[THE EFFECT OF MUSIC IN PRETERM ON RESTING ENERGY EXPENDITURE - A PROSPECTOVE RANDOMIZED CLINICAL TRIAL].

BACKGROUND: We have recently showed that Wolfgang Amadeus Mozart's music significantly lowers resting energy expenditure (REE) in preterm infants. Whether or not this effect is specific to Mozart is unknown. OBJECTIVES: To study whether familiar ("ethnic") music has the same effect on REE in preterm infants as music by Mozart. METHODS: A prospective, randomized clinical trial with cross-over was conducted in 9 healthy, appropriate weights for gestational age, gavage fed, preterm infants. Infants were randomized to be exposed to a 30-minute period of Mozart music or "ethnic" music or no music over 3 consecutive days. Metabolic measurements were performed by indirect calorimetry. RESULTS: A total of 27 REE measurements were performed. On average REE was lower in preterm infants who were exposed to "ethnic" music compared to preterm infants who were exposed to music by Mozart (p=0.388). REE was lower in preterm infants who didn't listen to music at all compared to Mozart (p=0.014) or to "ethnic" (p=0.134). CONCLUSIONS: Exposure to music by Mozart significantly elevated REE in healthy preterm infants compared to preterm infants who didn't listen to music at all. Nevertheless a trend of lower REE was demonstrated when preterm infants listened to "ethnic" music compared to Mozart. DISCUSSION: We were unable to demonstrate a significant decrease in REE by exposure of preterm infants to Mozart- or "familiar" music. At this time point we cannot recommend music therapy for preterm infants in order to lower the REE. We speculate that a larger study sample might show a definite effect.

Diffuse excessive high signal intensity in low-risk preterm infants at term-equivalent age does not predict outcome at 1 year: a prospective study.

INTRODUCTION: The outcome of premature infants with only diffuse excessive high signal intensity (DEHSI) is not clear. We explored the relationship between DEHSI, white matter (WM) diffusion characteristics, perinatal characteristics, and neurobehavioral outcome at 1 year in a homogenous group of preterm infants without major brain abnormalities. METHODS: Fifty-eight preterm infants, gestational age 29 ± 2.6 weeks, underwent an MRI at term-equivalent age (TEA). Griffiths Mental Developmental Scales, neurological assessment, and Parental Stress Index (PSI) were performed at 1 year corrected age. These measures were compared between preterm infants according to DEHSI classification (none, mild, moderate). Diffusion tensor imaging was used in major WM volumes of interest to objectively measure the degree of WM maturation. RESULTS: No significant differences were detected in the perinatal risk characteristics, neurobehavioral outcome, and PSI at 1 year between infants with different DEHSI classifications. In infants with DEHSI, increased axial and radial diffusivities were detected in the optic radiations, centrum semiovale, and posterior limb of the internal capsule, indicating less advanced maturation of the WM. Significant correlations were detected between the time interval from birth to MRI and the WM microstructure in infants without DEHSI. CONCLUSION: DEHSI in premature infants is neither a predictive measure for short-term adverse neurobehavioral outcome nor related to perinatal risk characteristics. Extrauterine exposure time had a differential effect on WM maturational trajectories in infants with DEHSI compared to those without. We suggest DEHSI may represent an alteration in WM maturational characteristics. Further follow-up studies may verify later consequences of DEHSI in premature infants.

Weight at weaning of preterm infants from incubator to bassinet: a randomized clinical trial.

OBJECTIVE: To evaluate thermal responses, weight gain, and resting energy expenditure (REE) in preterm infants weaned from an infant incubator to a warming bassinet after reaching a body weight of either 1,500 or 1,600 g, respectively. METHODS: Preterm infants weighing ≤ 1,500 g were randomly allocated for weaning from a convective incubator after reaching 1,500 g body weight (study group) or 1,600 g (controls). Postweaning body temperature was recorded at short intervals. REE was measured before and after weaning, while the weight gain was calculated daily. RESULTS: All 21 enrolled infants were weaned successfully to a bassinet (room temperature). REE inside the incubator and in the warming bassinette was similar between infants weaned at 1,500 g and at 1,600 g (2.9 ± 6.8 vs. 1.1 ± 4.8 kcal/kg/d, respectively (p = 0.7). REE increased slightly after weaning in both groups. Weight gain and days from randomization to discharge did not differ between groups. CONCLUSION: Weaning very low birth weight infants from an incubator to a warming bassinet at a body weight of 1,500 g is feasible and has no significant deleterious effects on weight gain and REE. The many benefits provided by such greater accessibility to premature infants are discussed.

