Summary Premature infants are at substantial risk for suffering from perinatal white matter injury. Though the gut microbiota has been implicated in early-life development, a detailed understanding of the gut-microbiota-immune-brain axis in premature neonates is lacking. Here, we profiled the gut microbiota, immunological, and neurophysiological development of 60 extremely premature infants, which received standard hospital care including antibiotics and probiotics. We found that maturation of electrocortical activity is suppressed in infants with severe brain damage. This is accompanied by elevated γδ T cell levels and increased T cell secretion of vascular endothelial growth factor and reduced secretion of neuroprotectants. Notably, Klebsiella overgrowth in the gut is highly predictive for brain damage and is associated with a pro-inflammatory immunological tone. These results suggest that aberrant development of the gut-microbiota-immune-brain axis may drive or exacerbate brain injury in extremely premature neonates and represents a promising target for novel intervention strategies.

OBJECTIVE: To evaluate the implementation of a neonatal pain and sedation protocol at 2 ICUs. METHODS:The intervention started with the evaluation of local practice, problems, and staff satisfaction. We then developed and implemented the Vienna Protocol for Neonatal Pain and Sedation. The protocol included well-defined strategies for both nonpharmacologic and pharmacologic interventions based on regular assessment of a translated version of the Neonatal Pain Agitation and Sedation Scale and titration of analgesic and sedative therapy according to aim scores. Health care staff was trained in the assessment by using a video-based tutorial and bedside teaching. In addition, we performed reevaluation, retraining, and random quality checks. Frequency and quality of assessments, pharmacologic therapy, duration of mechanical ventilation, and outcome were compared between baseline (12 months before implementation) and 12 months after implementation. RESULTS:Cumulative median (interquartile range) opiate dose (baseline dose of 1.4 [0.5-5.9] mg/kg versus intervention group dose of 2.7 [0.4-57] mg/kg morphine equivalents; P = .002), pharmacologic interventions per episode of continuous sedation/analgesia (4 [2-10] vs 6 [2-13]; P = .005), and overall staff satisfaction (physicians: 31% vs 89%; P , .001; nurses: 17% vs 55%; P , .001) increased after implementation. Time on mechanical ventilation, length of stay at the ICU, and adverse outcomes were similar before and after implementation.CONCLUSIONS: Implementation of a neonatal pain and sedation protocol at 2 ICUs resulted in an increase in opiate prescription, pharmacologic interventions, and staff satisfaction without affecting time on mechanical ventilation, length of intensive care stay, and adverse outcomes. Pediatrics 2013;132:e211-e218 AUTHORS:

Implementing a neonatal pain and sedation protocol increased opiate exposure, but had no effect on the in-hospital and neurodevelopmental outcomes of extremely preterm infants.

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The association of lower rates of CLD and ROP in the VC compared to the VONN might be related to differences in early respiratory management of VLBW infants at high risk of development of respiratory distress syndrome. This needs to be confirmed in a large multicenter trial.

Background: Methicillin-susceptible Staphylococcus aureus (MSSA) is a major contributor to infectious episodes of very low birth weight infants (VLBWI), resulting in significant morbidity and mortality. Objective: To examine the efficacy and safety of surveillance cultures and the decolonization of MSSA-colonized VLBWI. Methods: VLBWI admitted to our neonatal wards in 2011-2016 were retrospectively analyzed. Rates of MSSA-attributable infections were compared before and after the implementation of active surveillance cultures and the decolonization of MSSA-colonized patients. The mupirocin susceptibility of isolated MSSA strains was routinely tested. Results: A total of 1,056 VLBWI were included in the study, 552 in the pre-intervention period and 504 in the post-intervention period. The implementation of surveillance cultures and decolonization of colonized patients resulted in a 50% reduction of incidence rates per 1,000 patient-days of MSSA-attributable infections (1.63 [95% CI 1.12-2.31] vs. 0.83 [95% CI 0.47-1.35], p = 0.024). No adverse effects were observed from application of the decolonization protocol with mupirocin and octenidin. No mupirocin-resistant MSSA strains were detected during the study period. Conclusion: Implementation of an active surveillance and decolonization protocol resulted in a reduction of MSSA-attributable infections in VLBWI.

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BackgroundParenteral nutrition associated cholestasis (PNAC) is a frequently observed pathology in extremely low birth weight (ELBW) infants. Its pathogenesis is determined by the composition and duration of parenteral nutrition (PN) as well as the tolerance of enteral feeds (EF). “Aggressive” nutrition is increasingly used in ELBW infants to improve postnatal growth. Little is known about the effect of “aggressive” nutrition on the incidence of PNAC. We analyzed the influence of implementing an “aggressive” nutritional regimen on the incidence of PNAC and growth in a cohort of ELBW infants.MethodsELBW infants were nourished using a “conservative” (2005–6; n = 77) or “aggressive” (2007–9; n = 85) nutritional regimen that differed in the composition of PN after birth as well as the composition and timing of advancement of EFs. We analyzed the incidence of PNAC (conjugated bilirubin > 1.5 mg/dl (25 µmol/l)) corrected for confounders of cholestasis (i.e., NEC and/or gastrointestinal surgery, sepsis, birth weight, Z-score of birth weight, time on PN and male sex), growth until discharge (as the most important secondary outcome) and neonatal morbidities.ResultsThe incidence of PNAC was significantly lower during the period of “aggressive” vs. “conservative “nutrition (27% vs. 46%, P < 0.05; adjusted OR 0.275 [0.116–0.651], P < 0.01). Body weight (+411g), head circumference (+1 cm) and length (+1 cm) at discharge were significantly higher. Extra-uterine growth failure (defined as a Z-score difference from birth to discharge lower than −1) was significantly reduced for body weight (85% vs. 35%), head circumference (77% vs. 45%) and length (85% vs. 65%) (P < 0.05). The body mass index (BMI) at discharge was significantly higher (11.1 vs. 12.4) using “aggressive” nutrition and growth became more proportionate with significantly less infants being discharged below the 10th BMI percentile (44% vs. 9%), while the percentage of infants discharged over the 90th BMI percentile (3% vs. 5%) did not significantly increase.Discussion“Aggressive” nutrition of ELBW infants was associated with a significant decrease of PNAC and marked improvement of postnatal growth.