieved for a period after the treatment has ended in order to describe possible compensatory growth. Without weighing in some long‐term consequences, we may incorrectly document short‐term growth as a positive or negative effect of a certain treatment.

Children's growth: A health indicator and a diagnostic tool

UNLABELLED The publication of Werner and Bodin in Acta Paediatrica should inspire countries to use the growth of children as an indicator of health. The development of databases that cover all measurements of all children that have contact with healthcare and medical care will provide new knowledge in this area. Such databases will give us the opportunity to explore health in different areas of the country and to evaluate community projects in order to prevent obesity. CONCLUSION Growth charts that are used to identify sick children or children that have other causes for growth disturbances must reflect how a healthy child should grow. If such prescriptive growth charts are computerized together with regional databases, they will provide necessary growth data for descriptive health surveys.

Growth Hormone-Binding Protein Levels over One Year in Healthy Prepubertal Children: Intraindividual Variation and Correlation with Height Velocity

The role of GH-binding protein (GHBP) in growth regulation is still under debate. We investigated 29 prepubertal healthy children (13 girls/16 boys; mean age 9.3 y to study intraindividual variation in serum GHBP and to explore whether any such variation was related to changes in IGF-I, IGF-binding protein-3 (IGFBP-3) or urinary excretion of GH. The relationship between changes in GHBP concentrations, short-term height velocity, and changes in body composition was also studied. Blood samples were taken every month for 1 y, for measurements of GHBP, IGF-I, and IGFBP-3. The mean coefficient of variation in monthly GHBP concentrations in individual children was 18%(range, 6.7-33.0%). The values for each child were normalized by expressing the concentration as a ratio to the mean GHBP concentration. GHBP values were highest in January and lowest in August (22% difference). Maximal monthly changes in GHBP correlated with simultaneous changes in weight(rs = 0.38, p < 0.05) and IGF-I(rs = 0.38, p < 0.05). The mean GHBP concentration during the year correlated with height velocity(rs = 0.37, p < 0.05) and the mean serum concentration of IGF-I (rs = 0.42, p < 0.05) and IGFBP-3 (rs = 0.60, p < 0.001). We conclude that there is a significant monthly variation in GHBP concentrations in healthy prepubertal boys and girls, which is correlated to changes in weight and IGF-I. The mean GHBP concentration during the year is correlated with the mean serum concentrations of IGF-I, IGFBP-3, and with height velocity. Thus, the variation in GHBP concentrations appears to mirror GH sensitivity, because no parallel changes in urinary GH excretion were observed.

Overnight Urinary Growth Hormone in Normally Growing Prepubertal Children: Effect of Urine Volume

Growth hormone excretion can easily be measured in the urine using ultrasensitive methods. The large day-to-day variation has, however, restricted its diagnostic usefulness. The present study aimed to evaluate the individual variation of GH in the urine (uGH) during normal prepubertal growth. Eighty-four prepubertal normally growing children were followed monthly for 13 months. During this period, 3,207 overnight urine samples were collected. The urine collection time was unrelated to the uGH concentration (p > 0.05), while there was a significant negative correlation between the uGH concentration and urine volume (the Spearman correlation coefficient of –0.33, p < 0.0001), while the calculated excretion of GH in the urine showed a positive correlation with the urine volume (r = 0.35; p < 0.0001). A reference chart, based on SD scores, was developed in order to avoid this volume dependency and to optimally normalize the skewed distribution of the uGH concentrations. The use of this model reduced the individual day-to-day variation of uGH from a coefficient of variation of 43 to 21%. Differences in mean cross-sectional urinary GH concentration was found between different months exceeding the expected methodological variation. This variation showed no seasonal pattern. Only 0.2% of triplicate values (three consecutive overnight uGH values) were all below –2 SD scores and 0.1% were above +2 SD scores. The mean uGH SD score for the boys was 0.01 (SD = 0.98), which was similar to that for the girls (–0.04; SD = 1.06). We found that uGH excretion can be estimated in a more robust way, using a SD score based reference chart that handles both the positive correlation between urinary GH and urine volume and the skewed distribution of urinary GH. This model reduced the day-to-day variability of uGH by half. Overestimation of GH in large urine volumes may be due to increased gradient between GH in urine and serum following increased urine volumes.

