http://repub.eur.nl/res/aut/15050/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/23766/ 2011-01-01T00:00:00Z Objective: Previous studies showed conflicting data on the effect of prematurity on bone mineral density (BMD) in infants and children. Only a few studies investigated the long-term effects of prematurity on BMD in early adulthood. The objective of our study was to assess the long-term effects of preterm birth on BMD of the total body (BMDTB), lumbar spine (BMDLS) and bone mineral apparent density of the LS (BMAD LS). Design: Cross-sectional study. Methods: It consists of two hundred and seventy-six healthy subjects without serious postnatal complications, aged 18-24 years. The contribution of gestational age to the variance in BMD in young adulthood and the differences in BMD between 151 subjects born preterm (median gestational age 32.2 weeks (interquartile range (IQR) 30.3-34.0)) and 125 subjects born at term (median gestational age 40.0 weeks (IQR 39.0-40.0)) were investigated. BMD was determined by dual-energy X-ray absorptiometry. Results: There were no significant linear correlations between gestational age and BMDTB (r = 0.063, P = 0.30), BMDLS (r = 0.062, P = 0.31) and BMADLS (r = 0.069, P = 0.26). Also after adjustment for possible confounders, gestational age was no significant contributor to the variance in BMDTB (P = 0.27), BMDLS (P = 0.91) and BMADLS (P = 0.87). No significant differences were found between preterm and term subjects with regard to BMDTB, BMD LS and BMADLS. Conclusion: In our cohort of 276 young adults, aged 18-24 years, gestational age was not a significant determinant in the variance of BMD. Preterm birth without serious postnatal complications is not associated with a lower BMD in young adulthood. http://repub.eur.nl/res/pub/28068/ 2010-12-01T00:00:00Z Background/objectives: Preterm birth has been associated with reduced reproduction rates, and controversies remain regarding the effect of being born small for gestational age (SGA) on ovarian function. Recent findings in young men showed no effect of preterm and SGA birth on testis function. We hypothesised that follicle pool size in young adult women is also not affected by preterm and SGA birth. Design/methods: In 279 young women of the PROGRAM/PREMS study, aged 18-24 years, the influence of gestational age, birth length and birth weight on serum levels of anti-Müllerian hormone (AMH) was analysed with multiple regression modelling. Additionally, AMH levels were analysed in preterm- versus term-born females and in three subgroups: females born SGA with either short stature or catch-up growth (SGA-CU), and females born term and appropriate for gestational age with normal stature (AGA controls). Results: Preterm and SGA birth did not affect AMH and other hormone levels. Older age at menarche and oral contraceptive pill use (OC-use) were related to lower AMH levels, and maternal smoking during gestation was related to higher AMH levels. After correction for maternal smoking, lower socioeconomic status (SES) was associated with lower AMH levels. In subgroup comparisons, SGA-CU women showed higher AMH levels than AGA controls, also after adjustment for several factors. Conclusion: Preterm and SGA birth did not affect AMH levels. Factors associated with serum AMH levels were OC-use, age at menarche, maternal smoking during gestation and SES. We conclude that preterm- and/or SGA-born females are not likely to have a reduced follicle pool size. http://repub.eur.nl/res/pub/28082/ 2010-12-01T00:00:00Z Objective: Smaller size at birth has been associated with an increased risk of metabolic and cardiovascular disorders in adult life. Fetal programing of the hypothalamic - pituitary - adrenal axis has been suggested as a possible explanation. Fetal glucocorticoid (GC) overexposure has effects that suggest a role of GCs in this programing. The effects of GCs are mediated through the GC receptor (GR or NR3C1). Several functional polymorphisms have been described, which are associated with relative GC resistance or hypersensitivity. Our aim is to compare frequencies of GR haplotypes, characterized by the R23K, N363S, Bcl1, or 9β polymorphisms, in subjects born small for gestational age (SGA) and associate birth anthropometry data, response to GH treatment, blood pressure, glucose and insulin concentrations, and body composition with these haplotypes. Design: In total, 418 SGA subjects and 697 healthy controls