The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs

BACKGROUND: Recent reports have raised concerns that postnatal steroids may cause neuro-developmental impairment in preterm infants. This systematic review was performed with the objective of determining whether glucocorticoid therapy, to prevent or treat bronchopulmonary dysplasia, impairs neuro-developmental outcomes in preterm infants. METHOD: A systematic review of the literature was performed. Medline was searched and articles retrieved using predefined criteria. Data from randomized controlled trials with adequate neuro-developmental follow up (to at least one year) were entered into a meta-analysis to determine the effects of postnatal treatment of preterm infants with glucocorticoids. Cerebral palsy rates, and neuro-developmental impairment (developmental score more than 2SD below the mean, or cerebral palsy or blindness) were analyzed. The studies were divided into 2 groups according to the extent of contamination of the results by treatment of controls with steroids after the initial study period, those with less than 30% contamination, and those with more than 30% contamination or size of contamination not reported. RESULTS: Postnatal steroid therapy is associated with an increase in cerebral palsy and neuro-developmental impairment. The studies with less contamination show a greater effect of the steroids, consistent with a real direct toxic effect of steroids on the developing central nervous system. The typical relative risk for the development of cerebral palsy derived from studies with less than 30% contamination is 2.86 (95% CI 1.95, 4.19). The typical relative risk for the development of neuro-developmental disability among followed up infants from studies with less than 30% contamination is 1.66 (95% CI 1.26, 2.19). From this subgroup of studies, the number of premature infants who need to be treated to have one more infant with cerebral palsy (number needed to harm, NNH) is 7; to have one more infant with neuro-developmental impairment the NNH is 11. CONCLUSIONS: Postnatal pharmacologic steroid treatment for prevention or treatment of bronchopulmonary dysplasia is associated with dramatic increases in neuro-developmental impairment. As there is no clear evidence in the literature of long term benefit, their use for this indication should be abandoned

Surfactant status and respiratory outcome in premature infants receiving late surfactant treatment.

BACKGROUND:Many premature infants with respiratory failure are deficient in surfactant, but the relationship to occurrence of bronchopulmonary dysplasia (BPD) is uncertain. METHODS:Tracheal aspirates were collected from 209 treated and control infants enrolled at 7-14 days in the Trial of Late Surfactant. The content of phospholipid, surfactant protein B, and total protein were determined in large aggregate (active) surfactant. RESULTS:At 24 h, surfactant treatment transiently increased surfactant protein B content (70%, p < 0.01), but did not affect recovered airway surfactant or total protein/phospholipid. The level of recovered surfactant during dosing was directly associated with content of surfactant protein B (r = 0.50, p < 0.00001) and inversely related to total protein (r = 0.39, p < 0.0001). For all infants, occurrence of BPD was associated with lower levels of recovered large aggregate surfactant, higher protein content, and lower SP-B levels. Tracheal aspirates with lower amounts of recovered surfactant had an increased proportion of small vesicle (inactive) surfactant. CONCLUSIONS:We conclude that many intubated premature infants are deficient in active surfactant, in part due to increased intra-alveolar metabolism, low SP-B content, and protein inhibition, and that the severity of this deficit is predictive of BPD. Late surfactant treatment at the frequency used did not provide a sustained increase in airway surfactant

Postnatal dexamethasone, respiratory and neurodevelopmental outcomes at two years in babies born extremely preterm.

