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ObjectiveNecrotizing enterocolitis (NEC) is a devastating intestinal disease in premature infants. Local rates of NEC were unacceptably high. We hypothesized that utilizing quality improvement methodology to standardize care and apply evidence-based practices would reduce our rate of NEC.Study designA multidisciplinary team used the model for improvement to prioritize interventions. Three neonatal intensive care units (NICUs) developed a standardized feeding protocol for very low birth weight (VLBW) infants, and employed strategies to increase the use of human milk, maximize intestinal perfusion, and promote a healthy microbiome.ResultsThe primary outcome measure, NEC in VLBW infants, decreased from 0.17 cases/100 VLBW patient days to 0.029, an 83% reduction, while the compliance with a standardized feeding protocol improved.ConclusionThrough reliable implementation of evidence-based practices, this project reduced the regional rate of NEC by 83%. A key outcome and primary driver of success was standardization across multiple NICUs, resulting in consistent application of best practices and reduction in variation.

Determine the impact of standardization of care and counseling on survival and morbidities of neonates born at 22-23 weeks gestation. Retrospective cohort study of 244 neonates born at 22-23 weeks gestation between 2015 and 2023 in a large healthcare system. The primary outcome was survival of neonates receiving intensive care to NICU discharge. Secondary outcomes included morbidities and resource utilization. Neonates born at 22-23 weeks received more intensive care after care standardization (OR 5.4 (95% CI 2.3-12.6), p < 0.0001). Survival remained stable (aOR 0.93 (95% CI 0.32-2.7), p = 0.89) despite more neonates born at 22 weeks receiving intensive care. Resource utilization remained stable. Standardizing counseling and care increased the provision of antenatal steroids and intensive care for neonates born at 22 weeks gestation. This allowed neonates born at 22 weeks to survive to discharge without increasing morbidity and resource utilization.

BackgroundWe evaluated the epidemiology of fluid balance (FB) over the first postnatal week and its impact on outcomes in a multi-center cohort of premature neonates from the AWAKEN study.MethodsRetrospective analysis of infants <36 weeks’ gestational age from the AWAKEN study (N = 1007). FB was defined by percentage of change from birth weight. Outcome: Mechanical ventilation (MV) at postnatal day 7.ResultsOne hundred and forty-nine (14.8%) were on MV at postnatal day 7. The median peak FB was 0% (IQR: −2.9, 2) and occurred on postnatal day 2 (IQR: 1,5). Multivariable models showed that the peak FB (aOR 1.14, 95% CI 1.10–1.19), lowest FB in first postnatal week (aOR 1.12, 95% CI 1.07–1.16), and FB on postnatal day 7 (aOR 1.10, 95% CI 1.06–1.13) were independently associated with MV on postnatal day 7. In a similar analysis, a negative FB at postnatal day 7 protected against the need for MV at postnatal day 7 (aOR 0.21, 95% CI 0.12–0.35).ConclusionsPositive peak FB during the first postnatal week and more positive FB on postnatal day 7 were independently associated with MV at postnatal day 7. Those with a negative FB at postnatal day 7 were less likely to require MV.

BackgroundIn sick neonates admitted to the NICU, improper fluid balance can lead to fluid overload. We report the impact of fluid balance in the first postnatal week on outcomes in critically ill near-term/term neonates.MethodsThis analysis includes infants ≥36 weeks gestational age from the Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) study (N = 645). Fluid balance: percent weight change from birthweight. Primary outcome: mechanical ventilation (MV) on postnatal day 7.ResultsThe median peak fluid balance was 1.0% (IQR: −0.5, 4.6) and occurred on postnatal day 3 (IQR: 1, 5). Nine percent required MV at postnatal day 7. Multivariable models showed the peak fluid balance (aOR 1.12, 95%CI 1.08–1.17), lowest fluid balance in 1st postnatal week (aOR 1.14, 95%CI 1.07–1.22), fluid balance on postnatal day 7 (aOR 1.12, 95%CI 1.07–1.17), and negative fluid balance at postnatal day 7 (aOR 0.3, 95%CI 0.16–0.67) were independently associated with MV on postnatal day 7.ConclusionsWe describe the impact of fluid balance in critically ill near-term/term neonates over the first postnatal week. Higher peak fluid balance during the first postnatal week and higher fluid balance on postnatal day 7 were independently associated with MV at postnatal day 7.