The effect of olfactory stimulation on energy expenditure in growing preterm infants.

AIM: To test the hypothesis that olfactory stimulation in growing healthy preterm infants leads to an increase in resting energy expenditure (REE). DESIGN: A prospective, randomized clinical trial with crossover was conducted in 20 healthy, appropriate weights for gestational age, gavage-fed preterm infants. Infants were studied while asleep and cared for in a skin servo-controlled convective incubator. Using a pipette, 15 drops of saturated solution of vanillin (Aldrich, Fallavier, France) were dripped to a cloth diaper that was placed on the opposite side of the incubator. REE was measured by indirect calorimetry (DeltaTrac II, Helsinki, Finland) exactly 1 h after feeding. Each infant was studied twice by randomization: after a period of 20 min of vanillin odour or after 20 min without vanillin odour. RESULTS: We found no statistically significant difference in REE of preterm infants when exposed to vanillin odour (74.5 ± 10.1 kcal/kg/day) in comparison with their REE when not exposed to vanillin odour (79.0 ± 11.3 kcal/kg/day). CONCLUSIONS: Vanillin odour does not significantly influence REE in metabolically and thermally stable preterm infants.

Neonatal absolute nucleated red blood cell counts do not predict the development of cystic periventricular leukomalacia.

BACKGROUND: Infants with severe intraventricular-periventricular hemorrhage (IVH) have higher absolute nucleated red blood cell counts (aNRBC) at birth (a marker of intrauterine hypoxia) than controls. Periventricular leukomalacia (PVL) is known to be associated with prenatal and postnatal events. Whether PVL is also linked to intrauterine hypoxia is unknown. OBJECTIVES: To test the hypothesis that infants with PVL have higher aNRBC counts at birth than controls. METHODS: We studied 14 very low birth weight infants with PVL and compared them with 14 pair-matched controls without PVL. Head ultrasound scans were performed in all infants on days 3-5 and 21-25 of life. Paired tests, Fisher exact tests and stepwise logistic regression were performed for analysis. RESULTS: The groups were similar for gestational age (GA), birth weight (BW), prolonged rupture of membranes (PROM), Apgar scores, IVH, and aNRBC counts. PVL correlated significantly with low partial pressure of CO2 (PCO2) and IVH (P < 0.01). In logistic regression, when GA, gender, PROM, antenatal steroid therapy, 1 (or 5) minute Apgar scores, IVH grade, nosocomial sepsis, patent ductus arteriosus, necrotizing enterocolitis (NEC), need for pressors, aNRBC counts and lowest PCO2 were used as independent variables, PCO2 (P = 0.002), IVH grade (P= 0.001), GA (P = 0.038), NEC (P = 0.061) and use of dopamine (P = 0.010) remained in the analysis (total R2 = 68.2%). CONCLUSIONS: In contrast to severe IVH, aNRBC counts do not predict the development of PVL.

Therapeutic hypothermia for asphyxiated newborns: experience of an Israeli tertiary center.

