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We evaluated the relationship between fetal growth in preterm babies using the head circumference (HC)/chest circumference (CC) ratio and other anthropometric parameters at birth and at school age. Data were collected from 187 very low birth weight (VLBW) children born at less than 30 weeks of gestational age (GA) at birth and at 6 years. We assessed the correlation between the HC/CC ratio and body weight (BW), body length (BL), and HC z-scores at birth, and BW, body height (BH), and body mass index (BMI) z-scores at 6 years. Multiple regression analysis showed that BW z-score, BL z-score, and HC z-score at birth were significantly associated with HC/CC at birth. The BMI z-score at 6 years was also significantly associated with HC/CC at birth. The HC/CC ratio at birth is a reliable parameter for evaluating fetal growth restriction and a possible predictor of physical growth in VLBW children.

Objective:Little is known about physical constitution outcomes for very preterm infants. Here, we compare z-scores of anthropometric parameters up to 6 years of age in children born with very low birth weight (VLBW) at less than 30 weeks of gestation, with or without intrauterine growth restriction (IUGR).Design:Participants were divided into four subgroups: male (M), small for gestational age (SGA) (n = 30); M, appropriate for gestational age (AGA) (n = 59); female (F), SGA (n = 24); and F, AGA (n = 61). z-Scores of body weight (BW), body length (BL), and body mass index (BMI) were assessed at birth, 1 year corrected age, 3 years of age, and 6 years of age.Results:For boys, BW and BMI were significantly lower among SGA children than among AGA children at all assessments, but there was no difference in BL at 3 or 6 years. For girls, BW and BL were significantly lower among SGA children than among AGA children at all assessments, but no difference was detected in BMI after 1.5 years. No significant variation in the z-score of BW or BMI in either SGA group was observed after 1 year. BL z-score in all groups gradually increased until 6 years of age.Conclusion:IUGR affects BW and BMI in boys and BW and BL in girls during the first 6 years in VLBW children born at less than 30 weeks of gestation. SGA children did not catch up in BW or BMI from 1 to 6 years of age.

BACKGROUND Little is known about the relationship between fetal growth and size at school age in children born prematurely. We evaluated the relationships between gestational age and anthropometric z-scores at birth and size at 6 years of age in very-low-birth-weight infants born at less than 30 weeks' gestation. METHODS We collected data from the medical records of 187 preterm children at birth and 6 years of age. We evaluated correlations between gestational age and z-scores for weight, body length, and head circumference at birth and z-scores for weight, height, and body mass index at 6 years of age. RESULTS Simple regression analysis showed that in boys and the overall group, gestational age and z-scores for weight, body length, and head circumference at birth had significant association with z-scores for weight, height, and body mass index at 6 years of age. Whereas no significant association were found in girls, except for weight z-scores at 6 years with gestational age and head circumference z-scores at birth. Multiple regression analysis showed that gestational age and length z-score at birth were significantly and independently associated with weight and height z-score at 6 years. Gestational age was also significantly and independently associated with BMI z-score at 6 years. CONCLUSION Gestational age and fetal growth in length (assessed with the birth-length z-score) were associated with anthropometric z-scores at 6 years in very-low-birth-weight children born at < 30 weeks of gestation, especially in boys.

We aimed to determine the differences in the growth trajectories of the youngest gestational survivors (

Background: IGF1 is a key molecule in the regulation of growth and metabolism. Low IGF1 secretion is known to cause growth restriction in childhood, as well as deregulated lipid metabolism, cardiovascular disease, and diabetes in adulthood. The IGF1 gene P2 promoter is highly methylated, resulting in low secretion of IGF1 in small infants and children. However, it is unknown when this methylation occurs. The aim of study was to clarify the point when this epigenetic program occurs during intrauterine development. Methods: We analyzed 57 preterm infants born before 32 weeks of gestation, including 20 intrauterine growth restriction (IUGR) infants whose birth weights were lower than −2SD calculated by the Japanese datasets. We extracted genomic DNA from whole blood at birth; methylation of the IGF1 P2 promoter was analyzed by the bisulfite amplicon method using the MiSeq platform. Findings: In contrast to term infants and children, IGF1 promoter methylation levels were significantly reduced in infants with IUGR. Interpretation: These findings indicated that the IGF1 gene is epigenetically activated before 32 weeks of gestation in infants with IUGR, and that the activated gene may become suppressed after this time point. This study may provide new insights to prevent the onset of adult diseases and to aid in nutritional management for preterm birth infants in neonatal intensive care units. Funding Statement: This work was supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT)-Supported Program for the Strategic Research Foundation at Private Universities, 2015-2019, Japan (M.K.) and by Grants-in-Aid for General Scientific Research, No. 17k16309, Japan (N.I.). Declaration of Interests:The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Juntendo University Ethics Committee and conducted in accordance with the principles of the Declaration of Helsinki.

