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Background: Low vitamin D [25(OH)D] levels have been associated with type-2 diabetes mellitus. Children born large for gestational age (LGA) may exhibit increased indices of insulin resistance early in life., Objective: This study aims to prospectively examine serum 25(OH)D and parathormone (iPTH) levels in LGA and appropriate for gestational age (AGA) prepubertal children, in relation to the severity of macrosomia and insulin resistance., Methods: Children were examined at age 5-7.5 years, 38 born LGA and 39 AGA, matched for age, gender, body weight, height and body mass index (BMI). Twenty-one LGA had birth weights in the 90th-97th percentile and 17 >97th percentile. Fasting serum levels of glucose, insulin, 25(OH)D, and iPTH were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was estimated., Results: The insulin resistance indices were higher in the LGA >97th percentile subgroup than in the AGA group: HOMA-IR 1.53±0.66 vs. 1.04±0.53 and fasting insulin 6.92±3.1 vs. 4.78±2.2 μIU/mL (but similar to the AGA group), and in the LGA 90th-97th percentile subgroup: HOMA-IR 1.17±0.61 and insulin 5.53±2.2. There was no difference in 25(OH)D among the three subgroups. The iPTH was higher in the LGA >97th percentile subgroup than in the AGA group (26.8±7.6 and 22.6±7.2 pg/mL, respectively, p<0.05), although it was not correlated with insulin resistance indices. Birth weight was correlated negatively with fasting insulin and HOMA-IR in the entire cohort, independent of age, sex, waist circumference, and BMI (β=0.37, p<0.01 and β=0.30, p<0.05, respectively), while waist circumference was positively correlated with HOMA-IR (R=0.40, p<0.001)., Conclusion: Birth weight and current body composition appear to affect glucose homeostasis in LGA prepubertal children, while the serum levels of 25(OH)D and iPTH appear to be uninvolved.

Purpose: Brain functional connectivity (FC) changes and microstructural abnormalities are reported in infants born moderate and late preterm (MLPT). We evaluated the effect of low-grade (grades I, II) intraventricular hemorrhage (IVH) in MLPT babies on brain structural connectivity (SC) and FC. Methods: Babies born MLPT between January 2014 and May 2017 underwent brain ultrasound (US) at 72 h and 7 days after birth, and MRI at around term equivalent. The MRI protocol comprised T1- and T2-weighted sequences, diffusion tensor imaging (DTI), and resting-state functional MRI (fMRI). SC and FC were assessed using graph analysis. Results: Of 350 MLPT neonates, 15 showed low-grade IVH on US at 72 h, for which brain MRI was available in 10. These 10 infants, with mean gestational age (GA) 34.0 ± 0.8 weeks, comprised the study group, and 10 MLPT infants of mean GA 33.9 ± 1.1 weeks, with no abnormalities on brain US and MRI, were control subjects. All study subjects presented modularity, small world topology, and rich club organization for both SC and FC. The patients with low-grade IVH had lower FC rich club coefficient and lower SC betweenness centrality in the left frontoparietal operculum, and lower SC rich club coefficient in the right superior orbitofrontal cortex than the control subjects. Conclusions: Topological and functional properties of mature brain connectivity are present in MLPT infants. IVH in these infants was associated with structural and functional abnormalities in the left frontoparietal operculum and right orbitofrontal cortex, regions related to language and cognition. [ABSTRACT FROM AUTHOR]

Objective: To investigate the insulin resistance status in SGA infants at 12 months and its relationship with auxological and metabolic parameters. Methods: One group of 45 SGA and one of 50 appropriate for gestational age infants were followed from birth to the end of the first year of life. At 12 months, skinfold thickness, waist circumference, and blood levels of glucose, insulin, adiponectin, leptin, resistin, visfatin, retinol-binding protein 4, IGFs, lipids profile were determined, and the HOMA-IR index was calculated. Results: The SGAs had increased insulin (5.2 ± 2.7 versus 2.9 ± 2.4 μIU/ml,p = 0.012) and HOMA-IR (1.09 ± 0.9 versus 0.59 ± 0.55,p = 0.016). In multiple regression, insulin resistance indices were independently correlated with low-birth-weight (β = −2.92,p = 0.015 for insulin,β = −2.98,p = 0.011 for HOMA-IR) but not with catch-up growth in either height or weight or any other metabolic parameter. Resistin was higher in the SGAs (5.1 ± 2.1 versus 3.9 ± 2.1 ng/ml,p = 0.03) and independently correlated with low-birth-weight but not insulin resistance. Resistin was negatively correlated with total cholesterol (R = −0.33,p = 0.007) and positively with lipoprotein(a) (R = 0.49,p = 0.001). Conclusion: Low-birth-weight, but not catch-up growth or adiposity tissue hormones, was correlated with insulin resistance at 12 months in non-obese SGA infants. The higher resistin in SGA infants and its correlation with total cholesterol and lipoprotein(a) need further clarification. [ABSTRACT FROM PUBLISHER]