BACKGROUND: Major advances in the treatment of perinatal asphyxial-hypoxic ischemic encephalopathy (PA-HIE) followed the translation of hypothermia animal studies into successful randomized controlled clinical trials that substantially influenced the current standard of care. OBJECTIVES: To present our preliminary experience with the first cases of clinical application of therapeutic hypothermia for PA-HIE in what we believe is the first report on nonexperimental hypothermia for PA-HIE from Israel. METHODS: We reviewed the medical records, imaging scans, electroencephalograms and outcome data of the six identified asphyxiated newborns who were managed with hypothermia in our services in 2008-2009. RESULTS: All asphyxiated newborns required resuscitation and were encephalopathic. Systemic hypothermia (33.5 degrees C) was begun at a median age of 4.2 hours of life (range 2.5-6 hours) and continued for 3 days. All six infants showed a significantly depressed amplitude integrated electroencephalography background, and five had electrographic seizures. One infant died (16%) after 3.5 days. Major complications included fat necrosis and hypercalcemia (n=1), pneumothorax (n=1), and meconium aspiration syndrome (n=2). None of the infants developed major bleeding. Neurodevelopmental followup of the five surviving infants at median age 7.2 months (4.1-18.5 months) revealed developmental delays (Battelle screening), with their motor scores ranging from -1 to +1 standard deviation (Bayley scale). None developed feeding problems, oculomotor abnormalities, spasticity or seizures. CONCLUSIONS: Our preliminary experience with this novel modality in a large Tel Aviv neonatal service is consistent with the clinical findings of published trials.

Neonatal blood glucose concentrations in caesarean and vaginally delivered term infants.

BACKGROUND: Little is known about the glucose concentrations at and after birth of infants delivered by caesarean section (CS), when compared with infants born vaginally (VD). AIM: To compare venous cord blood glucose concentrations of term infants born after elective CS to infants born by VD. We studied the null hypothesis that mode of delivery does not affect neonatal blood glucose values. METHODS: We compared cord blood glucose concentrations in healthy term infants born after VD (n = 16) or by elective CS (n = 21). Glucose concentrations were obtained immediately at birth from the umbilical cord. Kruskal-Wallis was used to compare glucose concentrations and demographic variables between the groups. RESULTS: Gestational age was 39.6 ± 0.8 weeks in VD group vs. 38.7 ± 0.9 weeks in CS group, and birthweight was 3359 ± 494 vs. 3500 ± 528 g. Cord blood glucose concentration was higher in VD (81.3 ± 16.9 mg/dL) than CS infants (70.3 ± 9.7 mg/dL, p = 0.039). The change in blood glucose concentration over the first 2-h of life differed significantly between the two groups, being an increase in CS versus a decrease in VD infants (-3.5 ± 15.2 vs. -15.4 ± 24.6 mg/dL, p = 0.013). CONCLUSIONS: Glucose concentrations in VD infants are higher than in infants born by elective CS without labour.

A silent outbreak of vancomycin-resistant Enterococcus faecium in a neonatal intensive care unit.

OBJECTIVE: To describe the containment of a widespread silent outbreak of vancomycin-resistant Enterococcus faecium (VRE-fm) in the Tel-Aviv Medical Center (TASMC) neonatal intensive care unit (NICU). METHODS: Setting - an NICU, participants - 49 cases of VRE-fm-colonized neonatal inpatients. RESULTS: A newborn was transferred from the TASMC NICU to another hospital and screened positive for VRE-fm upon arrival. All TASMC NICU patients were then immediately screened for VRE and 21/38 newborns were identified as VRE carriers. Interventional measures were strictly enforced. By the end of the outbreak, 49 cases of VRE carriage had been identified. There were no VRE clinical infections. The source of the outbreak was not identified. CONCLUSION: Our study highlights the importance of screening implementation in a NICU setting since this outbreak could have been prevented by active screening of all out-born transfer patients and by having adopted mandatory screening into the NICU's routine procedures. Screening for multi-drug resistant organisms upon admission of all transferred patients to the NICU has been implemented.

When should phototherapy be stopped? A pilot study comparing two targets of serum bilirubin concentration.

