Search

UNLABELLED The body mass index or BMI (weight/height2) is a somewhat crude estimate of nutritional status. However, due to its simplicity and high correlation with total body fat, it has been the method of choice in both paediatric clinics and research over the years. Since BMI is not an equivalent measure of the percentage of body fat in different ethnic groups and in the two sexes, population-specific BMI reference data is needed. Several BMI reference values have been published for French, American, British and Hong Kong children in recent years. In Sweden, weight-for-age and height-for-age reference values, which were published in 1976, are still used as the current national growth reference values. Updated growth reference values are needed for assessing nutritional status due to the secular trend toward and increasing prevalence of childhood obesity. The aim of this study was to produce BMI reference values for Swedish children of paediatric age. The series came from a large Swedish population-based longitudinal growth study of 3650 full-term babies followed from birth to 18 y of age. The children in this data set were born in the early 1970s. The pattern and level of 50th centile BMI values presented here are quite similar to those of the Swedish cohort study in the 1950s. In comparison with the US BMI reference values, the Swedish values are much lower, especially for the higher centile values. CONCLUSION The new Swedish BMI chart from our study may provide a useful tool for paediatricians to assess body fat, and consequently nutritional status, in Swedish children.

Aim: To examine the relationship between growth hormone (GH) and psychological functioning, especially self-perception and well-being, in 60 prepubertal boys of short stature with a wide range of GH levels. Methods: A comparison was made of the well-being and self-perception of children with GH insufficiency, children with idiopathic short stature (ISS), a normative sample and healthy boys with normal stature. Results: Children with GH insufficiency had a more negative perception of their own physical appearance than the normative sample. They perceived themselves as more alert but also more inhibited than both the children with ISS and the healthy boys with normal stature. In comparison with the healthy boys with normal stature they perceived themselves as having more stability. The parents of the boys with GH insufficiency also perceived their children as being more stable compared with how the parents of boys with ISS perceived their children. To elucidate the effects of GH on psychological functioning a multiple regression analysis was performed. Conclusion: The lower the levels of GH the more inhibited were the boys of short stature, as perceived both by themselves and by their parents. The boys with GH insufficiency had a more negative perception of their physical appearance than the normative sample.

Dual-energy X-ray absorptiometry and laser (DXL) Calscan measures bone mineral density (BMD) in the calcaneus. In the present study, the DXL Calscan device has been modified for use in pediatric practice. It includes a function for measuring calcaneal height, which makes it possible to calculate volumetric bone mineral apparent density (BMAD). The aims of the present study were to evaluate the method when used in children, to create pediatric reference values in healthy Swedish 2-, 4-, and 7-yr-old children for BMD, bone mineral content (BMC), and BMAD, and to study whether these parameters were related to auxological data. The method was well tolerated by all children. Intraindividual coefficients of variation for BMC and BMD decreased with increasing age. The mean BMD was 0.17+/-0.003 g/cm2 in 2-yr-old children, 0.22+/-0.003 g/cm2 in 4-yr-old children, and 0.30+/-0.005 g/cm2 in 7-yr-old children. This study provides normative data as percentile values for BMD, BMC, and BMAD in young children measured with DXL Calscan. BMD was significantly correlated with age (p

To develop a cell-free system that can be used to measure cytokine bioactivity we have designed a soluble hybrid molecule consisting of the extracellular domain of the GH-receptor (GHR) and the intracellular domain of the epidermal growth factor receptor (EGFR). A DNA construct encoding this hybrid-receptor was inserted into a baculoviral expression vector and expressed in Sf9-cells. Activation of the hybrid-receptor by ligand-induced dimerization can be measured as the incorporation of radiolabeled phosphate into a biotinylated tyrosine kinase peptide substrate. The kinase activity in samples stimulated with GH (10 ng/ml) increased 5-fold compared to samples without addition of GH. This is the first example of a functional hybrid-receptor where the transmembrane domain has been deleted. Our results suggest that such hybrid-receptors may be used for detection of GH and other cytokine-receptor activating substances in biological fluids.

