Lean mass and fat mass accretion between term age and 6 months post-term in growth-restricted preterm infants.

Early growth restriction followed by nutritional intakes that permit accelerated growth may result in adiposity and metabolic disease in later life. This study compared growth, body composition and nutritional intake between term age and 6 months post-term in 83 appropriate-for-gestational-age preterm infants with growth restriction at term age (AGA GR+), 15 AGA without growth restriction at term age (AGA GR-) and 33 small-for-gestational-age (SGA) preterm infants. AGA GR+ and SGA preterm infants had higher protein intake, higher energy intake and higher gain in weight SDS between term age and 6 months post-term, with similar lean mass (LM) and lower fat mass (FM) at 6 months post-term compared with AGA GR- preterm infants. In conclusion, despite higher energy and protein intake compared with AGA GR- preterm infants during the first 6 months post-term, AGA GR+ and SGA preterm infants restore their LM without excessive FM.

The effect of enteral supplementation of specific neutral and acidic oligosaccharides on the faecal microbiota and intestinal microenvironment in preterm infants.

We aimed to determine the effects of enteral supplementation of a prebiotic mixture of neutral and acidic oligosaccharides (scGOS/lcFOS/pAOS) on the faecal microbiota and microenvironment in preterm infants. Furthermore, we determined the influence of perinatal factors on the development of the faecal microbiota. In a randomised controlled trial, preterm infants with gestational age <32 weeks and/or birth weight <1,500 g received enteral supplementation of scGOS/lcFOS/pAOS or placebo (maltodextrin) between days 3 and 30 of life. Faecal microbiota, as measured with fluorescent in situ hybridisation (FISH), and microenvironment [short-chain fatty acids (SCFAs), pH, sIgA] were measured at four time points: before the start of the study and at days 7, 14 and 30 of life. In total, 113 preterm infants were included. Enteral supplementation of the prebiotic mixture increased the total bacteria count at day 14 (Exp 3.92; 95 % confidence interval [CI] 1.18-13.04, p = 0.03), but not at day 30 (Exp 1.73; 95 % CI 0.60-5.03, p = 0.31). There was a trend toward increased bifidobacteria counts. There was a delayed intestinal colonisation of all bacteria. Enteral supplementation of the prebiotic mixture decreased the faecal pH (Exp 0.71; 95 % CI 0.54-0.93, p = 0.01) and there was a trend toward increased acetic acid compared to the placebo group (Exp 1.09; 95 % CI 0.99-1.20, p = 0.10). There was no effect on sIgA (Exp 1.94; 95 % CI 0.28-13.27, p = 0.50). Antibiotics decreased the total bacteria count (Exp 0.13; 95 % CI 0.08-0.22, p < 0.001). Enteral supplementation of a prebiotic mixture of neutral and acidic oligosaccharides increases the postnatal intestinal colonisation. However, the extensive use of broad-spectrum antibiotics in preterm infants decreased the growth of all intestinal microbiota, thereby, delaying the normal microbiota development.

The effect of neutral and acidic oligosaccharides on stool viscosity, stool frequency and stool pH in preterm infants.

AIM: To determine the effect of neutral oligosaccharides [small-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides (scGOS/lcFOS)] in combination with acidic oligosaccharides (pAOS) on stool viscosity, stool frequency and stool pH in preterm infants. METHODS: In this explorative RCT, preterm infants with gestational age <32 weeks and/or birth weight <1500 g received enteral supplementation with scGOS/lcFOS/pAOS or placebo (maltodextrin) between days 3 and 30 of life. Stool samples were collected at day 30 after birth. RESULTS: In total, 113 infants were included. Baseline and nutritional characteristics were not different between both groups. Stool viscosity at day 30 was lower in the prebiotics group (16.8N) (3.9-67.8) compared with the placebo group (26.3N) (1.3-148.0) (p = 0.03; 95% CI -0.80 to 0.03). There was a trend towards higher stool frequency in the prebiotics group (3.1 ± 0.8) compared with the placebo group (2.8 ± 0.7) (p = 0.15; 95% CI -0.08 to 0.52). Stool pH at day 30 was lower in the in the prebiotics group (5.9 ± 0.6) compared with the placebo group (6.2 ± 0.3) (p = 0.009; 95% CI 0.08 to 0.53). CONCLUSIONS: Enteral supplementation of a prebiotic mixture consisting of neutral (scGOS/lcFOS) and acidic oligosaccharides (pAOS) decreases stool viscosity and stool pH with a trend towards increased stool frequency in preterm infants. The inclusion of pAOS in a formula containing a mixture of scGOS/lcFOS does not add specific advantages to the formula in terms of stool viscosity, frequency, pH as well as feeding tolerance.

