rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial.

OBJECTIVE: To investigate recombinant human insulin-like growth factor 1 complexed with its binding protein (rhIGF-1/rhIGFBP-3) for the prevention of retinopathy of prematurity (ROP) and other complications of prematurity among extremely preterm infants. STUDY DESIGN: This phase 2 trial was conducted from September 2014 to March 2016. Infants born at a gestational age of 230/7 weeks to 276/7 weeks were randomly allocated to rhIGF-1/rhIGFBP-3 (250 µg/kg/ 24 hours, continuous intravenous infusion from <24 hours of birth to postmenstrual age 296/7 weeks) or standard neonatal care, with follow-up to a postmenstrual age of 404/7 weeks. Target exposure was ≥70% IGF-1 measurements within 28-109 µg/L and ≥70% intended therapy duration. The primary endpoint was maximum severity of ROP. Secondary endpoints included time to discharge from neonatal care, bronchopulmonary dysplasia, intraventricular hemorrhage, and growth measures. RESULTS: Overall, 61 infants were allocated to rhIGF-1/rhIGFBP-3, 60 to standard care (full analysis set); 24 of 61 treated infants achieved target exposure (evaluable set). rhIGF-1/rhIGFBP-3 did not decrease ROP severity or ROP occurrence. There was, however, a 53% decrease in severe bronchopulmonary dysplasia in the full analysis set (21.3% treated vs 44.9% standard care), and an 89% decrease in the evaluable set (4.8% vs 44.9%; P = .04 and P = .02, respectively) for severity distribution between groups. There was also a nonsignificant trend toward decrease in grades 3-4 intraventricular hemorrhage in the full analysis set (13.1% vs 23.3%) and in the evaluable set (8.3% vs 23.3%). Fatal serious adverse events were reported in 19.7% of treated infants (12/61) and 11.7% of control infants (7/60). No effect was observed on time to discharge from neonatal care/growth measures. CONCLUSIONS: rhIGF-1/rhIGFBP-3 did not affect development of ROP, but decreased the occurrence of severe bronchopulmonary dysplasia, with a nonsignificant decrease in grades 3-4 intraventricular hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01096784.

Social Determinants of Health Are Associated with Markers of Renal Injury in Adolescents with Type 1 Diabetes.

OBJECTIVE: To examine the relationship between the social determinants of health and markers of early renal injury in adolescent patients with type 1 diabetes (T1D). STUDY DESIGN: Renal outcomes included estimated glomerular filtration rate (eGFR) and albumin-creatinine excretion ratio (ACR). Differences in urinary and serum inflammatory markers also were assessed in relation to social determinants of health. Regression analysis was used to evaluate the association between the Ontario Marginalization Index (ON-Marg) as a measure of the social determinants of health, patient characteristics, ACR, eGFR, and renal filtration status (hyperfiltration vs normofiltration). RESULTS: Participants with T1D (n = 199) with a mean age of 14.4 ± 1.7 years and diabetes duration of 7.2 ± 3.1 years were studied. Mean eGFR was 122.0 ± 19.4 mL/min/1.73 m2. Increasing marginalization was positively associated with eGFR (P < .0001) but not with ACR (P = .605). Greater marginalization was associated with greater median levels of urinary interleukin (IL)-2, IL-12 (p40), macrophage-derived chemokine, monocyte chemoattractant protein-3, and tumor necrosis factor-ß and serum IL-2. ON-Marg was significantly associated with eGFR after we controlled for age, sex, body mass index z score, ethnicity, serum glucose, and hemoglobin A1c in linear regression. A similar association between hyperfiltration and ON-Marg score was observed in multivariable logistic regression. CONCLUSION: Increasing marginalization is significantly associated with both eGFR and hyperfiltration in adolescents with T1D and is associated with significant changes in urinary inflammatory biomarkers. These findings highlight a potentially important interaction between social and biological determinants of health in adolescents with T1D.

Efficacy of Growth Hormone Treatment in Children with Type 1 Diabetes Mellitus and Growth Hormone Deficiency-An Analysis of KIGS Data.

