Longitudinal growth during infancy and childhood in children from shanghai: predictors and consequences of the age at onset of the childhood phase of growth

The age at onset of the childhood phase of growth, normally occurring between 6 and 12 mo, is recognized to be an important time during postnatal human development. The aims of this present work were to identify predictors for the age at onset of the childhood phase of growth. Furthermore, this work aimed to examine the consequences that this timing would have on the subsequent heights of 1720 Shanghai children. The mean age of the infants at onset of the childhood phase of growth was 11.2 mo in boys and 10.7 mo in girls. Compared with their Swedish counterparts, these means occurred 1.3 mo later in boys and 1.4 mo later in girls. Both age at onset of the childhood phase of growth and length at 6 mo of age significantly (p < 0.05) contributed to the attained height from 12 mo of age onward; 1-mo delay in the onset of the childhood phase of growth reduced height at 5 y of age by 0.4 cm in boys and 0.5 cm in girls. The age at onset of the childhood phase of growth was negatively associated (p < 0.001) with mid-parental height, although positively related (p < 0.001) to height at 6 mo of age. There was a distinct body mass index pattern of Chinese children between birth and 6 y of age in comparison with white values. There was a sharp increase in body mass index in Shanghainese during their first 6 mo of life, followed by a gradual decline up to 24 mo. In conclusion, the age at childhood onset is equally important when studying children from Shanghai as it is with their Swedish counterparts.     

Insulin-like growth factor binding protein-3 proteolysis and growth of athyreotic infants in the first weeks of life

To gain a better understanding of the growth of athyreotic newborns in the first weeks of life, we evaluated auxological parameters and determined the serum levels of growth hormone (GH), insulin-like growth factor I (IGF-I) and free IGF-I, and IGF-binding protein-3 (IGFBP-3) in 15 hypothyroid infants (10 females) at a mean age of 25 d of life, immediately before the beginning of L-thyroxine therapy, and at 3 and 6 mo of life. Fourteen normal infants (9 females) of the same age were studied as controls. IGFBP-3 proteolytic activity was evaluated in 8 patients and in 8 controls at 25 d and 6 mo of life. There was no significant difference concerning weight and length between the patients and controls at birth, 25 d, 3 and 6 mo of life. The blood GH, IGF-I and IGFBP-3 levels were significantly lower in patients at diagnosis than in controls of the same age (p < 0.01 for all parameters), as well as IGFBP-3 studied by Western blotting. At diagnosis, the patients' free IGF-I level was within the control range, but the free IGF-I percentage of total IGF-I was higher than in the controls (p < 0.01). IGFBP-3 proteolytic activity was found to be greater in the patients (p < 0.01). At 6 mo of life, after therapy, none of these parameters was different from those of the controls. CONCLUSION: Increased IGFBP-3 proteolytic activity in our patients at diagnosis, favouring IGF-I bioavailability, could account for normal free IGF-I levels and in turn for their normal growth pattern during the first weeks of life and before the start of treatment.     

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 microg/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 microg/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 (r(s) = 0.42, p < 0.0005) and body mass index (r(s) = 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 (r(s) = 0.30, p < 0.05 and r(s) = 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.     

The effect of adenotonsillectomy on serum insulin-like growth factor-I and growth in children with obstructive sleep apnea syndrome.

OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) in children is frequently associated with growth interruption. The objective of this study was to evaluate the effect of OSAS and adenotonsillectomy on the insulin-like growth factor-I (IGF-I) axis in children. STUDY DESIGN: Thirteen prepubertal children (mean age, 6.0 +/- 2.8 years) were studied before and after adenotonsillectomy (T&A). Weight, height, overnight polysomnography, and IGF-I and IGF-binding protein-3 levels were evaluated before and 3 to 12 months after T&A. The children's weights and heights were monitored for 18 months. RESULTS: The respiratory disturbance index improved from 7.8 +/- 9.1 events/h to 1.0 +/- 2.1 events/h after T&A (P <.02). Slow-wave sleep increased from 29.1% +/- 7.2% to 34.6% +/- 9.8% after T&A (P <.02). The weight standard deviation score increased from 0.86 +/- 1 to 1. 24 +/- 0.9, 18 months after T&A (P <.01). Serum IGF-I levels increased from 146.3 +/- 76.2 ng/mL before T&A to 210.3 +/- 112.5 ng/mL after surgery (P <.01), but IGF-binding protein-3 levels did not change significantly. CONCLUSION: The respiratory improvement after T&A in children with OSAS is associated with a significant increase in serum IGF-I levels and weight. We conclude that the IGF-I axis is affected in children with OSAS.     

