Styliani Andronikou

Age-related grey matter changes in preterm infants: An MRI study

Grey matter (GM) maturation has not been previously studied in healthy preterm children. The purpose of this study was to evaluate the age dependency of GM development in 116 GM areas in preterm subjects. Sixty one preterm infants (corrected age: 13.7+/-9.92 months, gestational age: 33.4+/-1.9 weeks) with normal structural appearance on MRI were included in the study. Using a T1-weighted high resolution 3D spoiled gradient echo sequence, volumes of 116 GM areas were calculated after their segmentation using the Voxel Based Morphometry Toolboxes and the Individual Brain Atlas Statistical Parametric Mapping (IBASPM) software packages. Non linear regression analysis assessed age dependency of volume data for every GM area using the monoexponential function y=A-Bexp(-x/C). All supratentorial GM areas followed the monoexponential function model reasonably well. Cerebellar structures had a poor goodness of fit. Volume increase of the individual GM areas followed an inferior to superior and a posterior to anterior pattern. The putamen, thalamus, and caudate nucleus reached 99% of the final volume earlier than most cortical GM areas. The visual cortex and the postcentral and precentral cortices matured earlier than the parietal, frontal and temporal cortices. The fronto-occipital asymmetry or torque seen in adults was observed in the preterm infants; the left occipital areas reached maturation earlier than the right, while the right prefrontal and frontal areas matured earlier than the left. To conclude, GM development progresses in a region-specific manner coinciding with functional, phylogenetical and regional white matter (WM) maturation.

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.

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 ≥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 (99mTc-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 ≥III VUR in 13%. The majority (71%) of renal units with grade ≥III VUR had normal early DMSA scintigraphic results. The sensitivity and specificity of abnormal early DMSA scintigraphic results to predict grade ≥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 ≥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.

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.

Renal function and effect of aminoglycoside therapy during the first ten days of life

Abstract. The effect of aminoglycoside administration on kidney functional maturation was evaluated in groups of 30 preterm and 30 fullterm infants who were treated for 7 days because of suspected infection. One of three different aminoglycosides was administered to each subgroup of ten preterm and ten fullterm infants. Changes in tubular function in groups of ten preterm and ten fullterm infants who were not given antibiotics were also compared. The mean gestational age for preterm infants from 32.5 to 33.6 weeks and for fullterm infants between 39.2 and 39.5 weeks. The renal tubular function was assessed by examining the fractional excretion of sodium (FENa), potassium (FEK), phosphorus (FEP), magnesium (FEMg) and uric acid (FEUA) as well as by the urinary excretion of calcium as the calcium/creatinine (UCa/UCr) ratio. Gentamicin affected the normal plasma creatinine (PCr) decline in both treated groups (fullterm and preterm). Disturbances in FENa and UCa/UCr were more pronounced in treated preterm than in fullterm infants especially after netilmicin and gentamicin administration. FEMg was significantly affected in preterm infants treated with gentamicin. The findings of this study indicate that the effect of aminoglycosides on tubular function is dependent upon kidney maturity and the type of the aminoglycoside used for therapy.

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.

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 andP<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.

Acute effects of gentamicin on urinary electrolyte excretion in neonates

It has recently been shown that a single dose of gentamicin causes immediate and transient calcium and magnesium renal wasting in adults. The aim of this study was to determine the acute effect of gentamicin administration on renal electrolyte handling in preterm and full-term neonates. Twenty-three neonates treated with gentamicin for suspected infection were enrolled in the study. Serum and 3-h urine electrolytes were measured before and immediately after gentamicin infusion on the 1st, 3rd, 4th, and 7th day of treatment. Serum gentamicin levels were monitored. Gentamicin caused a statistically significant post-infusion increase in fractional excretion of sodium and magnesium and in the urine calcium to urine creatinine ratio. Potassium and phosphate fractional excretion remained unchanged. The disturbances in electrolyte excretion were observed in full-term as well as in preterm neonates. Serum electrolyte levels remained unchanged. In conclusion, therapeutic doses of gentamicin result in urinary loss of sodium, calcium, and magnesium in neonates immediately after the infusion of the drug. These electrolyte changes may be of clinical importance, especially for sick preterm neonates.

Renal venous thrombosis in an infant with predisposing thrombotic factors: color Doppler ultrasound and MR evaluation.

Abstract.We report a case of a neonate with hereditary thrombophilia presenting with renal venous thrombosis (RVT). Early color Doppler findings of RVT were lacking venous flow, and the arterial diastolic flow was reversed. This very high-resistance arterial flow is for the first time described in neonatal RVT. Magnetic resonance imaging showed low signal intensity of the renal pyramids on T1- and T2-weighted images, suggesting acute hemorrhage. After intravenous contrast injection, persistent cortical enhancement was observed along with lack of medullary enhancement. Despite the progressive reestablishment of some venous drainage, the kidney showed atrophy and loss of function.

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 (IF), 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 (IF 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 μg/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 μg/l, P < 0.05) than AGA children (11.3 ± 6.6 mg/l and 90.8 ± 24.2 μg/l, respectively) and lower IGF-1 and IGFBP-3 concentrations (162.6 ± 68.4 μg/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.