OBJECTIVE: To analyze first-year treatment growth response and growth hormone (GH) dosage in prepubertal patients with the combination of type 1 diabetes mellitus (T1DM) and growth hormone deficiency (GHD). STUDY DESIGN: A total of 69 patients with T1DM and GHD treated with GH have been enrolled in KIGS (Pfizer International Growth Database). Of these, 24 prepubertal patients had developed T1DM before GHD and were included in this analysis. Of 30 570 patients with GHD without T1DM, 15 024 were prepubertal and served as controls. Values are expressed as mean ± SD. RESULTS: Patients with T1DM and GHD had similar characteristics compared with the GHD-alone group. Neither age (10.2 ± 3.13 vs 8.42 ± 3.46 years, P = .14), height SDS corrected for midparental height SDS at start of treatment (-1.62 ± 1.38 vs -1.61 ± 1.51, P = .80), nor GH dosage (0.24 ± 0.08 mg/kg/wk vs 0.20 ± 0.04 mg/kg/wk, P = .09) were different between those with and without T1DM. First-year catch-up growth was comparable between the 2 patient groups (first treatment year height velocity 7.54 ± 3.11 cm/year compared with 8.35 ± 2.54 cm/year in control patients, P = .38). Height SDS of children with T1DM and GHD improved from -2.62 ± 1.04 to -1.88 ± 1.11 over 1 year of GH treatment. CONCLUSION: Short-term response to GH therapy appeared similar in subjects with T1DM who then developed GHD and in those with GHD alone. Thus, T1DM does not appear to compromise GH response in children with GHD and should not exclude GH treatment in these children. GH treatment was safe in both subgroups of patients.

Social Determinants of Health Are Associated with Modifiable Risk Factors for Cardiovascular Disease and Vascular Function in Pediatric Type 1 Diabetes.

OBJECTIVE: To evaluate the relationship between social determinants of health (SDH) and cardiovascular disease (CVD) risk factors as well as a measure of arterial stiffness in adolescents with type 1 diabetes (T1D). STUDY DESIGN: SDH were measured with the validated Ontario Marginalization Index, derived from deidentified postal code data and stratified by quintile (first = least deprived; fifth = most deprived). SDH dimensions included material deprivation; ethnic concentration; and measures of dependency and residential instability. Metabolic control (hemoglobin A1c), cardiovascular risk metrics, and pulse wave velocity, as a measure of arterial stiffness, were related to SDH. Data were evaluated from a cohort of Canadian adolescents within the Adolescent Diabetes Cardiorenal Intervention Trial, a T1D clinical trial RESULTS: A total of 704 participants were evaluated, and significant differences in hemoglobin A1c were evident at the extremes of material deprivation (8.4% vs 9.1% for least vs most deprived, P < .01). CVD risk factors were analyzed in 199 participants, with the most deprived reporting significantly less exercise (P = .004) and increased rates of smoking (P = .008). Increased material deprivation was associated with fewer metrics of "ideal" cardiovascular health attained. Arterial stiffness, as measured by pulse wave velocity, was associated positively with age, body mass index z score, and material deprivation. CONCLUSION: Increased material deprivation was associated with poorer glycemic control. Modifiable, lifestyle-related risk factors for CVD and early arterial wall change are associated with SDH and represent a target for clinical intervention to reduce future CVD burden in adolescents with T1D.

Age at Weaning and Infant Growth: Primary Analysis and Systematic Review.

OBJECTIVE: To test whether earlier age at weaning (age 3-6 months) may promote faster growth during infancy. STUDY DESIGN: Weaning at age 3.0-7.0 months was reported by 571 mothers of term singletons in a prospective birth cohort study conducted in Cambridge, UK. Infant weight and length were measured at birth and at age 3 months and 12 months. Anthropometric values were transformed into age- and sex-adjusted z-scores. Three linear regression models were performed, including adjustment for confounders in a stepwise manner. Measurements at age 3 months, before weaning, were used to consider reverse causality. RESULTS: Almost three-quarters (72.9%) of infants were weaned before age 6 months. Age at weaning of 3.0-7.0 months was inversely associated with weight and length (but not with body mass index) at 12 months (both P ≤ .01, adjusted for maternal and demographic factors). These associations were attenuated after adjustment for type of milk feeding and weight or length at age 3 months (before weaning). Rapid weight gain between 0 and 3 months predicted subsequent earlier age at weaning (P = .01). Our systematic review identified 2 trials, both reporting null effects of age at weaning on growth, and 15 observational studies, with 10 reporting an inverse association between age at weaning and infant growth and 4 reporting evidence of reverse causality. CONCLUSION: In high-income countries, weaning between 3 and 6 months appears to have a neutral effect on infant growth. Inverse associations are likely related to reverse causality.