Levels of insulin-like growth factor I in full- and preterm human milk in comparison to levels in cow's milk and in milk formulas

The content of insulin-like growth factor I (IGF-I) in human milk, cow's milk and cow's-milk-based infant formulas was determined by radioimmunoassay. The mean levels of IGF-I in full-term milk and preterm milk 0-4 days post partum 2.2 +/- 0.3 and 2.4 +/- 0.5 ng/mg protein, respectively. The IGF-I content in human milk was not affected by gestational age or birth weight and was constantly excreted up to 10 days post partum. The IGF-I content in human milk was significantly higher than that in cow's milk (0.6 +/- 0.1 ng/mg protein, p less than 0.01). IGF-I was not detected in the milk formulas. The IGF-I in human milk might be absorbed or could act locally in the intestine and may be of importance in the nutrition of neonates.     

New reference for the age at childhood onset of growth and secular trend in the timing of puberty in Swedish

The objectives of the present work were to present a new reference for the age at childhood onset of growth and to investigate the secular trend in the timing of puberty in a community‐based normal population in Sweden. A total of 2432 children with longitudinal length/height data from birth to adulthood were used to determine the two measures by visual inspection of the measured attained length/height and the change in growth velocity displayed on a computer‐generated infancy‐childhood‐puberty (ICP) based growth chart. The series represents a sample of normal full‐term children born around 1974 in Göteborg, Sweden. We found about 10% of children were delayed (>12 mo of age) in the childhood onset of growth based on the previous reported normal range, i.e. 14% in boys and 8% in girls. Distribution of the age at childhood onset of growth was skewed. The medians were 10 and 9 mo for boys and girls, respectively. After natural logarithmic transformation, the mean and standard deviation (SD) were 2.29 (anti‐log 9.9 mo) and 0.226 for boys, 2.23 (anti‐log 9.3 mo) and 0.220 for girls, respectively. The 95% normal ranges were 6.3‐15.4 and 6.0‐14.3 for boys and girls, respectively. The distribution of the timing of PHV was close to the normal distribution. The mean values were 13.5 y for boys and 11.6 y for girls with 1 y SD for both sexes. Conclusion: A downward secular trend in the onset of puberty was clearly shown in the population. The age at childhood onset of growth did not correlate with the timing of puberty (r=?0.01 and 0.05, p > 0.7 and 0.1 in boys and girls, respectively). Normal ranges of the age at childhood onset of growth are in need of revise, as this study indicates. The new reference presented here could be a reliable indicator in further studies.     

Physical growth and retinopathy in preterm infants: involvement of IGF-I and GH.

GH and IGF-I are important for physical growth. We measured serum levels of these factors in preterm infants. The study population (n = 81) was divided into three groups according to the gestational age. We evaluated differences in serum GH and IGF-I levels among groups with regard to physical growth and development of retinopathy of prematurity. Serum GH levels in extremely preterm infants born at <28 wk of gestational age were significantly higher than levels in those born between 28 and 34 wk at 1 and 2 mo of age. In contrast, serum IGF-I levels in extremely preterm infants remained low, whereas those in the other two groups gradually increased. Evaluation of the effects of GH and IGF-I on physical growth in very low birth weight infants (<1500 g) showed that IGF-I concentrations were positively related to physical growth for several months after birth, whereas no relationship was observed between GH and physical growth. Multivariate analysis demonstrated that high GH concentration at 1 mo of age was significantly associated with development of severe retinopathy of prematurity. In conclusion, persistent low serum IGF-I levels may explain the slow physical growth during neonatal life, and exposure of high GH may cause, at least in part, severe retinopathy of prematurity in preterm infants.     

