Functional and structural connectivity of the brain in very preterm babies: relationship with gestational age and body and brain growth.

BACKGROUND: Structural and functional changes of the brain have been reported in premature babies. OBJECTIVE: To evaluate the relationship of functional and structural connectivity with gestational age, body growth and brain maturation in very preterm babies. MATERIALS AND METHODS: We studied 18 very preterm babies (gestational age: mean ± standard deviation, 29.7±1.7 weeks). We examined functional connectivity by multivariate pattern analysis of resting-state functional MRI data. We assessed structural connectivity by analysis of diffusion tensor imaging data and probabilistic tractography. RESULTS: The average functional connectivity of the medial orbitofrontal cortex with the rest of the brain was positively associated with gestational age (P<0.001). Fractional anisotropy of the right inferior fronto-occipital fasciculus was positively associated with head circumference at term-equivalent age. Structural connectivity of the inferior fronto-occipital fasciculus with the medial orbitofrontal cortex was positively associated with head circumference at term-equivalent age. Body weight at term-equivalent age was the only independent predictor of average structural connectivity of the medial orbitofrontal cortex with the rest of the brain (P=0.020). CONCLUSION: Structural and functional connectivity of the medial orbitofrontal cortex with the rest of the brain depend on body growth and degree of prematurity, respectively.

Vitamin D, parathormone, and insulin resistance in children born large for gestational age.

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 (ß=0.37, p<0.01 and ß=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.

Body growth and brain development in premature babies: an MRI study.

BACKGROUND: Prematurity and intrauterine growth restriction are associated with neurodevelopmental disabilities. OBJECTIVE: To assess the relationship between growth status and regional brain volume (rBV) and white matter microstructure in premature babies at around term-equivalent age. MATERIALS AND METHODS: Premature infants (n= 27) of gestational age (GA): 29.8 ± 2.1 weeks, with normal brain MRI scans were studied at corrected age: 41.2 ± 1.4 weeks. The infants were divided into three groups: 1) appropriate for GA at birth and at the time of MRI (AGA), 2) small for GA at birth with catch-up growth at the time of MRI (SGAa) and 3) small for GA at birth with failure of catch-up growth at the time of MRI (SGAb). The T1-weighted images were segmented into 90 rBVs using the SPM8/IBASPM and differences among groups were assessed. Fractional anisotropy (FA) was measured bilaterally in 15 fiber tracts and its relationship to GA and somatometric measurements was explored. RESULTS: Lower rBV was observed in SGAb in superior and anterior brain areas. A positive correlation was demonstrated between FA and head circumference and body weight. Body weight was the only significant predictor for FA (P< 0.05). CONCLUSION: In premature babies, catch-up growth is associated with regional brain volume catch-up at around term-equivalent age, starting from the brain areas maturing first. Body weight seems to be a strong predictor associated with WM microstructure in brain areas related to attention, language, cognition, memory and executing functioning.

Brain growth in preterm infants is affected by the degree of growth restriction at birth.

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.

Morbidity and mortality patterns in small-for-gestational age infants born preterm.

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.

Pre-inflammatory mediators and lymphocyte subpopulations in preterm neonates with sepsis.

The aim of this study is to investigate prospectively specific immune system factors in preterm neonates with late-onset sepsis and infection-free controls. Matched preterm neonates (n = 82) were divided into three groups: suspected infection (n = 25), sepsis (n = 17), and infection-free controls (n = 40). Serial measurements were made of interleukin-6 (IL-6), IL-1ß, tumor necrosis factor-α (TNF-α), lymphocyte subsets [CD3+, CD4+, CD8+, natural killer (NK) cells, and B cells], the immunoglobulins (IgG, IgM, and IgA), C-reactive protein (CRP), and the total blood count, before, 2 days after initiation of treatment, and after stopping treatment. The percentages of NK and B cells were higher in the sepsis group, but those of CD3+, CD4+, and CD8+ showed no differences. IgG was lower in the sepsis group. IL-6 >30 pg/ml and TNF-α >30 pg/ml were sensitive sepsis predictors with sensitivity 1 (0.78-1) and 1 (0.79-1), respectively, but their specificity was poor. CRP was a specific [0.90 (0.80-0.96)] but not sensitive index [0.68 (0.48-0.85)], and its combination with IL-6 or TNF-α could enhance their diagnostic accuracy. It is concluded that NK and B cells may be elevated in late neonatal sepsis. IL-6 or TNF-α combined with CRP is a good diagnostic marker for late-onset sepsis in preterm neonates.

