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1.
Int J Mol Sci ; 19(5)2018 May 01.
Article in English | MEDLINE | ID: mdl-29724000

ABSTRACT

Preterm infants often experience intermittent hypoxia (IH) with resolution in room air (RA) or hyperoxia (Hx) between events. Hypoxia is a major inducer of vascular endothelial growth factor, which plays a key role in normal and aberrant retinal angiogenesis. This study tested the hypothesis that neonatal IH which resolved with RA is less injurious to the immature retina than IH resolved by Hx between events. Newborn rats were exposed to: (1) Hx (50% O2) with brief hypoxia (12% O2); (2) RA with 12% O2; (3) Hx with RA; (4) Hx only; or (5) RA only, from P0 to P14. Pups were examined at P14 or placed in RA until P21. Retinal vascular and astrocyte integrity; retinal layer thickness; ocular and systemic biomarkers of angiogenesis; and somatic growth were determined at P14 and P21. All IH paradigms resulted in significant retinal vascular defects, disturbances in retinal astrocyte template, retinal thickening, and photoreceptor damage concurrent with elevations in angiogenesis biomarkers. These data suggest that the susceptibility of the immature retina to changes in oxygen render no differences in the outcomes between RA or O2 resolution. Interventions and initiatives to curtail O2 variations should remain a high priority to prevent severe retinopathy.


Subject(s)
Hypoxia/metabolism , Oxygen/adverse effects , Retina/pathology , Retinopathy of Prematurity/metabolism , Air , Animals , Animals, Newborn , Astrocytes/pathology , Biomarkers/blood , Hyperoxia/metabolism , Insulin-Like Growth Factor I/metabolism , Photoreceptor Cells, Vertebrate/pathology , Rats , Rats, Sprague-Dawley , Retinal Neovascularization/chemically induced , Retinal Neovascularization/metabolism , Retinopathy of Prematurity/chemically induced , Vascular Endothelial Growth Factor A/blood
2.
J Pediatr ; 158(3): 403-9, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21067771

ABSTRACT

OBJECTIVE: This is a repeat cohort study in which we sought to determine whether an association of necrotizing enterocolitis (NEC) <48 hours of a packed red blood cells (PRBC) transfusion was a prior sampling artifact. STUDY DESIGN: All very low birth weight neonates with NEC Stage ≥ IIB admitted over an 18-month period were categorized for NEC: (1) <48 hours after a PRBC transfusion; (2) unrelated to the timing of PRBCs; and (3) never transfused. RESULTS: Eight hundred eighty-three admissions over 18 months were reviewed; 256 were very low birth weight that resulted in 36 NEC cases and 25% were associated with PRBC (n = 9). PRBC-associated cases had lower birth weight, hematocrit, and rapid onset of signs (<5 hours). The timing of association of PRBC transfusion and NEC differed from random, showing a distribution that was not uniform over time (χ(2) = 170.7, df = 40; P < .000001) consistent with the possibility of a causative relationship in certain cases of NEC. Current weight at onset of NEC did not differ; however, the more immature the neonate the later the onset of NEC creating a curious centering of occurrence at a median of 31 weeks postconceptual age. CONCLUSIONS: We conclude that PRBC-related NEC exists. Transfusion-related acute gut injury is an acronym we propose to characterize a severe neonatal gastrointestinal reaction proximal to a transfusion of PRBCs for anemia. The convergence at 31 weeks postconceptual age approximates the age of presentation of other O(2) delivery and neovascularization syndromes, suggesting a link to a generalized systemic maturational mechanism.


Subject(s)
Enterocolitis, Necrotizing/etiology , Erythrocyte Transfusion/adverse effects , Infant, Very Low Birth Weight , Enterocolitis, Necrotizing/epidemiology , Female , Humans , Infant, Newborn , Linear Models , Male , New York/epidemiology , Retrospective Studies , Risk Factors , Time Factors
3.
Adv Ther ; 27(7): 476-82, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20586001

ABSTRACT

INTRODUCTION: The objective of this study was to compare the pulmonary inflammatory response of premature infants with respiratory distress following instillation of one of two commonly available surfactant preparations. METHODS: This was a prospective, randomized investigation of preterm infants who were less than 30 weeks of gestational age, weighed less than 1 kg at birth, and who qualified to receive surfactant. Infants with multiple congenital anomalies or whose mothers were taking anti-inflammatory medications were ineligible. Tracheal aspirates (TAs) were collected on days 1, 3, 5, and 7 and airway cytokines from TAs were assayed for interleukin (IL)-8 and IL-6. RESULTS: Infants were evenly matched by gestation (26+/-2 days and 26+/-1 days [mean+/-SD], Surfactant A and B, respectively) and birth weight (730+/-141 g and 732+/-167 g). TA cytokine levels were not different between or within groups. Ventilator requirements and clinical outcomes were similar between the two groups. CONCLUSION: The postnatal airway inflammatory response observed in preterm infants is not altered by the instillation of either surfactant preparation.


Subject(s)
Cytokines/metabolism , Infant, Premature , Pulmonary Surfactants/therapeutic use , Respiratory Distress Syndrome, Newborn/metabolism , Female , Humans , Infant, Newborn , Interleukin-6/metabolism , Interleukin-8/metabolism , Male , Respiratory Distress Syndrome, Newborn/drug therapy , Respiratory Distress Syndrome, Newborn/physiopathology , Respiratory Physiological Phenomena , Trachea/metabolism
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