Lipidomic analyses, breast- and formula-feeding, and growth in infants.

OBJECTIVE: To evaluate lipidomic differences between breast- and formula-fed infants. STUDY DESIGN: We utilized high-resolution mass-spectrometry methods to analyze 3.2 mm dried blood spot samples collected at ages 3 months (n = 241) and 12 months (n = 144) from a representative birth cohort study. Lipidomic profiles were compared between infants exclusively breast-fed, formula-fed, or mixed-fed, and related to 12-month infancy weight. Data analysis included supervised multivariate statistics (partial least squares discriminant analysis), and univariate analysis with correction for multiple testing. RESULTS: Distinct differences in 3-month lipidomic profiles were observed between exclusively breast-fed and formula-fed infants; mixed-fed infants showed intermediate profiles. Principle lipidomic characteristics of breast-fed infants were lower total phosphatidylcholines (PCs), with specifically lower short chain unsaturated PC but higher long chain polyunsaturated PC; higher cholesterol esters; and variable differences in sphingomyelins. At 12 months, lipidomic profiles were markedly different to those at 3 months, and differences between the earlier breast/formula/mixed-feeding groups were no longer evident. However, several specific lipid species, associated with breast-feeding at 3 months, also correlated with differences in 3- to 12-month weight. CONCLUSIONS: State-of-the-art dried blood spot sample lipidomic profiling demonstrated striking differences between breast-fed and formula-fed infants. Although these changes diminished with age, breast-fed lipidomic profiles at 3 months were associated with infancy weight and could potentially represent biomarkers of infant nutrition.

Relationship between insulin-like growth factor I levels, early insulin treatment, and clinical outcomes of very low birth weight infants.

OBJECTIVES: Insulin regulates the secretion of insulin-like growth factor I (IGF-I) in the newborn, and low levels of IGF-I have been linked to neonatal morbidity. As part of the Neonatal Insulin Replacement Therapy in Europe Trial, we investigated the impact of early insulin treatment on IGF-I levels and their relationship with morbidity and growth. STUDY DESIGN: Prospective cohort analyses of data collected as part of an international randomized controlled trial. Blood samples (days 1, 3, 7, and 28), were taken for IGF-I bioassay from 283 very low birth weight infants (<1500 g). RESULTS: Early insulin treatment led to a late increase in IGF-I levels between day 7 and 28 (P = .028). In the first week of life IGF-I levels were lower in infants with early hyperglycemia; mean difference -0.10 µg/L (95% CI -0.19, -0.02, P = .02). Lower levels of IGF-I at day 28 were independently associated with an increased risk of chronic lung disease, OR 3.23 (95% CI, 1.09-9.10), and greater IGF-I levels were independently associated with better weight gain, 0.10 kg (95% CI, 0.03-0.33, P = .02). CONCLUSIONS: Early intervention with insulin is related to increased IGF-I levels at 28 days. Low IGF-I levels are associated with hyperglycemia, increased morbidity, and reduced growth. Increasing IGF-I levels may improve outcomes of very low birth weight infants.

Prevalence and determinants of hyperglycemia in very low birth weight infants: cohort analyses of the NIRTURE study.

OBJECTIVES: To investigate the prevalence and determinants of hyperglycemia in the preterm population, as part of the Neonatal Insulin Therapy in Europe (NIRTURE) Trial. STUDY DESIGN: We conducted prospective cohort analyses of continuous glucose monitoring data from control infants participating in an international randomized controlled trial. Data were collected from 188 very low birth weight infants (<1500 g). RESULTS: In the first week of life, 80% of infants had evidence of glucose levels >8 mmol/L, and 32% had glucose levels >10 mmol/L >10% of the time. Independent risk factors for hyperglycemia included increasing prematurity, small size at birth, use of inotropes, lipid infusions, and sepsis. There was a lack of association between rate of dextrose infused and risk of hyperglycemia. CONCLUSION: The prevalence of hyperglycemia in the very low birth weight infant is high, with marked variability in prevalence between infants, not simply related to rates of glucose infused, but to other potentially modifiable risk factors.

Traumatic brain injury is a rarely reported cause of growth hormone deficiency.