BackgroundNeonates with serum creatinine (SCr) rise ≥0.3 mg/dL and/or ≥50% SCr rise are more likely to die, even when controlling for confounders. These thresholds have not been tested in newborns. We hypothesized that different gestational age (GA) groups require different SCr thresholds.MethodsNeonates in Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) with ≥1 SCr on postnatal days 1–2 and ≥1 SCr on postnatal days 3–8 were assessed. We compared the mortality predictability of SCr absolute (≥0.3 mg/dL) vs percent (≥50%) rise. Next, we determine usefulness of combining absolute with percent rise. Finally, we determined the optimal absolute, percent, and maximum SCr thresholds that provide the highest mortality area under curve (AUC) and specificity for different GA groups.ResultsThe ≥0.3 mg/dL rise outperformed ≥50% SCr rise. Addition of percent rise did not improve mortality predictability. The optimal SCr thresholds to predict AUC and specificity were ≥0.3 and ≥0.6 mg/dL for ≤29 weeks GA, and ≥0.1 and ≥0.3 mg/dL for >29 week GA. The maximum SCr value provides great specificity.ConclusionUnique SCr rise cutoffs for different GA improves outcome prediction. Percent SCr rise does not add value to the neonatal AKI definition.

ObjectiveTo investigate whether NICU discharge summaries documented neonatal AKI and estimate if nephrology consultation mediated this association.Study designSecondary analysis of AWAKEN multicenter retrospective cohort. Exposures: AKI severity and diagnostic criteria. Outcome: AKI documentation on NICU discharge summaries using multivariable logistic regression to estimate associations and test for causal mediation.ResultsAmong 605 neonates with AKI, 13% had documented AKI. Those with documented AKI were more likely to have severe AKI (70.5% vs. 51%, p < 0.001) and SCr-only AKI (76.9% vs. 50.1%, p = 0.04). Nephrology consultation mediated 78.0% (95% CL 46.5–109.4%) of the total effect of AKI severity and 82.8% (95% CL 70.3–95.3%) of the total effect of AKI diagnostic criteria on documentation.ConclusionWe report a low prevalence of AKI documentation at NICU discharge. AKI severity and SCr-only AKI increased odds of AKI documentation. Nephrology consultation mediated the associations of AKI severity and diagnostic criteria with documentation.

Background Studies in adults showed a relationship between low hemoglobin (Hb) and acute kidney injury (AKI). We performed this study to evaluate this association in newborns. Methods We evaluated 1891 newborns from the Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN) database. We evaluated the associations for the entire cohort and 3 gestational age (GA) groups: <29, 29–<36, and ≥36 weeks’ GA. Results Minimum Hb in the first postnatal week was significantly lower in neonates with AKI after the first postnatal week (late AKI). After controlling for multiple potential confounders, compared to neonates with a minimum Hb ≥17.0 g/dL, both those with minimum Hb ≤12.6 and 12.7–14.8 g/dL had an adjusted increased odds of late AKI (aOR 3.16, 95% CI 1.44–6.96, p  = 0.04) and (aOR 2.03, 95% CI 1.05–3.93; p  = 0.04), respectively. This association was no longer evident after controlling for fluid balance. The ability of minimum Hb to predict late AKI was moderate ( c -statistic 0.68, 95% CI 0.64–0.72) with a sensitivity of 65.9%, a specificity of 69.7%, and a PPV of 20.8%. Conclusions Lower Hb in the first postnatal week was associated with late AKI, though the association no longer remained after fluid balance was included. Impact The current study suggests a possible novel association between low serum hemoglobin (Hb) and neonatal acute kidney injury (AKI). The study shows that low serum Hb levels in the first postnatal week are associated with increased risk of AKI after the first postnatal week. This study is the first to show this relationship in neonates. Because this study is retrospective, our observations cannot be considered proof of a causative role but do raise important questions and deserve further investigation. Whether the correction of low Hb levels might confer short- and/or long-term renal benefits in neonates was beyond the scope of this study.