Events occurring early in life or prenatally are able to play important roles in the pathogenesis of diseases in adult life. Different sorts of stress or hormonal influences, during particular periods of pregnancy, may result in persisting or transient changes in physiology. Glucocorticoids are used for the treatment of a variety of diseases, to promote organ maturation and to prevent preterm delivery. Glucocorticoids are also known to affect skeletal growth and adult bone metabolism. The aim of the present study was to investigate whether exposure to dexamethasone (Dex) during fetal life has any effect on skeletal growth and/or bone mineral density in adult rat offspring. Pregnant rats were given injections of either Dex (100 micro g/kg) or vehicle on days 9, 11 and 13 of gestation. Dex-exposed male but not female rat offspring showed transient increases in crown-rump length and tibia and femur lengths at 3-6 weeks of age. In contrast, the cortical bone dimensions were altered in 12-week-old female but not male Dex-exposed offspring. The areal bone mineral densities of the long bones and the spine, as determined by dual X-ray absorptiometry, and trabecular as well as cortical volumetric bone mineral density, as measured using peripheral quantitative computerized tomography, were unchanged in both male and female Dex-exposed offspring. In conclusion, prenatal Dex exposure affects skeletal growth in a gender-specific manner, while the mineralization of bones is unaffected in both male and female offspring.

Comprehensive recommendations on the diagnosis of Turner syndrome (TS) and the care of affected individuals were published in 1994. In the light of recent advances in diagnosis and treatment of TS, an international multidisciplinary workshop was convened in March 2000, in Naples, Italy, in conjunction with the Fifth International Symposium on Turner Syndrome to update these recommendations. The present paper details the outcome from this workshop. The genetics and diagnosis of the syndrome are described, and practical treatment guidelines are presented.

Final height was evaluated in 369 patients with idiopathic growth hormone deficiency (IGHD) enrolled in KIGS--the Pharmacia & Upjohn International Growth Database. At the start of growth hormone (GH) therapy, the patients were 9.8 years of age, their mid-parental height SDS was -0.8, and their height SDS was -3.1. Of the 369 patients, 50% had multiple hormone deficiencies, and puberty was induced in 31%. Patients were 18 years of age at completion of GH therapy, and had received GH at a dose of 0.49 IU/kg/week (0.16 mg/kg/week), with a mean of 5.2 injections/week for 8.1 years. Final height SDS was -1.5, final minus initial height SDS was 1.7 and final minus mid-parental height SDS was -0.5. A Swedish subgroup (n = 69) received conventional GH therapy throughout at 0.65 IU/kg/week (0.22 mg/kg/week), with seven injections/week for a mean of 9.4 years. These patients achieved their genetic potential (final minus mid-parental height SDS, 0.03), with a normal final height SDS of -0.3. For the total group, the following variables were associated with final height: mid-parental height SDS (r = 0.62), injection frequency (r = 0.37), duration of GH treatment (r = 0.28), peak stimulated GH concentration (r = -0.25), age (r = -0.19) (all p < 0.001) and height velocity SDS in the first year of treatment (r = 0.20, p = 0.004). In conclusion, genetic potential, expressed as the mid-parental height, is the variable with the greatest identified influence on final height during GH treatment in IGHD. Current GH regimens will lead to a normal height and attainment of mid-parental height. However, higher dose, individualized GH regimens are likely to be necessary for patients with IGHD who are disadvantaged at the time of commencing GH therapy, such as those with short parents, those whose treatment began in late childhood or adolescence and those with less severe GHD.

Turner syndrome (TS) is a sex-chromosome disorder, occurring in 1 in 2500 female births. The principal features of TS are short stature and dysfunctional gonads, resulting in a lack of sex hormones, incomplete pubertal development and impaired fertility. The aim of this paper is to review the literature on the psychological effects of TS. The main areas covered relate to well-being and psychopathology, self-esteem, social functioning, gender identity, partner relations and sexual functioning, coping, family aspects and clinical aspects of cognitive impairment. Research on the psychological effects of medical intervention is described, and the methods used for psychological and educational support are presented. Finally, methodological issues are discussed and areas for future research are proposed.