were enrolled in this study. Methods: Anthropometry data were obtained, as well as blood samples to determine fasting glucose and insulin concentrations. Dual energy X-ray absorptiometry scans were used to measure the amount of fat and lean mass. Results: No differences were found between GR haplotype frequencies in SGA children compared with healthy controls. No associations were found between GR haplotypes and birth length and birth weight, growth response during GH treatment, blood pressure, glucose and insulin concentrations, and body composition. Conclusion: GR haplotypes and their effect on GC sensitivity do not seem to play a significant role in GH-induced catch-up growth and the risk factors of developing metabolic and cardiovascular disorders in adult life of SGA children. http://repub.eur.nl/res/pub/25378/ 2009-11-01T00:00:00Z Background/Objectives: Preterm birth has been associated with reduced reproduction rates and being born small for gestational age (SGA) with reduced gonadal function. We hypothesized that alterations concerning gonadal function in young men are not due to preterm birth or being born SGA, but are due to other (environmental) factors. Methods: In 207 young men of the PROGRAM/PREMS cohort study, aged 18-24 yr, the influence of preterm birth, birth length, and birth weight on serum levels of anti-Mullerian hormone, inhibin B, testosterone, SHBG, non-SHBG-bound testosterone, LH, and FSH was analyzed with multiple regression modeling. In addition, markers of male gonadal function were analyzed in four subgroups: men born SGA with either short stature or catch-up growth, or men born appropriate for gestational age with idiopathic short stature or with normal stature (control). Results: Preterm birth and SGA did not affect gonadal function. After adjustment for age, birth size, adult height, fat mass, and socioeconomic status (SES), preterm birth even showed a positive relation with inhibin B. Higher SES was associated with higher inhibin B levels. Higher fat mass was associated with decreased testosterone and SHBG levels and maternal smoking with increased LH and non-SHBG-bound testosterone levels. After adjustment for confounders, there were no significant differences in gonadal function between the subgroups. Conclusion: Preterm birth and SGA did not affect gonadal function in young men. Factors that affected gonadal function were: lower SES, a higher fat mass, and maternal smoking during pregnancy. Copyright http://repub.eur.nl/res/pub/24766/ 2009-07-01T00:00:00Z Context We previously reported that short, small for gestational age (SGA) children who were born preterm have a lower body fat percentage and a higher blood pressure, insulin secretion and disposition index than short SGA children born at term. Whether preterm birth also influences these parameters during GH treatment is unknown. Objective To compare blood pressure, insulin sensitivity, beta-cell function and body composition during 4 years of GH treatment, between preterm and term short SGA children. Patients A total of 404 prepubertal non-GH-deficient short SGA children were divided into 143 preterm (< 36 weeks) and 261 term children. Outcome measures Height, blood pressure (n = 404), body composition measured by dual energy X-ray absorptiometry (DXA) (n = 138) and insulin sensitivity and beta-cell function calculated from a frequent sampling intravenous glucose tolerance test (FSIGT) with tolbutamide (n = 74) or from the homeostasis model assessment of insulin resistance (HOMA-IR) (n = 204). Results In preterm and term children, GH treatment resulted in a similar decrease in systolic and diastolic blood pressure, body fat percentage, limb fat/total fat ratio and insulin sensitivity, and a similar increase in insulin secretion and disposition index. Lean body mass (LBM) corrected for gender and height increased in term children and did not change in preterm children. Multiple regression analysis revealed that this difference in GH effect on LBM was not associated with gestational age. Conclusion The effect of GH treatment on metabolic and cardiovascular risk factors is similar in preterm and term short, SGA children. http://repub.eur.nl/res/pub/24370/ 2009-06-01T00:00:00Z Context: IGF-I and IGFBP-3 play a central role in fetal and postnatal growth and levels are low in short SGA children. The -202 A/C and -185 C/T SNPs are located near elements involved in directing IGFBP3 promoter activity and