Low gestational age and chronic lung disease are synergistic risk factors for retinopathy of prematurity.

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) <32 weeks born in a well-defined geographical region. STUDY DESIGN-SUBJECTS: The study population included all preterm infants born alive with GA 24-32 weeks 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 O(2) needs, hypoxic/hyperoxic episodes, patent ductus arteriosus (PDA), sepsis, using multiple logistic regression analysis. RESULTS: Of 189 infants without congenital anomalies born at GA 24-32 weeks 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.

Renal function and kidney length in preterm infants with nephrocalcinosis: a longitudinal study.

Renal injury in early life may lead to hypertension and renal disease in adulthood. In this prospective study, we estimated renal glomerular and tubular function and kidney length (KL) during the first 2 years of life of preterm infants with nephrocalcinosis (NC) associated with prematurity. The study cohort comprised 107 preterm children, 63 with NC and 44 control subjects without NC who were matched for gender, gestational age and birth weight. Kidney function was estimated based on measurements of serum creatinine (Scr), estimated glomerular filtration rate (eGFR), fractional excretion (FE) of sodium (Na), potassium (K), phosphate (P), magnesium (Mg) and uric acid (UA) and on the ratios of urinary Ca, oxalate (UOx) and citrate (UCit) to urinary creatinine (UCa/Ucr, UOx/Ucr and UCit/Ucr, respectively) calculated from morning urine collections. KL was measured by ultrasonography. Measurements were made at 40 weeks postmenstrual age and at 3, 6, 12 and 24 months of age. At 3 and 6 months, the NC group had higher UCa/Ucr, FEK and FEUA than the control group; at 12 months, only the UCa/Ucr and FEUA was still higher. The UCa/UCit ratio was higher in the NC group. Scr and eGFR did not differ between the groups at any time point. The NC group had a shorter KL up to 12 months of life (left kidney) or 24 months (right kidney). Based on these results, we conclude that NC in the preterm infants enrolled in our study was associated with impaired renal tubular function and a shorter KL in the first year of life.

Renal glomerular and tubular function in neonates with perinatal problems.

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.

Prothrombotic state, cardiovascular, and metabolic syndrome risk factors in prepubertal children born large for gestational age.

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.

Kidney growth in twin children born small for gestational age.

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.

Periventricular leukomalacia in preterm children: assessment of grey and white matter and cerebrospinal fluid changes by MRI.

BACKGROUND: Brain plasticity in patients with periventricular leukomalacia (PVL) may suggest grey matter (GM) changes. OBJECTIVE: To assess the volume of 116 GM areas and total volume of GM, white matter (WM) and cerebrospinal fluid (CSF) in preterm children with PVL, using the Statistical Parametric Mapping (SPM5) and the Individual Brain Atlases Statistical Parametric Mapping (IBASPM) toolboxes. MATERIALS AND METHODS: Ten preterm children (gestational age 31.7 +/- 4.2 weeks, corrected age 27.8 +/- 21.7 months) with PVL and 46 matched, preterm control subjects were studied using a three-dimensional T1-weighted sequence. Volumes were calculated using SPM5 and IBASPM. RESULTS: GM volume in frontal superior orbital, posterior cingulum and lingual gyrus, the putamen and thalamus was significantly higher in children with PVL (3.6 +/- 0.6 cm(3), 2.0 +/- 0.5 cm(3), 9.7 +/- 1.7 cm(3), 2.5 +/- 0.6 cm(3), 2.6 +/- 0.9 cm(3), respectively) than in controls (3.1 +/- 0.7 cm(3), 1.5 +/- 0.2 cm(3), 8.2 +/- 1.3 cm(3), 1.7 +/- 1.4 cm(3), 1.8 +/- 0.4 cm(3), respectively). White matter volume was lower (182.1 +/- 40.5 cm(3)) and CSF volume was higher (300.8 +/- 56.2 cm(3)) in children with PVL than in controls (222.9 +/- 67.2 cm(3), 219.0 +/- 61.8 cm(3), respectively), P < 0.05. No significant difference was found in the total GM volume and the volume of neocortex. CONCLUSION: Preterm children with PVL show regional GM volume increase, possibly explained by axonal sprouting, neuronal hypertrophy and neurogenesis, which in turn may reflect brain plasticity.

Implications of 99mTc-DMSA scintigraphy performed during urinary tract infection in neonates.