Urea production and arginine metabolism are reduced in the growth restricted ovine foetus.

Urea production may be impaired in intrauterine growth restriction (IUGR), increasing the risk of toxic hyperammonaemia after birth. Arginine supplementation stimulates urea production, but its effects in IUGR are unknown. We aimed to determine the effects of IUGR and arginine supplementation on urea production and arginine metabolism in the ovine foetus. Pregnant ewes and their foetuses were catheterised at 110 days of gestation and randomly assigned to control or IUGR groups. IUGR was induced by placental embolisation. At days 120 and 126 of gestation, foetal urea production was determined from [14C]-urea kinetics and arginine metabolism was determined from the appearance of radioactive metabolites from [3H]-arginine, both at baseline and in response to arginine or an isonitrogenous mixed amino acid supplementation. Urea production decreased with gestational age in the embolised animals (13.9 ±  3.1 to 11.2 ±  3.0 µmol/kg per min, P ≤ 0.05) but not in the controls (13.3 ±  3.5 to 14.8 ±  6.0 µmol/kg per min). Arginine supplementation increased urea production in both groups, but only at 126 days of gestation (control: 15.0 ±  8.5 to 17.0 ±  9.4 µmol/kg per min; embolised: 11.7 ±  3.1 to 14.3 ±  3.1 µmol/kg per min, P ≤ 0.05). Embolisation reduced foetal arginine concentrations by 20% ( P ≤ 0.05) while foetal arginine consumption was reduced by 27% ( P ≤ 0.05). The proportions of plasma citrulline and hydroxyproline derived from arginine were reduced in the embolised animals. These data suggest that foetal urea production and arginine metabolism are perturbed in late gestation after placental embolisation.

Predictive value of neonatal MRI with respect to late MRI findings and clinical outcome. A study in infants with periventricular densities on neonatal ultrasound.

PURPOSE: The aim of this study was to correlate hypoxic-ischemic white matter damage on neonatal MRI with MRI appearance and neurological outcome at the age of 1 1/2 years. PATIENTS AND METHODS: A sequential cohort of infants with periventricular densities on neonatal ultrasound was studied with neonatal MRI. Images of 46 infants with a mean gestational age of 31 weeks were obtained at a mean age of 20 days after birth and at 1 1/2 years. To establish agreement between the neonatal and follow-up MRI (general, motor, and visual scores), the weighted Cohen's kappa test was used. To establish the predictive power of neonatal MRI with respect to the neurologic indices at the age of 1 1/2 years, the sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: There was a moderately good to good agreement between the general, motor, and visual neonatal and follow-up MRI scores: weighted kappa = 0.59 (95% CI: 0.44 - 0.74), 0.82 (95% CI: 0.72 - 0.93), and 0.70 (95% CI: 0.56 - 0.84), respectively. Neonatal MRI scores provided a good prediction of the three neurological outcome measures (developmental delay, cerebral palsy, and cerebral visual impairment): sensitivity, specificity, and predictive values were high, with little difference between the three MRI scores. The 32 patients with (nearly) normal neonatal MRI scores were neurologically (nearly) normal at 1 1/2 years on all three outcome measures, whereas 8 patients with seriously abnormal neonatal MRI scores were neurologically abnormal at 1 1/2 years on all three outcome measures. CONCLUSION: Neonatal MRI is able to predict the precise localization and size of perinatal leukomalacia on follow-up MRI and provides a good prediction of neurological outcome at 1 1/2 years.