Objective: Documentation of examination of brain structural development by magnetic resonance imaging (MRI) beyond the neonatal period is scarce for both preterm and small for gestational age (SGA) infants. Aim: To investigate structural brain development during infancy in preterm children born SGA by MRI. Methods: A total of 205 preterm infants, 139 appropriate for gestational age (AGA) and 66 SGA, of which 33 had birth weight (BW) < 3rd percentile and 33 had BW 3rd-10th percentile, were examined prospectively by brain MRI at the corrected age of 5 months. The total volume of the brain, ventricles and cerebellum, the area of vermis and corpus callosum, and the height of the pituitary, mesencephalon and pons were estimated on MRI. Results: Brain volume was smaller in the SGA < 3rd percentile infants, independent of other perinatal factors. Chronic lung disease was an independent predictor of low brain volume. Pituitary height was greater in SGA < 3rd percentile than in AGA infants. The corpus callosum area was less in SGA < 3rd percentile than in SGA of 3rd-10th percentile infants. Conclusions: Preterm infants born SGA with BW < 3rd percentile had differences in brain structural measurements at the corrected age of 5 months, compared with preterm AGA infants, which could have implications for their neurocognitive development. [ABSTRACT FROM AUTHOR]

Objective. Small-for-gestational age (SGA) neonates born prematurely may be at higher risk for adverse effects during the early postnatal period than premature neonates born appropriate for gestational age (AGA).This study aims to study comparatively morbidity and mortality in SGA and AGA neonates born with low gestational age (GA). Methods. The study population included all preterm infants born alive with GA 24-31 weeks in Northwestern Greece during a 9-year period and hospitalized in the regional neonatal intensive care unit (NICU). The association of SGA status with neonatal death, and with chronic lung disease (CLD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), respiratory distress syndrome (RDS), patent ductus arteriosus (PDA), and sepsis was assessed, using multiple logistic regression analysis. Results. Of 210 infants without congenital anomalies born at GA 24-31 weeks, 51 were SGA and 159 were AGA. CLD was more common in SGA than in AGA neonates (57.1%% vs 29.3%%, p < 0.05), but no differences were found in the rates of IVH, NEC, ROP, RDS, and sepsis. The mortality rate in the SGA group was 33.3%% vs 17%% in the AGA group ( p < 0.01), and in the subgroups 28-31 weeks 24.1%% vs 6.3%%, respectively, ( p < 0.01). In logistic regression analysis, SGA status was strongly associated with increased mortality and CLD, independent of confounding factors [[odd ratios and confidence intervals: 3.4 (CI: 1.8-10.6) p == 0.03 and 3.9 (CI: 1.7-11.5) p < 0.01, respectively. Conclusions. SGA neonates with GA 24-31 weeks were at increased risk of development of CLD and of neonatal death compared with AGA neonates of the same GA. [ABSTRACT FROM AUTHOR]

Abstract: Aims: This retrospective, population based study was designed to investigate risk factors for development of retinopathy of prematurity (ROP) and their possible interrelationships, in neonates of gestational age (GA) <32weeks born in a well-defined geographical region. Study design—subjects: The study population included all preterm infants born alive with GA 24–32weeks in Northwestern Greece during a 9-year period and hospitalised in the regional neonatal intensive care unit (NICU). Outcome measurements: The association was assessed of the presence of ROP with maternal factors: age, pathology of pregnancy, in-vitro fertilisation, multiple gestation, mode of delivery, perinatal factors: gender, antenatal steroids, transportation, resuscitation, GA, birth weight (BW), small for GA status and postnatal morbidity: chronic lung disease (CLD), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC), respiratory distress syndrome (RDS), maximum O2 needs, hypoxic/hyperoxic episodes, patent ductus arteriosus (PDA), sepsis, using multiple logistic regression analysis. Results: Of 189 infants without congenital anomalies born at GA 24–32weeks ROP was diagnosed in 24 (12.7%) (>grade 2: 6). Logistic regression analysis showed ROP to be strongly associated with GA, odds ratio (OR) 2.1, confidence interval (CI) 1.3–3.3, p<0.01 and CLD, OR 10.2, CI 2.3–44, p<0.01, respectively, independent of confounding factors. By estimating interaction on an additive scale it was shown that the combined risk effect of GA and CLD was larger than the sum of the individual risk effects, implying synergistic effect. Conclusions: ROP was closely and independently related to both low GA and the diagnosis of CLD, which were interrelated in the development of ROP. [Copyright &y& Elsevier]

