Vitamin D levels and insulin resistance in children born with severe growth restriction.

This study was designed to examine differences in serum 25(OH)D levels between small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) prepubertal children in correlation with birth weight and indices of insulin resistance and ß-cell function. Sixty-five nonobese children were examined at age 5-7.5 years; 27 born SGA and 38 matched AGA. Body weight, height, BMI, and waist circumference were recorded and fasting serum levels of glucose, insulin, 25(OH)D, and parathyroid hormone (PTH) were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) and the ß-cell function index (HOMA-ß%) were estimated. The mean level of 25(OH)D was higher in the SGA group (26.2±10 vs. 17.2±7 ng/ml, p<0.01) but that of PTH was no different. The insulin resistance and ß-cell function indices were higher in the SGA group: HOMA-IR 1.34±0.67 vs. 0.99±0.53, and HOMA-ß% 135±56 vs. 97±60 in the SGA and AGA groups, respectively. In the SGA group, 25(OH)D was correlated with HOMA-ß% but not with HOMA-IR or insulin. In multiple regression, in the total cohort 25(OH)D and HOMA-IR were independently negatively correlated with birth weight (ß= - 0.31, ß= - 0.36, p<0.05) respectively. In conclusion, at prepuberty severely in utero growth restricted children have increased birth weight dependent levels of 25(OH)D, which might exert a regulatory role on ß-cell function.

Visfatin levels in prepubertal children born small or large for gestational age.

Children born small (SGA) or large (LGA) for gestational age are prone to develop insulin resistance (IR) during childhood. Visfatin, a hormone with insulin-mimetic actions, has been associated with IR. This study was designed to examine whether serum level of visfatin is correlated with metabolic indices of IR, in prepuberty in association with the intrauterine growth pattern. The following parameters were evaluated at a mean age of 6.5±1.2 years in 155 prepubertal children born appropriate for the gestational age (AGA) (n=63), or SGA (n=42), or LGA (n=50): serum levels of visfatin, adiponectin, leptin, fasting glucose (G(F)) and insulin (I(F)), the homeostasis model assessment IR index (HOMA-IR), plasma lipids, anthropometric indices at birth and the time of evaluation, and obesity indices [waist circumference (WC), body mass index (BMI) and skinfold thickness]. The mean serum level of visfatin was lower in the SGA than in the AGA and the LGA children (9±5.2 vs. 11.8±5.1 and 12.7±5.6 ng/ml, respectively, p<0.01). Girls had lower visfatin levels than boys (10.4±4.3 ng/ml vs. 12.5±6.7 ng/ml, p<0.05). Visfatin was not correlated with IR indices. In multiple regression analysis visfatin level was positively correlated with birth weight z-score (t=2.56, beta=0.24, p<0.01) and crown to heel z-score (t=2.46, beta=0.22, p=0.014), independent of age, gender, maternal weight before pregnancy, maternal weight gain during pregnancy, BMI z-score, WC z-score, serum leptin and adiponectin, and HOMA-IR. In conclusion serum visfatin level was lower in prepubertal SGA children but not correlated with IR indices. Low birth weight was an independent predictor of visfatin level.

Vitamin D and parathormone levels of late-preterm formula fed infants during the first year of life.

BACKGROUND/OBJECTIVES: Preterm infants are at risk for low vitamin D but documentation on late-preterm infants is sparse. This prospective study monitored longitudinally vitamin D and parathormone (PTH) levels in late-preterm formula fed infants during the first year of life, taking into consideration in utero and postnatal growth, and season and diet. SUBJECTS/METHODS: The study population comprised 128 infants of gestational age (GA) 32-36 weeks, of which 102 were appropriate (AGA) and the remaining 26 were small for GA (SGA). Serum levels of vitamin D (25(OH)D), PTH calcium, phosphate (P) and alkaline phosphate were estimated at 2 and 6 weeks, and at 3, 6, 9 and 12 months of age. RESULTS: The 25(OH)D levels were relatively low at 2 and 6 weeks in both AGA and SGA infants (21±11, 20±7 ng/ml and 25±16, 23±8 ng/ml, respectively), but increased at 6 months (45±14, 47±10 ng/ml) and remained stable thereafter. SGA infants had lower 25(OH)D levels at 9 and 12 months (AGA 45±14, 47±18 ng/ml vs SGA 38±13, 37±13 ng/ml, P<0.05). Deficiency of 25(OH)D (<20 ng/ml) was found in 18.5% of measurements in 92 (72%) infants, and its insufficiency (20-32 ng/ml) was found in 29.2% of measurements in 99 (77.3%) infants. Most measurements with vitamin D <32 ng/ml were observed at the first three study points, where PTH showed an inverse association with 25(OH)D, reaching a plateau thereafter. CONCLUSIONS: Late-preterm, formula fed infants may have suboptimal vitamin D levels and elevated PTH, especially, during the first 3 months. Those born SGA may have lower vitamin D levels up to the end of the first year of life.