Predictive value of EEG in neonates with periventricular leukomalacia.

The aim of this study was to evaluate whether EEG (i.e. positive Rolandic sharp waves) can be used to predict neurodevelopment in newborn infants with periventricular leukomalacia and compare the predictive value with that of MRI. A sequential cohort of neonates (n=45; 33 males, 12 females; mean gestational age 31.2 weeks, SD 2.7, range 27 to 37.8 weeks; mean birthweight 1592 g, SD 601 g) with periventricular hyperechogenicities on cranial ultrasound was recruited for this study. EEGs were analyzed for positive Rolandic sharp waves. Neurodevelopment was evaluated at the ages of 12 and 18 months. In the whole group the probability of a poor outcome was 24% and the probability of any impairment was 33%. If the number of positive Rolandic sharp waves was no more than 0.1 per minute, the probability of a poor outcome was reduced to 9% (95% confidence interval [95%CI] 2 to 27%) and the probability of any impairment was reduced to 13% (95%CI 4 to 32%). In all infants with more than 0.1 positive Rolandic sharp waves per minute the probability of a poor outcome was 41% (95%CI 23 to 61%) and of any impairment was 55% (95%CI 34 to 73%). In these infants MRI identified infants with a poor outcome with a sensitivity of 1.00 (95%CI 0.70 to 1.00) and a specificity of 0.92 (95%CI 0.67 to 0.99), and infants with any impairment with a sensitivity of 0.83 (95%CI 0.55 to 0.95) and a specificity of 1.00 (95%CI 0.72 to 1.00). Results suggest that if an EEG of an infant with periventricular leukomalacia contains no more than 0.1 positive Rolandic sharp waves per minute the probability of a normal or mildly delayed development is high (0.91, 95%CI 0.73 to 0.98). MRI enhances the accuracy of the outcome prediction slightly; however, owing to a wide confidence interval, this advantage is negligible. However, if the frequency of the positive Rolandic sharp waves exceeds 0.1per minute, MRI can significantly enhance the precision of the prediction of outcome.

Dietary supplementation of long-chain polyunsaturated fatty acids in preterm infants: effects on cerebral maturation.

AIM: To study the influence of dietary-supplied long-chain polyunsaturated fatty acids on structural brain maturation in preterm infants and to investigate parameters of functional brain development, relating them to structural maturation. Other studies have suggested that dietary supplementation of long-chain polyunsaturated fatty acids in preterm infants may enhance their visual development. The influence on structural brain development has never been evaluated. METHODS: In a prospective, double-blind study, 42 formula-fed premature infants were randomized to be fed either a standard preterm formula without long-chain polyunsaturated fatty acids or an identical formula supplemented with docosahexaenoic acid (0.015 g/100 ml) and arachidonic acid (0.031 g/100 ml). Infants with significant cerebral damage, retinopathy, chronic disease or feeding problems were excluded. Follow-up was focused on assessment of cerebral myelination by MRI. Psychomotor, mental and visual development was analysed and flash-visual evoked potentials were recorded. RESULTS: It was found that progress of myelination, mental and motor development and latencies of visual evoked potentials were not positively influenced by supplementation of long-chain polyunsaturated fatty acids. At each test age, visual acuity was slightly better in the supplemented infants than in the non-supplemented infants, but the difference never reached significance level CONCLUSION: Supplementation of long-chain polyunsaturated fatty acids did not have a demonstrable positive influence on structural brain maturation. Related to this finding, in this small cohort of preterm infants without significant neurological damage, sample size being restricted by strict inclusion criteria and MRI procedures, no significant positive effects were found on psychomotor, mental and visual development.