OBJECTIVE: To evaluate prospectively whether normal scintigraphic results during urinary tract infections (UTIs) in neonates were predictive of the absence of dilating vesicoureteral reflux (VUR) (grade > or =III) and permanent renal damage (PRD). METHODS: Term neonates with a first symptomatic, community-acquired UTI participated in the study. Urinary tract ultrasonography and technetium-99m-labeled dimercaptosuccinic acid ((99m)Tc-DMSA) scintigraphy were performed within 72 hours after diagnosis and voiding cystourethrography within 1 to 2 months. DMSA scintigraphy, to determine the development of PRD, was repeated 6 months after UTI. RESULTS: Seventy-two neonates (144 renal units) were enrolled. Acute pyelonephritis was diagnosed through early DMSA scintigraphy in 19% of renal units, VUR in 22%, and grade > or =III VUR in 13%. The majority (71%) of renal units with grade > or =III VUR had normal early DMSA scintigraphic results. The sensitivity and specificity of abnormal early DMSA scintigraphic results to predict grade > or =III VUR were 29% (95% confidence interval: 11%-55%) and 82% (95% confidence interval: 74%-88%), respectively. PRD was found in 7% of renal units, all of which had abnormal early DMSA scintigraphic results. PRD was significantly more frequent among renal units with grade > or =III VUR than among nonrefluxing renal units (P < .05). CONCLUSIONS: Normal early DMSA scintigraphic results for neonates with symptomatic UTIs were helpful in ruling out later development of PRD but were not predictive of the absence of dilating VUR. To rule out dilating VUR, voiding cystourethrography may be required.

Growth restriction at birth and kidney function during childhood.

BACKGROUND: Individuals born small for gestational age (SGA) are at risk of developing hypertension and kidney disease later in life. The time that this may occur is unknown. This study aims to examine kidney function in preschool children who were SGA. STUDY DESIGN: A case-control study. SETTINGS & PARTICIPANTS: The study included 100 children, 60 SGA and 40 appropriate-for-gestational-age (AGA) controls matched with the SGA children according to birth characteristics (gestational age and sex) and characteristics at the time of the study (body weight, body height, body mass index, and age). SGA children were classified according to severity of growth restriction into 2 groups: birth weight less than the 3rd percentile (n = 25) and birth weight from the 3rd to 10th percentile (n = 35). PREDICTORS: Being SGA and severity of growth restriction at birth. OUTCOMES & MEASUREMENTS: Kidney function was estimated at a mean age of 5 years by using serum creatinine level; estimated glomerular filtration rate; urinary albumin excretion; fractional excretion of sodium, potassium, phosphate, magnesium, and uric acid; transtubular potassium gradient; and urinary calcium-creatinine ratio calculated from 3-hour urine collections. Blood pressure and kidney length also were measured. RESULTS: Kidney length, serum creatinine level, and estimated glomerular filtration rate did not differ among the 3 groups. Systolic and diastolic blood pressures were greater in SGA children with birth weight less than the third centile versus controls (107.5 +/- 11 versus 102 +/- 10 mm Hg [P = 0.03] and 69 +/- 7.5 versus 65 +/- 8.6 mm Hg [P = 0.02] for systolic and diastolic blood pressure, respectively). Both groups of SGA children had greater urinary calcium excretion than AGA children (urinary calcium-creatinine ratio, 0.16 +/- 0.08 and 0.16 +/- 0.10 in SGA with birth weight < 3rd and 3rd to 10th percentiles versus 0.10 +/- 0.09 in AGA; P = 0.04 and P = 0.03, respectively). SGA children also had lower uric acid excretion despite greater serum uric acid levels (fractional excretion of uric acid, 7.4% +/- 4% and 6.9% +/- 5% versus 10.5% +/- 5.9%; P = 0.02 and P = 0.003, respectively). LIMITATIONS: Relatively small sample size, blood pressure was measured on a single visit. CONCLUSIONS: Children born SGA showed alterations in calcium and uric acid urinary excretion at preschool age, and blood pressure was related to the severity of growth restriction.

Growth factors and adipocytokines in prepubertal children born small for gestational age: relation to insulin resistance.

