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      Oxygen desaturations in the early neonatal period predict development of bronchopulmonary dysplasia

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          Abstract

          Background:

          Bradycardia and oxygen desaturation episodes are common among preterm very low birthweight (VLBW) infants in the Neonatal Intensive Care Unit (NICU), and their association with adverse outcomes such as bronchopulmonary dysplasia (BPD) is unclear.

          Methods:

          For 502 VLBW infants we quantified bradycardias (HR <100 for ≥ 4 seconds) and desaturations (SpO 2 <80% for ≥ 10 seconds), combined bradycardia and desaturation (BD) events, and percent time in events in the first 4 weeks after birth (32 infant-years of data). We tested logistic regression models of clinical risks (including a respiratory acuity score incorporating FiO 2 and level of respiratory support) to estimate the risks of BPD or death and secondary outcomes. We then tested the additive value of the bradycardia and desaturation metrics for outcomes prediction.

          Results:

          BPD occurred in 187 infants (37%). The clinical risk model had ROC area for BPD of 0.874. Measures of desaturation, but not bradycardia, significantly added to the predictive model. Desaturation metrics also added to clinical risks for prediction of severe intraventricular hemorrhage, retinopathy of prematurity and prolonged length of stay in the NICU.

          Conclusions:

          Oxygen desaturations in the first month of the NICU course are associated with risk of BPD and other morbidities in VLBW infants.

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          Most cited references28

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          Target ranges of oxygen saturation in extremely preterm infants.

          Waldemar A Carlo, Neil N Finer, Michele C Walsh … (2010)
          Previous studies have suggested that the incidence of retinopathy is lower in preterm infants with exposure to reduced levels of oxygenation than in those exposed to higher levels of oxygenation. However, it is unclear what range of oxygen saturation is appropriate to minimize retinopathy without increasing adverse outcomes. We performed a randomized trial with a 2-by-2 factorial design to compare target ranges of oxygen saturation of 85 to 89% or 91 to 95% among 1316 infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. The primary outcome was a composite of severe retinopathy of prematurity (defined as the presence of threshold retinopathy, the need for surgical ophthalmologic intervention, or the use of bevacizumab), death before discharge from the hospital, or both. All infants were also randomly assigned to continuous positive airway pressure or intubation and surfactant. The rates of severe retinopathy or death did not differ significantly between the lower-oxygen-saturation group and the higher-oxygen-saturation group (28.3% and 32.1%, respectively; relative risk with lower oxygen saturation, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P=0.21). Death before discharge occurred more frequently in the lower-oxygen-saturation group (in 19.9% of infants vs. 16.2%; relative risk, 1.27; 95% CI, 1.01 to 1.60; P=0.04), whereas severe retinopathy among survivors occurred less often in this group (8.6% vs. 17.9%; relative risk, 0.52; 95% CI, 0.37 to 0.73; P<0.001). There were no significant differences in the rates of other adverse events. A lower target range of oxygenation (85 to 89%), as compared with a higher range (91 to 95%), did not significantly decrease the composite outcome of severe retinopathy or death, but it resulted in an increase in mortality and a substantial decrease in severe retinopathy among survivors. The increase in mortality is a major concern, since a lower target range of oxygen saturation is increasingly being advocated to prevent retinopathy of prematurity. (ClinicalTrials.gov number, NCT00233324.) 2010 Massachusetts Medical Society
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            Prediction of bronchopulmonary dysplasia by postnatal age in extremely premature infants.