Objective. To investigate perinatal risk factors that may be associated with impaired renal function during the first 2 weeks of life. Methods. The case notes of 150 neonates of gestational age (GA) 34-36 weeks and 494 of GA > 36 weeks were studied. Clinical risk factors were retrieved, along with indices of renal function: serum creatinine (SeCr), fractional excretion (FE) of sodium (FENa) and potassium (FEK), and the urinary calcium to creatinine ratio (UCa/UCr). Associations were identified by multiple and logistic regression analysis. Results. In infants with GA > 36 weeks, raised SeCr was related to perinatal stress, odds ratio (OR): 1.9, confidence interval (CI): 1.2-2.9, p < 0.05, and to duration of treatment with aminoglycosides (AGs) ( t = 2.4, p < 0.01); FEK was associated with jaundice ( t = −3.1, p < 0.01), and FENa with duration of AGs treatment ( t = 2.6, p < 0.01). Full-term neonates with both hypoxic-ischemic encephalopathy (HIE) and AGs administration had an 80% increase in OR for impaired SeCr levels. In infants of GA 34-36 weeks, SeCr was related to perinatal stress (OR: 9, CI: 1.3-38, p < 0.05), FEK to jaundice ( t = −2.1, p < 0.05), and FENa to duration of AGs administration ( t = 2.2, p < 0.05) and antenatal steroid treatment (OR: 0.8, CI: 0.6-0.95, p < 0.05). Conclusion. In neonates, renal impairment, being multifactorial in origin, may be caused by the additive effect of different perinatal factors. The strong negative relationship observed between jaundice and K excretion merits further investigation. [ABSTRACT FROM AUTHOR]

Background. Low birth weight (LBW) is associated with adult-onset diseases, including hypertension and renal disease; altered renal development after intrauterine growth restriction (IUGR) may underlie related prenatal programming. No data are available on longitudinal renal growth in twin infants born small for gestational age (SGA). The aim of this prospective longitudinal study was to estimate the renal size during the first 2 years of life in SGA twin infants.Methods. The study included 613 children, of which 145 were SGA twins, 141 twins appropriate for gestational age (AGA), 148 matched AGA singletons and 179 matched SGA singletons, classified according to GA into two groups (28–36 and >36 weeks). The SGA children were also classified according to the degree of IUGR: birth weight (BW) <3rd percentile and BW 3rd–10th percentiles. Serial renal ultrasonography (US) for kidney length (KL) measurement was performed at the ages of 36 and 40 weeks corrected age (CA) and 3, 6, 12 and 24 months of age, and KL was related to other anthropometric indices. Twin data were examined both as individuals and as members of twin pairs.Results. A total of 2317 measurements were performed. KL was lower at 40 weeks CA in all the SGA twin subgroups. In the SGA twins with GA >36 weeks, KL increased thereafter and became similar to AGA twins and single AGA control subjects. Among pre-term infants of GA <36 weeks, only those with BW 3rd–10th percentile experienced catch-up in KL, while in those with BW <3rd percentile, KL remained lower than in AGA infants throughout the study period, both in absolute terms and relative to other anthropometric indices. No differences in KL were found between twin SGA and singleton SGA or between twin AGA and singleton AGA infants. Intrapair BW differences were correlated with the intrapair differences in KL.Conclusions. Twin SGA infants born prematurely with BW <3rd percentile are unable to achieve catch-up in KL in the first 24 months of life, and long-term follow-up is recommended. [ABSTRACT FROM AUTHOR]

