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The fetal circulation, pathophysiology of hypoxemic respiratory failure and pulmonary hypertension in neonates, and the role of oxygen therapy

Journal of Perinatology volume 36, pages S3–S11 (2016)Cite this article

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Abstract

Neonatal hypoxemic respiratory failure (HRF), a deficiency of oxygenation associated with insufficient ventilation, can occur due to a variety of etiologies. HRF can result when pulmonary vascular resistance (PVR) fails to decrease at birth, leading to persistent pulmonary hypertension of newborn (PPHN), or as a result of various lung disorders including congenital abnormalities such as diaphragmatic hernia, and disorders of transition such as respiratory distress syndrome, transient tachypnea of newborn and perinatal asphyxia. PVR changes throughout fetal life, evident by the dynamic changes in pulmonary blood flow at different gestational ages. Pulmonary vascular transition at birth requires an interplay between multiple vasoactive mediators such as nitric oxide, which can be potentially inactivated by superoxide anions. Superoxide anions have a key role in the pathophysiology of HRF. Oxygen (O2) therapy, used in newborns long before our knowledge of the complex nature of HRF and PPHN, has continued to evolve. Over time has come the discovery that too much O2 can be toxic. Recommendations on the optimal inspired O2 levels to initiate resuscitation in term newborns have ranged from 100% (pre 1998) to the currently recommended use of room air (21%). Questions remain about the most effective levels, particularly in preterm and low birth weight newborns. Attaining the appropriate balance between hypoxemia and hyperoxemia, and targeting treatments to the pathophysiology of HRF in each individual newborn are critical factors in the development of improved therapies to optimize outcomes.

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Acknowledgements

This article is based on discussions at a roundtable meeting supported by a grant from Mallinckrodt Pharmaceuticals, formerly Ikaria. Presentations and discussions were developed solely by the participants, without grantor input. The meeting chair Robin Steinhorn, MD, determined the agenda and attendees. SL and ODS developed the presentations and led the discussions upon which this article is based, provided critical review and revisions to the outline and manuscript drafts, provided final approval of the version to be published, and are accountable for the integrity of the content and for addressing questions. We gratefully acknowledge Robin Steinhorn, MD, for critical review of the manuscript and the contributions of the following individuals who participated in discussion that shaped the content of this article: Namasivayam Ambalavanan, MD; Judy L Aschner, MD; Jason Gien, MD; John Kinsella, MD; G Ganesh Konduri, MD; Robin Steinhorn, MD. Writing and editorial assistance was provided by Saema Magre, Sharon Suntag and Julie Gerke of Quintiles.

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  1. Department of Pediatrics, University of Buffalo, Buffalo, NY, USA

    S Lakshminrusimha

  2. Department of Pediatric Research, University of Oslo and Oslo University Hospital, Oslo, Norway

    O D Saugstad

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Correspondence to S Lakshminrusimha.

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SL and ODS received honoraria for their participation in a roundtable meeting supported by a grant from Mallinckrodt Pharmaceuticals, formerly Ikaria. SL was a member of the speaker’s bureau for Ikaria from June 2010 to October 2014 and has received grant support from the American Academy of Pediatrics and Canadian Pediatric Society. SL also received an NIH grant (5R01HD072929-03).

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Lakshminrusimha, S., Saugstad, O. The fetal circulation, pathophysiology of hypoxemic respiratory failure and pulmonary hypertension in neonates, and the role of oxygen therapy. J Perinatol 36 (Suppl 2), S3–S11 (2016). https://doi.org/10.1038/jp.2016.43

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