expression. Changes in promoter CpG methylation status affect transcription factor binding and transcriptional activation of IGFBP3 in vitro. Objective: To assess the relationship between IGFBP3 promoter SNPs, IGFBP-3 levels, spontaneous growth and growth response to GH treatment in short prepubertal SGA children. To assess promoter methylation status in a subgroup of short SGA subjects and controls. Patients: 292 Short prepubertal SGA children, 39 short young SGA adults and 85 young adults with normal stature. Intervention: Short prepubertal SGA children received GH 1 mg/m2/day. Outcome measures: Fasting levels of IGF-I and IGFBP-3, baseline and delta height SDS. Results: At baseline, IGFBP-3 levels were highest in SGA children with -202 AA genotype and lower in children with 1 or 2 copies of the C-allele (P < 0.001). Children with C-202/C-185haplotype, compared to children with A-202/C-185haplotype, had lower IGFBP-3 levels (P = 0.003) and were shorter (P = 0.03). During GH treatment, children with C-202/C-185haplotype showed a significantly greater increase in IGFBP-3 SDS and in height SDS than children with A-202/C-185haplotype, resulting in similar IGFBP-3 levels and similar height SDS after 12 months of GH treatment. CpG methylation patterns showed a trend towards more methylation of CpGs involved in transcription factor binding in short young SGA adults compared to controls. Conclusion: Polymorphic variation in the IGFBP3 promoter region is correlated with IGFBP-3 levels, spontaneous growth and response to GH treatment in short SGA children. http://repub.eur.nl/res/pub/25366/ 2009-05-01T00:00:00Z Background: In 2005, 12.7% of all babies were born preterm, and the incidence is rising. Nowadays, due to improved survival, an increasing number of children born preterm reach young adulthood. A recent report suggested lower insulin sensitivity in children born preterm, which may put them at risk for the development of type 2 diabetes. It is, however, still unknown whether this reduced insulin sensitivity persists into adulthood. Methods: We determined insulin sensitivity and β-cell function with frequently sampled iv glucose tolerance tests in 305 young adults (aged 18-24 yr; 169 preterm and 136 term). Adult body composition was measured by dual energy x-ray absorptiometry. We investigated the effect of gestational age, size at birth, and adult body composition on insulin sensitivity. Results: In contrast to previous reports, we found no evidence that preterm birth has a deleterious effect on insulin sensitivity in young adulthood. Adult trunk fat and the use of oral contraceptives in women were the most important determinants of insulin insensitivity, independently of size at birth and duration of pregnancy. Conclusion: Contrary to our hypothesis, preterm birth was not associated with reduced insulin sensitivity in young adulthood. Copyright http://repub.eur.nl/res/pub/24765/ 2009-04-01T00:00:00Z Objective To investigate whether prematurity has an independent influence on the response to GH treatment in short, small for gestational age (SGA) children. Design A longitudinal 3-year GH study. Patients A total of 392 prepubertal non-GH-deficient, short SGA children, comprising 138 preterm (< 36 weeks) and 254 term (≥ 36 weeks) children. Measurements Height, weight, head circumference, skinfolds and serum IGF-I and IGFBP-3 levels were measured before start of GH treatment and after 6 months, 1, 2 and 3 years of treatment. Results Preterm short SGA children were significantly lighter and shorter at birth after correction for gestational age than term short SGA children (P < 0·001). At start of GH treatment, preterm children were significantly shorter than term children when height was corrected for target height (TH). Preterm children were also significantly leaner as shown by a lower body mass index (BMI) standard deviation score (SDS) and a lower sum of four skinfolds SDS. Prematurity had no influence on childhood IGF-I and IGFBP-3 levels. The response to GH treatment was similar for preterm and term SGA children. Conclusions Within a population of short SGA children, prematurity is associated with a smaller size for gestational age and a shorter height corrected for TH and leaner phenotype in childhood. The response to GH treatment is similar for preterm and term short SGA children. http://repub.eur.nl/res/pub/25364/ 2009-04-01T00:00:00Z Context: IGF binding protein (IGFBP)-I is the only acute