Growth factors, adiponectin, leptin and body mass index in pre-pubertal children born large for gestational age.

OBJECTIVE: To examine whether the IGF axis in pre-pubertal children born large for gestational age (LGA) differs from that of those born appropriate for gestational age (AGA). RESEARCH DESIGN AND METHODS: The study population consisted of 98 non-obese children aged 5.5-8 yr, of whom 37 were LGA, with birth weight (BW) > 90th percentile, and 61 AGA. The LGA children were subdivided into two subgroups, with BW 90th-97th percentile (no.=24) and BW > 97th percentile (no.=13), respectively. Total and free IGF-I, their binding proteins 1 and 3 (IGFBP-1 and IGFBP-3), leptin, adiponectin, fasting glucose (GF) and insulin (IF) were measured, and the homeostasis model assessment for insulin resistance (HOMA-IR index) was determined. RESULTS: IGF-I, free IGF-I and IGFBP-1 were similar in both groups. Both LGA subgroups had lower IGFBP-3 levels than the AGA group (2.34 ± 0.61 and 2.70 ± 0.90, respectively, vs 3.92 ± 1.1 µg/ml, p < 0.01). Adiponectin was higher in the 90th-97th percentile LGA subgroup than the AGA group (p<0.01). GF and IF were higher in the LGA group (86.5 ± 5.6 mg/dl, p < 0.01, and 5.84 ± 2.13 µU/ml, respectively, p < 0.05) than in the AGA group (82.6 ± 7.7 mg/dl and 4.62 ± 1.9 µU/ml, respectively), as was the HOMA-IR index (1.27 ± 0.60 vs 0.94 ± 0.43, p < 0.01). These three parameters were also found higher in the >97th percentile LGA subgroup. CONCLUSION: The IGF axis was not different in pre-pubertal children born LGA or AGA, with the exception of IGFBP-3, which was lower in the LGA children. In LGA pre-pubertal children the severity of intrauterine overgrowth was associated with the insulin resistance indices.

Changes in red cell phosphate metabolism of preterm and fullterm infants with perinatal problems during their first month of life.

The effects of perinatal problems on red cell phosphate metabolism were studied in two groups of infants (preterms B and fullterms D) during the first month of life. All infants started milk feeding from day three after birth. The results were compared to those of healthy preterms (A) and fullterms (C), respectively. Comparisons were also made between the preterm and fullterm groups B and D. The preterms with perinatal problems (B) showed a significant delay in catching up with the plasma and red cell inorganic phosphate (Pi) levels of controls (A) throughout the first month of life (p < 0.05). In parallel, the erythrocyte 2,3 diphosphoglycerate (2,3-DPG) concentrations of the sick preterms lagged significantly behind those of controls (p < 0.001); but the ATP levels were comparable between the two groups. The fullterms behaved slightly differently. No significant differences in plasma Pi (Pl Pi) and red cell 2,3-DPG were seen between the sick and healthy neonates during the month of study, while red cell Pi (RBC Pi) and ATP were found to be lower in the sick ones (p < 0.05). The fullterms with perinatal problems (D) had significantly higher Pl Pi (p < 0.05) and RBC Pi (p < 0.01) than preterms with problems (B) from the first week of life and continued in a similar pattern until the end of the month. Red cell 2,3-DPG concentrations were found to be significantly correlated with Pl Pi and RBC Pi in both preterm groups (p < 0.01) and in the sick fullterms (p < 0.001) during the time of the study. In the healthy fullterms 2,3-DPG was found to correlate only with red cell Pi (p < 0.05). Perinatal problems seem to affect Pi metabolism to a different degree in preterm and fullterm neonates in the first month of life.

Vitamin D: a necessity for children and adolescents in Greece.