A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. A previous metanalysis of four trials revealed that GH treatment over a period of 2 years induced a dose-dependent acceleration of linear growth and, to a lesser extent, of the rate of bone maturation in short, prepubertal children born SGA. The rate of bone maturation and the change in height SDS for bone age from the previous 2-year metanalysis have been re-analysed according to chronological age (two prepubertal age groups: group A, 3.0-5.9 years old; group B, 6.0-8.9 years old). The rate of bone maturation was slower in younger than in older prepubertal children; this difference was more marked in children receiving high-dose (0.2 or 0.3 IU/kg/day) GH treatment (p < or = 0.01). Accordingly, the change in height SDS for bone age was increased by high-dose GH treatment in both age groups (p < or = 0.01), and was more pronounced in younger than in older children (1.45 +/- 0.28 versus 0.63 +/- 0.20; p < or = 0.01). Height SDS data from 100 short, prepubertal children born SGA have been analysed over 4 years. The change in height SDS appeared to be related to the average dose of GH. A mean GH dose of 0.1 IU/kg/day over 4 years was administered either as 0.1 IU/kg/day for 4 years (continuous) or as 0.2 IU/kg/day for 2 years, followed by 2 years without GH treatment (discontinuous). After 4 years of treatment, the increase in height SDS for the continuous and discontinuous treatment schedules was similar, being 1.42 +/- 0.10 SDS and 1.58 +/- 0.17 SDS, respectively. In a second regimen, a mean GH dose of 0.2 IU/kg/day over 3 years was administered either as 0.2 IU/kg/day for 3 years (continuous) or as 0.3 IU/kg/day for 2 years, followed by 1 year without GH treatment (discontinuous). After 3 years, the increase in height SDS with the continuous and discontinuous treatment schedules was similar, being 2.01 +/- 0.18 SDS and 2.22 +/- 0.16 SDS, respectively. GH administration was well tolerated in all treatment groups. In conclusion, the rate of bone maturation in short, prepubertal children born SGA treated with GH appeared to depend not only on the dose of GH, but also on the age of the child. GH treatment resulted in a prolonged increase in height SDS, the magnitude of the rise being dependent on the average GH dose rather than on the continuous or discontinuous mode of GH administration.

The aim of this study was to identify predictors of the growth response to growth hormone (GH) during the first 2 years of GH treatment, using auxological data and the maximum GH response (GHmax) to provocation tests. The patients were 169 prepubertal short children (27F, 142M), with Gmax values ranging from 0 to 65 mU/l. Their mean age (+/- SD) was 8.3 +/- 2.4 years (range 3-13 years), mean height SDS -3.0 +/- 0.7 (range -1.5 to -6.0 SDS) and mean pretreatment height velocity was normal (+/- 0.0 SDS) (range -1.6 to +0.9 SDS). The increase in height SDS during the first 2 years of GH treatment (0.1 U/kg/day) varied from 0.10 to 3.75 SDS, with younger children having a better growth response. Individual growth responses correlated (p < 0.001) with GHmax (r = -0.37), age (r = -0.35), 1-year pretreatment delta SDS (r = -0.25), mid-parental height SDS (r = 0.34), height SDS at start of treatment (r = -0.22) and difference between height SDS of an individual child at the onset of GH treatment and mid-parental height expressed in SDS (diff SDS) (r = -0.43). In a multiple stepwise linear regression model, diff SDS and log GHmax were found to be the strongest predictors of the magnitude of the growth response. In the short children in this study who exhibited a broad range of GHmax values, 33% of the growth response during the first 2 years of treatment could be predicted.

Measurements of final height were made on more than 4000 children in the final grade of school in Gothenburg in 1992; at the same time, mid-parental heights were recorded. These data were combined with other information (sex, length of gestation, size at birth, estimated age at peak height velocity (PHV) and height measurements made before 8 years of age) and used in a multiple regression analysis to assess the strength of the linear relationship between attained final height and these other potentially predictive measures of adult height. The R2 value increased from 0.16 at birth to 0.64 when the child was 8 years old. The inclusion of mid-parental height in the regression analysis contributed significantly to the explained variation in final height, especially at the earlier ages; the further addition of size at birth and age at PHV provides a small increase in the explained variation. The probability that the final height of a child will be below -2 or above +2 standard deviation scores (SDS) was assessed, based on previous SDS values for height when younger and on mid-parental height SDS. As a result of the large sample size included in the analyses, considerable confidence can be placed on the accurate prediction of final height values in the range -2.5 to +2.5 SDS.