We determined the frequency of traumatic brain injury (TBI)-related growth hormone deficiency (GHD) from a large registry of growth hormone-deficient subjects and compared these subjects' clinical characteristics with those of children with idiopathic growth hormone deficiency (IGHD). A surprisingly small number of subjects with TBI-induced GHD (n = 141) were registered compared with those with IGHD (n = 23,722). At onset of treatment, the subjects with TBI-induced GHD were older (P = .045), had lower height velocity (P < .001), had a greater number of other pituitary hormone deficiencies (P < .001) and, after a year of recombinant human GH treatment, demonstrated a greater change in height velocity (P = .016). We speculate that TBI-induced GHD may be a neglected phenomenon in childhood, and recommend prospective longitudinal studies to explore its natural history and frequency.

Early elective insulin therapy can reduce hyperglycemia and increase insulin-like growth factor-I levels in very low birth weight infants.

OBJECTIVE: To investigate the use of insulin throughout the first week of life in very low birth weight (VLBW) infants (birth weight <1.5 kg) to improve glucose control and increase insulin-like growth factor-I (IGF-I) levels. IGF-I is the dominant hormone involved in fetal growth, and low levels have been implicated in neonatal morbidities, such as retinopathy of prematurity. STUDY DESIGN: In this pilot randomized controlled study (n = 16), the intervention group received insulin (0.025 U/kg/hr) on days 1 to 7, with 20% dextrose to maintain normoglycemia. Control infants received standard neonatal care. All infants received continuous glucose monitoring. RESULTS: The intervention and standard care groups had similar mean gestational age (+/- standard deviation), 26.2 (+/- 2.5) vs 26.9 (+/- 2.7) weeks, and birth weight, 0.79 (+/- 0.26) vs 0.73 (+/- 0.16) kg. The standard care infants were hyperglycemic (sensor glucose >10 mmol/L [180 mg/dL]) for 35.9% of the study period, compared with 7.6% for the insulin-treated infants (P = .035). The duration of time with hypoglycemia (<2.6 mmol/L [47 mg/dL]) did not differ between the 2 groups (P = .746). The insulin-treated group had a 2.4-fold increase in mean IGF-I bioactivity (P = .005). CONCLUSIONS: Early insulin therapy improves blood glucose control and increases IGF-I bioactivity levels. This could result in less morbidity associated with hyperglycemia and reduced IGF-I levels.

Longitudinal changes in insulin-like growth factor-I, insulin sensitivity, and secretion from birth to age three years in small-for-gestational-age children.

INTRODUCTION: Insulin resistance (IR) develops as early as age 1 to 3 yr in small for gestational age (SGA) infants who show rapid catch-up postnatal weight gain. In contrast, greater insulin secretion is related to infancy height gains. We hypothesized that IGF-I levels could be differentially related to gains in length and weight and also differentially related to IR and insulin secretion. METHODS: In a prospective study of 50 SGA (birth weight < 5th percentile) and 14 normal birth weight [appropriate for gestational age (AGA)] newborns, we measured serum IGF-I levels at birth, 1 yr, and 3 yr. IR (by homeostasis model assessment) and insulin secretion (by short iv glucose tolerance test) were also measured at 1 yr and 3 yr. RESULTS: SGA infants had similar mean length and weight at 3 yr compared with AGA infants. SGA infants had lower IGF-I levels at birth (P < 0.0001), but conversely they had higher IGF-I levels at 3 yr (P = 0.003) than AGA infants. Within the SGA group, at 1 yr IGF-I was associated with length gain from birth and insulin secretion (P < 0.0001); in contrast at 3 yr IGF-I was positively related to weight, body mass index, and IR. CONCLUSIONS: IGF-I levels increased rapidly from birth in SGA, but not AGA children. During the key first-year growth period, IGF-I levels were related to beta-cell function and longitudinal growth. In contrast, by 3 yr, when catch-up growth was completed, IGF-I levels were related to body mass index and IR, and these higher IGF-I levels in SGA infants might indicate the presence of relative IGF-I resistance.

Adiponectin levels in the first two years of life in a prospective cohort: relations with weight gain, leptin levels and insulin sensitivity.