IMPORTANCE: Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes. OBJECTIVE: Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors. MATERIALS AND METHODS: The study included 412 infants born at 23-28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken. RESULTS: After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26). CONCLUSIONS: Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities

Specification and guideline for technical aspects and scanning parameter settings of neonatal lung ultrasound examination

Lung ultrasound (LUS) is now widely used in the diagnosis and monitor of neonatal lung diseases.Nevertheless, in the published literatures,the LUS images may display a significant variation in technical execution,while scanning parameters may influence diagnostic accuracy.The inter- and intra-observer reliabilities of ultrasound exam have been extensively studied in general and in LUS.As expected,the reliability declines in the hands of novices when they perform the point-of-care ultrasound (POC US).Consequently,having appropriate guidelines regarding to technical aspects of neonatal LUS exam is very important especially because diagnosis is mainly based on interpretation of artifacts produced by the pleural line and the lungs.The present work aimed to create an instrument operation specification and parameter setting guidelines for neonatal LUS.Technical aspects and scanning parameter settings that allow for standardization in obtaining LUS images include (1)select a high-end equipment with high-frequency linear array transducer (12-14 MHz).(2)Choose preset suitable for lung examination or small organs.(3)Keep the probe perpendicular to the ribs or parallel to the intercostal space.(4)Set the scanning depth at 4-5 cm.(5)Set 1-2 focal zones and adjust them close to the pleural line.(6)Use fundamental frequency with speckle reduction 2-3 or similar techniques.(7)Turn off spatial compounding imaging.(8)Adjust the time-gain compensation to get uniform image from the near-to far-field

The Role of Growth Retardation in Lasting Effects of Neonatal Dexamethasone Treatment on Hippocampal Synaptic Function

BACKGROUND: Dexamethasone (DEX), a synthetic glucocorticoid, is commonly used to prevent or lessen the morbidity of chronic lung disease in preterm infants. However, evidence is now increasing that this clinical practice negatively affects somatic growth and may result in long-lasting neurodevelopmental deficits. We therefore hypothesized that supporting normal somatic growth may overcome the lasting adverse effects of neonatal DEX treatment on hippocampal function. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we developed a rat model using a schedule of tapering doses of DEX similar to that used in premature infants and examined whether the lasting influence of neonatal DEX treatment on hippocampal synaptic plasticity and memory performance are correlated with the deficits in somatic growth. We confirmed that neonatal DEX treatment switched the direction of synaptic plasticity in hippocampal CA1 region, favoring low-frequency stimulation- and group I metabotropic glutamate receptor agonist (S)-3,5,-dihydroxyphenylglycine-induced long-term depression (LTD), and opposing the induction of long-term potentiation (LTP) by high-frequency stimulation in the adolescent period. The effects of DEX on LTP and LTD were correlated with an increase in the autophosphorylation of Ca(2+)/calmodulin-dependent protein kinase II at threonine-286 and a decrease in the protein phosphatase 1 expression. Neonatal DEX treatment resulted in a disruption of memory retention subjected to object recognition task and passive avoidance learning. The adverse effects of neonatal DEX treatment on hippocampal synaptic plasticity and memory performance of the animals from litters culled to 4 pups were significantly less than those for the 8-pup litters. However, there was no significant difference in maternal care between groups. CONCLUSION/SIGNIFICANCE: Our results demonstrate that growth retardation plays a crucial role in DEX-induced long-lasting influence of hippocampal function. Our findings suggest that therapeutic strategies designed to support normal development and somatic growth may exert beneficial effects to reduce lasting adverse effects following neonatal DEX treatment