regulator of IGF-I bioavailability. Its production is suppressed by insulin, and low levels are associated with hyperinsulinemiaand cardiovascular disease risk in adults. Data on IGFBP-1 levels in short, small for gestational age (SGA) subjects are scarce, and associations with IGFBP1 promoter single nucleotide polymorphisms have not been established. Objective: The aim of the study was to determine IGFBP-1 levels in short SGA subjects compared with those in controls, to assess genotype frequency of the -575 G/A single nucleotide polymorphism, and to determine its impact on IGFBP-1 levels. Subjects: A total of 272 short subjects born SGA and 330 subjects with normal stature (245 children, 85 young adults) participated in the study. Outcome Measures: We measured fasting levels of IGFBP-1, IGF-I, insulin and lipid parameters, and body composition. Results: IGFBP-1 sd score (SDS) was comparable to controls in lean, short, SGA children but significantly lower in short SGA adults with normal fat mass (P <0.001). IGFBP-1 SDS correlated significantly with insulin levels, systolic blood pressure SDS, and various lipid parameters. Baseline IGFBP-1 SDS was lowest in SGA children with-575 GG genotype and significantly higher in SGA children with one or two copies of the A allele. In response to a given insulin level, children with the AA genotype had a significantly higher IGFBP-1 SDS compared to children with the GG genotype. Conclusion: Normal IGFBP-1 levels in lean, short, SGA children may reflect a normal metabolic state, despite reported hyperinsulinemia. IGFBP-1 is modulated by polymorphic variability and seems to be an additional player in the complex interaction between the IGF-IGFBP axis, glucose homeostasis, and lipid metabolism. Copyright http://repub.eur.nl/res/pub/28973/ 2008-09-01T00:00:00Z Context: GH treatment reduces insulin sensitivity (Si). For small-for-gestational-age (SGA) subjects, who might have an increased risk to develop cardiovascular disease and type 2 diabetes, it is still uncertain how Si, β-cell function, and body composition change over time after stopping GH treatment. Objective: Our objective was to investigate longitudinal changes in Si, β-cell function, and body composition after cessation of long-term GH treatment. Design and Patients: We conducted a longitudinal study that included 48 SGA adolescents studied at adult height, while still on GH, and 6 months after GH stop and compared them with 38 appropriate-for-gestational-age (AGA) controls at both time points. Outcome Measure: We took paired measurements of Si and β-cell function, assessed by frequently sampled iv glucose tolerance tests with tolbutamide, and body composition, measured by dualenergy x-ray absorptiometry. Results: After stopping GH, Si (P = 0.006), glucose effectiveness (Sg; P = 0.009) and β-cell function (disposition index; P = 0.024) increased, whereas insulin secretion (acute insulin response; not significant) decreased. Fat percentage increased (P < 0.0005), and lean body mass decreased (P < 0.0005), but fat distribution remained unaltered, and body composition remained within the normal range. Compared with AGA controls, Si was lower during GH and became similar after GH stop, acute insulin response was higher at both time points, and glucose effectiveness and disposition index became higher. Conclusions: The GH-induced lower Si in SGA adolescents increases after stopping long-term GH treatment and becomes similar to that of AGA controls. Discontinuation of GH treatment is, however, also associated with an increase in percent body fat and with a decrease in lean body mass, without changes in fat distribution. Copyright http://repub.eur.nl/res/pub/29595/ 2008-08-01T00:00:00Z Context: Disturbances in thyroid function have been described in small-for-gestational age (SGA) children but the influence of prematurity is unclear. In addition, the effect of GH treatment on thyroid function has not been studied in short SGA children. Objectives: To determine whether short SGA children have higher TSH levels compared to age-matched controls and evaluate the influence of gestational age. To investigate whether GH treatment alters thyroid function. Patients: A total of 264 short SGA children (116 preterm), prepubertal and non-GH deficient. Measurements: Serum FT4 and TSH at baseline and after 6, 12 and 24 months of GH treatment. Results: Baseline mean TSH was higher in preterm short SGA children than in