Early inhaled budesonide for the prevention of bronchopulmonary dysplasia

BACKGROUND Systemic glucocorticoids reduce the incidence of bronchopulmonary dysplasia among extremely preterm infants, but they may compromise brain development. The effects of inhaled glucocorticoids on outcomes in these infants are unclear. METHODS We randomly assigned 863 infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to early (within 24 hours after birth) inhaled budesonide or placebo until they no longer required oxygen and positive-pressure support or until they reached a postmenstrual age of 32 weeks 0 days. The primary outcome was death or bronchopulmonary dysplasia, confirmed by means of standardized oxygen-saturation monitoring, at a postmenstrual age of 36 weeks. RESULTS A total of 175 of 437 infants assigned to budesonide for whom adequate data were available (40.0%), as compared with 194 of 419 infants assigned to placebo for whom adequate data were available (46.3%), died or had bronchopulmonary dysplasia (relative risk, stratified according to gestational age, 0.86; 95% confidence interval [CI], 0.75 to 1.00; P = 0.05). The incidence of bronchopulmonary dysplasia was 27.8% in the budesonide group versus 38.0% in the placebo group (relative risk, stratified according to gestational age, 0.74; 95% CI, 0.60 to 0.91; P = 0.004); death occurred in 16.9% and 13.6% of the patients, respectively (relative risk, stratified according to gestational age, 1.24; 95% CI, 0.91 to 1.69; P = 0.17). The proportion of infants who required surgical closure of a patent ductus arteriosus was lower in the budesonide group than in the placebo group (relative risk, stratified according to gestational age, 0.55; 95% CI, 0.36 to 0.83; P = 0.004), as was the proportion of infants who required reintubation (relative risk, stratified according to gestational age, 0.58; 95% CI, 0.35 to 0.96; P = 0.03). Rates of other neonatal illnesses and adverse events were similar in the two groups. CONCLUSIONS Among extremely preterm infants, the incidence of bronchopulmonary dysplasia was lower among those who received early inhaled budesonide than among those who received placebo, but the advantage may have been gained at the expense of increased mortality

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: Study protocol for a randomized controlled trial

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. Methods/design: In this study, 206 spontaneously breathing infants born at 24+0-27+6 weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation. Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. Trial registration: ClinicalTrials.gov identifier: NCT02482766. Registered on 1 June 2015

Refining the Definition of BPD: Characterization of Intercurrent Episodes

Background: The main definitions of bronchopulmonary dysplasia (BPD), proposed by Jobe-Bancalari, Shennan et al., and Walsh et al., focus on oxygen (O2)-need and ventilatory support for the first weeks of life and at 36 weeks of post-menstrual age (PMA). Oxygen need at 36 weeks of PMA is sometimes due to intercurrent episodes (IEs) other than BPD. The aim of this retrospective study was to characterize IEs and determine their impact on BPD in preterm infants born at Methods: O2-dependence for > 28 days and at 36 weeks of PMA (±10 days) was analyzed. We classified each infant according to the three BPD definitions. Patients requiring O2 or ventilator support at 36 weeks of PMA, with no need for O2 in the first 28 days of life, were qualified for having IEs if their O2/ventilator dependence (at 36 weeks) had a limited duration and/or could be ascribed to a known condition. Then, the contribution of IEs to the BPD rate was evaluated.Results: Out of 1,210 patients, the BPD infants were 431 (35.6%), 169 (14.0%), and 186 (15.4%) according to Jobe-Bancalari, Shennan et al., and Walsh et al., respectively. Twenty-eight patients had IEs (16.6% of those on O2 at 36 weeks of PMA) indicating a mild BPD overestimation (P=0.065).Conclusion: We proposed a definition of IEs and found that IEs could lead to a potential BPD overestimation. Further research is needed to find out if patients with IE, similarly to infants with BPD, are prone to childhood complications and need preventive measures

Non contact measurement of body temperature for the identification of thermoregulation abilities in preterm patients

In this paper, a novel contactless measurement method for the assessment of the thermoregulatory abilities of preterm infants is proposed. It is based on the use of an infrared (IR) thermo-camera allowing precise, multipoint and contactless measurement of the skin temperature of the preterm patient. The method proposed has been designed to verify the ability of the preterm patients to correctly operate the process of thermoregulation on his/her body. Results show a mean difference of 0.01°C between IR camera measurements and values simultaneously measured with a standard contact thermo-resistance. No dependence from the temperature value was shown on the physiological range of temperatures (28-36°C). From the experimental data it is possible to extrapolate the empirical model of the thermoregulation mechanism of patients, allowing to individuate deviation from normal behavior for those patients with reduced abilities to self-regulate his/her body temperature

A measurement procedure for the assessment of thermoregulatory activitity in premature babies

Many important vital signs need to be measured on preterm patients when they are recovered in intensive care units: cardiac rate, respiration activity, blood saturation, temperature. The later is, in particular, a key quantity to assess when the aim is to verify if the patient has fully developed the capacity to regulate his/her temperature. Presently, the procedure followed by clinicians is based on a subjective test, which sees the heating system of the curl switched off; if the central temperature of the patient will not be reduced below 35°C in the following two hours, the patient is considered able to thermoregulate himself. The aim of this paper is to propose a measurement procedure aiming to verify if the patient has the ability to autonomously thermoregulate. The procedure is based on the use of a multipoint (up to 16 sensing points), measurement system of the superficial temperature, that can assess the patient temperature (on 6 sites) and the surrounding temperature (inside and outside the crib), while the heating system is switched off. In this paper, 48 premature patients (mean gestation age 34 week and mean weight 1791 g) have been tested. Results demonstrate that from the measured data, it is possible to correctly identify patients with an adequate thermoregulation capacity (sensitivity of 0.81 and specificity of 0.89) and with a rapid procedure (< 5 min)

Low Gestational Age Is the Strongest Predictor for Severe Retinopathy of Prematurity and Adverse Outcomes at Two-Year Follow-Up in a Low Incidence Setting

We aimedto determine the risk factors for type 1 ROP and outcomes at 2 years of corrected ageamong preterms born &lt; 30 weeks of gestational age (GA) in a low-incidence setting. A cohort study with 447 infants was conducted. Those who underwent laser therapy for type 1 ROP were compared with controls by univariate and multivariate analysis. Neurological development was assessed by Bayley scales. Using univariate analysis, gestational age, sepsis, necrotizing enterocolitis, and insulin administration were found to be associated with type 1 ROP. Only GA remained significant with logistic regression. Infants with type 1 ROP had worse visual and neurodevelopmental outcomes at 2 years. Predictors of impaired neurodevelopment were type 1 ROP, surfactant administration, and bronchopulmonary dysplasia. Low GA was found to be a strong predictor of type 1 ROP, which was associated (along with surfactant administration and bronchopulmonary dysplasia) with worse neurological development