Age related IGF-I changes and IGF-I generation in thalassemia major

We measured serum concentrations of insulin like growth factor-I (IGF-I) in 20 thalassemic males with short stature (height SDS <-2) and/or slow growth velocity (GV <-1 SD) throughout their childhood and adolescence, compared these data with normal reference data validated in our lab, and evaluated their growth hormone secretion in response to clonidine and glucagon stimulation. We also performed IGF-I generation test on 26 patients with beta thalassemia major (BTM) before and after blood transfusion to evaluate the effect of increased hemoglobin (Hb) on IGF-I and its response to GH. We obtained the following results. 1) No statistical difference in age, HSDS, target height SDS or bone age was observed between BTM patients with growth hormone deficiency (GHD) compared to those with normal GH secretion (GHS). 2) The age-related levels in serum total IGF-I in thalassemic males were significantly decreased from early childhood to 18 years of age compared to normal subjects. Thalassemic males with GHD did not show any significant peak of IGF-I levels until 18 years of age, whereas thalassemic males with normal GH response to provocation (GHS) achieved a significant peak level of IGF-I that was attenuated and late compared to normal males. The basal serum IGF-I concentrations at different ages did not differ between the GHD and GHS groups until the age of 12 years. After 12 years of age, IGF-I levels were significantly higher in thalassemic children with GHS. A significant increase in the circulating basal IGF-I concentrations from 53 +/-35 ug/l to 82.6 +/- 39 ug/L was achieved with increasing Hb concentration after blood transfusion. The serum total IGF-I levels increased significantly with the administration of human growth hormone (hGH) for 4 days, both before and after blood transfusion. The peak IGF-I response to GH injections did not differ before compared to after blood transfusion. The percent increment of IGF-I levels generated after GH injections was higher in thalassemic children with GHD as compared to those with GHS both before and after blood transfusion. In conclusion, our results showed that agerelated serum IGF-I concentrations were significantly lower in short thalassemic patients, with and without GHD, during childhood and adolescence, compared to normal standards. Correction of anemia significantly increased serum concentration of IGF-I but does not affect the increase of IGF-I in response to GH stimulation.     

Reduction of serum insulin-like growth factor-I by dietary protein restriction is age dependent

We have determined if dietary protein restriction for 1 wk has differential effects on growth, serum IGF-I, and liver growth hormone receptors at various stages of development. Female Wistar rats were fed a low (5%) protein diet for 7 d at 3, 4, 6, 8, and 12 wk of age, whereas controls were maintained on a normal (15%) protein diet. Body wt gain was impaired in the groups fed the low protein diet, despite normal energy intake, and the effect was attenuated with age. Liver cell number (DNA content) was reduced by low protein feeding in the 3-, 4-, and 6-wk age groups (p less than 0.01), but not in the older animals. Protein restriction caused a dramatic decrease in serum IGF-I in the younger animals (90 and 82% reduction versus normal fed age-matched controls, at 3 and 4 wk, respectively; p less than 0.001), and this effect was progressively attenuated with increasing age (49, 40, and 25% reductions of serum IGF-I at 6, 8, and 12 wk, respectively). Changes in serum IGF-I correlated with those of liver cell number (r = 0.80; p less than 0.001). Total and free liver growth hormone receptors were slightly decreased in the low protein diet groups at 4 (p less than 0.05) and 6 wk (total: p less than 0.001; free: p less than 0.01) but not in the other age groups. The occurrence of profound diet induced reductions in IGF-I without proportional reductions in liver GH receptors suggest that the apparent GH resistance occurs at a postreceptor level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin, insulin-like growth factors-I and -II and insulin-like growth factor binding protein-3 in newborn serum: association with normal fetal head growth and head circumference

