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Management of hypoxemic respiratory failure and pulmonary hypertension in preterm infants

Journal of Perinatology volume 36, pages S20–S27 (2016)Cite this article

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Abstract

While diagnoses of hypoxemic respiratory failure (HRF) and pulmonary hypertension (PH) in preterm infants may be based on criteria similar to those in term infants, management approaches often differ. In preterm infants, HRF can be classified as ‘early’ or ‘late’ based on an arbitrary threshold of 28 postnatal days. Among preterm infants with late HRF, the pulmonary vascular abnormalities associated with bronchopulmonary dysplasia (BPD) represent a therapeutic challenge for clinicians. Surfactant, inhaled nitric oxide (iNO), sildenafil, prostacyclin and endothelin receptor blockers have been used to manage infants with both early and late HRF. However, evidence is lacking for most therapies currently in use. Chronic oral sildenafil therapy for BPD-associated PH has demonstrated some preliminary efficacy. A favorable response to iNO has been documented in some preterm infants with early PH following premature prolonged rupture of membranes and oligohydramnios. Management is complicated by a lack of clear demarcation between interventions designed to manage respiratory distress syndrome, prevent BPD and treat HRF. Heterogeneity in clinical phenotype, pathobiology and genomic underpinnings of BPD pose challenges for evidence-based management recommendations. Greater insight into the spectrum of disease phenotypes represented by BPD can optimize existing therapies and promote development of new treatments. In addition, better understanding of an individual’s phenotype, genotype and biomarkers may suggest targeted personalized interventions. Initiatives such as the Prematurity and Respiratory Outcomes Program provide a framework to address these challenges using genetic, environmental, physiological and clinical data as well as large repositories of patient samples.

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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. NA and JLA 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 the contributions of the following individuals who participated in discussion that shaped the content of this article: Jason Gien, MD; John Kinsella, MD; G Ganesh Konduri, MD; Satyan Lakshminrusimha, MD; Ola Didrik Saugstad, MD, PhD, FRCPE; and Robin Steinhorn, MD. Writing and editorial assistance was provided by John Kross, Sharon Suntag and Julie Gerke of Quintiles.

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Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA

    N Ambalavanan

  2. Department of Pediatrics, and Obstetrics, Gynecology and Women’s Health, Albert Einstein College of Medicine; Children’s Hospital at Montefiore,

    J L Aschner

  3. Children’s Hospital at Montefiore, Bronx, NY, USA

    J L Aschner

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  1. N Ambalavanan
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  2. J L Aschner
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Correspondence to N Ambalavanan.

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Competing interests

JLA and NA received honoraria for their participation in a roundtable meeting supported by a grant from Mallinckrodt Pharmaceuticals, formerly Ikaria. JLA owns stock in Gilead, and is named on an intellectual property rights patent for the use of intravenous citrulline for neonatal lung diseases. NA has received research support from Pfizer, and has received research support as a mentor from Ikaria. NIH Grants: 1U01HL101456 (JLA); U01 HL122626 and R01 HD067126 (NA).

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Ambalavanan, N., Aschner, J. Management of hypoxemic respiratory failure and pulmonary hypertension in preterm infants. J Perinatol 36 (Suppl 2), S20–S27 (2016). https://doi.org/10.1038/jp.2016.45

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