OBJECTIVE: The aim of this study was to test whether being born small for gestational age (SGA) has an impact on adiponectin and leptin levels and the IGF system in relation to insulin sensitivity, taking into consideration the severity of growth restriction. RESEARCH DESIGN AND METHODS: Serum levels of adiponectin, leptin, fasting glucose, fasting insulin (I(F)), the homeostasis model assessment insulin resistance index (HOMA-IR), IGF-1, free IGF-1, IGF-binding protein (IGFBP)-1 and -3, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were evaluated in 57 children at age 4-10 years. Of these, 32 had been born appropriate size for gestational age (AGA) and 25 SGA (14 in the <3rd percentile and 11 in the 3rd-10th percentile). RESULTS; The SGA 3rd-10th percentile children were already insulin resistant at prepubertal age (I(F) 39.6 +/- 16.8 vs. 27 +/- 12 pmol/l, P < 0.01, and HOMA-IR 1.4 +/- 0.6 vs. 0.95 +/- 0.42 in SGA vs. AGA children, P < 0.05). Their IGF-1 and IGFBP-3 concentrations were significantly lower than those in AGA children (160.4 +/- 66.2 vs. 207 +/- 66.8 microg/l, P < 0.05 and 2.3 +/- 0.4 vs. 3.51 +/- 1.21 mg/l in SGA vs. AGA children, P < 0.01). The SGA <3rd percentile children had higher adiponectin (15.6 +/- 5.7 mg/l, P < 0.05) and IGFBP-1 levels (113.5 +/- 33.9 microg/l, P < 0.05) than AGA children (11.3 +/- 6.6 mg/l and 90.8 +/- 24.2 microg/l, respectively) and lower IGF-1 and IGFBP-3 concentrations (162.6 +/- 68.4 microg/l, P < 0.05 and 2.4 +/- 0.7 mg/l, P < 0.01). They also had significantly lower waist circumference (P < 0.05). Leptin levels did not differ among groups, but an inverse correlation with IGFBP-1 (r = -0.55, P < 0.01) was found in the pooled SGA group. CONCLUSIONS: Intrauterine growth restriction appears to affect the IGF axis at prepubertal age, and its severity plays a role in insulin sensitivity.

The effects of gestational age and growth restriction on compensatory kidney growth.

BACKGROUND: Low birth weight is associated with altered renal development, adult onset hypertension and renal disease. The aim of this prospective longitudinal study was to estimate the renal growth during the first 2 years of life in small-for-gestational age (SGA) infants of varied gestational age (GA) and with differing degrees of growth retardation (GR) at birth. Material and methods. The study included 466 children: SGA, n = 243, and appropriate-for-gestational age (AGA), n = 223, classified according to GA into three groups (28-34, 34-36 and >36 weeks, respectively). The SGA children were also classified according to the degree of GR: birth weight <3rd percentile, and birth weight 3-10th percentiles. Serial renal ultrasonography (US) for kidney length (KL) measurement was performed at the ages of 36 and 40 weeks corrected age and 3, 6, 12 and 24 months of chronological age. The ratios of KL(3) to crown to heel length (CHL), body weight (BW) and body surface area (BSA) were used as estimators of relative kidney length (RKL). RESULTS: A total of 1898 measurements were performed. In the full-term and near-term SGA infants (GA >36 weeks), RKL was similar to or even higher than that in AGA controls (P < 0.05 at 12 and 24 months). In two groups of preterm infants (GA 34-36, 28-34 weeks), RKL was lower than in AGA controls either after the first 6 months (GA 34-36 group, P < 0.05) or throughout the study period (GA 28-34 group, P < 0.05). The absolute KL was more severely affected in the preterm babies (GA <36 weeks) with BW <3rd percentile than in those of GA 3rd-10th percentile. CONCLUSION: While in full-term and near-term SGA infants RKL is similar to or even higher than that of AGA infants, in smaller preterm babies (<36 weeks of GA) the RKL is impaired up to the second year of life.

Serum transferrin receptor, ferritin, and reticulocyte maturity indices during the first year of life in 'large' preterm infants.

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 microg/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 microg/L had lower sTfr than those with sFer >12 microg/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.

Tubular disorders in low birth weight neonates after prolonged antibiotic treatment.

BACKGROUND: Aminoglycosides (AGs) and vancomycin (VM) are potentially nephrotoxic antibiotics and their co-administration increases the incidence of nephrotoxicity in adult patients. Their combined effects on renal function in extremely low birth weight (ELBW) infants (<1,000 g) have not been previously reported. OBJECTIVES: Investigation of tubular disturbances in five ELBW neonates following repeated and prolonged treatment with a variety of AGs combined with VM. RESULTS: The drug levels were maintained in the neonatal therapeutic range. Renal tubular wasting of potassium, phosphate, and calcium, along with hypokalemia, was documented in all neonates studied while associated hypophosphatemia was observed in three of the five neonates and a transient rise in serum creatinine in four. The renal disturbances resolved completely 1-2 weeks after cessation of treatment. CONCLUSION: Renal tubular disturbances due to AG and VM treatment in ELBW neonates may be more common than they are diagnosed. Early detection and appropriate electrolyte supplementation may help to normalize serum electrolyte levels in these infants.