Although magnesium (Mg) contents are different between breast milk and formula, few studies have investigated the blood Mg level in breast fed or formula fed preterm infants. We examined the influence of feeding type on serum Mg and whole blood ionized Mg (iMg) levels in preterm infants soon after birth. We included 115 preterm infants born between gestational weeks 32 and 35. Infants were separated into two groups: breast milk (BM) dominant group (n = 30) receiving ≥70% of Mg intake from BM and mixed-fed (MF) group (n = 85) receiving ≥30% of Mg intake from formula. Blood levels of Mg, iMg, Ca, and iCa at day 1 of age and at discharge from the hospital were compared between the groups. No differences in the Mg and iMg levels at day 1 of age were observed between the two groups. The Mg and iMg levels at discharge were significantly lower (P 0.05) in the BM group than in the MF group; 0.86 (interquartile range 0.81-0.91) versus 0.91 (0.86-0.99) mmol/L and 0.46 (0.41-0.51) versus 0.52 (0.47-0.57) mmol/L, respectively. There were no differences in the Ca and iCa levels between the two groups. By stepwise multiple regression analysis, the percentage of BM intake was a significant independent predictor of the Mg and iMg levels. The feeding type influenced serum Mg and blood iMg levels in preterm infants soon after birth. Further studies are needed to investigate the influence of Mg on growth and the optimal range of blood Mg levels.

Aim Poor post-natal growth is related to later morbidity and poor cognitive development in preterm infants. We investigated the relationship between plasma insulin-like growth factor 1 (IGF-1), leptin, active ghrelin levels and post-natal growth in preterm infants small for gestational age (SGA). Methods Plasma IGF-1, leptin and active ghrelin levels were measured at birth and at 2, 4, 6 and 8 weeks after birth in 42 very low birthweight (VLBW) infants (born between 27 and 31 weeks of gestation), including 14 SGA infants with extrauterine growth restriction (EUGR), 6 SGA infants without EUGR and 22 appropriate-for-gestational-age infants. Results At birth, IGF-1 levels in SGA infants without EUGR did not differ significantly from those in SGA infants with EUGR. However, IGF-1 levels in SGA infants without EUGR were as high as those observed in appropriate-for-gestational-age infants and were significantly different from those in SGA infants with EUGR at 4 and 8 weeks of age. Leptin and ghrelin levels did not differ significantly among the three groups at any time point. Conclusion IGF-1 is related to catch-up growth in SGA VLBW infants during neonatal intensive care unit admission; however, this does not appear to be the case for leptin and ghrelin. IGF-1 level monitoring may be useful for predicting EUGR in preterm VLBW infants.

Background Insulin-like growth factor-I (IGF-I) is essential for perinatal growth and development; low serum IGF-I has been observed during intrauterine growth restriction (IUGR). We investigated the effects of recombinant human (rh) IGF-I in IUGR rats during the early postnatal period. Methods Intrauterine growth restriction was induced by bilateral uterine artery ligation in pregnant rats. IUGR pups were divided into two groups injected daily with rhIGF-I (2 mg/kg; IUGR/IGF-I, n = 16) or saline (IUGR/physiologic saline solution (PSS), n = 16) from postnatal day (PND) 7 to 13. Maternal sham-operated pups injected with saline were used as controls (control, n = 16). Serum IGF-I and IGF binding proteins (IGFBP) 3 and 5 were measured on PND25. The expression of Igf-i, IGF-I receptor (Igf-ir), Igfbp3, and 5 mRNA in the liver and brain was measured using real-time polymerase chain reaction on PND25. Immunohistochemical staining of the liver for IGF expression was performed. Results Mean bodyweight on PND3 and PND25 in the IUGR pups (IUGR/IGF-I and IUGR/PSS) was significantly lower than that of the control pups. Serum IGF-I and hepatic Igf-ir mRNA in the IUGR pups were significantly lower than those in the control pups. In the IUGR/IGF-I group, hepatic Igfbp3 mRNA and liver immunohistochemical staining were increased. In the IUGR/PSS and control pups, there were no significant differences between these two groups in serum IGFBP3 and IGFBP5, hepatic Igf-i and Igfbp-5 mRNA, or brain Igf mRNA. Conclusions No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period.