Body composition in infants with chronic lung disease after treatment with dexamethasone.

UNLABELLED: The aim of this study was to study the effect of chronic lung disease (CLD) and dexamethasone treatment on body composition in preterm infants (birthweight < 1500 g). In addition, anthropometric measurement of body composition were compared with dual-energy X-ray absorptiometry (DXA). Fourteen preterm infants with CLD and a comparison group of 18 preterm infants were studied until 3 mo corrected age. CLD infants received approximately 20 kcal kg-1 per day extra nutritional intake during dexamethasone treatment until term. At term no differences were found between CLD and no CLD infants for percentage bone mass (1.4 +/- 0.2 vs 1.4 +/- 0.1%), fat mass (18.7 +/- 4.5 vs 17.4 +/- 3.5%), lean body mass (79.9 +/- 4.6 vs 81.2 +/- 3.5%) or bone mineral density (0.15 +/- 0.02 vs 0.15 +/- 0.01%). At 3 mo corrected age both groups were also similar for bone mass (1.6 +/- 0.1 vs 1.6 +/- 0.2%), fat mass (22.6 +/- 5.5 vs 24.5 +/- 5.7%), lean body mass (75.8 +/- 5.7 vs 74.0 +/- 5.8%) and bone mineral density (0.20 +/- 0.02 vs 0.20 +/- 0.01%). All anthropometric measurements showed a high correlation with body composition. However, calculated fat mass was 56.7 +/- 8.8% lower than fat mass measured with DXA. CONCLUSION: Body composition at term and 3 mo corrected age in preterm infants treated with dexamethasone for CLD, who received extra caloric intake until term, did not differ from that in preterm infants without CLD.

Development of the hypothalamic-pituitary-adrenal axis in the fetus and preterm infant.

The development of the hypothalamic-pituitary-adrenal (HPA) axis in the human fetus is a complex process. The feto-placental unit may be responsible for important maturational processes in vital organ systems in the fetus. A late gestational cortisol surge may be important in fetal maturation, particularly maturation of the lungs. Several striking differences exist between the function of the HPA axis in the fetus and in adults, such as a relative deficiency of 3beta-hydroxysteroid dehydrogenase in the fetal adrenal cortex. With the transition from intrauterine to extra-uterine life several changes occur in the function of the HPA axis. In infants born before term, the function of the HPA axis may still be immature at both the central and adrenal level. This immaturity of the HPA axis may be important in the development of neonatal morbidity. The present review describes the development of the HPA axis in the fetus and in preterm infants and discusses the possible role of HPA immaturity in the development of neonatal morbidity.

Fetal growth and the function of the adrenal cortex in preterm infants.

Small for gestational age preterm infants have a higher risk of neonatal morbidity compared to appropriate for gestational age preterm infants. A diminished adrenal response to stress may be involved in the higher postnatal morbidity. The adrenal cortex response in relation to fetal growth was studied by ACTH stimulation tests in 43 preterm infants (born < or = 32 wk). The cortisol and 17-hydroxyprogesterone (17-OHP) responses to 1 microg/kg ACTH were analyzed in relation to birth weight SD scores (BW-SDS) corrected for gestational age, gender, and parity. BW-SDS was significantly associated with the cortisol and 17-OHP response. Infants with the lowest BW-SDS had the lowest cortisol levels after stimulation. No effect of size at birth was found on the ratio between cortisol and 17-OHP. In addition, basal cortisone levels in a single blood sample were higher in infants with the lowest BW-SDS than in infants with higher BW-SDS, but the ratio between cortisol and cortisone was comparable in the two groups. We conclude that the response of cortisol and 17-OHP to ACTH stimulation in preterm infants is related to fetal growth. The lack of influence of fetal growth on the ratio between cortisol and 17-OHP after ACTH stimulation suggests that the activities of 21- and 11 beta-hydroxylase are not affected. The lower adrenal response to stimulation may be important in neonatal morbidity and possibly the development of disease in later life in growth-restricted preterm infants.