Adiponectin, a novel adipocytokine with insulin sensitizing properties, is inversely related to obesity and insulin resistance in adults. We recently reported large variations in weight gain and insulin sensitivity during the first year in infants born small for gestational age (SGA) or appropriate for gestational age (AGA). We now determined whether adiponectin levels were related to postnatal growth and insulin sensitivity in a prospective cohort followed from birth to two years old (n = 85) (55 female/30 male, 65 SGA/20 AGA). Serum adiponectin levels at one year and two years were higher compared to reported levels in adults and older children, and decreased from one year (21.6 +/- 0.6 microg/ml) to two years (15.7 +/- 0.7 microg/ml) (p < 0.05). At two years adiponectin levels were lower in females (15.3 +/- 0.4 microg/ml) than males (16.4 +/- 0.6 microg/ml) (p < 0.05), but no gender difference was seen in leptin or insulin levels. No differences in adiponectin levels were seen between SGA and AGA infants at one or two years. However, in SGA infants changes in adiponectin between one to two years old were inversely related to weight gain (r = -0.310, p < 0.05). Changes in leptin levels between one to two years were positively related to weight gain in both SGA and AGA infants (r = 0.450 and r = 0.500 respectively, both p < 0.05). Adiponectin levels were unrelated to insulin levels at one or two years, nor to change in insulin levels between one to two years. In multiple regression analysis, adiponectin levels were related only to postnatal age; omitting age from the model, the determinants of higher adiponectin levels were male gender (p = 0.03), lower postnatal body weight (p < 0.001), and higher birth weight SD score (p = 0.004). In conclusion, fall in serum adiponectin levels during the first two years of life were related to increasing age and greater weight gain SGA infants, but were unrelated to insulin sensitivity.

Insulin sensitization early after menarche prevents progression from precocious pubarche to polycystic ovary syndrome.

OBJECTIVE: Girls with low birth weight (LBW) and with a history of precocious pubarche in childhood (PP) are at high risk of polycystic ovary syndrome (PCOS) in adolescence. In formerly LBW-PP girls, we examined whether initiation of insulin sensitization therapy early after menarche could prevent progression of PCOS features. Study design Twenty-four girls, small at term birth (mean weight, 2.4 kg), who presented with PP (at mean age 6.7 years) and were currently (mean age, 12.4 years) postmenarcheal, with hyperinsulinemic hyperandrogenemia but nonobese, were randomly assigned to receive metformin (850 mg/d) or no treatment for 12 months. Six-month fasting blood samples were collected, and body composition was assessed by dual-energy x-ray absorptiometry. In addition, overnight growth hormone (GH) and gonadotropin secretion was analyzed in 10 girls (6 treated; 4 untreated) at 0 and 6 months. RESULTS: At baseline, compared with healthy control subjects, LBW-PP girls had dyslipidemia, excess truncal fat, reduced lean body mass, and increased insulin-like growth factor-I and GH levels. In untreated girls, insulin sensitivity, serum androgens, lipids, total and truncal fat mass, and lean body mass significantly diverged further from normal over 12 months. In metformin-treated girls, all these abnormalities significantly reversed within 6 months, and body composition continued to improve between 6 and 12 months. CONCLUSIONS: Early metformin therapy prevents progression from PP to PCOS in a high-risk group of formerly LBW girls. This confirms the key role of hyperinsulinemic insulin resistance in the ontogeny of PCOS. Furthermore, normalization of body composition, lipid profiles, and GH secretion could reduce long-term cardiovascular risk.

Insulin sensitivity and secretion are related to catch-up growth in small-for-gestational-age infants at age 1 year: results from a prospective cohort.

Strong associations between low birth weight and insulin resistance have been described. However, most of these studies have been retrospective. We aimed to determine whether infants born small for gestational age (SGA: birth weight <5th percentile for gestational age) have decreased insulin sensitivity, compared with appropriate for gestational age (AGA: birth weight >10th percentile) at 1 yr of age. We studied blood lipids, fasting insulin levels, other markers of insulin sensitivity, and insulin secretion during an iv glucose tolerance test in a cohort of 85 SGA and 23 AGA 1-yr-old infants. In addition, SGA infants were stratified according to catch-up growth (CUG) in weight (WCUG) or length (LCUG) during the first year of life. At 1 yr, SGA infants had a clear tendency to higher triglycerides. Fasting insulin was significantly higher in SGA infants with WCUG, compared with those who did not catch up and AGA infants (mean +/- SEM, 32.6 +/- 4.6 vs. 14.9 +/- 2.3 vs. 21.4 +/- 3.3 pM, respectively; P < 0.05). Length increment (in SD score) was the principal determinant of postload insulin secretion (R(2) = 0.1, P < 0.01). We conclude that insulin secretion and sensitivity are closely linked to patterns of rapid WCUG and LCUG during early postnatal life. Fasting insulin sensitivity is more related to WCUG and current body mass index, whereas insulin secretion seems to be directly related to LCUG.

