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

Safety of a Triple-Chamber Bag Parenteral Nutrition in Children Aged up to 24 Months: An Observational Study

Objectives Hypermagnesemia has been reported in preterm neonates treated with commercial pediatric triple-chamber bag (3CB) parenteral nutrition (PN). This postmarketing study was requested by the European Medicines Agency to assess the safety of a 3CB PN product in full-term neonates and children up to 24 months of age. Methods This prospective, multicenter, observational study enrolled hospitalized, full-term, newborn infants and children up to 24 months of age receiving >70% of nutrition as PN and requiring ≥50% of nutrition as PN for ≥5 days. All patients received 3CB PN during the study for ≤15 days. The primary outcome was serum magnesium, summarized by age group (0.1 month, >1.12 months, and >12.24 months). Secondary outcomes were nutritional intake and adverse events (AEs), including clinically significant abnormal laboratory results and vital signs. Results A total of 102 eligible patients were included. Median (interquartile range) parenteral magnesium intake was 0.23 (0.18.0.30) mmol/kg/day. Mean serum magnesium showed no consistent changes during treatment in any age group. One moderate and 3 mild AEs of hypermagnesemia were reported in 4 patients (3.9%), all aged 0 to 1 month. Other AEs in >2 patients were hypertriglyceridemia (6.9%), laryngitis (3.9%), hyperkalemia, hypokalemia, hyponatremia, hypophosphatemia, and neonatal hypotension (each 2.9%). Other serum electrolytes were stable and revealed no safety concerns. Conclusions Mean serum magnesium levels were not affected by 3CB PN in full-term neonates and children up to 24 months of age. The risk of hypermagnesemia AEs was low when providing median parenteral magnesium of 0.2.0.3 mmol/kg/day in this population. © 2019 The Author(s)