Type 2B von Willebrand disease (VWD) is frequently associated with distinct platelet morphology. Here we present a familial case of type 2B VWD with a novel VWF mutation (p.R1308S), which caused neonatal thrombocytopenia. The mother had been treated for refractory immune thrombocytopenia (ITP) for more than 20years. The most important hematological features of this case were large platelets and platelet aggregates detected on peripheral blood smears. Hemostatic tests showed enhanced ristocetin-induced platelet agglutination at low-ristocetin concentrations, absence of high-molecular weight von Willebrand factor (VWF) multimers, and low VWF cofactor activity/antigen ratio. In patients with intractable ITP, family history of ITP and consecutive neonatal thrombocytopenia, the differential diagnosis of congenital thrombocytopenia is mandatory. For this purpose, the identification of large platelets and platelet aggregates on peripheral blood smears is the key aspect of type 2B VWD diagnosis.

Background Reactive oxygen species may be involved in serious diseases in premature infants. The objective of this study was to assess the relationship between neurodevelopmental outcome and oxidative stress marker level in the urine of very low-birthweight (VLBW) infants. Methods Spot urine samples were collected from 35 VLBW infants. Urinary excretion of 8-hydroxy-2″-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and 8-iso-prostaglandin F2α (8-isoPGF), a marker of lipid peroxidation, was measured at 1, 2, 4, and 6 weeks of age. Neurodevelopmental outcome at 18 months’ corrected age was assessed using the Bayley Scales of Infant Development (BSID)-II. Results Significant correlations were found between urinary 8-OHdG at 2 and 4 weeks and the Mental Development Index of the BSID-II. No significant correlation was found between urinary 8-isoPGF and indices of the BSID-II. Conclusions In VLBW infants, urinary 8-OHdG level correlated with mental development rather than psychomotor development at 18 months’ corrected age; urinary 8-OHdG might be a predictive marker of neurodevelopmental outcome in VLBW infants.

Aim: The intra-uterine environment affects the risk of development of cardiovasculardisease in adulthood. The aim of this study was to determine the influence of prematurityand foetal growth restriction on lipid metabolism, by assessing atherogenic indices soonafter birth in preterm infants. Methods: Blood samples were collected within 20 min of birth from 80 preterm infantswith a gestational age of ≤35 weeks. Serum total cholesterol (TC), low-density lipoproteincholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1)and apolipoprotein-B (apoB) levels were measured. The ratio of TC/HDLc, LDLc/HDLcand apoB/apoA1 were also calculated. Correlations between these indices and gestationalage,birthweightandthestandarddeviation(SD)scoreforbirthweightwerealsodetermined. Results: Gestational age, birth weight and SD score for birth weight were negativelycorrelated with the TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios. Conclusion: In preterm infants, prematurity and poor foetal growth may influence lipid andapolipoprotein metabolism and affect atherogenic indices at birth.INTRODUCTIONAdvances in neonatal intensive care in recent decades havebrought about dramatic improvement in the prognosis forpremature infants (1). However, as noted by Barker andOsmond in 1986 (2), evidence has accumulated that indicesof foetal growth, such as size at birth, are inverselyassociated with cardiovascular morbidity and mortality(3–5). The intra-uterine environment and early postnatallife are now generally accepted as important determinantsof the risk of cardiovascular disease in adulthood. Althoughthe exact mechanisms are unknown, it has been suggestedthat abnormalities in the metabolism of serum lipids mayexplain these associations (6). Lipid metabolism is a subjectof major importance in the nutrition of neonates becauselipids are the main structural components of cell mem-branes and therefore affect growth and development. In ahuman study (7), low birth weight (BW) was found to beassociated with higher total cholesterol (TC) concentrationsin adult men. However, a recent systematic review of theliterature on BW and blood cholesterol concluded thatthere was only a weak association between low BW andhigher TC (8).The lipoprotein profile in foetuses is quite different fromthat in adults because lipoprotein synthesis is low due toimmature hepatic function and the absence of intestinallipid absorption. The major plasma lipoprotein in foetuses ishigh-density lipoprotein (HDL), whereas in adults it is low-density lipoprotein (LDL) (9,10). Serum lipoprotein profilesin children are predictive of those in adulthood (11,12), andthere is evidence that this association with adult levels mayoriginate at birth (13,14). Several lipoprotein ratios or‘atherogenic indices’ have been defined in an attempt tooptimise the predictive capacity of the lipid profile. TC/HDL cholesterol (HDLc) and LDL cholesterol (LDLc)/HDLc ratios are risk indicators with a greater predictivevalue than isolated parameters used independently (15).The major apoprotein present in HDL is apolipoprotein-A1 (apoA1), which provides structural stability to thespherical molecule. In LDL, apolipoprotein-B (apoB) con-stitutes most of the protein content. The apoB/apoA1 ratiois therefore also of great value in detecting atherogenic riskand is often more useful than TC/HDLc and LDLc/HDLcratios (15).