The insulin-like growth factors (IGF) and their binding proteins (IGFBP) have been implicated in the regulation of fetal weight and length. The aim of our study was to determine the relationship between head circumference at birth and serum levels of IGF-I, IGF-II, IGFBP-3 and insulin in full-term appropriate-for-gestational age (AGA) infants. Serum samples were obtained from 77 singleton full-term neonates, 69 AGA and 8 small-for-gestational age (SGA). The AGA infants were divided into three groups by head circumference: Group 1: < or = 3rd percentile; Group 2: at 50th percentile; Group 3: > or = 97th percentile. Serum levels of IGF-I, IGF-II, IGFBP-3 and insulin were determined with commercial kits and immunometric methods. There were no statistically significant differences in mean serum levels of IGF-I, IGF-II and IGFBP-3 between the groups. A significantly higher mean serum insulin level was noted in the AGA infants with a head circumference > or = 97th percentile compared to those with a head circumference < or = 3rd percentile (4.6 +/- 0.3 vs 3.3 +/- 0.6 microU/ml; p = 0.04), and in AGA infants with a head circumference above the 50th percentile compared to those with a head circumference below the 50th percentile (4.4 +/- 0.4 vs 3.3 +/- 0.3 microU/ml; p = 0.01). AGA infants with a head circumference above or below the 50th percentile did not differ statistically in their mean IGF-II and IGFBP-3 serum level, while IGF-I differed statistically between the groups (18 +/- 2.7 vs 11.6 +/- 1.6 ng/ml, respectively; p = 0.045). Using univariate analysis, head circumference correlated positively with insulin (r = 0.29; p = 0.016) and with IGF-I (r = 0.26; p = 0.03). A stepwise multivariate linear regression analysis, however, did show statistically significant correlation of head circumference with birth weight (f = 36; p = 0.0001), and only marginally with birth length (f = 4.7; p = 0.06) and insulin (f = 3.4; p = 0.07). No correlations were found between head circumference and IGF-I, IGF-II or IGFBP-3. These data suggest that apart from genetic and nutritional factors, insulin may play a role in promoting intrauterine head growth, as reflected by head circumference at birth.     

Inflammatory and growth mediators in growing preterm infants

Little is understood about the optimal balance between IGF-I and antagonistic inflammatory mediators, such as IL-6, in growing preterm infants. Using a prospective cohort study, we investigated the relationship between postnatal growth of preterm infants and key growth and inflammatory mediators. We studied 51 stable, growing preterm infants (mean gestational age: 27.8 +/- 0.4 weeks, mean birth weight: 1,032.8 +/- 50.6 g). IL-6 and IL-1ra (reflecting stress/ inflammation) and IGF-I and GHBP (reflecting anabolic activity and GH sensitivity) were measured at enrollment and discharge using ELISA. During the observation period (mean 6.1 +/- 0.34 weeks) there was a significant increase in weight (1,396 +/- 81 g, p < 0.0001). IGF-I increased from 46.6 +/- 4.1 to 88.7 +/- 5.2 ng/ml (p < 0.001). In contrast, IL-6 decreased from 9.5 +/- 1.0 to 2.3 +/- 0.34 pg/ml (p <0.001) and IL-1ra from 6,042 +/- 362 to 4,851 +/- 365 ng/ml (p = 0.007). GHBP increased from 65.8 +/- 6.7 to 82.5 +/- 7.9 ng/ml (p = 0.003). IL-6 was inversely correlated with IGF-I (p < 0.001). In addition, a multiple regression model showed IGF-I levels correlated positively and IL-6 levels inversely with various parameters of growth. Growth in preterm infants is characterized by increases in IGF-I and GHBP with simultaneous decreases in IL-6 and IL-1ra. Efforts to optimally balance inflammatory and growth mediators may benefit somatic growth in infants very early in life.     