Gentamicin pharmacokinetics in preterm infants with a patent and a closed ductus arteriosus.

BACKGROUND AND AIM: A patent ductus arteriosus (PDA) may influence renal and hepatic blood flow and hence pharmacokinetics of drugs in neonates compared to neonates with a closed ductus arteriosus (CDA). A 10-percent difference of gentamicin pharmacokinetic parameters between PDA and CDA has been reported; but its implications are unclear. The relevance of this difference relative to the variability within the neonatal population was investigated. METHODS: Twenty-four neonates (12 with a PDA and 12 with a CDA) treated with gentamicin were retrospectively included. Before closing treatment of the PDA, serum levels were drawn and analysed for regular therapeutic drug monitoring of gentamicin. Data were analysed using the standard two-stage approach (STS) and an iterative 2-stage Bayesian population analysis approach (It2B). RESULTS: Both types of analysis showed no significant differences between both populations for gentamicin total body clearance per kg bodyweight (CL/kg). Volume of distribution per kg bodyweight (Vd/kg) tended to be larger and elimination rate (Kel) tended to be smaller in neonates with PDA. Multiple regression analysis showed for both populations highly significant correlations between total body clearance and body weight (p < 0.0001) or gestational age (p < 0.0001), and between volume of distribution and body weight (p < 0.0001) or gestational age (p < 0.0001). CONCLUSION: Although neonates with a PDA may have small differences in gentamicin pharmacokinetics compared to neonates with a CDA, this is not relevant for clinical practice taking the variability within that population into account.

Glucocorticoids and lung development in the fetus and preterm infant.

During the final prenatal period of fetal lung development in humans, important maturational processes occur, including the production of surfactant necessary to decrease surface tension at the air-liquid interface of the alveoli. During early gestation, the glucocorticoid receptor is expressed in the fetal lung, and glucocorticoids stimulate the production of surfactant-associated proteins and increase phospholipid synthesis by enhancing the activity of phosphatidylcholine. Other glucocorticoid-induced effects may include stimulation of cell maturation and differentiation, inhibition of DNA synthesis, changes in interstitial tissue components, stimulation of antioxidant enzymes, and regulation of pulmonary fluid metabolism. Recently, it was suggested that glucocorticoids are also important in postnatal pulmonary development, and may be related to the development of neonatal lung disease in preterm infants. Surfactant deficiency that can be prevented by antenatal corticosteroid treatment causes infant respiratory distress syndrome and requires mechanical ventilation. Ventilation by itself or in combination with high levels of oxygen, fluid overload, pulmonary infections, sepsis, and air leak syndrome causes an acute pulmonary inflammatory reaction that may result in chronic lung disease or bronchopulmonary dysplasia. Glucocorticoids are effective in the treatment of chronic lung disease of prematurity and regulate the inflammatory response by the interaction with transcription factors such as nuclear factor kappaB and activated protein 1. Indeed, inflammatory cells and the levels of chemokines and cytokines in bronchoalveolar fluid decrease after dexamethasone treatment. However, treatment of fetuses and preterm infants with repeated and/or high doses of corticosteroids may have considerable long-term side effects on somatic, brain, and lung growth. The difficult balance between short-term gain and the possible long-term side effects of glucocorticoids in preterms remains a difficult issue.

Pharmacokinetics of meropenem in preterm neonates.

