Published online October 2, 2006
PEDIATRICS Vol. 118 No. 4 October 2006, pp. 1640-1653 (doi:10.1542/10.1542/peds.2006-0653)
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ARTICLE

Cerebral Outcomes in a Preterm Baboon Model of Early Versus Delayed Nasal Continuous Positive Airway Pressure

Michelle Loeliger, PhDa, Terrie Inder, MBChBb,c, Sarah Cain, BSca, Rajalakshmi C. Ramesh, BSca, Emily Camm, PhDa, Merran A. Thomson, MB, ChBd, Jacqueline Coalson, PhDe and Sandra M. Rees, PhDa

a Department of Anatomy and Cell Biology, University of Melbourne, Victoria, Australia
b Department of Pediatrics, Royal Children's Hospital, Parkville, Victoria, Australia
c Department of Pediatrics, St Louis Children's Hospital, Washington University, St Louis, MO
d Division of Clinical Sciences, Imperial College, London, United Kingdom
e Departments of Pathology, University of Texas Health Science Center, San Antonio, Texas

BACKGROUND. The survival of prematurely born infants has greatly increased in recent decades because of advances in neonatal intensive care, which have included the advent of ventilatory therapies. However, there is limited knowledge as to the impact of these therapies on the developing brain. The purpose of this work was to evaluate the influence of randomized respiratory therapy with either early continuous positive airway pressure or delayed continuous positive airway pressure preceded by positive pressure ventilation on the extent of brain injury and altered development in a prematurely delivered primate model.

METHODS. Fetal baboons were delivered at 125 days of gestation (term: ~185 days of gestation) by cesarean section. Animals were maintained for 28 days postdelivery with either: early continuous positive airway pressure (commencing at 24 hours; n = 6) or delayed continuous positive airway pressure (positive pressure ventilation for 5 days followed by nCPAP; n = 5). Gestational controls (n = 4) were delivered at 153 days of gestation. At the completion of the study, animals were killed, the brains were assessed histologically for growth and development, and evidence of cerebral injury and indices for both parameters were formulated.

RESULTS. Brain and body weights were reduced in all of the nasal continuous positive airway pressure animals compared with controls; however, the brain/body weight ratio was increased in early continuous positive airway pressure animals. Within both nasal continuous positive airway pressure groups compared with controls, there was increased gliosis in the subcortical and deep white matter and cortex and a persistence of radial glia. Early continuous positive airway pressure was associated with less cerebral injury than delayed continuous positive airway pressure therapy. Neuropathologies were not observed in controls.

CONCLUSIONS. Premature delivery, in the absence of potentiating factors, such as hypoxia or infection, is associated with a decrease in brain growth and the presence of subtle brain injury, which seems to be modified by respiratory therapies with early continuous positive airway pressure being associated with less overall cerebral injury.

Key Words: nonhuman primate • prematurity • cerebral injury • white matter injury • nasal continuous positive airway pressure • positive pressure ventilation • neuropathology • brain development

Abbreviations: nCPAP—nasal continuous positive airway pressure • EnCPAP—early nasal continuous positive airway pressure • DnCPAP—delayed nasal continuous positive airway pressure • dg—days of gestation • PPV—positive pressure ventilation • PIP—peak inspiratory pressure • PEEP—positive end-expiratory pressure • FIO2—fraction of inspired oxygen • PaO2—partial arterial pressure of oxygen • PaCO2—partial arterial pressure of carbon dioxide • H&E—hematoxylin and eosin • LFB—luxol fast blue • GFAP—glial fibrillary acidic protein • SFI—surface folding index • HR—heart rate • MAP—mean arterial pressure

Accepted May 24, 2006.


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