Anticholinergic treatment improves glycaemic control in adolescent girls with insulin-dependent diabetes mellitus

Metabolic control often deteriorates during puberty in girls with insulin-dependent diabetes. It is well accepted that there is an abnormality in the growth hormone (GH)-insulin-like growth factor-I (lGF-I) axis in these girls, resulting in reduced IGF-I levels and elevated GH. As GH antagonizes insulin, attempts have previously been made to reduce excess GH secretion through anticholinergic treatment. However, most of these studies have been performed on adult patients. The aim of the present study was to evaluate the effects of 12 wk of oral anticholinergic treatment with Pirenzepine, 100 mg twice daily, in 16 adolescent girls with diabetes. Serum samples of IGF-I, glycated haemoglobin and fasting IGF-binding protein 1 were analysed at initiation and after 3, 8 and 12 wk of Pirenzepine therapy. Nocturnal urinary GH excretion was also examined. Glycated haemoglobin declined significantly after 3 wk of Pirenzepine therapy (9.8 +/- 0.18 vs 9.2 +/- 0.17; p < 0.001) and was still improved at the end of the study. Unexpectedly, nocturnal urinary GH excretion did not change. Serum IGF-I continuously increased during the study, while IGF-binding protein 1 levels were not significantly altered. Conclusion: Anticholinergic treatment with Pirenzepine improves glycaemic control in adolescent girls with diabetes. Although nocturnal urinary GH excretion was unchanged there may still be changes in pituitary GH secretion to explain the improvement. Effects of Pirenzepine on gastrointestinal motility can represent other possible mechanisms behind the improved metabolic control.     

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目的探讨血胰岛素样生长因子I(IGFI)与早产儿早期营养、生长调控的关系。方法采用酶联免疫法测定41例早产适于胎龄儿出生后第8、15天的血清IGFI质量浓度。同时监测早产儿的体重、Kaup指数以及每天实际摄入的能量、蛋白质和母乳量。结果早产儿出生后第8天血清IGFI质量浓度与胎龄、出生体重以及出生后3～7d实际摄入的能量、蛋白质的量呈正相关(P<0.05)。第15天血清IGFI质量浓度与出生后8～14d实际摄入的能量、蛋白质的量呈正相关(P<0.05),而与胎龄、出生体重不相关(P>0.05)。早产儿在出生体重、胎龄、摄入的蛋白质和能量的量同等的情况下,摄入母乳量对血清IGFI质量浓度有正性影响(P<0.05)。血清IGFI质量浓度随着早产儿的日龄而上升,与体重增长速度和Kaup指数呈正相关(P<0.05)。结论血清IGFI质量浓度受到早产儿摄入能量、蛋白质、母乳量和日龄的影响,是早产儿生后早期的生长调控激素,IGFI可作为反映早产儿早期营养和生长的一个指标。     

Insulin-like growth factors in childhood-onset Gaucher disease

There is a high prevalence of growth retardation in children with type 1 Gaucher disease. The cause of this poor growth is not yet known; however, studies have shown acceleration of growth with enzyme replacement therapy (ERT). IGF are recognized as important determinants of somatic growth. It has been proven that chronic diseases with liver involvement might cause IGF deficiency. The aim of this study was to assess the IGF system in patients with childhood-onset Gaucher disease, before and after ERT, and its association with other clinical and analytical parameters. Twenty-two patients with type I Gaucher disease were included. The diagnosis was established before 14 y of age in all patients. Baseline determinations of total IGF-I, free IGF-I, and IGF binding protein 3 (IGFBP-3) were obtained in 19 patients before starting ERT at a mean age of 13.8 +/- 11.2 y. A Spearman test was performed to establish the association with other clinical and analytical parameters. In a group of 13 patients receiving IGF, changes were evaluated during the initial 2 y of treatment. A Wilcoxon test was performed for the statistical analysis. Total IGF-I, free IGF-I, and IGFBP-3 were expressed as SD scores (SDS). We found low levels of IGF and its binding proteins before ERT. A significant association was found between the total IGF-I SDS before treatment and the age-adjusted severity score index: r = -0.62, p < 0.05. Total IGF-I and IGFBP-3 SDS correlated negatively with the presence of the L444P mutation (r = -0.53 and -0.5, respectively, p < 0.05). Height SDS correlated with total IGF-I and IGFBP-3 SDS in eight children (r = 0.84 and 0.78, respectively, p < 0.05). Total IGF-I SDS increased from -1.8 +/- 0.8 to -0.8 +/- 1.4 (p = 0.005) and free IGF-I increased from -1.2 +/- 1 to 1.1 +/- 2.1 after 12 +/- 6.8 mo (p = 0.011) of ERT. IGFBP-3 SDS increased from -1.3 +/- 0.6 to -0.2 +/- 1.2 (p = 0.012) after 12 +/- 4.5 mo of ERT. Type 1 Gaucher disease is associated with low levels of IGF and its binding proteins, which could be a consequence of liver involvement. Total IGF-I deficiency is associated with the severity of the illness. Growth retardation in pediatric patients with Gaucher disease is related to the alterations in IGF axis. Total IGF-I and IGFBP-3 are the two parameters that better correlate with height before treatment. ERT results in significant increase of total IGF-I, free IGF-I, and IGFBP-3 during the first year of treatment.     

