Prevention of severe brain injury in very preterm neonates: A quality improvement initiative.

OBJECTIVE: To determine the impact of neuroprotection interventions bundle on the incidence of severe brain injury or early death (intraventricular hemorrhage grade 3/4 or death by 7 days or ventriculomegaly or cystic periventricular leukomalacia on 1-month head ultrasound, primary composite outcome) in very preterm (270/7 to ≤ 296/7 weeks gestational age) infants. STUDY DESIGN: Prospective quality improvement initiative, from April 2017-September 2019, with neuroprotection interventions bundle including cerebral NIRS, TcCO2, and HeRO monitoring-based management algorithm, indomethacin prophylaxis, protocolized bicarbonate and inotropes use, noise reduction, and neutral positioning. RESULT: There was a decrease in the incidence of the primary composite outcome in the intervention period on unadjusted (N = 11/99, pre-intervention to N = 0/127, intervention period, p < 0.001) and adjusted analysis (adjusted for birthweight and Apgar score <5 at 5 min, aOR = 0.042, 95% CI = 0.003-0.670, p = 0.024). CONCLUSIONS: Neuroprotection interventions bundle was associated with significant decrease in severe brain injury or early death in very preterm infants.

Early airway microbial metagenomic and metabolomic signatures are associated with development of severe bronchopulmonary dysplasia.

The pathogenesis of bronchopulmonary dysplasia (BPD) is not well understood. We previously identified differences in the airway microbiome at birth between preterm infants who were BPD predisposed versus those who were BPD resistant. In this study, we attempted to identify mechanisms by which the airway microbiome could modify the risk for BPD. We used a software-based method to predict the metagenome of the tracheal aspirate (TA) microbiome from 16S rRNA sequencing data in preterm infants and to identify functional ortholog genes that were differentially abundant in BPD-predisposed and BPD-resistant infants. We also identified metabolites that were differentially enriched in these samples by use of untargeted mass spectrometry and mummichog to identify the metabolic pathways involved. Microbial metagenome analysis identified specific pathways that were less abundant in the functional metagenome of the microbiota of BPD-predisposed infants compared with BPD-resistant infants. The airway metabolome of BPD-predisposed infants was enriched for metabolites involved in fatty acid activation and androgen and estrogen biosynthesis compared with BPD-resistant infants. These findings suggest that in extremely preterm infants the early airway microbiome may alter the metabolome, thereby modifying the risk of BPD. The differential enrichment of sex steroid metabolic pathways supports previous studies suggesting a role for sexual dimorphism in BPD risk. This study also suggests a role for metabolomic and metagenomic profiles to serve as early biomarkers of BPD risk.

Acute kidney injury is associated with bronchopulmonary dysplasia/mortality in premature infants.

BACKGROUND: Acute kidney injury (AKI) impairs electrolyte balance, alters fluid homeostasis and decreases toxin excretion. More recent data suggest it also affects the physiology of distant organs. METHODS: We performed a prospective cohort study which invloved 122 premature infants [birth weight (BW) ≤1200 g and/or gestational age (GA) <31 weeks] to determine relationships between AKI and bronchopulmonary dysplasia (BPD)/mortality. Days until oxygen discontinuation was compared between those with and without AKI in survivors who received oxygen for ≥24 h. RESULTS: Acute kidney disease, defined by a rise in serum creatinine (SCr) of ≥0.3 mg/dl or an increase in SCr of ≥150%, occurred in 36/122 (30%) of the premature infants. Those with AKI had a 70% higher risk of oxygen requirement or of dying at 28 days of life [relative risk (RR) 1.71, 95% confidence interval (CI) 1.22-2.39; p < 0.002]. This association remained after controlling for GA, pre-eclampsia, 5 min Apgar score and percentage maximum weight change (max % weight Δ) in the first 4 days (RR 1.45, 95% CI 1.07-1.97); p < 0.02). Similar findings were noted for receipt of mechanical ventilation/death by day 28 (adjusted RR 1.53, 95% CI 1.05-2.22; p < 0.03). Those without AKI were 2.5-fold more likely to come off oxygen [hazard ratio (HR) 1.3-5; p < 0.02) than those with AKI, even when controlling for GA, pre-eclampsia, 5 min Apgar and max % weight Δ (multivariate HR 2.0, 95% CI 0.9-4.0; p < 0.06). CONCLUSIONS: In premature infants, AKI is associated with BPD/mortality. As AKI could lead to altered lung physiology, interventions to ameliorate AKI could improve long-term BPD.