Background: Preterm infants are at risk of developing iron deficiency; among the iron status and hemopoiesis indices the serum transferrin receptor (sTfr) has been shown to be a useful indicator in assessing iron status, while immature reticulocyte production is regarded as an estimator of erythropoiesis. Objective: To investigate age-related changes in iron status infants born ‘moderately’ preterm, with a gestational age (GA) of 32–36 wk, and identify associations between sTfr and other hematological and biochemical iron indices. Design: Hospital-based prospective, longitudinal study in preterm infants. Methods: Iron and erythropoiesis parameters were evaluated in 181 formula-fed preterm infants at 2 and 6 wk and 3, 6, 9, and 12 months chronological age. Hemoglobulin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), reticulocytes, serum iron (sFe), serum ferritin (sFer), sTfr, and reticulocyte subpopulations were measured. Results: A total of 756 measurements were performed. After an initial decline, Hb rose from month 3 to 12 of life. SFe and sFer and immature reticulocyte count decreased from the second week to the third month and remained stable thereafter. STfr was lower up to 6 wk and stable from month 3 to 12. Iron deficiency anemia (IDA) was found in 5.5% of infants. In 76 measurements sFer was <12 μg/L, implying storage iron deficiency (SID). A negative correlation was observed between sTfr and other indices of iron status such as Hb, Hct, MCV, sFe, and sFer. Infants with sFer <12 μg/L had lower sTfr than those with sFer >12 μg/L. Reticulocyte production was positively associated with STfr, but this association was dependent on the chronological age of the infant. Conclusion: Iron depletion is common in formula-fed preterm (32–36 wk GA) infants between month 3 and 12 of life. STfr appears to be an indicator of iron status in preterm infants during the first year of life. [ABSTRACT FROM AUTHOR]

OBJECTIVE- To evaluate metabolic syndrome and cardiovascular disease risk factors in prepubertal children born large for gestational age (LGA) to nondiabetic, nonobese mothers. RESEARCH DESIGN AND METHODS-- At 6-7 years of age, the comparison of various factors was made between 31 LGA and 34 appropriate-for-gestational-age (AGA) children: fibrinogen, antithrombin III, protein C and S, fasting insulin, glucose, homeostasis assessment model of insulin resistance (HOMA-IR) index, adiponectin, leptin, visfatin, IGF-1, IGF-binding protein (IGFBP)-1, IGFBP-3, lipids, and the genetic factors V Leiden G1691A mutation, prothrombin 20210A/G polymorphism, and mutation in the enzyme 5,10-methylenetetrahydrofolate-reductase gene (MTHFR-C677T). RESULTS -- LGA children had higher levels of leptin (P < 0.01), fasting insulin (P < 0.01), and HOMA-IR (P < 0.01), but lower IGFBP-3 (P = 0.0001), fibrinogen (P = 0.0001), and lipoprotein(a) (P < 0.001) than AGA children. Significantly more LGA children were homozygous for the MTHFR-C677T mutation (P = 0.0016). CONCLUSIONS-- Being born LGA to nondiabetic, nonobese mothers is associated with diverse effects on cardiometabolic risk factors at prepuberty. [ABSTRACT FROM AUTHOR]

Evidence supports that growth trajectory during infancy has a major impact on body composition. We aimed to examine body composition in children born small for gestational age (SGA) or appropriate for gestational age (AGA) adjusted for postnatal growth velocity. We enrolled 365 children, 75 SGA and 290 AGA, aged 7 to 10 years, examining anthropometrics, skinfold thickness, and body composition using bioelectrical impedance analysis. Growth velocity was defined as rapid or slow (weight gain > or <0.67 z -scores, respectively). Gestational age, sex, delivery mode, gestational diabetes, hypertension, nutrition, exercise, parental body mass index (BMI), and socioeconomic status were considered. At a mean of 9 years of age, SGA compared with AGA-born children, had significantly lower lean mass. BMI was negatively associated with SGA status (beta = 0.80, P =.046), after adjusting for birth weight, delivery mode, and breastfeeding. The lean mass index was negatively associated with SGA status (beta = 0.39, P =.018), after adjusting for the same factors. SGA-born participants with slow growth velocity had significantly lower lean mass in comparison to AGA-born counterparts. SGA-born children with rapid compared with those with slow growth velocity had significantly higher absolute fat mass. BMI was negatively associated with a slow postnatal growth pattern (beta = 0.59, P =.023), and the lean mass index was negatively associated with a slow postnatal growth pattern (beta = 0.78, P =.006), after adjusting for the same factors. In conclusion, SGA-born children presented a lower lean mass in comparison to AGA-born counterparts, whereas BMI and lean mass index were negatively associated with slow postnatal growth velocity. Children born small for gestational age (SGA) with a slow postnatal growth velocity had lower lean mass in comparison to children born appropriate for gestational age. Moreover, children born SGA with rapid postnatal growth velocity had a significantly higher absolute fat mass in comparison to those with slow postnatal growth velocity. The Figures of the graphical abstract were partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license. [Display omitted] [ABSTRACT FROM AUTHOR]