An open label 12-month pilot trial on the effects of the aromatase inhibitor anastrozole in growth hormone (GH)-treated GH deficient adolescent boys

OBJECTIVE: To investigate whether 12 mo treatment with the aromatase inhibitor anastrozole can achieve sustained suppression of estrogen production and delay epiphyseal fusion in growth hormone deficient (GHD) adolescent males. STUDY DESIGN: 20 adolescents with GHD were recruited (mean age +/- SE: 14.7 +/- 0.5 yr). Ten continued on GH (control group), and 10 on GH and anastrozole (Rx group) for 12 mo. RESULTS: After 12 mo E2 concentrations declined 60% in the Rx group (from 1.8 +/- 0.5 to 0.7 +/- 0.3 pg/ml, p <0.05) whereas they increased in controls (from 1.2 +/- 0.7 to 1.8 +/- 0.7, p <0.05). Testosterone increased 117% in the Rx group (from 304 +/- 31 to 626 +/- 64 ng/dl), 47% in controls (from 274 +/- 89 to 398 +/- 51) (p = 0.03, ANOVA between groups). IGF-I increased 42% in controls (454 +/- 22 to 711 +/- 109 ng/ml, p <0.05), but remained invariant in the Rx group (446 +/- 29 to 540 +/- 80, p = NS). Bone markers, plasma lipids, insulin, glucose, and liver function tests were all unchanged between groups with no differences either in body composition or bone mineral density accrual. There were no differences in growth velocity, height SDS, bone age advancement, predicted adult height or testicular volumes between groups after 12 mo. CONCLUSIONS: Anastrozole treatment potently decreases estrogen concentrations in adolescent males with GHD while allowing normal virilization, without deleterious effects on body composition, plasma lipids, bone metabolism or the tempo of puberty. Twelve months of treatment, however, did not increase predicted adult height. Further studies are needed to ascertain whether more prolonged estrogen blockade is helpful in the treatment of growth retardation in puberty.     

Effect of zinc supplementation on growth hormone secretion, IGF-I, IGFBP-3, somatomedin generation, alkaline phosphatase, osteocalcin and growth in prepubertal children with idiopathic short stature