Demographic and auxological data were analysed from 818 girls with Turner's syndrome treated with recombinant human growth hormone (GH) and entered into the Kabi Pharmacia International Growth Study. Size at birth was low and correlated with the heights of both parents. The median age at start of GH treatment was 11.4 years and the parents had a median height SDS of -2.9. Height SDS at the start of treatment correlated with parental heights. Height velocities conformed to Turner-specific standards. The weight-for-height index increased sharply above 9 years of age. The frequency of spontaneous appearance of Tanner breast stage 2 was high (34.1% of girls > 10 years of age). Bone age (Greulich and Pyle) data were described by the equation: bone age = 1.61(chronological age) - 0.04(chronological age)2 - 3.61. This equation was used to correct adult height predictions. The median initial dose of GH was 0.8 IU/kg/week and was maintained during the first 3 years of treatment. The median frequency of injections was six/week. Height velocity increased from 4.1 to 6.8 cm/year in the first year, and height velocity SDS for chronological age remained positive for 4 years. The height prediction corrected for bone age increased over the first 2 years only. Differences in demography and auxology were described according to karyotype and country of origin. A greater height velocity SDS was observed at higher GH doses and when oxandrolone was used concomitantly.

The auxological characteristics and the response to growth hormone (GH) treatment of children with idiopathic short stature were studied, using the database of the Kabi Pharmacia International Growth Study. Pretreatment data from a total of 271 children were analysed. The children were selected for a birth weight above -2 SDS. The correlation coefficient of birth weight SDS and birth length SDS was 0.51, compared with 0.72 for the reference population. Median length at birth was -0.6 SDS, which fell to -2.5 SDS by 3 years of age. Thereafter, there was no further loss in height SDS. The response to GH treatment was studied in 222 of these prepubertal children who were given six or seven injections/week over a 3-year period. During this time, the median height SDS increased from -2.5 to -1.5, with those children receiving more than 0.65 IU/kg/week having a greater gain in height SDS than those on 0.5 IU/kg/week or less. The degree of bone age delay did not appear to influence the response to GH therapy.

Growth retardation is common in children with chronic renal disease. Final adult height is often reduced, even in children with a functioning renal transplant. The five European studies considered here aim to investigate the efficacy and safety of recombinant human growth hormone therapy (rhGH) in two groups of short children with chronic renal disease. The first group comprises 29 prepubertal children with preterminal chronic renal failure (i.e. before renal transplantation), and the second group comprises 39 prepubertal and pubertal children with functioning renal transplants. The median bone age retardation in the groups at the start of treatment was between 2.2 and 3.7 years; this did not change during the first year of treatment. This interim report concentrates on patients who have been treated for at least 1 year (i.e. 22 children from the first group, and 28 children from the transplant group (15 prepubertal and 13 pubertal children). The median height velocity increased from 4.8 cm/year to 10.0 cm/year in the first group (the chronic renal failure group), from 2.6 cm/year to 6.2 cm/year in prepubertal children with renal transplants and from 3.8 cm/year to 6.7 cm/year in pubertal children with renal transplants. The corresponding changes in height velocity SDS were from -1.3 to 5.1 for the chronic renal failure group and -2.8 to 2.3 for the prepubertal children with renal transplants. Renal function declined in the chronic renal failure group but this decline corresponded to expected progression of the disease. Some of the children with renal transplants showed a decreased renal function, which in most cases was explained by non-compliance or chronic rejection.

To determine the regional prevalence, secular and family-related trends of obesity and overweight among 10-y-old children.A cross-sectional study of 10-y-old children, born in 1990, was performed during September 2000 to June 2001 at school health centres in three communities in the western part of Sweden. Evaluation was performed in 6311 children, or 81% of the target population. Data from a cohort of children, born in 1974, who form the national growth charts, were available for comparison.The mean body mass index was 17.9 kg/m2 in 10-y-old children born in 1990 and 17.0 kg/m2 for 10-y-olds born in 1974 (p0.0001). Of the 10-y-old children in 2000-2001, born in 1990, 18% were overweight and 2.9 % obese, which corresponds to a twofold increase in presence of overweight and a fourfold increase in presence of obesity among 10-y-old children from 1984 to 2000. There was a significant correlation between parental and child body mass index. The prevalence of obesity and being overweight appeared to be higher in children whose parents did not participate in the study.During a 16-y period, from 1984 to 2000, a twofold increase in being overweight and a fourfold increase in obesity were seen among 10-y-old children in the western part of Sweden. Parental ponderosity or reluctance to participate in the study was related to a higher prevalence of being overweight or obese in the children. There is a need for the healthcare system to recognize the threats to the health of the population of this new "epidemic" and initiate preventive measures and treatment programmes.