Children and adolescents with the high bone turnover comprise a high risk population for vitamin D insufficiency. A sample of 178 clinically healthy children aged 3 to 18 years who came from public schools and lived in North West of Greece participated in the study. They were grouped into three age groups (I: 3-10, II: 11-14 and III: 15-18 years of age). Blood samples were taken during winter and summer months for determining calciotropic hormones, calcium, phosphate and biochemical markers of bone synthesis.A high percentage (47%) of the subjects aged 15-18 years was found to have 25OHD <10 ng/ml in winter but much less (13-14%) of the younger ages (13-14 years), while in the summer they were all >10 ng/ml. The prevalence was even higher in the girls of the older group accompanied by lower Pi concentrations again in winter (win:1.19+/-0.03, sum:1.93+/-0.03 mmol/l, p < 0.001). The 24,25(OH)(2)D levels were changing in parallel to 25OHD, but again in the older subjects, during winter, they were by 2/3 lower than the summer ones (0.73+/-0.10 vs. 2.41+/-0.20 ng/ml, p < 0.001). No significant differences were found between seasons and groups in the 1,25(OH)(2)D levels. The biochemical markers of bone synthesis, osteocalcin (OC) and total alkaline phosphatase (ALP), were found significantly lower in the girls of the older group both in winter and summer respectively. Even in a sunny country like Greece the adolescents living in an urban area are in high risk for vitamin D deficiency during winter. Supplementation with vitamin D of milk, of popular beverages and perhaps some foods would be of help.

Effects of intranasal salmon calcitonin in juvenile idiopathic arthritis: an observational study.

The aim of this study was to follow the changes in bone mineral density (BMD) and biochemical markers of bone turnover in 10 children (7.5-17.5 years of age) with severe juvenile idiopathic arthritis (JIA), during a 3-year therapy with salmon calcitonin (100 IU/day 2 months on and 2 off for a year and 200 IU/day for 2 years) and calcium (500 mg/day). All patients were functional classes III and IV and were measured at yearly intervals with a dual photon absorptiometer at the lumbar spine. The changes observed were 7.2-9.5% per year for BMD and 2.0-6.0% for volumetric bone mineral density (BMDvol). The bone resorption markers showed significant decreases after a year's treatment (Pyr/Cr from 175+/-15 to 108+/-15 nm/mm, P < 0.001, Pyr-D/Cr from 24.3+/-3.5 to 13.3+/-1.9 nm/mm, P < 0.05, and OHPr/Cr from 57.4+/-11 to 35.1+/-8.4 microg/mg) and smaller changes thereafter. No significant changes were observed in the bone formation markers of osteocalcin and alkaline phosphatase. Serum iPTH, the vitamin D metabolites, and calcium concentrations fluctuated within normal, while calcium excretion increased from 0.3+/-0.1 to 1.9+/-0.4 mg/kg/24 hours, P < 0.001. In conclusion, the present study, despite its limitations of not being placebo controlled, shows possible beneficial effects of intranasal calcitonin on bone resorption and pain relief in JIA patients.

Effect of recombinant human erythropoietin in preterm infants.

Twenty-five premature infants (mean gestational age+/-SD, 31.4+/-1.9 weeks) were administered subcutaneously recombinant human erythropoietin (rHuEpo) at a dose of 300 u/kg of body weight three times a week beginning on the third day of life and continuing for 6 weeks. The controls (n=23) were premature infants with a mean gestational age of 32.2+/-2.3 weeks who did not receive rHuEpo. Haematological indices, haemoglobin and serum phosphate (Pi), and red blood cell (RBC) phosphate metabolites (ATP, 2,3-DPG, RBCPi) were tested monthly until the 6th month and thereafter at the 9th and 12th months of life. The level of serum soluble transferrin receptors (sTfR) correlated significantly with rHuEpo (p<0.05). The ratio of sTfR to log (ferritin) was significantly higher (p<0.001) in the infants treated with rHuEpo than the controls. Intracellular organic and inorganic Pi changes were not affected by the Epo administration. The RBC 2,3-DPG seemed adequate in infants receiving rHuEpo.

Effect of aminoglycoside therapy on renal function in full-term infants.

The effect of aminoglycosides on renal function was evaluated in 30 full-term infants who were treated within 24 h of birth with either amikacin (10 infants, group A), gentamicin (9 infants, group B), or netilmicin (10 infants, group C). Renal function was assessed before, during, and 48 h after discontinuation of therapy by measuring the plasma creatinine concentration (PCr), the fractional excretion of sodium (FENa), potassium, magnesium, phosphate (FEP), uric acid, and the urinary excretion of calcium (UCA/UCr ratio) immediately before (trough) and after (peak) the infusion of the aminoglycosides. The results were compared with 10 control newborns who did not receive antibiotics. Significant alterations in renal function were observed only during therapy with gentamicin (group B). These consisted of a sustained elevation of FENa and UCa/UCr ratio throughout therapy, a latent increase in FEP on the 7th day (P < 0.05), and lack of the normal postnatal decline of PCr in 3 of 9 infants (P < 0.01). These abnormalities persisted up to 2 days after discontinuation of therapy. Therapeutic doses of gentamicin may result in significant electrolyte disturbances in sick full-term infants.