The original version of this article unfortunately contained a mistake. The collaborators of the Neonatal Kidney Collaborative (NKC) were not named individually. The list of all collaborators is given below.

Understanding spatial variation in biodiversity along environmental gradients is a central theme in ecology. Differences in species compositional turnover among sites (β diversity) occurring along gradients are often used to infer variation in the processes structuring communities. Here, we show that sampling alone predicts changes in β diversity caused simply by changes in the sizes of species pools. For example, forest inventories sampled along latitudinal and elevational gradients show the well-documented pattern that β diversity is higher in the tropics and at low elevations. However, after correcting for variation in pooled species richness (γ diversity), these differences in β diversity disappear. Therefore, there is no need to invoke differences in the mechanisms of community assembly in temperate versus tropical systems to explain these global-scale patterns of β diversity.

Key Points Reactive oxygen species (ROS) include superoxide, hydrogen peroxide, singlet oxygen, ozone, hypohalous acids and organic peroxides. They interact with and share some of the actions of other classes of small, reactive, endogenous signalling molecules — reactive nitrogen species such as NO • and NO 2 • ; H 2 S or its anion, HS − ; and carbon monoxide. ROS can both promote and prevent cell death, cancer, ageing and inflammation. For example, ROS mediate inflammasome activation, but patients with chronic granulomatous disease, who lack a functional form of a principal ROS-producing enzyme, NADPH oxidase 2 (NOX2), demonstrate considerable susceptibility to infection, as well as non-resolving inflammation. The numerous enzymatic sources of ROS include mitochondria and multiple isoforms of NOXs. The first NOX, now called NOX2, was discovered in neutrophils, but NOXs contribute to signal transduction in diverse cell types. ROS are produced following B and T cell receptor stimulation and can dictate whether T cell activation is fostered or impeded. Many antioxidant systems contribute to the regulation of ROS, including superoxide dismutases, catalases and the enzymes of the glutathione redox cycle, which reflects the widespread functional effects of ROS. Reactions involving ROS demonstrate atomic rather than molecular specificity. That is, ROS preferentially react with certain types of atoms and most readily with a subset of those atoms, but the atomic targets of ROS are distributed in many different macromolecules. For example, ROS preferentially react with the sulphur atom in some but not other cysteine residues; the cysteine thiols that are most susceptible include many that participate in enzyme active sites, such as in phosphatases. This kind of specificity equips ROS to influence many different signalling pathways simultaneously. The immunosuppressive capacity of myeloid-derived suppressor cells and regulatory T cells results in part from their production of ROS. Tumour cells also produce ROS, which can contribute to their immunosuppressive and metastatic potential. Recent research has shed light on the complex regulation and functions of reactive oxygen species (ROS) signalling. In this Review, Nathan and Cunningham-Bussel provide an update on ROS biology, and they highlight some important roles for ROS in innate and adaptive immunity. Reactive oxygen species (ROS) react preferentially with certain atoms to modulate functions ranging from cell homeostasis to cell death. Molecular actions include both inhibition and activation of proteins, mutagenesis of DNA and activation of gene transcription. Cellular actions include promotion or suppression of inflammation, immunity and carcinogenesis. ROS help the host to compete against microorganisms and are also involved in intermicrobial competition. ROS chemistry and their pleiotropy make them difficult to localize, to quantify and to manipulate — challenges we must overcome to translate ROS biology into medical advances.