OBJECTIVE: The objective of this study was to compare the outcome of two groups of jaundiced newborns randomized to one of the two targets of total serum bilirubin (TSB) for phototherapy discontinuation. DESIGN: Infants treated with phototherapy were assigned to two groups: in the 'high-threshold' group, phototherapy was interrupted when TSB decreased to >/=1 mg/dL (17 micromol/L) below the limit requiring phototherapy and in the 'low-threshold' group when TSB decreased to >/=3 mg/dL (51 micromol/L) below the same limit. RESULTS: Fifty-two infants were enrolled, 25 in the high- and 27 in the low-threshold group. Phototherapy duration was significantly shorter in the high- than in the low-threshold group (22.3 +/- 13 vs. 27.6 +/- 12 h, respectively, p = 0.03). Length of hospital stay was 84+/-30 h in the high- and 94 +/- 24 h in the low-threshold group (p = 0.05). Additional phototherapy was required in 20% of the high- versus 18% of the low-threshold group (p = 0.58). In the presence of haemolysis or G6PD deficiency, 28% of the infants required re-phototherapy and 8.3% when such factors were absent (p = 0.06). CONCLUSION: Phototherapy duration may be shortened by using higher TSB limits for interruption. When hyperbilirubinaemia is accompanied by risk factors, the infants should be followed for longer periods, since some of them will need re-phototherapy.

The motor and visual networks in preterm infants: An fMRI and DTI study.

Knowledge regarding the association between functional connectivity and white-matter (WM) maturation of motor and visual networks in preterm infants at term equivalent age (TEA) and their association with behavioral outcome is currently limited. Thirty-two preterm infants born <34 weeks gestational-age without major brain abnormalities were included in this study, underwent resting-state fMRI at TEA. Thirteen infants also underwent diffusion tensor imaging (DTI). Neurobehavioral assessments were performed at one and two years corrected age using the Griffiths Mental Developmental Scales. Functional connectivity between homolog motor and visual regions were detected, which may reflect that a level of organization in these domains is present already at TEA. DTI parameters of WM tracts at TEA demonstrated spatial-temporal variability, with the splenium of the corpus-callosum (CC) found to be the most mature fiber bundle. Correlations between DTI parameters, functional connectivity and behavioral outcome were detected, yet did not show the same pattern of diffusivity changes in the different networks. Visual functional connectivity was negatively correlated with radial-diffusivity (RD) in the optic radiation, while motor functional connectivity was positively correlated with RD in the splenium. In addition, axial-diffusivity (AD) and RD in the genu and midbody of the CC were positively correlated with neurobehavioral outcome at one and 2 years of age. This study highlights the importance of understanding the spatial-temporal changes occurring during this sensitive period of development and the potential effect of extrauterine exposure on the microstructural changes as measured by DTI; their correlation with functional connectivity; and their long term relationship with neuro-behavioral development.

Adenosine bronchial provocation with computerized wheeze detection in young infants with prolonged cough: correlation with long-term follow-up.

BACKGROUND: Chronic cough in babies is often associated with bronchial hyperreactivity (BHR). The objective documentation of BHR in babies is difficult, and acoustic methods have been described (provocative concentration of a substance causing wheeze) for conducting bronchial provocation tests (BPTs). We conducted a study to evaluate automatic computerized wheeze detection (CWD) in determining BHR in young infants with prolonged cough, and its correlation with the subsequent development of wheezing. METHODS: Infants aged < 24 months with prolonged cough (ie, > 2 months) underwent acoustic BPTs with the response determined by CWD and auscultation by a physician. Telephone interviews with parents were conducted after 1 month and yearly for the next 3 years. RESULTS: A total of 28 infants who were 4 to 24 months old with prolonged cough were included in the study. Twenty of these infants (71.4%) had BHR as determined by a positive acoustic BPT result. In 11 of these 20 tests, the CWD occurred earlier, and in 9 tests it occurred at the same step as auscultation by a physician. Rhonchi or whistles often preceded wheezes. Seventeen of the 20 patients with BHR completed 3 years of follow-up. Of these, 14 had recurrent episodes of wheezing and shortness of breath, and 3 were well. Six of the eight adenosine-negative patients completed 3 years of follow-up and had no symptoms of BHR. CONCLUSIONS: Acoustic BPT is a technically feasible test for the detection of BHR in young infants. CWD provides an earlier detection of wheeze than stethoscope auscultation. In our group of infants, a positive acoustic BPT result had high correlation with symptoms compatible with BHR over the next 3 years.

