Aikaterini Drougia

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.

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 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.

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.

Comparison of Misoprostol and Dinoprostone for elective induction of labour in nulliparous women at full term: A randomized prospective study

BackgroundThe objective of this randomized prospective study was to compare the efficacy of 50 mcg vaginal misoprostol and 3 mg dinoprostone, administered every nine hours for a maximum of three doses, for elective induction of labor in a specific cohort of nulliparous women with an unfavorable cervix and more than 40 weeks of gestation.Material and MethodsOne hundred and sixty-three pregnant women with more than 285 days of gestation were recruited and analyzed. The main outcome measures were time from induction to delivery and incidence of vaginal delivery within 12 and 24 hours. Admission rate to the neonatal intensive care unit within 24 hours post delivery was a secondary outcome.ResultsThe induction-delivery interval was significantly lower in the misoprostol group than in the dinoprostone group (11.9 h vs. 15.5 h, p < 0.001). With misoprostol, more women delivered within 12 hours (57.5% vs. 32.5%, p < 0.01) and 24 hours (98.7% vs. 91.4%, p < 0.05), spontaneous rupture of the membranes occurred more frequently (38.8% vs. 20.5%, p < 0.05), there was less need for oxytocin augmentation (65.8% vs. 81.5%, p < 0.05) and fewer additional doses were required (7.5% vs. 22%, p < 0.05). Although not statistically significant, a lower Caesarean section (CS) rate was observed with misoprostol (7.5% vs. 13.3%, p > 0.05) but with the disadvantage of higher abnormal fetal heart rate (FHR) tracings (22.5% vs. 12%, p > 0.05). From the misoprostol group more neonates were admitted to the intensive neonatal unit, than from the dinoprostone group (13.5% vs. 4.8%, p > 0.05). One woman had an unexplained stillbirth following the administration of one dose of dinoprostone.ConclusionsVaginal misoprostol, compared with dinoprostone in the regimens used, is more effective in elective inductions of labor beyond 40 weeks of gestation. Nevertheless, this is at the expense of more abnormal FHR tracings and more admissions to the neonatal unit, indicating that the faster approach is not necessarily the better approach to childbirth.

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

Abstract 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.

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.

Perinatal and neonatal mortality in Northwest Greece (1996–2004)

Objective. An improvement in perinatal mortality is reported in various countries. This is a retrospective analysis of perinatal and neonatal mortality in Northwest (NW) Greece. Methods. Analysis was made of the births and deaths register in NW Greece and records of the regional referral tertiary care center and the National Hospitals at the same area for the period 1996–2004. Perinatal mortality was analysed according to birthweight (BW) and gestational age (GA) for two separate periods, 1996–1999 (I) and 2000–2004 (II), corresponding to an increase in antenatal steroid use from 20% to 63%. Results. Neonatal mortality improved between the two periods in infants with very low BW [very low birth weight (VLBW), <1500 g] and the very preterm infants (<28 weeks GA). Severe respiratory distress syndrome (RDS) decreased (p < 0.001) for infants with GA ≤ 34 weeks and those with BW 751–1500 g (p < 0.02), and perinatal asphyxia is no longer a leading cause of death. Intrauterine transfer increased (p < 0.001) for infants with BW ≤ 1500 g. The main cause of death as derived from birth records and neonatal intensive care unit records is prematurity, alone or with complications. Conclusions. With the introduction of antenatal steroids and increase in intrauterine transfer there has been a decrease in neonatal mortality of VLBW infants in NW Greece.