The objective of this study was to evaluate and compare the pharmacokinetics of meropenem in premature neonates, both after the first dose and during steady state at day 5, after a 1-minute intravenous administration to evaluate the possibility of twice-daily administration. Seven premature neonates received 15 mg/kg meropenem twice daily on clinical grounds as a 1-minute infusion. After the first dose and during steady state at day 5, serum levels of meropenem were measured for 12 hours after intravenous administration. Meropenem pharmacokinetics at the first dose were studied in seven children (mean birth weight 925 g, mean postnatal age 21 days). Serum concentration-time curves could be described with a one-compartment model. Mean total body clearance was 0.157 L/kg per hour, volume of distribution was 0.74 L/kg, and half-life was 3.4 hours. At day 5 at steady state, pharmacokinetic properties did not differ significantly. No side effects were noted. A 1-minute intravenous administration is feasible. Pharmacokinetic properties are comparable at day 5 compared with the first dose, and half-life is such that twice-daily administration of 15 mg/kg produces adequate serum concentrations.

Improved use of the [13C]octanoic acid breath test as intra-individual parameter to study the effect of a prokinetic drug on gastric emptying in preterm infants with oral feeding intolerance.

The [13C]octanoic acid breath test was used for the measurement of differences in gastric emptying in preterm infants for the evaluation of pharmacological therapy. In order to perform a good intra-individual comparison of the gastric emptying in preterm infants under non-standardisable test conditions, we adjusted t1/2 for variations in non-recovered label (=label retention) and introduced an "effective half 13CO2 breath excretion time" t1/2eff = t1/2/m expressed as min per percentage of the cumulative dose recovered. In a pilot study, we investigated the action of the gastrointestinal prokinetic drug cisapride on gastric emptying in seven premature infants, of whom four suffered from gastric stasis and three had constipation. The postnatal age and weight at the start of treatment ranged from 15 to 64 days and from 815 to 1635 g, respectively. All infants received the standard formula for premature infants (Nenatal, Nutricia). Cisapride was administered orally 0.2 mg/kg, four times daily. The changes in gastrointestinal motility were studied using the total bowel transit time of carmine red. After 7 days of treatment in all children, the gastric emptying coefficient and the half 13CO2 breath excretion time adjusted for label retention were improved (n=7, the gastric emptying coefficient range before treatment was 1.69-3.34 (mean 2.59 +/- 0.80) and after treatment it was 2.79-3.76 (mean 3.28 +/- 0.30); the half 13CO2 breath excretion time adjusted for label retention range before treatment was 3.0-14.7 min/% dose (mean 7.0 +/- 5.0) and after treatment 2.6-4.0 min/% dose (mean 3.1 +/- 0.6). The total bowel transit time was only slightly improved in two patients (n=7, mean total bowel transit time before: 23.7 h compared to mean total bowel transit time after 7 days of treatment: 35.5 h). Side effects during cisapride treatment were not seen. We conclude that in premature infants cisapride is effective in shortening gastric emptying time and reducing gastric stasis; the therapeutic role in constipation has to be further investigated.

Supraventricular escape rhythms during transient episodes of bradycardia in preterm infants.

OBJECTIVE: To evaluate the origin of transient episodes of sinus bradycardia, atrial escape rhythm, and atrioventricular nodal escape rhythm in preterm infants. MATERIAL AND METHODS: The study was observational, and was carried out in a third level neonatal intensive care unit. We studied 19 spontaneously breathing infants born healthy but prior to term, the examinations being carried out between the ages of 3 and 28 days. The mean gestational age was 29.2 +/- 1.9 weeks, and the mean birth weight was 1154 +/- 264 g. Transient episodes of bradycardia were defined as a decline in heart rate equal to or greater than 25% from baseline, lasting for at least 3 successive RR-intervals. To discriminate between different types of escape mechanisms, we used the P wave and the P axis of the electrocardiogram. Sinus bradycardia was diagnosed when the P axis was from +0 to +90 degrees; atrial escape rhythm when it was from +91 to +359 degrees, and atrioventricular nodal escape rhythm when the P wave was absent, hidden, or followed the QRS complex. RESULTS: The mean P axis was +50 +/- 11 degrees. We observed 60 transient episodes of bradycardia in 11 of the 19 infants. Of these, 34 (57%) were classified as sinus bradycardia, and 13 (22%) as atrial escapes. Atrioventricular nodal escapes developed during 6 episodes (10%), while 7 episodes (11%) could not be classified. CONCLUSIONS: Atrial excitation as evidenced by the P axis during sinus rhythm is similar in very preterm infants to that seen in children and adults. Escape rhythms with different origins occur during transient episodes of bradycardia in healthy preterm infants. In at least one third, the episodes are due to atrial or atrioventricular nodal escape.

