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Early Neonatal Oxygen Exposure Predicts Pulmonary Morbidity and Functional Deficits at 1 Year - 22/07/20

Doi : 10.1016/j.jpeds.2020.04.042 
Andrew M. Dylag, MD 1, , Hannah G. Kopin, MPH 2, Michael A. O'Reilly, PhD 1, Hongyue Wang, PhD 3, Stephanie D. Davis, MD 4, Clement L. Ren, MD 5, Gloria S. Pryhuber, MD 1
1 Division of Neonatology, Department of Pediatrics, University of Rochester, Rochester, NY 
2 School of Medicine, School of Public Health Sciences, University of Rochester, Rochester, NY 
3 Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY 
4 Department of Pediatrics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 
5 Division of Pediatric Pulmonology, Allergy and Sleep Medicine, Riley Hospital for Children, Indiana University, Indianapolis, IN 

Reprint requests: Andrew M. Dylag, MD, Division of Neonatology, Department of Pediatrics, Golisano Children's Hospital, University of Rochester Medical Center, 601 Elmwood Ave, Box 651, Rochester, NY 14642.Division of NeonatologyDepartment of PediatricsGolisano Children's HospitalUniversity of Rochester Medical Center601 Elmwood AveBox 651RochesterNY14642

Abstract

Objective

To evaluate the predictive value of cumulative oxygen exposure thresholds over the first 2 postnatal weeks, linking them to bronchopulmonary dysplasia (BPD) and 1-year pulmonary morbidity and lung function in extremely low gestational age newborns.

Study design

Infants (N = 704) enrolled in the Prematurity and Respiratory Outcomes Program, a multicenter prospective cohort study, that survived to discharge were followed through their neonatal intensive care unit hospitalization to 1-year corrected age. Cumulative oxygen exposure (OxygenAUC14) thresholds were derived from univariate models of BPD, stratifying infants into high-, intermediate-, and low-oxygen exposure groups. These groups were then used in multivariate logistic regressions to prospectively predict post-prematurity respiratory disease (PRD), respiratory morbidity score (RMS) in the entire cohort, and pulmonary function z scores (N = 108 subset of infants) at 1-year corrected age.

Results

Over the first 14 postnatal days, infants exposed to high oxygen averaged ≥33.1% oxygen, infants exposed to intermediate oxygen averaged 29.1%-33.1%, and infants exposed to low oxygen were below both cutoffs. In multivariate models, infants exposed to high oxygen showed increased PRD and RMS, whereas infants exposed to intermediate oxygen demonstrated increased moderate/severe RMS. Infants in the high/intermediate groups had decreased forced expiratory volume at 0.5 seconds/forced vital capacity ratio.

Conclusions

OxygenAUC14 establishes 3 thresholds of oxygen exposure that risk stratify infants early in their neonatal course, thereby predicting short-term (BPD) and 1-year (PRD, RMS) respiratory morbidity. Infants with greater OxygenAUC14 have altered pulmonary function tests at 1 year of age, indicating early evidence of obstructive lung disease and flow limitation, which may predispose extremely low gestational age newborns to increased long-term pulmonary morbidity.

Trial registration

ClinicalTrials.gov: NCT01435187.

Le texte complet de cet article est disponible en PDF.

Keywords : bronchopulmonary dysplasia, neonatology, pulmonary function

Abbreviations : AUC, BPD, ELGAN, FEF25-75, FEV0.5, FIO2, FVC, MAP, msBPD, NICU, OxygenAUC14, PFT, PRD, PROP, RMS, sBPD


Plan


 The Prematurity and Respiratory Outcomes Program (PROP) was supported by National Institutes of Health; National Heart, Lung, and Blood Institute (NHLBI); and Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01 HL101794 [to University of Pennsylvania, B. Schmidt]; U01 HL101456 [to Vanderbilt University, J.L. Aschner]; U01 HL101798 [to University of California San Francisco, P.L. Ballard and R.L. Keller]; U01 HL101813 [to University of Rochester and University at Buffalo, G.P., R. Ryan, and T. Mariani]; U01 HL101465 [to Washington University, A. Hamvas and T. Ferkol]; U01 HL101800 [to Cincinnati Children's Hospital Medical Center, A.H. Jobe and C.A. Chougnet]; and 5R01HL105702 [to Indiana University and Duke University, C.M. Cotton, S.D. Davis, and J.A. Voynow]). This research was conducted through cooperative agreements with NHLBI and in collaboration with the PROP Steering Committee. The authors declare no conflicts of interest.


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Vol 223

P. 20 - août 2020 Retour au numéro
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