Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

Impact of low-grade intraventricular hemorrhage on neurodevelopmental outcome in very preterm infants at two years of age.

BACKGROUND: High-grade intraventricular hemorrhage (IVH) in very preterm infants is a known risk factor for adverse neurodevelopmental outcome. Prognosis is less clear for low-grade (grades I/II) IVH however, with conflicting study results in recent years. OBJECTIVE: To evaluate the impact of low-grade IVH on neurodevelopmental outcome at 2 years corrected age in preterm infants born below 32 weeks gestation at the University hospital of Zurich between 2009 and 2014. METHODS: Among 843 live-born preterm infants born during the observation period, 509 were included in our study. Exclusion criteria were death, high-grade IVH, cystic periventricular leukomalacia and congenital malformations. Infants were grouped into those with or without low-grade IVH according to cranial ultrasound. Neurodevelopmental impairment (NDI) was defined as cognitive or motor developmental score > 2 standard deviations below the mean and/or CP grades 2-5 and/or moderate/severe vision loss and/or hearing problem corrected with hearing aids. Multivariate linear regression was used to assess effect of low-grade IVH on endpoints while adjusting for other risk factors. RESULTS: 87 preterm infants had low-grade IVH (42 grade I, 45 grade II) on cranial ultrasound. These were compared to 422 preterm infants without IVH. Follow-up rate was 82.4 %. Preterm infants with low-grade IVH had higher rates of NDI (21.8 vs 13.3 %, p = 0.047). Infants with IVH grade II had significantly higher rates for CP (8.9 % vs 3.6 %, p = 0.003), visual impairment (20.5 % vs 8.3 %, p = 0.009) and NDI (33.3 % vs 13.3 %, p < 0.001). CONCLUSION: In our study, low-grade IVH - and especially IVH grade II - is associated with adverse neurodevelopmental outcome at 2 years of corrected age.

Inhaled Corticosteroids for Bronchopulmonary Dysplasia: A Meta-analysis.

CONTEXT: Bronchopulmonary dysplasia (BPD) in preterm infants remains a major health burden despite many therapeutic interventions. Inhaled corticosteroids (IC) may be a safe and effective therapy. OBJECTIVE: To assess the safety and efficacy of IC for prevention or treatment of BPD or death in preterm infants. DATA SOURCES: PubMed, the Cochrane Library, Embase, and CINAHL from their inception until November 2015 together with other relevant sources. STUDY SELECTION: Randomized controlled trials of ICs versus placebo for either prevention or treatment of BPD. DATA EXTRACTION: This meta-analysis used a random-effects model with assessment of quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Thirty-eight trials were identified, and 16 met inclusion criteria. ICs were associated with a significant reduction in death or BPD at 36 weeks' postmenstrual age (risk ratio [RR] = 0.86, 95% confidence interval [CI] 0.75 to 0.99, I2 = 0%, P = .03; 6 trials, n = 1285). BPD was significantly reduced (RR = 0.77, 95% CI 0.65 to 0.91, I2 = 0%, 7 trials, n = 1168), although there was no effect on death (RR = 0.97, 95% CI 0.42 to 2.2, I2 = 50%, 7 trials, n = 1270). No difference was found for death or BPD at 28 days' postnatal age. The use of systemic steroids was significantly reduced in treated infants (13 trials, n = 1537, RR = 0.87, 95% CI 0.76 to 0.98 I2 = 3%,). No significant differences were found in neonatal morbidities and other adverse events. LIMITATIONS: Long-term follow-up data are awaited from a recent large randomized controlled trial. CONCLUSIONS: Very preterm infants appear to benefit from ICs with reduced risk for BPD and no effect on death, other morbidities, or adverse events. Data on long-term respiratory, growth, and developmental outcomes are eagerly awaited.

Use of inhaled corticosteroids for the prevention and/or treatment of bronchopulmonary dysplasia in preterm infants: a systematic review protocol.

BACKGROUND: Inhaled steroids have been studied for both prevention and treatment of bronchopulmonary dysplasia (BPD). Results have been inconsistent. Recently, a large randomized controlled trial (RCT) has been reported. METHODS/DESIGN: We will perform a comprehensive systematic literature search for randomized and quasi-randomized controlled trials that studied the efficacy and safety of inhaled corticosteroids administered to preterm infants (22-36 weeks) for either the prevention or treatment of BPD diagnosed by both clinical and physiological outcome criteria. We will assess potential risk of bias for each RCT meeting our selection criteria using the Cochrane risk of bias tool for RCTs. The primary outcome of interest will be mortality or BPD or both at 28 days postnatal age or 36 weeks postmenstrual age. Pooled estimates will be calculated using RevMan software with a random effects model as primary analysis. We will assess the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. DISCUSSION: Meta-analytic estimates of eligible RCTs, potentially including a new large RCT, may significantly influence neonatal practice in the prevention and treatment of respiratory problems in preterm infants. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015019628.

Effect of propofol in the immature rat brain on short- and long-term neurodevelopmental outcome.

BACKGROUND: Propofol is commonly used as sedative in newborns and children. Recent experimental studies led to contradictory results, revealing neurodegenerative or neuroprotective properties of propofol on the developing brain. We investigated neurodevelopmental short- and long-term effects of neonatal propofol treatment. METHODS: 6-day-old Wistar rats (P6), randomised in two groups, received repeated intraperitoneal injections (0, 90, 180 min) of 30 mg/kg propofol or normal saline and sacrificed 6, 12 and 24 hrs following the first injection. Cortical and thalamic areas were analysed by Western blot and quantitative real-time PCR (qRT-PCR) for expression of apoptotic and neurotrophin-dependent signalling pathways. Long-term effects were assessed by Open-field and Novel-Object-Recognition at P30 and P120. RESULTS: Western blot analyses revealed a transient increase of activated caspase-3 in cortical, and a reduction of active mitogen-activated protein kinases (ERK1/2, AKT) in cortical and thalamic areas. qRT-PCR analyses showed a down-regulation of neurotrophic factors (BDNF, NGF, NT-3) in cortical and thalamic regions. Minor impairment in locomotive activity was observed in propofol treated adolescent animals at P30. Memory or anxiety were not impaired at any time point. CONCLUSION: Exposing the neonatal rat brain to propofol induces acute neurotrophic imbalance and neuroapoptosis in a region- and time-specific manner and minor behavioural changes in adolescent animals.