Value of fluid-attenuated inversion recovery sequences in early MRI of the brain in neonates with a perinatal hypoxic-ischemic encephalopathy.

The aim of our study was to assess the usefulness of fluid-attenuated inversion recovery (FLAIR) sequences in comparison with conventional spin-echo and inversion MR imaging in neonates for evaluation of myelination and for detection of hypoxic-ischemic brain injury. We reviewed early MR scans of 18 neonates with suspected hypoxic-ischemic brain damage. Myelination could be evaluated with confidence using conventional MR imaging in all but 2 infants; however, the presence of myelin was very difficult to assess on FLAIR images. Overall, 53 lesions or groups of lesions were identified. The FLAIR technique was more sensitive in 11 of the lesions; especially (pre)cystic lesions could be identified much better and more cysts were found. Conventional MR imaging failed to identify 2 of the lesions and was more sensitive in 14 of the lesions; especially punctate hemorrhages and lesions in basal ganglia or thalami could be better determined. The FLAIR technique missed 3 of these lesions. In the remaining 28 lesions conventional MR and FLAIR images were equally diagnostic. The FLAIR technique and conventional MR imaging are complementary in detecting early sequelae of hypoxic-ischemic brain injury in neonates. The FLAIR technique is not suitable for assessing myelination of the neonatal brain; therefore, FLAIR cannot replace conventional MR imaging.

MR patterns of hypoxic-ischemic brain damage after prenatal, perinatal or postnatal asphyxia.

The relationship between MR patterns of brain damage and type or timing of perinatal hypoxia-ischemia was studied. MR images of 104 children with evidence of bilateral posthypoxic-ischemic brain damage and neonatal records were reviewed. Three different MR patterns were found. Periventricular leukomalacia occurred in 73 children, in 82% after a history of subacute or chronic hypoxia-ischemia, in 71% after preterm birth. Predominant lesions of basal ganglia and thalamus occurred in 21 children, in 95% preceded by acute profound asphyxia, in 85% after term birth. Multicystic encephalopathy occurred in 10 infants, in 70% preceded by mild signs of hypoxia-ischemia, followed by an unexpectedly severe encephalopathy, in 60% after term birth. Statistical analysis showed that the patterns of injury were primarily related to the type of hypoxia-ischemia. We conclude that the type of hypoxia-ischemia, rather than the postconceptional age at occurrence determines the pattern of brain injury.

Early MR features of hypoxic-ischemic brain injury in neonates with periventricular densities on sonograms.

BACKGROUND AND PURPOSE: In the early 1980s, diagnosing periventricular leukomalacia (PVL) in neonates by using cranial sonography was possible for the first time. Our purpose was to investigate the possibility of diagnosing PVL in the acute stage by using MR imaging. We evaluated early MR features of hypoxic-ischemic brain injury in neonates with periventricular densities (flares) on cranial sonograms to determine the added value of MR imaging over sonography alone for early diagnosis of brain damage. METHODS: In a prospective study, infants who showed flares and/or cysts on sonograms underwent MR imaging during the (sub)acute stage. RESULTS: Fifty infants were classified according to the highest sonographic grade up to the day of MR imaging: 23 infants had sonographic grade 1 (flares < 1 week), 15 had sonographic grade 2 (flares > or = 1 week), four had sonographic grade 3 (small localized cysts), and eight had sonographic grade 4 (extensive periventricular cysts); none had sonographic grade 5 (multicystic leukomalacia) on the day of MR imaging. Overall, the additional information provided by MR imaging (over sonography alone) consisted of the depiction of hemorrhagic lesions in 64% of the infants. Extent and severity of the hemorrhages varied from isolated punctate lesions to extensive hemorrhages throughout the white matter; the latter were followed by cystic degeneration at autopsy in two infants. In nine of the 12 infants with cystic PVL, MR images showed more numerous or more extensive cysts. In addition, in two infants, MR images showed cysts not present on sonograms. In 32% of the infants, MR imaging provided no additional information; in these children, all but one had flares on sonograms whereas MR images showed no abnormalities or a zone of mild periventricular signal change. CONCLUSION: MR imaging can depict the precise site and extent of hypoxic-ischemic brain injury at an earlier stage and allows a wider differentiation of lesions as compared with sonography alone. Hemorrhagic PVL is considered to be rare, but was present in 64% of our study population.