Girls adopted from developing countries often have early or precocious puberty, requiring treatment with gonadotrophin-releasing hormone (GnRH) analogues. During such treatment, decreased growth velocity is frequent.To study whether the addition of growth hormone (GH) to GnRH analogue treatment improves final height in girls with early or precocious puberty.Forty-six girls with early or precocious puberty (ageor =9.5 y) adopted from developing countries were randomized for treatment for 2-4 y with GnRH analogue, or with a combination of GH and GnRH analogue.During treatment, the mean growth velocity in the GH/GnRH analogue group was significantly higher compared to the control group. Combined GH/GnRH analogue treatment resulted in a higher final height: 158.9 cm compared to 155.8 cm in the GnRH analogue-treated group. Three out of 24 girls (13%) in the combined group and nine of the 22 girls (41%) treated with GnRH analogue alone attained a final height below -2 standard deviation scores (SDS).The difference between the two groups is statistically significant, and possibly of clinical importance. A future challenge is to identify a subgroup with clinically significant advantage of GH addition to GnRH analogue treatment. Being very short on arrival in Sweden and being short and young at start of treatment are possible indicators.

Abnormalities in the GH-IGF-I axis, consistent with GH insensitivity (GHI), have been reported in some patients with idiopathic short stature (ISS). The standard IGF-I generation test (IGFGT) has not demonstrated mild GHI in subjects with ISS. The aim of this study was to investigate the GH-IGF-I axis in ISS by performing standard and novel low-dose IGFGTs together with determination of spontaneous GH secretion.Twenty-one (17 male) prepubertal children with ISS, mean age 8.3 years (4.5-12.2), mean height -3.48 SD (-5.40 to -1.79), mean peak GH to provocation with glucagon/clonidine 32.3 mU/l (14.1-66.0) were studied. Serum IGF-I and IGFBP-3 levels were measured during standard (GH 0.033 mg/kg/day x 4) and low (GH 0.011 mg/kg/day x 4) dose IGFGTs at 0, 12, 36 and 84 h. The low-dose IGFGT was performed in seven naive GH-deficient patients (4 male), mean age 8.5 years (range 4.1-11.1). Determination of spontaneous 24-h GH secretion was performed in the 21 ISS patients.Basal IGF-I and IGFBP-3 standard deviation scores (SDS) in ISS patients were -1.39 (-2.4-1.16) and -0.45 (-1.13-0.38), respectively, IGF-I being lower than IGFBP-3 (P0.0001). IGF-I increased in the standard IGFGT at 12 h (P0.005), 36 h (P0.001) and 84 h (P0.001); maximal increment 1.54 (-0.32-3.48), and in the low-dose test at 12 h (P0.005), 36 h (P0.001) and 84 h (P0.005); maximal increment 0.53 (0.08 to -1.23). IGFBP-3 SDS increased in the standard IGFGT at 36 h (P0.01) and 84 h (P0.001); maximal increment 0.72 (-0.44-1.96), and in the low-dose test at 84 h (P0.005); maximal increment 0.33 (-0.08-0.87). Five/19 patients with an IGF-I response2 x coefficient of variation (CV) of assay in the standard test failed to respond in the low-dose test, suggestive of mild GHI. In GH-deficient patients, IGF-I increased at each time point (P0.05) and IGFBP-3 at 36 h (P0.05). Mean GH secretion, expressed in SDS, compared with 66 normal stature controls was: basal GH -0.48 (-0.84-0.93), height of GH peaks compared with zero -0.36 (-1.26-1.51) (both P0.05), total GH secretion -0.76 (-1.22-0.42), total GH secretion above baseline -0.67 (-1.21-0.94) (both P0.01).In children with ISS, basal IGF-I and IGFBP-3 SDS values were below the mean, IGF-I showing a greater response in both IGFGTs. In the standard IGFGT, the IGF-I increase at 36 h was equal to that at 84 h. The low-dose IGFGT, in combination with the standard test, may identify patients with mild GHI.