Controversy exists about the effect of zinc on growth and the GH-IGF system. Zinc supplementation has been shown to stimulate linear growth in zinc-deficient children. However the mechanism of this effect has not been well characterized. Furthermore, the effect of zinc supplementation on non-zinc-deficient short children is unknown. We investigated the effect of zinc supplementation on endogenous GH secretion, serum IGF-I and IGFBP-3 concentrations, IGF-I and IGFBP-3 generation in response to exogenous GH, bone formation markers, and linear growth of non-zinc-deficient children with idiopathic short stature. We analyzed prospectively serum zinc, IGF-I, IGFBP-3, alkaline phosphatase, osteocalcin, and GH response to clonidine test, and performed a somatomedin generation test before and 6 weeks after zinc supplementation in 22 (16 M, 6 F) prepubertal children with idiopathic short stature. Serum IGF-I increased from 67.4+/-70.6 to 98.2+/-77.3 ng/ml (p <0.001), IGFBP-3 from 2326+/-770 to 2758+/-826 ng/ml (p <0.001), alkaline phosphatase from 525+/-136 to 666+/-197 U/l (p <0.0001), and osteocalcin from 16.8+/-10.6 to 25.8+/-12.8 ng/ml (p <0.05) after zinc supplementation despite there being no difference in GH response to clonidine after zinc supplementation (peak GH 11.6+/-6.9 vs 13.4+/-7.8 ng/ml, GH area under the curve during clonidine test 689+/-395 vs 761+/-468, NS). Percent change in IGF-I and IGFBP-3 during the somatomedin generation test was not significantly affected by zinc supplementation (118% vs 136% and 57% vs 44%, respectively). There was no significant correlation between percentage increase in zinc levels and percentage increase in parameters tested. Height SDS or weight SDS did not improve significantly in 17 patients who continued on zinc supplementation for at least 6 months (6-12 months) (-2.59 vs -2.53 SDS and -1.80 vs -1.67 SDS, respectively). Zinc supplementation increased basal IGF-I, IGFBP-3, alkaline phosphatase and osteocalcin without changing GH response to clonidine. Zinc supplementation did not affect sensitivity to exogenous GH as tested by IGF-I and IGFBP-3 generation test. These results suggest a direct stimulatory effect of zinc on serum IGF-IGFBP-3, alkaline phosphatase and osteocalcin. Despite improvements in the above parameters, zinc supplementation to children with idiopathic short stature with normal serum zinc levels did not significantly change height or weight SDS during 6-12 months follow-up.     

Maternal and fetal serum insulin-like growth factor-I (IGF-I) IGF binding protein-3 (IGFBP-3), leptin levels and early postnatal growth in infants born asymmetrically small for gestational age

This study was planned to investigate the relationship between birth weight and insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), and leptin levels in neonates with normal growth (appropriate for gestational age: AGA) and retarded growth (small for gestational age: SGA); and to evaluate these growth factors' effects in early postnatal growth. All newborns were full-term: gestational age 3,841 weeks. Of 50 neonates, 25 were SGA. IGF-I, IGFBP-3 and leptin levels were measured in maternal serum and venous cord blood at birth and at 15 days of life of neonates using specific RIAs. Maternal serum leptin concentrations were significantly higher than cord blood leptin concentrations (p < 0.001). Maternal serum IGF-I, IGFBP-3 and leptin levels did not show correlations with birth weight. In contrast, there were significantly positive correlations between birth weight and venous cord blood IGF-I, IGFBP-3 and leptin levels (p < 0.001). In the SGA group, the newborns with a slow postnatal growth pattern had lower umbilical cord serum IGF-I levels compared with newborns with a normal growth pattern. A similar result was also found in the AGA group. Similar results were not found for serum leptin and IGFBP-3. In conclusion, cord blood IGF-I, IGFBP-3 and leptin levels play an important role in the regulation of fetal and neonatal growth. It is likely that IGF-I has a more important role than the other factors in early postnatal growth.     

Effect of exercise on cytokines and growth mediators in prepubertal children.