Bone minerals in beta-thalassemia minor.

Homozygous beta-thalassemia is a severe hereditary disorder associated with osteopenia. Recently it was suggested that thalassemia minor may be a risk factor for osteoporosis. The purpose of the present study was to investigate this suggestion. Bone mineral status was assessed in 22 premenopausal women and 21 men with beta-thalassemia minor. In vivo neutron activation analysis was applied to measure hand-bone phosphorus (HBP), single-photon absorptiometry to measure forearm bone mineral content (BMC), and dual-energy X-ray absorptiometry to measure spinal bone mineral density (BMD). Comparison of the HBP, BMC, and BMD values with those of sex- and age-matched healthy subjects without the beta-thalassemia trait failed to indicate a statistically significant difference for either sex group. Concerning the biochemical markers of bone metabolism that were studied (serum calcium, phosphate, alkaline phosphatase, osteocalcin, and parathyroid hormone, and 3-h fasting urine calcium-to-urine creatinine ratio) no difference was observed between the study subjects and matched controls. In conclusion, the present study showed that subjects with beta-thalassemia minor are not at risk for osteoporosis.

Renal function in premature infants during aminoglycoside therapy.

The effect of three different aminoglycosides on renal function was evaluated in 30 premature infants of similar gestational age who were treated within 24 h of birth with either amikacin (10 infants, group A), gentamicin (10 infants, group B) or netilmicin (10 infants, group C), for a period of 7 days. Ten infection-free premature infants of similar post-conceptional age were used as controls. Serial determinations of plasma creatinine concentration (PCr), as well as the fractional excretion of sodium (FENa), potassium, magnesium (FEMg), phosphate (FEP) and uric acid (FEUA), and the urinary excretion of calcium (UCa/UCr ratio) were assessed before, during and after treatment. During the treatment period a significant increase in FENa, FEMg and UCa/UCr was observed in group B (P < 0.05 and P < 0.01, respectively) and an increase in FENa and UCa/UCr in group C (P < 0.01) compared with controls. These disturbances were observed with trough concentrations of aminoglycosides but were accentuated at peak serum concentrations and were restored to normal 2 days after stopping therapy. In addition, a significant correlation was demonstrated between FENa, FEMg and UCa/UCr ratio in treated patients. PCr levels decreased similarly in all patient groups, but in 8 of 30 infants (27%) they remained elevated and returned to control values only 10 days after stopping therapy. Such renal functional disturbances, although transient, may result in significant electrolyte and mineral imbalance in the sick premature infant.

Phosphate metabolism in the red cell of sick prematures.

The effect of different amounts of phosphorus supplementation on phosphate metabolism was studied in two groups of sick preterms (B and C) during the first week of life. Group B included prematures that started formula milk feeding from day 3 and group C neonates on total parenteral nutrition with phosphate supplementation for 7 days. Twelve healthy preterm neonates on formula milk feeding from day 2 (group A) were used as controls. On the 7th day of life all phosphate parameters measured in group C (plasma and red cell inorganic phosphate and erythrocyte ATP and 2,3-diphosphoglycerate) were found significantly lower than in the controls (1.60 +/- 0.07; 0.60 +/- 0.08; 1.45 +/- 0.09 and 4.42 +/- 0.18 vs. 2.05 +/- 0.10; 0.94 +/- 0.11; 1.69 +/- 0.07 and 6.24 +/- 0.42 mmol/l, respectively). The renal tubular reabsorption of phosphate was also lower in this group (86.8 +/- 3.2 vs. 97.3 +/- 1.0%). No significant differences were observed between groups B and A. Higher phosphorus intake that was better achieved through early milk feeding prevented phosphate depletion and the decline of 2,3-diphosphoglycerate in the erythrocytes even of sick neonates which in turn might help to improve tissue oxygenation. The amount of parenteral phosphate supplementation that could have beneficial effects on red cell phosphate parameters needs further investigation.

Cortisol secretion in stressed babies during the neonatal period.

The present study investigates the developmental pattern of serum cortisol secretion in sick fullterm and preterm neonates in comparison to that of normal babies over the first 30 days of life. Four groups of babies (15 in each group) were studied sequentially during the first 4 weeks of life. Serial venous blood samples were drawn at 08.00, 14.00, 20.00 and 02.00 h from each baby. The higher cortisol levels (p < 0.001) observed in sick preterm and full-term neonates, when compared to their respective controls, suggest an appropriate response to stress. Fullterm and preterm babies with no problem were found to have a free running rhythm in serum cortisol levels during the first 4 weeks of life.