Glucose and lipid metabolism in small for gestational age infants at 48 hours of age.

OBJECTIVE: To study the consequences of low birth weight on glucose and lipid metabolism 48 hours after delivery. METHODS: We studied 136 small for gestational age (SGA) and 34 appropriate for gestational age (AGA) term neonates who were born in Santiago, Chile. Prefeeding venous blood was obtained 48 hours after birth for determination of glucose, free fatty acids, beta-hydroxy butyrate, insulin, C-peptide, leptin, sex hormone-binding globulin, insulin-like growth factor-binding protein-1 (IGFBP-1), and cortisol. RESULTS: SGA newborns had lower glucose (SGA versus AGA, median [interquartile range]: 3.6 mmol/L [2.9-4.1 mmol/L] vs 3.9 mmol/L [3.6-4.6 mmol/L]) and insulin levels (31.3 pmol/L [20.8-47.9 pmol/L] vs 62.5 pmol/L [53.5-154.9]) than AGA infants, and they had higher glucose/insulin ratios (13.9 mg/dL/uIU/mL [8.6-19.1 mg/dL/uIU/mL] vs 8.2 mg/dL/uIU/mL [4.6-14.1 mg/dL/uIU/mL]). SGA infants also had higher levels of IGFBP-1 (5.1 nmol/L [4.4-6.7 nmol/L] vs 2.9 nmol/l [1.4-4.2 nmol/L]), free fatty acids (0.72 mEq/L [0.43-1.00 mEq/L] vs 0.33 mEq/L [0.26-0.54 mEq/L]) and beta-hydroxy butyrate (0.41 mEq/L [0.15-0.91 mEq/L] vs 0.09 mEq/L [0.05-0.13 mEq/L]). Sex-hormone binding globulin levels were not significantly different between the 2 groups. CONCLUSIONS: In early postnatal life, SGA infants display an increased insulin sensitivity with respect to glucose disposal but not with respect to suppression of lipolysis, ketogenesis, and hepatic production of IGFBP-1. It will be important to determine how these differential sensitivities to insulin vary with increasing age.

Fasting and post-glucose ghrelin levels in SGA infants: relationships with size and weight gain at one year of age.

Wide ranges in postnatal weight gain are seen in infants born small for gestational age (SGA); most show some catch-up growth and this may be driven by increased appetite. Ghrelin, the natural ligand of the GH secretagogue receptor, has potent orexigenic effects. In adults circulating ghrelin levels are increased in anorexia, decreased in obesity and show post prandial suppression. The aim of the present study was to test the hypothesis that rate of weight gain over the first year in SGA infants may relate to variable suppression of circulating ghrelin levels. Serum ghrelin levels were measured in 1 y old infants born SGA (n = 85) and in control infants born adequate for gestatitional age (AGA) (n = 22) fasting and 10 minutes after intravenous (iv) glucose (0.5 g/Kg of 25% dextrose). Sex- and gestational age-adjusted SD scores (SDS) for body weight were calculated at birth and at 1 y, and delta weight SDS between 0-1 y was calculated as an index of postnatal weight gain. In both SGA and AGA groups, ghrelin levels reduced from fasting (mean +/- SE: 104.4 +/- 6.4 fmol/ml) to 10 minutes post-iv glucose (82.7 +/- 5.3, p < 0.005). There were no differences in ghrelin levels between SGA and AGA infants (fasting or post-iv glucose). However, in SGA infants ghrelin levels post-glucose, but not fasting, were psitively related to current length (r = 0.28, p < 0.05), weight (r = 0.23, p < 0.05) and to change in weight SDS 0-1 y (r = 0.22, p < 0.05). SGA infants who showed poor catch-up growth showed a larger decline in ghrelin concentrations post-iv glucose. In conclusion, circulating ghrelin levels rapidly decreased after iv glucose. Higher ghrelin levels or lower reductions in circulating levels following iv glucose were seen in SGA infants who showed greater infancy weight gain, suggesting that sustained orexigenic drive could contribute to postnatal catch-up growth.