age-matched controls (P < 0.05). Mean FT4 was not significantly different between short SGA children and controls. Baseline FT4 or TSH did not correlate with gestational age, or SDS for birth weight, birth length, height, body mass index, IGF-I or IGFBP-3. Mean FT4 decreased significantly during the first 6 months of GH treatment, but remained within the normal range. TSH did not change during treatment. The change in FT4 did not correlate with the change in height SDS during 24 months of GH treatment. Conclusion: Preterm short SGA children have higher, although within the normal range, TSH levels than controls. The level of TSH does not correlate with gestational age, birth weight SDS or birth length SDS. FT4 decreases during GH treatment, but is neither associated with an increase in TSH nor does it affect the response to GH treatment. As these mild alterations in thyroid function do not appear clinically relevant, frequent monitoring of thyroid function during GH therapy is not warranted in short SGA children. http://repub.eur.nl/res/pub/29663/ 2008-08-01T00:00:00Z Context: Short small-for-gestational-age (SGA) children have an increased systolic blood pressure (BP) that decreases during long-term GH treatment. The underlying mechanism is still unknown. Matrix metalloproteinases (MMPs) are zinc-dependent endoproteinases that are involved in the remodelling of the extracellular matrix (ECM) and are thought to play a role in atherosclerosis. High MMP-9 levels are found in hypertensive patients and predict cardiovascular mortality. Objectives: To investigate whether GH treatment affects plasma MMP-9 levels in short SGA children and whether these are related to BP. Design: Case-control study. Intervention: GH treatment vs. no treatment during 36 months. Patients: Thirty-eight short SGA children receiving GH treatment vs. 17 sex- and age-matched untreated short SGA controls. Outcome measure: Plasma MMP-9 levels and BP were measured at baseline, and after 6, 12 and 36 months of study. Results: MMP-9 decreased significantly during 3 years of GH treatment but remained similar in untreated SGA controls. After 3 years of GH treatment, MMP-9 levels were significantly lower in the GH group than in the untreated SGA controls. Systolic BP SDS significantly decreased in the GH group but remained unaltered in the untreated SGA controls. MMP-9 levels did not correlate with systolic or diastolic BP. Conclusions: Plasma MMP-9 levels and systolic BP SDS decreased to almost 50% of baseline values in the GH group but remained unchanged in untreated SGA controls. Our data indicate that GH has a positive effect on both MMP-9 levels and systolic BP SDS. http://repub.eur.nl/res/pub/28853/ 2008-07-01T00:00:00Z Small for gestational age (SGA) children have a higher prevalence of cardiovascular risk factors at a young age. It is not known whether this increased risk is caused by their size at birth, a familial predisposition for cardiovascular disease or smallness at birth or a combination of these factors. The cardiovascular risk profile of parents of SGA children is unknown. We compared anthropometry, blood pressure, fasting serum lipid, glucose, and insulin levels of 482 parents (mean age 41 y) and 286 short SGA children with age- and sex-matched references. We also investigated whether these parameters correlated between parents and their offspring. Mothers had higher systolic blood pressure, fathers had a higher body mass index and parents had more frequently high fasting glucose levels than age- and sex-matched references. Children had significantly higher systolic and diastolic blood pressure than sex- and height-matched references. Twenty-four percent (mothers) and 10% (fathers) were born SGA but they did not have more cardiovascular risk factors than those born appropriate for gestational age. Cardiovascular risk factors did not correlate between parents and children. In conclusion, parents of short SGA children have a modest increase in some cardiovascular risk factors but risk factors did not correlate between parents and children. Copyright http://repub.eur.nl/res/pub/13134/ 2008-06-05T00:00:00Z This doctoral thesis describes cardiovascular and metabolic risk factors in children and young adults with a small size at birth, either due to preterm or SGA birth. For those born SGA with persistent short stature, the effects of GH treatment on these risk factors were studied. This first chapter describes