BackgroundSingle-center studies suggest that neonatal acute kidney injury (AKI)
is associated with poor outcomes. However, inferences regarding the
association between AKI, mortality, and hospital length of stay are limited
due to the small sample size of those studies. In order to determine whether
neonatal AKI is independently associated with increased mortality and longer
hospital stay, we analyzed the Assessment of Worldwide Acute Kidney
Epidemiology in Neonates (AWAKEN) database.MethodsAll neonates admitted to 24 participating neonatal intensive care
units from four countries (Australia, Canada, India, United States) between
January 1 and March 31, 2014, were screened. Of 4273 neonates screened, 2022
(47·3%) met study criteria. Exclusion criteria included: no
intravenous fluids ≥48 hours, admission ≥14 days of life,
congenital heart disease requiring surgical repair at <7 days of life,
lethal chromosomal anomaly, death within 48 hours, inability to determine
AKI status or severe congenital kidney abnormalities. AKI was defined using
a standardized definition —i.e., serum creatinine rise of
≥0.3 mg/dL (26.5 mcmol/L) or ≥50% from previous
lowest value, and/or if urine output was <1 mL/kg/h on postnatal days 2
to 7.FindingsIncidence of AKI was 605/2022 (29·9%). Rates varied
by gestational age groups (i.e., ≥22 to <29 weeks
=47·9%; ≥29 to <36 weeks
=18·3%; and ≥36 weeks
=36·7%). Even after adjusting for multiple potential
confounding factors, infants with AKI had higher mortality compared to those
without AKI [(59/605 (9·7%) vs. 20/1417
(1·4%); p< 0.001; adjusted OR=4·6
(95% CI=2·5–8·3);
p=<0·0001], and longer hospital stay
[adjusted parameter estimate 8·8 days (95%
CI=6·1–11·5);
p<0·0001].InterpretationNeonatal AKI is a common and independent risk factor for mortality
and longer hospital stay. These data suggest that neonates may be impacted
by AKI in a manner similar to pediatric and adult patients.FundingUS National Institutes of Health, University of Alabama at
Birmingham, Cincinnati Children’s, University of New Mexico.
BACKGROUND-High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established.
METHODS-In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth.
Background & Aims-Premature neonates are predisposed to necrotizing enterocolitis (NEC), an idiopathic, inflammatory bowel necrosis. We investigated the hypothesis that NEC occurs in the preterm intestine due to incomplete 'non-inflammatory' differentiation of intestinal macrophages, which increases the risk of a severe mucosal inflammatory response to bacterial products.
The combination of early Epo and iron as administered in this study stimulated erythropoiesis in infants who were =1250 g at birth. However, the lack of impact on transfusion requirements fails to support routine use of early Epo.neonate, intravenous iron, donor exposure.
Background
Bronchopulmonary dysplasia and emphysema are life-threatening diseases resulting from impaired alveolar development or alveolar destruction. Both conditions lack effective therapies. Angiogenic growth factors promote alveolar growth and contribute to alveolar maintenance. Endothelial colony-forming cells (ECFCs) represent a subset of circulating and resident endothelial cells capable of self-renewal and de novo vessel formation. We hypothesized that resident ECFCs exist in the developing lung, that they are impaired during arrested alveolar growth in experimental bronchopulmonary dysplasia, and that exogenous ECFCs restore disrupted alveolar growth.
Methods and Results
Human fetal and neonatal rat lungs contain ECFCs with robust proliferative potential, secondary colony formation on replating, and de novo blood vessel formation in vivo when transplanted into immunodeficient mice. In contrast, human fetal lung ECFCs exposed to hyperoxia in vitro and neonatal rat ECFCs isolated from hyperoxic alveolar growth–arrested rat lungs mimicking bronchopulmonary dysplasia proliferated less, showed decreased clonogenic capacity, and formed fewer capillary-like networks. Intrajugular administration of human cord blood–derived ECFCs after established arrested alveolar growth restored lung function, alveolar and lung vascular growth, and attenuated pulmonary hypertension. Lung ECFC colony- and capillary-like network-forming capabilities were also restored. Low ECFC engraftment and the protective effect of cell-free ECFC-derived conditioned media suggest a paracrine effect. Long-term (10 months) assessment of ECFC therapy showed no adverse effects with persistent improvement in lung structure, exercise capacity, and pulmonary hypertension.
Conclusions
Impaired ECFC function may contribute to arrested alveolar growth. Cord blood–derived ECFC therapy may offer new therapeutic options for lung diseases characterized by alveolar damage.
Erythropoietin concentrations did not correlate with Psychomotor Development Index or overall incidence of neurodevelopmental impairment; however, infants with elevated erythropoietin concentrations had higher Mental Development Index scores than those with lower erythropoietin concentrations. Close follow-up of infants who are enrolled in large, multicenter, high-dose erythropoietin studies is required to determine whether a correlation exists between elevated erythropoietin concentrations and improved neurodevelopmental outcome.
Objectives
To identify variables associated with successful elective extubation, and to determine neonatal morbidities associated with extubation failure in extremely preterm neonates.
Study design
This study was a secondary analysis of the National Institute of Child Health and Human Development Neonatal Research Network’s Surfactant, Positive Pressure, and Oxygenation Randomized Trial that included extremely preterm infants born at 240/7 to 276/7 weeks’ gestation. Patients were randomized either to a permissive ventilatory strategy (continuous positive airway pressure group) or intubation followed by early surfactant (surfactant group). There were prespecified intubation and extubation criteria. Extubation failure was defined as reintubation within 5 days of extubation.
Results
Of 1316 infants in the trial, 1071 were eligible; 926 infants had data available on extubation status; 538 were successful and 388 failed extubation. The rate of successful extubation was 50% (188/374) in the continuous positive airway pressure group and 63% (350/552) in the surfactant group. Successful extubation was associated with higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within the first 24 hours of age and prior to extubation, lower partial pressure of carbon dioxide prior to extubation, and non-small for gestational age status after adjustment for the randomization group assignment. Infants who failed extubation had higher adjusted rates of mortality (OR 2.89), bronchopulmonary dysplasia (OR 3.06), and death/bronchopulmonary dysplasia (OR 3.27).
Conclusions
Higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within first 24 hours of age, lower partial pressure of carbon dioxide and fraction of inspired oxygen prior to extubation, and nonsmall for gestational age status were associated with successful extubation. Failed extubation was associated with significantly higher likelihood of mortality and morbidities.
Trial registration
ClinicalTrials.gov: NCT00233324.
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