Retrospective comparison between a regular and a split-dose protocol of 5-fluorouracil, cisplatin, and mitoxantrone for the treatment of far advanced hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>In patients with advanced hepatocellular carcinoma (HCC), combination chemotherapy using 5- fluorouracil, cisplatin, and mitoxantrone (FMP) could achieve a response rate > 20%, but the beneficial effect was compromised by formidable adverse events. Chemotherapy given in a split-dose manner was associated with reduced toxicities. In this retrospective study, we compared the efficacies and side effects between a regular and a split-dose FMP protocol approved in our medical center.</p> <p>Methods</p> <p>From 2005 to 2008, the clinical data of 84 patients with far advanced HCC, who had either main portal vein thrombosis and/or extrahepatic metastasis, were reviewed. Of them, 65 were treated by either regular (n = 27) or split-dose (n = 38) FMP and had completed at least one therapeutic course. The remaining 19 patients were untreated. Clinical parameters, therapeutic responses, survivals and adverse events were compared.</p> <p>Results</p> <p>The median overall survival was 6.0, 5.2, and 1.5 months, respectively, in patients receiving regular FMP, split-dose FMP, and no treatment (regular versus split-dose group, P = 0.447; regular or split-dose versus untreated group; P < 0.0001). Patients receiving split-dose treatment had a significantly lower risk of grade 3/4 neutropenia (51.9 versus 10.5%, P = 0.0005). When the two treated groups were combined, the median overall survival was 10.6 and 3.8 months respectively for patients achieving disease control and progressive disease (P < 0.001). Cox proportion hazard model identified Child-Pugh stage B (hazard ratio [HR], 2.216; P = 0.006), presence of extrahepatic metastasis (HR, 0.574; P = 0.048), and achievement of disease control (HR, 0.228; P < 0.001) as independent factors associated with overall survival. Logistic regression analysis revealed that anti-hepatitis C virus antibody (odds ratio [OR], 9.219; P = 0.002) tumor size (OR, 0.816; P = 0.036), and previous anti-cancer therapy (OR, 0.195; P = 0.017) were significantly associated with successful disease control.</p> <p>Conclusions</p> <p>Comparable overall survival was observed between patients receiving regular and split-dose FMP therapies. Patients receiving split-dose therapy had a significantly lower risk of grade 3/4 neutropenia. Positive anti-hepatitis C virus antibody, smaller tumor size, and absence of previous anti-cancer therapy were independent predictors for successful disease control.</p

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Retinopathy of prematurity and risk factors: a prospective cohort study

BACKGROUND: Increased survival of extremely low birth infants due to advances in antenatal and neonatal care has resulted in a population of infants at high risk of developing retinopathy of prematurity (ROP). Therapeutic interventions include the use of antenatal and postnatal steroids however, their effects on the severity of ROP is in dispute. In addition, it has not been investigated whether severe ROP is due to therapeutic interventions or due to the severity of illness. The aim of the present study was to assess the association between the incidence of severe retinopathy of prematurity (greater than stage 2 – International classification of ROP) and mechanical ventilation, oxygen therapy, gestational age, antenatal and postnatal steroids in extremely low birth weight infants. METHODS: Neonates admitted to the neonatal intensive care unit in Lansing, Michigan, during 1993–2000 were followed to determine factors influencing the development of severe retinopathy of prematurity. Ophthalmologic examinations were started at 6 weeks and followed until resolution. We used logistic regression to estimate the relative risk (odds ratio) associated with risk factors of ROP. RESULTS: Of the neonates with ≤ 1500 g birth weight, admitted to the neonatal intensive care unit, 85% (616/725) survived. Severe retinopathy of prematurity was detected in 7.8% of 576 neonates who had eye examinations. Neonates of lower gestational age (≤ 25 weeks and 26–28 weeks) had an increased odds ratio of 8.49 and 3.19 for the development of severe retinopathy of prematurity, respectively, compared to those 29 weeks and older. Late postnatal steroid treatment starting after 3 weeks of life showed 2.9-fold increased odds ratio, in particular administration for two weeks and more (OR: 4.09, 95% CI: 1.52–11.03). With increasing antenatal steroids courses the risk of severe retinopathy of prematurity decreased, however, it was not significant. Lower gestational age, dependence on ventilation, and use of postnatal steroids were intertwined. Simultaneous presence of these factors seems to indicate severe disease status. CONCLUSION: Prolonged and late postnatal steroids treatment in very low birth weight infants may pose an increased risk for the development of severe retinopathy of prematurity; however, use of postnatal steroids may also be a marker for severity of illness. Further studies need to focus on biologic markers in the pathogenesis of retinopathy of prematurity and to better understand the influence of therapies