Modelling individual longitudinal human growth from fetal to adult life − QEPS I

BACKGROUND Only one mathematical model to date describes human growth and its different phases from fetal life until adult height. AIM To develop a model describing growth from fetal life to adult height taking maturation/biological tempo into consideration. METHODS SUBJECTS The model was developed based on longitudinal mean height values obtained from published growth references for a cohort of 3650 healthy Swedish children followed from birth circa 1974 until adult height combined with birth-length for circa 400 000 healthy infants born 1990-1995. RESULTS The QEPS-model for individual growth was constructed with a combination of four basic shape-invariant growth functions: a quadratic Q-function and a negative exponential E-function, both started during fetal life, 8 months before birth; the E-function levelled off after birth, whereas the Q-function continued until end of growth. A specific nonlinear pubertal P-function started at onset of puberty, and a stop S-function ended growth according to both the Q-function continuing during puberty and the specific P-function. For each function, an individual height-scale parameter was defined, and for the E- and P-functions, a time-scale parameter; giving six modifying parameters in total. In addition standardized proportional scores were used for biological interpretations. The QEPS-model was used to fit and generate mathematical functions suitable to describe the growth of the healthy population of Swedish children; thereafter, the model was modified using four height-scale parameters to model individual height in cm, and two time-scale parameters to adjust for the individual tempo of growth. Individual confidence intervals were calculated for all parameters. CONCLUSIONS A new shape-invariant growth model, QEPS, was developed, that requires only four basic growth functions to describe the total pattern of growth in height from fetal life to adult height, with addition of height- and time-scale parameters describing individual growth. The model can describe a wide variety of growth curves. Moreover, it is the first model to provide confidence intervals which enable us to describe the precision/quality of individual parameters.

Pubertal height gain is inversely related to peak BMI in childhood

Background:Childhood BMI may influence subsequent growth in height as well as the timing of puberty. The aim of the present study was to investigate associations between BMI in childhood and subsequent height gain/pubertal growth.Methods:Longitudinal growth data were used (GrowUp1990Gothenburg cohort, n = 1,901). The QEPS growth-model was used to characterize height gain in relation to the highest BMISDS value between 3.5 and 8 y of age. Children were defined as overweight/obese (OwOb) or normal weight/underweight (NwUw), using the 2012 International Obesity Task Force criteria.Results:A negative association between childhood BMISDS and pubertal height gain was observed. Already at birth, OwOb children were heavier than NwUw children, and had a greater height velocity during childhood. Onset of puberty was 3.5/3.0 mo earlier in OwOb girls/boys, and they had 2.3/3.1 cm less pubertal height gain from the QEPS-models specific P-function than NwUw children. Adult height was not related to childhood BMI.Conclusion:We found that pubertal height gain was inversely related to peak BMI in childhood. Higher childhood BMISDS was associated with more growth before onset of puberty, earlier puberty, and less pubertal height gain, resulting in similar adult heights for OwOb and NwUw children.

Effects of Acute Intravenous Injection of Two Growth Hormone-Releasing Hormones (GHRH 1–40 and 1–29) on Serum Growth Hormone and Other Pituitary Hormones in Short Children with Pulsatile Growth Hormone Secretion

We administered two different growth hormone-releasing hormones (GHRH) to 20 short, prepubertal children who had spontaneous secretion of growth hormone (GH), assessed from 24-hour GH secretion profiles (72 sampling periods of 20 min). We compared one i.v. injection of 1 microgram/kg of GHRH 1-40 with that of GHRH 1-29 regarding serum concentrations of GH, prolactin, luteinizing hormone, follicle-stimulating hormone and IGF-I. The children were allocated to two groups without statistical randomization. Both groups were given both peptides, with at least 1 week in between. The first group started with GHRH 1-40, the other with GHRH 1-29. The peptides both induced an increased serum concentration of GH of the same magnitude: mean maximal peak of 89 +/- 12 mU/l after GHRH 1-40 and 94 +/- 10 mU/l after GHRH 1-29 (n.s.). The mean difference in maximum serum GH concentration in each child after injection was 52 +/- 9 mU/l, range 1-153 mU/l. GHRH 1-29 also induced a short-term, small increase in the concentrations of prolactin (p less than 0.05), luteinizing hormone (p less than 0.01) and follicle-stimulating hormone (p less than 0.05). We conclude that the shorter sequence GHRH 1-29, when given in a dose of 1 microgram/kg, gives a rise in serum concentration of GH similar to that after the native form GHRH 1-40.