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  • Article: Functional brain maturation assessed during early life correlates with anatomical brain maturation at term equivalent age in preterm infants.
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    ABSTRACT: Background:Amplitude-integrated electroencephalogram (aEEG) is a reliable monitoring tool for electro-cortical activity with good predictive value in preterm infants. Magnetic resonance imaging is a good neuroimaging tool to detect brain lesions and to evaluate brain maturation. We hypothesized that early aEEG measures, recorded over the first three days of life in very preterm infants correlate with brain maturation and injury score assessed by conventional MRI at term equivalent age.Methods:39 infants born at a mean (range) gestational age (GA) of 29.5 (27.0-31.9) weeks and birth weight 1230 (680-2020) grams had continuous aEEG during the first postnatal 72-84 hours. aEEG maturity scores and average maximum and minimum amplitudes were evaluated. Conventional brain MRI was performed at 41.2 (37.1-44.1) weeks postmenstrual age on a 3T GE system and scored qualitatively for injury and maturation.Results:The average aEEG total maturity score and its cycling subscore were positively and significantly associated with the total MRI maturation score after adjustment for GA, morphine sedation, and postmenstrual age at MRI examination. No association was found between the aEEG measures and the MRI injury scores.Conclusion:Early aEEG maturity seems to relate to structural MRI brain maturation at term equivalent age in preterm infants.Pediatric Research (2013); doi:10.1038/pr.2013.57.
    Pediatric Research 04/2013; · 2.70 Impact Factor
  • Article: Outcome at two years of age in a Swiss national cohort of extremely preterm infants born between 2000 and 2008.
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    ABSTRACT: BACKGROUND: While survival rates of extremely preterm infants have improved over the last decades, the incidence of neurodevelopmental disability (ND) in survivors remains high. Representative current data on the severity of disability and of risk factors associated with poor outcome in this growing population are necessary for clinical guidance and parent counselling. METHODS: Prospective longitudinal multicentre cohort study of preterm infants born in Switzerland between 240/7 and 276/7 weeks gestational age during 2000--2008. Mortality, adverse outcome (death or severe ND) at two years, and predictors for poor outcome were analysed using multilevel multivariate logistic regression. Neurodevelopment was assessed using Bayley Scales of Infant Development II. Cerebral palsy was graded after the Gross Motor Function Classification System. RESULTS: Of 1266 live born infants, 422 (33%) died. Follow-up information was available for 684 (81%) survivors: 440 (64%) showed favourable outcome, 166 (24%) moderate ND, and 78 (11%) severe ND. At birth, lower gestational age, intrauterine growth restriction and absence of antenatal corticosteroids were associated with mortality and adverse outcome (p < 0.001). At 360/7 weeks postmenstrual age, bronchopulmonary dysplasia, major brain injury and retinopathy of prematurity were the main predictors for adverse outcome (p < 0.05). Survival without moderate or severe ND increased from 27% to 39% during the observation period (p = 0.02). CONCLUSIONS: In this recent Swiss national cohort study of extremely preterm infants, neonatal mortality was determined by gestational age, birth weight, and antenatal corticosteroids while neurodevelopmental outcome was determined by the major neonatal morbidities. We observed an increase of survival without moderate or severe disability.
    BMC Pediatrics 12/2012; 12(1):198. · 1.88 Impact Factor
  • Article: Delayed Cyclic Activity Development on Early Amplitude-Integrated EEG in the Preterm Infant with Brain Lesions.
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    ABSTRACT: Background: Maturation of amplitude-integrated electroencephalogram (aEEG) activity is influenced by both gestational age (GA) and postmenstrual age. It is not fully known how this process is influenced by cerebral lesions. Objective: To compare early aEEG developmental changes between preterm newborns with different degrees of cerebral lesions on cranial ultrasound (cUS). Methods: Prospective cohort study on preterm newborns with GA <32.0 weeks, undergoing continuous aEEG recording during the first 84 h after birth. aEEG characteristics were qualitatively and quantitatively evaluated using pre-established criteria. Based on cUS findings three groups were formed: normal (n = 78), mild (n = 20), and severe cerebral lesions (n = 6). Linear mixed models for repeated measures were used to analyze aEEG maturational trajectories. Results: 104 newborns with a mean GA (range) 29.5 (24.4-31.7) weeks, and birth weight 1,220 (580-2,020) g were recruited. Newborns with severe brain lesions started with similar aEEG scores and tendentially lower aEEG amplitudes than newborns without brain lesions, and showed a slower development of the cyclic activity (p < 0.001), but a more rapid increase of the maximum and minimum aEEG amplitudes (p = 0.002 and p = 0.04). Conclusions: Preterm infants with severe cerebral lesions manifest a maturational delay in the aEEG cyclic activity already early after birth, but show a catch-up of aEEG amplitudes to that of newborns without cerebral lesions. Changes in the maturational aEEG pattern may be a marker of severe neurological lesions in the preterm infant.