Objective: To describe parents’ experiences of having an infant diagnosed with Turner syndrome and to determine whether receiving the diagnosis influenced the parents’ perceptions of their child's development and/or problems during infancy. In addition, we set out to determine whether the late development of the infant and the perceived problems were related to genotype. Methods: In this retrospective study, 54 parents (39 mothers and 15 fathers) from different families, each containing a girl with Turner syndrome, were interviewed in order to describe the development, feeding and overall well-being of their daughter during infancy (defined as being before the age of 2 years). Results: Late development was reported to occur in the areas of motor activity (39%), fine motor control (59%), speech (37%) and language (37%). Feeding problems were frequent (74%) and screaming periods occurred in 41%. No differences were found between the responses of the parents whose children were diagnosed before 2 years of age and the responses of those whose children were diagnosed after 2 years of age. No differences were found concerning development and/or problems between the genotypes. Conclusions: Parents reported delayed development and problems to do with feeding and crying during infancy. These problems had an effect on their everyday life and that of their families, especially the problems relating to feeding. Parents reported that support and advice would have been of significant benefit in coping with the feeding difficulties. Parents were particularly concerned that the personnel at well-baby clinics should be more knowledgeable about the difficulties that can occur in families with an infant with Turner syndrome.

To examine the relationship between growth hormone (GH) and psychological functioning, especially self-perception and well-being, in 60 prepubertal boys of short stature with a wide range of GH levels.A comparison was made of the well-being and self-perception of children with GH insufficiency, children with idiopathic short stature (ISS), a normative sample and healthy boys with normal stature.Children with GH insufficiency had a more negative perception of their own physical appearance than the normative sample. They perceived themselves as more alert but also more inhibited than both the children with ISS and the healthy boys with normal stature. In comparison with the healthy boys with normal stature they perceived themselves as having more stability. The parents of the boys with GH insufficiency also perceived their children as being more stable compared with how the parents of boys with ISS perceived their children. To elucidate the effects of GH on psychological functioning a multiple regression analysis was performed.The lower the levels of GH the more inhibited were the boys of short stature, as perceived both by themselves and by their parents. The boys with GH insufficiency had a more negative perception of their physical appearance than the normative sample.

This study aimed to update growth reference values for height, weight and head circumference in order to reflect the changes in body size in the Swedish population during the past two decades. The data came from a large longitudinal growth study on 3650 full-term healthy Swedish children who were born between 1973 and 1975. All of these 1801 girls and 1849 boys had longitudinal data for height and weight from birth to final height. Comparison with previous Swedish growth reference values based on children born between 1955 and 1958 revealed that there have been secular changes in body size. For instance, at 18 y of age, the updated height and weight reference values are 180.4 cm for males and 167.7 cm for females, i.e. 1.9 cm taller and 5.7 kg heavier for males and 2.3 cm taller and 3.4 kg heavier for females compared with the previous reference values.These new growth reference values provide current national standards for growth monitoring and evaluation since the year 2000.

The aim of this study was to describe the heterogeneity in body proportions of infants born small for gestational age (SGA), defined by birthweight, and to study the relationship of placental size with neonatal anthropometric measurements. Anthropometry was evaluated in 107 symmetrically and asymmetrically growth-retarded infants born SGA (birthweight-2 SD) and compared with 181 appropriate-for-gestational age infants (AGA; birthweight and length +/- 2 SD). Study children were born at Kaunas University Hospital during the period from 1 January 1998 to 25 August 2000. Two-thirds of SGA children were light (SGA(W)) and one-third was both light and short (SGA(WL)) for gestational age. Infants in both SGA groups were significantly leaner than AGA children. SGA(WL) infants had significantly larger heads in relation to their length compared with SGA(W) and even AGA children, probably indicating a brain-sparing effect. SGA(WL) children had the lowest mean placental weight, but the highest placental weight to birthweight (PW/BW) ratio. The PW/BW ratio was inversely correlated with most infant measurements; the strongest negative relationship was observed with birthlength and lower leg length.There is heterogeneity in children born SGA, defined by birthweight. It is suggested that the two SGA groups represent the continuum of intrauterine growth retardation, with an initial reduction in trophic growth and a subsequent retardation of linear growth. The PW/BW ratio is a strong indicator for impaired prenatal linear growth.