Aim: Conventional soybean lipid emulsions contain no docosahexaenoic acid (DHA) or arachidonic acid (AA). We investigated the relationship between blood DHA and AA status in 27 very-low-birth-weight (VLBW) infants with or without parenteral lipid emulsion. Methods: Sixteen infants received parenteral lipid emulsion, and 11 infants were control group. The fatty acid composition of the erythrocyte membrane was analysed at birth and at 2 weeks of age. Results: No significant difference in AA levels was observed in the lipid emulsion group between the two time points, whereas the AA levels at 2 weeks were significantly lower than at birth in the control group. The DHA levels in both groups at 2 weeks were significantly lower than at birth, but no group differences were observed at both time points. Conclusion: The use of parenteral soybean oil lipid emulsions in VLBW infants in the postnatal period may prevent the decline in the AA level but does not appear to influence the DHA level.

Enterococcus faecalis is rarely involved in neonatal meningitis. Several studies have indicated that the cytokines related to bacterial infection may induce nerve cell damage; therefore, the cytokine levels in cerebrospinal fluid (CSF) could represent a valuable hallmark for rapid recognition of the disease and evaluation of the degree of neurological involvement. We analyzed cytokine levels in the CSF of a neonate with E. faecalis meningitis over time. Tumor necrosis factor-α (TNF-α) tended to be elevated during the acute phase of infection, and then decreased during the convalescent stage after treatment. CSF inflammatory cytokine measurement may provide important clues for predicting the development of complications in the host because some of these cytokines, such as TNF-α, can injure neurons.

Background: Ghrelin has effects on appetite and growth. Recent reports suggest effects on cardiac function, but no study has evaluated the ghrelin levels of congenital heart disease (CHD) infants with heart failure. The purpose of the present study was therefore to investigate the relationship between ghrelin level and growth and cardiac function in CHD infants. Methods: Twenty-eight infants with CHD were eligible for the study. Blood samples were obtained at the time of insertion of intracardiac catheter and correlation was examined between ghrelin plasma level and anthropometric parameters, including z score of height and weight, body mass index (BMI), and %bodyweight gain rate, severity of heart failure, and the levels of leptin and insulin-like growth factor-1. Results: In the CHD group, active ghrelin (A-Ghr) had a significant negative correlation with z score of bodyweight, and a significant positive correlation with cardiac function. There were no correlations, however, with height and BMI. A-Ghr levels were significantly higher in the high heart failure index score group. Significant correlation between A-Ghr and desacyl-ghrelin in the CHD group was observed. Conclusions: A-Ghr is involved in cardiac function and has little effect on their physique in infants with CHD.