            Roger Faix, Wade Rich, Johannes van Goudoever … (2011)
            Benefits of identifying risk factors for bronchopulmonary dysplasia in extremely premature infants include providing prognostic information, identifying infants likely to benefit from preventive strategies, and stratifying infants for clinical trial enrollment. To identify risk factors for bronchopulmonary dysplasia, and the competing outcome of death, by postnatal day; to identify which risk factors improve prediction; and to develop a Web-based estimator using readily available clinical information to predict risk of bronchopulmonary dysplasia or death. We assessed infants of 23-30 weeks' gestation born in 17 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and enrolled in the Neonatal Research Network Benchmarking Trial from 2000-2004. Bronchopulmonary dysplasia was defined as a categorical variable (none, mild, moderate, or severe). We developed and validated models for bronchopulmonary dysplasia risk at six postnatal ages using gestational age, birth weight, race and ethnicity, sex, respiratory support, and Fi(O(2)), and examined the models using a C statistic (area under the curve). A total of 3,636 infants were eligible for this study. Prediction improved with advancing postnatal age, increasing from a C statistic of 0.793 on Day 1 to a maximum of 0.854 on Day 28. On Postnatal Days 1 and 3, gestational age best improved outcome prediction; on Postnatal Days 7, 14, 21, and 28, type of respiratory support did so. A Web-based model providing predicted estimates for bronchopulmonary dysplasia by postnatal day is available at https://neonatal.rti.org. The probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.
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              Oxygen Saturation and Outcomes in Preterm Infants

              Lisa M Askie, Brian Fleck, Ursula Bowler … (2013)
              The clinically appropriate range for oxygen saturation in preterm infants is unknown. Previous studies have shown that infants had reduced rates of retinopathy of prematurity when lower targets of oxygen saturation were used. In three international randomized, controlled trials, we evaluated the effects of targeting an oxygen saturation of 85 to 89%, as compared with a range of 91 to 95%, on disability-free survival at 2 years in infants born before 28 weeks' gestation. Halfway through the trials, the oximeter-calibration algorithm was revised. Recruitment was stopped early when an interim analysis showed an increased rate of death at 36 weeks in the group with a lower oxygen saturation. We analyzed pooled data from patients and now report hospital-discharge outcomes. A total of 2448 infants were recruited. Among the 1187 infants whose treatment used the revised oximeter-calibration algorithm, the rate of death was significantly higher in the lower-target group than in the higher-target group (23.1% vs. 15.9%; relative risk in the lower-target group, 1.45; 95% confidence interval [CI], 1.15 to 1.84; P=0.002). There was heterogeneity for mortality between the original algorithm and the revised algorithm (P=0.006) but not for other outcomes. In all 2448 infants, those in the lower-target group for oxygen saturation had a reduced rate of retinopathy of prematurity (10.6% vs. 13.5%; relative risk, 0.79; 95% CI, 0.63 to 1.00; P=0.045) and an increased rate of necrotizing enterocolitis (10.4% vs. 8.0%; relative risk, 1.31; 95% CI, 1.02 to 1.68; P=0.04). There were no significant between-group differences in rates of other outcomes or adverse events. Targeting an oxygen saturation below 90% with the use of current oximeters in extremely preterm infants was associated with an increased risk of death. (Funded by the Australian National Health and Medical Research Council and others; BOOST II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry numbers, ACTRN12605000055606 and ACTRN12605000253606.).
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 0100714
                Journal ID (pubmed-jr-id): 6400
                Journal ID (nlm-ta): Pediatr Res
                Journal ID (iso-abbrev): Pediatr. Res.
                Title: Pediatric research
                ISSN (Print): 0031-3998
                ISSN (Electronic): 1530-0447
                Publication date Nihms-submitted: 25 October 2018
                Publication date (Electronic): 29 October 2018
                Publication date PMC-release: 29 April 2019
                Electronic Location Identifier: 10.1038/s41390-018-0223-5
                Affiliations
                [1 ]Department of Pediatrics, University of Virginia, Charlottesville, VA
                [2 ]School of Medicine Research Computing, University of Virginia, Charlottesville, VA
                [3 ]Department of Medicine, University of Virginia, Charlottesville, VA
                Author notes
                Corresponding author: Karen Fairchild, Dept. of Pediatrics, P.O. Box 800386, University of Virginia, Charlottesville, VA 22908 kdf2n@ 123456virginia.edu office: (434)924-5428 fax: (434)924-2816
                Article
                Manuscript ID: NIHMS1509913
                DOI: 10.1038/s41390-018-0223-5
                PMC ID: 6488465
                PubMed ID: 30374050
                SO-VID: a4ee3afd-f368-4035-9450-01fda36c9d96
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                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

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                ScienceOpen disciplines: Pediatrics
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                ScienceOpen disciplines: Pediatrics

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