definitions, prevalence and etiologies of SGA, and clinical and endocrinological aspects associated with SGA. Finally, the aims of the study and outline of this thesis are described. http://repub.eur.nl/res/pub/29107/ 2008-02-01T00:00:00Z Context: Both small-for-gestational-age (SGA) and preterm birth have been associated with an increased incidence of adult cardiovascular disease and diabetes mellitus type 2. However, it is unclear whether preterm birth has an additional effect on cardiovascular risk factors in short children born SGA. Objective: Our objective was to investigate whether prematurity has an independent influence on several cardiovascular risk factors within a population of short SGA children. Design: A cross-sectional observational study was performed. Patients: A total of 479 short SGA children (mean age 6.8 yr), divided into preterm (<36 wk) and term (≥36 wk) children, was included in the study. Outcome Measure: Insulin sensitivity, β-cell function, body composition, and lipid levels were studied in subgroups, and blood pressure (BP), anthropometry at birth and during childhood in the total group. Results: Preterm SGA children were significantly lighter and shorter at birth after correction for gestational age than term SGA children (P < 0.001) but had a comparable head circumference. In preterm SGA children, we found a significantly higher systolic (P = 0.003) and diastolic BP SD score (P = 0.026), lower percent body fat SD score (P = 0.011), and higher insulin secretion (P = 0.033) and disposition index (P = 0.021), independently of the degree of SGA. Insulin sensitivity, serum lipid levels, muscle mass, and body fat distribution were comparable for preterm and term SGA children. Conclusions: Within a population of short SGA children, preterm birth has divergent effects on several cardiovascular risk factors. Whereas preterm SGA children had a higher systolic and diastolic BP, they also had a lower percent body fat and a higher insulin secretion and disposition index than term SGA children. Copyright http://repub.eur.nl/res/pub/29699/ 2008-02-01T00:00:00Z Context: Low birth weight is associated with increased risks for adult cardiovascular disease (CVD) and diabetes mellitus type 2 (DM2). Adiponectin and resistin are hormones, considered, respectively, protective and disadvantageous regarding these risks. No data exist on the effect of long-term GH treatment on these hormones and inflammatory markers in children born small for gestational age (SGA). Objective: To describe longitudinal changes in inflammatory markers and adipocytokines during and after a long-term dose-response GH study. Design: Longitudinal dose-response study [group A: 1 mg/m2body surface area (BSA) (approximately 0.033 mg/kg/day) vs. group B: 2 mg/m2BSA (approximately 0.067 mg/kg/day)] and comparison with age-related controls. Patients: One hundred and three SGA children. Measurements: We measured adiponectin, resistin, interleukin-6 (IL-6) and C-reactive protein (CRP) levels at baseline, after 1 and 7 years of GH treatment and 6 months after discontinuation of GH. Results: Adiponectin levels decreased over time, but remained comparable with controls. Resistin levels increased and remained lower or comparable with controls. There were no significant differences between the GH dosage groups. After the GH treatment was stopped, adiponectin was decreased in group B and resistin increased in group A. GH therapy did not affect IL-6 and CRP levels at any time point. An increase in body mass index (BMI) standard deviation score (SDS) over time was associated with a decrease in adiponectin levels. None of the markers were associated with insulin sensitivity. Conclusions: Long-term GH treatment is not associated with disadvantageous changes in adiponectin, resistin, IL-6 and CRP levels, neither during nor after GH treatment. http://repub.eur.nl/res/pub/29691/ 2008-01-01T00:00:00Z Aim: We determined whether subclassification of short small for gestational age (SGA) children according to birth anthropometrics could delineate different patterns in gestation, delivery, postnatal growth, response to growth hormone (GH) treatment and parental height. Methods: 201 short SGA children were divided into three groups, SGAL, SGAL+Wand SGAL+W+HC, according to birth length (L), weight (W) and head circumference (HC) ≤-2.00 standard deviation score (SDS). Results: SGAL+W+HCchildren were born after the shortest gestational age and more