Poor post-natal growth is related to later morbidity and poor cognitive development in preterm infants. We investigated the relationship between plasma insulin-like growth factor 1 (IGF-1), leptin, active ghrelin levels and post-natal growth in preterm infants small for gestational age (SGA).Plasma IGF-1, leptin and active ghrelin levels were measured at birth and at 2, 4, 6 and 8 weeks after birth in 42 very low birthweight (VLBW) infants (born between 27 and 31 weeks of gestation), including 14 SGA infants with extrauterine growth restriction (EUGR), 6 SGA infants without EUGR and 22 appropriate-for-gestational-age infants.At birth, IGF-1 levels in SGA infants without EUGR did not differ significantly from those in SGA infants with EUGR. However, IGF-1 levels in SGA infants without EUGR were as high as those observed in appropriate-for-gestational-age infants and were significantly different from those in SGA infants with EUGR at 4 and 8 weeks of age. Leptin and ghrelin levels did not differ significantly among the three groups at any time point.IGF-1 is related to catch-up growth in SGA VLBW infants during neonatal intensive care unit admission; however, this does not appear to be the case for leptin and ghrelin. IGF-1 level monitoring may be useful for predicting EUGR in preterm VLBW infants.

Insulin-like growth factor-I (IGF-I) is essential for perinatal growth and development; low serum IGF-I has been observed during intrauterine growth restriction (IUGR). We investigated the effects of recombinant human (rh) IGF-I in IUGR rats during the early postnatal period.Intrauterine growth restriction was induced by bilateral uterine artery ligation in pregnant rats. IUGR pups were divided into two groups injected daily with rhIGF-I (2 mg/kg; IUGR/IGF-I, n = 16) or saline (IUGR/physiologic saline solution (PSS), n = 16) from postnatal day (PND) 7 to 13. Maternal sham-operated pups injected with saline were used as controls (control, n = 16). Serum IGF-I and IGF binding proteins (IGFBP) 3 and 5 were measured on PND25. The expression of Igf-i, IGF-I receptor (Igf-ir), Igfbp3, and 5 mRNA in the liver and brain was measured using real-time polymerase chain reaction on PND25. Immunohistochemical staining of the liver for IGF expression was performed.Mean bodyweight on PND3 and PND25 in the IUGR pups (IUGR/IGF-I and IUGR/PSS) was significantly lower than that of the control pups. Serum IGF-I and hepatic Igf-ir mRNA in the IUGR pups were significantly lower than those in the control pups. In the IUGR/IGF-I group, hepatic Igfbp3 mRNA and liver immunohistochemical staining were increased. In the IUGR/PSS and control pups, there were no significant differences between these two groups in serum IGFBP3 and IGFBP5, hepatic Igf-i and Igfbp-5 mRNA, or brain Igf mRNA.No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period.

Background Some children with incontinentia pigmenti exhibit encephalopathic features with severe seizures and disturbed consciousness, from the neonatal through the early infantile period. However, the pathological mechanism of brain lesion development is not fully understood. Methods We measured the cerebrospinal fluid levels of cytokines and oxidative stress markers (8-hydroxy-2-deoxyguanosine and the hexanoyl-lysine adduct) in a young girl with incontinentia pigmenti complicated by an encephalopathic event that occurred on her first day of life. Magnetic resonance imaging revealed widespread reduction of water diffusion in the basal ganglia, the periventricular and subcortical white matter, and the corpus callosum. Results Oxidative stress markers were elevated at 4 days of age but decreased mildly by 25 days of age. Elevated levels of soluble tumor necrosis factor receptor 1 were observed at both 4 and 25 days of age, although tumor necrosis factor-α levels were below the limit of detection. No other cytokine levels were elevated, except for those of interleukin-10 at 25 days of age. Conclusions Tumor necrosis factor-α expression and oxidative stress are involved in the pathogenesis of brain lesions in children with incontinentia pigmenti, and elevated cerebrospinal fluid cytokine levels may not be apparent during encephalopathic events.

Enterococcus faecalis is rarely involved in neonatal meningitis. Several studies have indicated that the cytokines related to bacterial infection may induce nerve cell damage; therefore, the cytokine levels in cerebrospinal fluid (CSF) could represent a valuable hallmark for rapid recognition of the disease and evaluation of the degree of neurological involvement. We analyzed cytokine levels in the CSF of a neonate with E. faecalis meningitis over time. Tumor necrosis factor-α (TNF-α) tended to be elevated during the acute phase of infection, and then decreased during the convalescent stage after treatment. CSF inflammatory cytokine measurement may provide important clues for predicting the development of complications in the host because some of these cytokines, such as TNF-α, can injure neurons.