The need for continued GH replacement in patients with childhood-onset GH deficiency (GHD) into adulthood has been recognized. The consequences of discontinuing GH treatment on bone mineralization in adolescent patients with GHD and short stature were examined over a period of 2 years.Forty adolescents (aged 16-21 years) treated with GH for more than 3 years and 16 closely matched healthy controls were studied. After a baseline visit, GH treatment was discontinued. The patients were then re-examined with the same protocol after 1 and 2 years. Twenty-one patients had continuing severe GHD into adulthood, while 19 patients were regarded as having sufficient endogenous GH secretion (GHS).At baseline, there were no differences between the groups in total bone mineral content (BMC) or bone mineral density (BMD). After 2 years without GH treatment, BMC increased similarly in the GHD and GHS groups. BMC of the lumbar spine (L2-L4) increased only in the GHD group. Lumbar spine BMD increased in the GHD and the GHS groups. No changes were observed in the femoral neck region. Biochemical measurements showed that carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) and bone specific alkaline phosphates (ALP) were higher in the GHD and GHS groups at baseline compared with controls. Osteocalcin, carboxy-terminal propeptide of type I procollagen (PICP), ICTP and ALP decreased during the 2 years off treatment in both the GHD and GHS groups. PICP was also lower after 2 years in the GHD group compared with both the GHS group and controls.After discontinuation of GH therapy in adolescents at or near final height, there was a continued increase in BMC and BMD both for adolescents with growth hormone deficiency and for those classified as growth hormone sufficient. These groups did not differ from controls at baseline or after 2 years. In the growth hormone deficiency group, biochemical markers for bone formation decreased to levels below those in the growth hormone sufficient and healthy control groups. Although the number of patients and controls in this study were small, the results indicate that the present treatment of Swedish GH-deficient children to final height results in normal BMD.

Body mass index (BMI) is an important indicator of nutritional status. Many studies have been done to present BMI reference values in centile values rather than mean and SD values since its statistical distribution is positively skewed. Both height and weight growth charts are usually available in terms of mean and 1, 2 and 3 SD around the means; it would be of clinical value to produce BMI reference charts in a similar way. The aim of this work was to derive the mean and +/- 1, 2 and 3 SD BMI reference ranges as a supplement to the BMI centile reference values published previously for the same group of Swedish children. The method was based on an age-dependent Box transformation, and the beta-value was given as a third-degree polynomial function over the paediatric age. The BMI reference values can be given from mathematical functions in addition to values for specific ages.The BMI reference values and charts derived as described effectively reflect the nature of the variant age-dependent positive skewed statistical distribution of BMI values in the population, and can serve as a valid supplementary tool in the evaluation of growth and nutrition during paediatric years.

While previous research has suggested that body thinness is related to subsequent linear growth in children, it is unclear whether thinness at birth is related to linear growth in newborns and catch-up growth in small-forgestational age newborns. Drawing on data from a longitudinal growth study of 3,650 full-term Swedish babies, this study examines linear growth from birth to 6 months of age in three groups of newborns with short (-2 SDS), appropriate (-2 to 2 SDS) and long (2 SDS) body length for gestational age. Among infants short at birth, the Benn Index (kg/m2.69) at birth was not related to the odds of short stature (-2 SDS) at age 6 months (odds ratio = 1.03; p0.10). Nonetheless, the Benn Index was positively related to growth velocity in the first 6 months of life in the short (p = 0.060), appropriate (p0.05), and tall (p0.05) for gestational age newborns. Use of the Ponderal Index (kg/m3) would give similar results. The findings suggest that nutritional status at birth is related to linear growth velocity in newborns.

Various prediction models have been developed, based on data documented within KIGS (Pharmacia International Growth Database), for use in the growth hormone (GH) treatment of children with short stature resulting from GH deficiency (GHD) or other causes. In addition to the practical value of such models as part of a 'forward strategy' guiding GH treatment, we now propose that prediction models may also be useful for the identification of individual variance in responsiveness. In a comparison involving 1,800 children with idiopathic GHD (IGHD), 151 children who acquired GHD after treatment for medulloblastoma and 192 children with GHD accompanying craniopharyngioma, it was shown that the responsiveness to GH of patients with craniopharyngioma equalled that of IGHD patients, whereas patients with medulloblastoma were less responsive. These observations and the identification of 'good' and 'poor' responders to GH have practical clinical consequences (e.g. modification of treatment), and will, in the future, lead to the identification of those factors which determine the variability of sensitivity to GH. This will improve the efficacy and safety of GH treatment as well as reducing the costs involved.