often by caesarean section than SGALchildren (36.3 vs. 38.1 weeks, 68.4 vs. 24.4%). SGAL+Wchildren had an intermediate pattern and experienced most gestational hypertension (p = 0.01). At birth, SGAL+W+HCchildren were shorter than SGALor SGAL+W(-4.12 vs. -2.67 and -3.72 SDS, p ≤ 0.001). During the first 3 years of life, SGAL+W+HCchildren exhibited an increased growth in height (0.98 SDS) and HC (1.28 SDS) than SGAL(height, -0.06 SDS; HC, -0.30 SDS) and SGAL+W(height, 0.62 SDS; HC, -0.31 SDS). However, HC SDS remained smaller for SGAL+W+HCthan the other groups at age 3. The groups did not differ in growth response during GH treatment. SGALchildren tended to have shorter parents and target height than SGAL+W+HCchildren. Conclusions: Our study shows that subclassification of short SGA children might be a useful method for investigating SGA children as the subgroups revealed a different gestation, delivery and postnatal growth pattern. Response to GH treatment was not different between the groups. Copyright http://repub.eur.nl/res/pub/36019/ 2007-10-01T00:00:00Z Context: Alterations in the GH-IGF-I axis in short small-for-gestational- age (SGA) children might be associated with abnormalities in bone mineral density (BMD) and body composition. In addition, birth weight has been inversely associated with diabetes and cardiovascular disease in adult life. Data on detailed body composition in short SGA children and long-term effects of GH treatment are very scarce. Objective: To investigate effects of long-term GH treatment on body composition and BMD by dual energy X-ray absorptiometry (DXA) in short SGA children. Design: Longitudinal 6-year GH study with a randomized controlled part for 3 years. Results: At baseline, fat percentage standard deviation score (SDS) and lumbar spine BMD SDS corrected for height (BMADLSSDS) were significantly lower than zero. Lean body mass (LBM) SDS adjusted for age was also reduced, but LBM adjusted for height (LBM SDSheight) was not decreased. GH treatment induced a decrease in fat percentage SDS and an increase in BMADLSSDS. LBM SDSheightremained similar in GH-treated children, but deteriorated in untreated controls. When these untreated controls subsequently started GH treatment, their LBM SDSheightrapidly normalized to values comparable with zero. Conclusion: During long-term GH treatment in short SGA children, fat percentage SDS decreased and BMADLSSDS increased. These effects of GH treatment were most prominent in children who started treatment at a younger age and in those with greater height gain during GH treatment. LBM SDSheightremained around 0 SDS in GH-treated children, but declined to low normal values in untreated controls. http://repub.eur.nl/res/pub/14097/ 2007-01-01T00:00:00Z BACKGROUND: Adiponectin and resistin are fat cell-derived hormones, which are thought to be respectively protective and disadvantageous with regard to the development of cardiovascular disease and diabetes mellitus type 2. Low birth weight has been associated with increased risks for the development of these diseases. In short, small-for-gestational-age (SGA) children, GH therapy has several positive effects regarding cardiovascular risk factors. On the other hand, concern has been expressed about the effects of GH therapy on insulin sensitivity. METHODS: We measured adiponectin and resistin levels in 136 short prepubertal children born SGA and their association with cardiovascular risk parameters and growth factors. Also, we compared the levels with normal-statured controls. The effect of GH treatment was evaluated in 50 short SGA children vs. baseline and vs. an untreated sex- and age-matched SGA control group. RESULTS: Short SGA children had similar adiponectin and lower resistin levels, compared with normal-statured controls. In GH-treated SGA children, neither adiponectin nor resistin levels changed significantly during 2 yr of GH treatment. Compared with untreated sex- and age-matched SGA controls, GH-treated SGA children had similar adiponectin and lower resistin levels. Adiponectin correlated inversely with age but not any cardiovascular risk parameter or growth factor. Higher IGF-I levels in GH-treated children were associated with lower resistin levels. CONCLUSIONS: Compared with normal-statured controls, short prepubertal SGA children had similar adiponectin and lower resistin levels. Two years of GH treatment had no effect on their adiponectin and resistin levels.