    Neonatology 12/2012; 103(2):134-140. · 2.66 Impact Factor
  • Article: Rectal Paracetamol in Newborn Infants after Assisted Vaginal Delivery May Increase Pain Response.
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    ABSTRACT: OBJECTIVE: To assess the efficacy of paracetamol (acetaminophen) for neonatal pain relief. STUDY DESIGN: Randomized, double-blind placebo-controlled trial in 3 Swiss university hospitals. Term and near-term infants (n = 123) delivered by forceps or vacuum were randomized to receive 2 suppositories with paracetamol (60/80/100 mg in infants <3000 g/3000-4000 g/>4000 g birth weight) or placebo at 2 and 8 hours of life. Pain and discomfort during the first 24 hours was assessed by the échelle de douleur et d'inconfort du nouveau né [neonatal pain and discomfort scale] score. The response to the subsequent heel prick for metabolic screening at days 2-3 of life was investigated by the Bernese Pain Scale for Neonates (BPSN). RESULTS: The échelle de douleur et d'inconfort du nouveau né [neonatal pain and discomfort scale] pain scale ratings after assisted vaginal delivery were low and declined within 4 hours of life (P < .01) irrespective of paracetamol administration. At 2-3 days of life, BPSN scores after heel prick were significantly higher in infants who had received paracetamol, compared with controls, both when BPSN were scored by nurses at the bedside (median [IQR] 4 [2-7] vs 2 [0-5], P = .017) or off-site from videos (4 [2-8] vs 2 [1-7], P = .04). Thirty-five of 62 (57%) infants treated with paracetamol cried after heel prick, compared with 25 of 61 (41%) controls (P = .086). CONCLUSIONS: Infants born by assisted vaginal delivery have low pain scores in the immediate period after birth. Paracetamol given to newborns soon after birth may aggravate a subsequent stress response.
    The Journal of pediatrics 07/2012; · 4.02 Impact Factor
  • Article: Urinary erythropoietin concentrations after early short-term infusion of high-dose recombinant epo for neuroprotection in preterm neonates.
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    ABSTRACT: Background: High-dose recombinant human erythropoietin (rEpo) has first been administered in clinical trials for neuroprotection in very preterm neonates at high risk of brain injury and in (near-) term neonates with hypoxic-ischemic encephalopathy. However, recent trials in adults raised concerns about the safety of high-dose rEpo for neuro- and cardioprotection. Objectives: To evaluate the putative accumulation or renal leakage of Epo as a function of developmental stage after repetitive early short-term infusion of high-dose rEpo (3 × 3,000 U/kg within 42 h after birth; NCT00413946) for neuroprotection in very preterm infants. Methods: Epo concentrations were measured using the ELISA technique in the first two consecutive urine specimens after each rEpo infusion. Results: Renal Epo excretion was significantly higher in preterm infants with gestational ages <29 weeks than in more mature infants and reached up to 23% of the administered rEpo within 8 h after each infusion. The urinary Epo concentration did not increase after three repetitive infusions of high-dose rEpo. The ratio of urinary Epo to total protein concentrations was the same in infants with gestational ages <29 weeks and in those with gestational ages ≥29 weeks. Conclusions: Our data suggest that the higher renal Epo excretion in more immature infants may be attributed to a higher glomerular filtration leakage due to the lower maturation of the kidneys and argue against saturation kinetics after multiple doses of 3,000 U/kg rEpo. This information should be considered in future trials on the use of rEpo for neuroprotection in neonates.
    Neonatology 07/2012; 102(3):172-7. · 2.66 Impact Factor

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