Short-term growth and substrate use in very-low-birth-weight infants fed formulas with different energy contents.

BACKGROUND: Currently available preterm formulas with energy contents of 3350 kJ (800 kcal)/L promote weight and length gain at rates at or above intrauterine growth rates but disproportionately increase total body fat. OBJECTIVE: The objective of this study was to determine whether fat accretion in formula-fed, very-low-birth-weight (VLBW) infants could be decreased and net protein gain maintained by reducing energy intakes from 502 kJ (80 kcal)*kg(-)(1)*d(-)(1) [normal-energy (NE) formula] to 419 kJ (100 kcal)*kg(-)(1)*d(-)(1) [low-energy (LE) formula] while providing similar protein intakes (3.3 g*kg(-)(1)*d(-)(1)). DESIGN: The study was a randomized, controlled trial enrolling 20 appropriate-for-gestational-age (AGA) and 16 small-for-gestational-age (SGA) VLBW infants (mean birth weight: 1.1 kg; mean gestational age: 31 wk); energy expenditure and nutrient balance were measured at 4 wk of age and anthropometric measurements were made when infants weighed 2 kg. RESULTS: The percentage of fat in newly formed tissue was significantly lower in AGA infants fed the LE formula (n = 9) than in those fed the NE formula (n = 10) (9% compared with 23%; analysis of variance, P = 0.001). Energy expenditure was higher in AGA infants fed the NE formula than in those fed the LE formula. Skinfold thickness was markedly lower in AGA infants fed the LE formula than in those fed the NE formula, resulting in a lower estimated percentage body fat (8.0 +/- 1.9% and 10.8 +/- 3.5%, respectively; P < 0.05). Three of 6 SGA infants fed the LE formula were excluded during the study because of poor weight gain. CONCLUSIONS: Body composition can easily be altered by changing the energy intakes of formula-fed VLBW infants. Energy intakes in these infants should be >419 kJ (100 kcal)*kg(-)(1)*d(-)(1).

Predictive value of neonatal MRI as compared to ultrasound in premature infants with mild periventricular white matter changes.

A follow-up study was performed in 42 premature infants in whom serial neonatal ultrasound and a single neonatal MRI of the brain was normal, or showed mild periventricular white matter changes. The aim of the study was to evaluate the clinical significance of periventricular signal intensity changes on MRI and to compare the predictive value of neonatal MRI with that of ultrasound. The infants underwent repeated standardised motor assessments and developmental tests. MRI was repeated at the corrected age of 12 months. Pronounced periventricular signal intensity changes on neonatal MRI and periventricular echodensities (flaring) on ultrasound were associated with a high incidence of transient motor problems during infancy. The degree of echogenicity carried the highest predictive value, as compared to duration of flaring on ultrasound and degree of periventricular signal intensity change on MRI. It is concluded that signal intensity changes on neonatal MRI represent the same ischaemic change of the periventricular white matter as flaring on ultrasound and that routine neonatal MRI screening is not warranted in premature infants without clinical evidence of neurological problems and with normal or mildly abnormal ultrasound scans. Recording of the degree of echogenicity should become a routine procedure in neonatal cerebral ultrasonography.