Urinary mineral excretion in preterm neonates during the first month of life.

BACKGROUND: Estimation of urinary parameters in preterm infants is a useful method for identifying metabolic derangements. OBJECTIVES: A prospective, longitudinal, hospital-based study was designed to examine the variability and the associations in renal excretion of calcium (Ca), magnesium (Mg), phosphate (P) and sodium (Na) in formula-fed preterm infants during the first month of life. PATIENTS: Thirty-four infants <32 weeks gestational age, clinically stable, not receiving nephrotoxic drugs. METHODS: Measurements of serum and 8-hour urinary mineral and creatinine (Cr) concentrations were made in all infants during three periods (at 7-10, 14-17 and 21-26 days postnatally). The urinary parameters, FENa, FEP, UCa/UCr, UMg/UCr were calculated. 24- hour urinary excretion was estimated by extrapolation of the 8-hour values. RESULTS: The 24-hour excretion values (median and range) (mmol/kg) during the three study periods were, respectively, for Ca: 0.027 (0.015-0.15), 0.030 (0.007-0.12), 0.031 (0.008-0.12), for P: 0.26 (0.07-0.83), 0.29 (0.06-0.67), 0.41 (0.22-0.70), for Mg: 0.025 (0.007-0.14), 0.025 (0.008-0.16), 0.027 (0.010-0.10) and for Na: 2.85 (0.8-15), 1.45 (0.3-17), 1.56 (0.6-4.3). Na excretion declined while the excretion of the other minerals remained stable. A positive correlation was observed between excretion of Ca, Mg and Na (Ca vs. Na r = 0.63, p < 0.0001; Ca vs. Mg r = 0.65, p < 0.0001; Na vs. Mg r = 0.38, p = 0.012) as well as between the renal parameters FENa, FEP, UCa/UCr, UMg/UCr and the respective 24-hour excretion values (r = 0.80, 0.86, 0.84, 0.81) CONCLUSIONS: Urinary excretion of Ca, P, and Mg in preterm formula-fed infants is stable during the first month of life while urinary Ca, Na and Mg are closely correlated during the same period.

Serum adiponectin and leptin levels and insulin resistance in children born large for gestational age are affected by the degree of overweight.

OBJECTIVE: Children born large for gestational age (LGA) are prone to develop insulin resistance later in life. One factor that affects insulin sensitivity is the hormone adiponectin. The aim of this study was to determine whether being LGA has an impact on serum adiponectin and leptin levels and insulin resistance parameters during childhood, taking into account the severity of overweight. STUDY DESIGN: Serum levels of adiponectin, leptin, fasting glucose and insulin, homeostasis model assessment insulin resistance index (HOMA-IR), and anthropometric indices were evaluated in groups of non-obese children aged 6.5-8 years, born appropriate for gestational age (AGA, n = 40) or LGA (n = 41), matched for age, gender, height, weight and body mass index. The LGA group was divided in two subgroups according to the degree of overweight: (a) LGA with birthweight 90th-97th percentile (n = 25); and (b) LGA with birthweight > 97th percentile (n = 16). RESULTS: LGA children had a higher mean serum adiponectin level than AGA children: 17.0 +/- 9 vs. 11.1 +/- 5 (microg/ml) (P < 0.01). LGA children had also higher insulin 6.2 +/- 2.8 vs. 4.8 +/- 2.4 (microU/ml) (P < 0.05) and HOMA-IR 1.32 +/- 0.66 vs. 1.02 +/- 0.55 (P < 0.01) than AGA children. Children born LGA > 97th percentile had a significantly higher mean serum leptin level than both AGA and LGA 90th-97th percentile children (17 +/- 13, 9.6 +/- 9.5, 7.8 +/- 7.9 ng/ml, respectively, P < 0.05), and more severely affected insulin resistance indices than LGA 90th-97th percentile children. In the regression analysis, birthweight was found to be an independent predictor of adiponectin serum levels. CONCLUSION: Prepubertal LGA-born children had a higher mean serum adiponectin levels than matched AGA controls despite the fact that they were more insulin resistant. The degree of excess in utero weight gain appears to influence the metabolic profile in LGA-born prepubertal children. Further studies are needed to delineate the role of adiponectin in the risk of development of insulin resistance in children born LGA.