It has become common practice to apply GH treatment in short Turner syndrome patients with the objective of promoting growth. The variability in response and the high costs of this treatment demand the individualization and optimization of therapy. Based on 686 prepubertal Turner patients from the Kabi International Growth Study (KIGS; PharmaciaUpjohn, Inc. International Growth Database), we undertook a multiple regression analysis of height velocity (centimeters per yr) by using various parameters of potential relevance. Derived prediction models for the first 4 yr of GH treatment were validated with 76 additional KIGS patients and 81 patients from Tuebingen, Germany. Among the 6 predictors identified, the most influential variable for first year growth response was the natural log (ln) of the weekly GH dose. The first year growth response was also correlated with age and distance between height and target height (SD score; both negative) and body weight SD, number of GH injections per week, and oxandrolone treatment given additionally (positive). The first year model explains 46% of the variability, with 1 SD of 1.26 cm. For the second to fourth years, 5 predictors were identified: height velocity during previous years, weekly GH dose (ln), weight SD, oxandrolone therapy (all positive), and age (negative). These models explained 32%, 29%, and 30% of the variability, respectively, with SD scores of 1.1, 1.0, and 1.0 cm, respectively. When the models were applied to the other cohorts, no significant difference was noted between observed and predicted responses. Although the parameters used in our models do not entirely explain the variability in the growth response in Turner syndrome, the parameters themselves were clinically relevant to our present understanding and proved to be of high precision. Some of the tested markers, such as karyotype, do not contribute to the growth response. These variables make the models practical and suitable for planning beneficial and cost-effective therapy.

The aim of this project was to study the craniofacial morphology, dental occlusion, dental maturation and tooth eruption in short-statured boys with growth hormone secretion ranging from low to high. The measurements from lateral and posteroanterior cephalograms, orthopantomograms and plaster models were used. Almost all linear measurements of the facial structures were significantly smaller. A disproportionate growth in the cranial base structures as well as in the jaws resulted in facial retrognathia, a proportionately smaller posterior than anterior facial height, and a steep vertical inclination of the mandible. Dental crowding was more common and the overbite was small. Dental maturity and tooth eruption were delayed 1.2 and 1.3 yr, respectively. No significant differences between the idiopathic short-statured and the growth hormone-deficient group in any of the above-mentioned variables were found. It can be concluded that although most of the cephalometric variables measured differed significantly from the average, the facial appearance of the boys is not conspicuous and is of minor clinical importance. However, the short-statured boys might be in greater need of orthodontic treatment due to the higher percentage of dental crowding.

We report an epi-analysis of 6-yr growth responses obtained with GH treatment in short children born small for gestational age (SGA). Four randomized, multicenter studies explored the effects of continuous and discontinuous regimens of GH treatment in short, non-GH-deficient SGA children. A total of 49 untreated and 139 treated children were followed over 2 and 6 yr, respectively. At the start of the study, the age of these 188 children averaged 5.2 yr (range, 2-8 yr), height was -3.4 SD score, and height adjusted for parental height was -2.4 SD score. Onset of puberty was observed in 46% of the GH-treated cohort, on the average, at 10.7 yr in girls and 11.7 yr in boys. Two studies essentially investigated the effects of continuous GH treatment at a dose of 33 or 67 microg/kg, day, and two studies focused on the growth characteristics during an initial GH treatment for 2-3 yr (dose range, 33-100 microg/kg x day), followed by a withdrawal phase of 1-2 yr, and then by either no or 1 or more episodes of further GH treatment (33 or 67 microg/kg x day). Continuous GH treatment for 6 yr resulted in height increments of 2.0 +/- 0.2 SD (33 microg/kg x day; n = 35) and 2.7 +/- 0.2 SD (67 microg/kg x day; n = 27). Discontinuous GH treatment was given to 77 children, most of them experiencing only 1 (n = 47) or 2 (n = 26) treatment phases with an average duration of 2.0 yr. All these children received GH during the first 2 yr; the dose was only 32 microg/kg x day when averaged over 6 yr. Some individualization of treatment schedules was allowed, and the majority of investigators seemed to aim for a low normal height level, adjusted for parental height. After 2 yr, the mean adjusted height SD score had increased to -0.4 +/- 0.1 and stabilized thereafter. Bone maturation progressed similarly in all treatment subgroups, and after 6 yr of study, bone age remained slightly delayed compared to chronological age. Multivariate analysis identified the average GH dose over 6 yr, parental-adjusted height SD score, and age at start as prime predictors of the growth response. GH treatment was well tolerated. In conclusion, this epi-analysis of growth responses over 6 yr confirms the administration of GH as an effective approach to normalize the stature of short, non-GH-deficient SGA children, at least during childhood and early puberty. In addition, it is now increasingly apparent that a relatively broad spectrum of GH regimens is effective, and this experience should facilitate the design of more individualized treatment schedules in the future, in particular for young children.