Many of the anabolic effects of exercise are mediated through insulin-like growth factor-I (IGF-I), but in adolescents, brief exercise training leads to reductions, rather than the expected increase, in circulating IGF-I. Certain cytokines--interleukin-(IL) 1beta (IL-1beta), IL-6 (IL-6), and tumor necrosis factor-alpha--are increased by exercise in adults and are known to inhibit IGF-I. To test the hypothesis that these cytokines might play a role in the adaptation to exercise, we measured the acute effects of exercise on selected cytokines and growth factors in 17 healthy 8- to 11-y-old children (4 females). Designed to mimic patterns and intensity of exercise found in the real lives of American children, the exercise protocol consisted of a 1.5-h soccer practice (of which about 40 min constituted of vigorous exercise). Pre- and postexercise urine and saliva samples were obtained in all subjects and both blood and urine in nine subjects. The exercise led to significant increases in circulating tumor necrosis factor-alpha (18 +/- 7%, p < 0.05) and IL-6 (125 +/- 35%, p < 0.01) as well as a significant increase in the antiinflammatory cytokine IL-1 receptor antagonist (33 +/- 10%, p < 0.01). Urine levels of IL-6 were also substantially increased by exercise (440 +/- 137%, p < 0.0001). Circulating levels of IGF-I were reduced to a small but significant degree (-6.4 +/- 3.2%, p < 0.05), although IGF-binding protein-1 (known to inhibit IGF-I) was substantially increased (156 +/- 40%, p < 0.001). Cytokines are systemically increased after relatively brief exercise in healthy children. This increase may alter critical anabolic agents such as IGF-I and its binding proteins.     

Linear growth in early treated children with congenital hypothyroidism

Length/height was studied from birth to 6 years of age in 103 children with congenital hypothyroidism identified by the Norwegian or Swedish screening programs. We used the "infancy-childhood-puberty (ICP) growth model". This model describes normal linear growth during the first 3 years of life by an infancy component with the addition of a childhood component, the latter acting from the second half of the first year. In comparison with reference children, children with hypothyroidism had reduced growth from 6 to 12 months, and increased growth after 12 months of age. Mean onset of the childhood component of growth was delayed from 8.1 months (SD 1.9) to 10.4 months (SD 2.2) in girls, and from 8.9 months (SD 2.0) to 11.0 months (SD 2.1) in boys. Age at onset of the childhood component was correlated with age at start of treatment ( r = 0.24), and in children with more severe hypothyroidism (pretreatment serum thyroxine <40 nmol/l) inversely correlated with the L-thyroxine dose at start of treatment ( r = -0.40). Change in height standard deviation score from 1 to 3 years of age was correlated with the serum thyroxine concentration at age 1 year ( r = 0.30). The delay in the onset of the childhood component of growth and the association with age at start of treatment and initial L-thyroxine dose indicate that thyroid hormones during the first months of life are essential for normal onset of the childhood component of growth, which otherwise is assumed to be growth hormone-dependent.     

Serum insulin-like growth factor-I (IGF-I), IGF-binding protein-3, and growth hormone levels in collodion babies: a case-control study

AIM: Because growth failure occurs in many collodion babies, we investigated serum growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels in collodion babies admitted to Gevher Nesibe Hospital, Kayseri, Turkey between 1999 and 2006. PATIENTS AND METHOD: The newborns diagnosed clinically as 'collodion baby' were included in the study group (group 1). Because collodion babies are usually born small for gestational age (SGA) and/or premature, a control group (group 2) was formed by selecting the first infant admitted immediately after each study infant who matched for gestational age (+/- 7 days) and birth weight (+/- 100 g). All infants' blood samples were collected within the first 2 h of life for measurements of serum GH, IGFBP-3 and IGF-I levels. RESULTS: Group 1 consisted of 23 collodion babies (13 males and 10 females) with gestational ages ranging from 32 to 42 weeks, and birth weights ranging from 1,300 to 3,600 g. Ten were born premature and 16 were SGA. Serum IGF-I and IGFBP-3 levels were lower but serum GH levels were higher in collodion babies than in controls. Birth weight was positively correlated with serum IGF-I (r = 0.310, p = 0.046) and IGFBP-3 (r = 0.389, p = 0.011) levels. Serum GH level was negatively correlated with birth weight (r = -0.376, p = 0.014), serum IGF-I (r = -0.567, p <0.001) and IGFBP-3 (r = -0.444, p = 0.003). CONCLUSION: Collodion babies had lower serum IGF-I and IGFBP-3 levels but higher serum GH levels than controls in the present case-control study. The underlying mechanism needs to be explored.