Reactive oxygen species may be involved in serious diseases in premature infants. The objective of this study was to assess the relationship between neurodevelopmental outcome and oxidative stress marker level in the urine of very low-birthweight (VLBW) infants.Spot urine samples were collected from 35 VLBW infants. Urinary excretion of 8-hydroxy-2″-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and 8-iso-prostaglandin F2α (8-isoPGF), a marker of lipid peroxidation, was measured at 1, 2, 4, and 6 weeks of age. Neurodevelopmental outcome at 18 months' corrected age was assessed using the Bayley Scales of Infant Development (BSID)-II.Significant correlations were found between urinary 8-OHdG at 2 and 4 weeks and the Mental Development Index of the BSID-II. No significant correlation was found between urinary 8-isoPGF and indices of the BSID-II.In VLBW infants, urinary 8-OHdG level correlated with mental development rather than psychomotor development at 18 months' corrected age; urinary 8-OHdG might be a predictive marker of neurodevelopmental outcome in VLBW infants.

Aim Conventional soybean lipid emulsions contain no docosahexaenoic acid (DHA) or arachidonic acid (AA). We investigated the relationship between blood DHA and AA status in 27 very-low-birth-weight (VLBW) infants with or without parenteral lipid emulsion. Methods Sixteen infants received parenteral lipid emulsion, and 11 infants were control group. The fatty acid composition of the erythrocyte membrane was analysed at birth and at 2 weeks of age. Results No significant difference in AA levels was observed in the lipid emulsion group between the two time points, whereas the AA levels at 2 weeks were significantly lower than at birth in the control group. The DHA levels in both groups at 2 weeks were significantly lower than at birth, but no group differences were observed at both time points. Conclusion The use of parenteral soybean oil lipid emulsions in VLBW infants in the postnatal period may prevent the decline in the AA level but does not appear to influence the DHA level.

Ghrelin has effects on appetite and growth. Recent reports suggest effects on cardiac function, but no study has evaluated the ghrelin levels of congenital heart disease (CHD) infants with heart failure. The purpose of the present study was therefore to investigate the relationship between ghrelin level and growth and cardiac function in CHD infants.Twenty-eight infants with CHD were eligible for the study. Blood samples were obtained at the time of insertion of intracardiac catheter and correlation was examined between ghrelin plasma level and anthropometric parameters, including z score of height and weight, body mass index (BMI), and %bodyweight gain rate, severity of heart failure, and the levels of leptin and insulin-like growth factor-1.In the CHD group, active ghrelin (A-Ghr) had a significant negative correlation with z score of bodyweight, and a significant positive correlation with cardiac function. There were no correlations, however, with height and BMI. A-Ghr levels were significantly higher in the high heart failure index score group. Significant correlation between A-Ghr and desacyl-ghrelin in the CHD group was observed.A-Ghr is involved in cardiac function and has little effect on their physique in infants with CHD.

Aim: We investigated the relationship between plasma insulin-like growth factor I (IGF-I), leptin, active ghrelin levels, and postnatal growth in very low birth weight (VLBW) infants. Method: Plasma IGF-I, leptin, and active ghrelin levels were measured at birth and at 2, 4, 6 and 8 weeks after birth in 61 VLBW infants, including 31 appropriate-for-gestational-age (AGA) and 30 small-for-gestational-age (SGA) infants. Results: Insulin-like growth factor I levels were the lowest at birth, but increased gradually over the first 8 weeks of life. IGF-I was positively correlated with body weight, body length and body mass index at all time points. Leptin levels did not change over the study period. Ghrelin levels were significantly lower at birth; however, there were no significant differences between the levels after 2 weeks of age. Leptin and ghrelin levels were not correlated with anthropometrical measures. IGF-I levels at birth were significantly lower in SGA than in AGA infants, but the leptin and ghrelin levels were not significantly different between the two groups. Conclusion: Insulin-like growth factor I is related to length and weight gain in the prenatal and the early postnatal periods in VLBW infants, but this does not appear to be the case for leptin and ghrelin.