Neonatal neuropsychology: emerging relations of neonatal sensory-motor responses to white matter integrity.

The neonatal period is considered to be essential for neurodevelopment and wellbeing throughout the life span, yet little is known about brain-behavior relationships in the neonatal period. The aim of this study was to evaluate the association between neonatal sensory-motor regulation and white-matter (WM) integrity of major fiber tracts in the neonatal period. We hypothesized that WM integrity of sensory-motor systems would predict neurobehavioral maturation during the first month of life. Forty-nine premature neonates underwent magnetic-resonance-imaging at term. Diffusion-tensor-imaging analysis was performed in major WM tracts along with repeated neonatal neurobehavioral evaluations assessing sensory reactivity and motor regulation. Difficulties in one or more behavioral sub-category, mostly in auditory and visual attention, hypotonicity and jitteriness, were documented in 78.3% infants at term. Sixty-six percent of infants experienced difficulties, mostly in auditory attention, head-neck control, hypotonicity and motor asymmetry, at 44 weeks. Attention difficulties were associated with reduced integrity of cerebral and superior cerebellar peduncles; while tonicity was associated with reduced integrity of the corpus-callosum and inferior-posterior tracts. Overall, results showed that early maturing tracts were related with the degree of typicality of sensory reactivity status while late maturing tracts were related with the degree of typicality of tonic regulation. WM integrity and maturation factors explained 40.2% of the variance in neurobehavior at 44 weeks. This study suggests that in preterm neonates, deviant sensory-motor reactivity can be detected very early in development in manners that are related to lower integrity/maturational level of early and late maturing fiber tracts.

Brain diffusivity in infants with hypoxic-ischemic encephalopathy following whole body hypothermia: preliminary results.

Hypoxic-ischemic encephalopathy is an important cause of neuropsychological deficits. Little is known about brain diffusivity in these infants following cooling and its potential in predicting outcome. Diffusion tensor imaging was applied to 3 groups: (1) three infants with hypoxic-ischemic encephalopathy: cooled; (2) three infants with hypoxic-ischemic encephalopathy: noncooled; and (3) four controls. Diffusivity values at the corticospinal tract, thalamus, and putamen were correlated with Apgar scores and early neurodevelopmental outcome. While cooled infants exhibited lower Apgar scores than noncooled infants, their developmental scores at a mean age of 8 months were higher. All groups differed in their diffusivity values with the cooled infants showing better values compared with the noncooled, correlating with early neurodevelopmental outcome. These preliminary results indicate that diffusion tensor imaging performed at an early age in infants with hypoxic-ischemic encephalopathy may forecast clinical outcome and support the neuroprotective effect of hypothermia treatment.

Energy expenditure for breastfeeding and bottle-feeding preterm infants.

OBJECTIVE: We hypothesized that resting energy expenditure (REE) would be higher after breastfeeding than after bottle-feeding. METHODS: Nineteen preterm infants (gestational age: 32 weeks) in stable condition who were nourished entirely with their mothers' breast milk were assigned randomly to feeding either by bottle or at the breast. Each infant served as his or her own control subject. REE was measured for 20 minutes after feeding. Breast milk quantity was evaluated with prefeeding and postfeeding weighing. REE values for bottle-feeding and breastfeeding were compared with paired t tests. RESULTS: Contrary to our null hypothesis, the group's mean REE values after bottle-feeding and breastfeeding were very similar (284.7 +/- 26.8 kJ/kg per day [68.3 +/- 6.4 kcal/kg per day] vs 282.6 +/- 28.5 kJ/kg per day [67.5 +/- 6.8 kcal/kg per day]; not significant). The duration of feeding was significantly longer for breastfeeding than for bottle-feeding (20.1 +/- 7.9 vs 7.8 +/- 2.9 minutes; P < .0001). CONCLUSION: There was no significant difference in REE when infants were breastfed versus bottle-fed. Longer feeding times at the breast did not increase REE. We speculate that it is safe to recommend feeding at the breast for infants born at >32 weeks when they can tolerate oral feeding.